Photographs on the cover are provided courtesy of the Lance Armstrong Foundation.
Closing the Gap:
Research and Care Imperatives for Adolescents and
Young Adults with Cancer
Report of the Adolescent and Young Adult Oncology
Progress Review Group
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Cancer Institute
LIVE
STRONG
™ Young Adult Alliance
Report of the Adolescent and Young Adult Oncology Progress Review Group
FROM THE ADOLESCENT AND YOUNG ADULT ONCOLOGY PROGRESS REVIEW GROUP
It is our great privilege to submit this Report of the Adolescent and Young Adult Oncology Progress Review Group
(AYAO PRG) to the Advisory Committee to the Director of the National Cancer Institute (NCI). This document is
the product of an innovative, collaborative effort, the fi rst public-private partnership of its kind, between NCI and
the Lance Armstrong Foundation (LAF). The nation’s leading researchers and clinicians in adolescent and young
adult oncology joined with cancer survivors, advocates, pediatricians, gerontologists, disease-specifi c experts,
statisticians, and insurance and pharmaceutical industry representatives to develop recommendations for a national
agenda to advance adolescent and young adult oncology. The AYAO PRG is only the second PRG not to be disease-
specifi c, and the cross-disciplinary nature of this collaboration is refl ected in the diversity of its membership.
We hope this report will raise the awareness of the health care and research communities and the general public to
the reality of cancer as a major health problem in this population and the unique challenges faced by adolescents
and young adults diagnosed with cancer. We fully expect the recommendations in the report to act as catalysts for
future programs and initiatives. An implementation meeting, sponsored by the LIVE
STRONG
™ Young Adult
Alliance, has been arranged to discuss how these recommendations can most effectively and effi ciently be realized
to improve the outcomes and quality of life for adolescents and young adults with cancer. We look forward eagerly
to this discussion and the development of concrete strategies for action.
Karen Albritton, M.D. Michael Caligiuri, M.D. Barry Anderson, M.D., Ph.D.
PRG Co-Chair PRG Co-Chair PRG Executive Director
Cherie Nichols, M.B.A. Doug Ulman
National Cancer Institute Lance Armstrong Foundation
Representative Representative
Report of the Adolescent and Young Adult Oncology Progress Review Group
Brad Pollock, M.P.H., Ph.D.
Amelie G. Ramirez, Dr.P.H.
Amelie G. Ramirez, Dr.P.H.
Lynn Ries, M.S.
Lorna Rodriguez-Rodriguez, M.D., Ph.D.
Lydia A. Shrier, M.D., M.P.H.
Muneesh Tewari, M.D., Ph.D.
Beth Virnig, Ph.D., M.P.H.
Beth Virnig, Ph.D., M.P.H.
Karen Weiss, M.D.
Karen Weiss, M.D.
Bruce Williams
Brock Yetso
Brock Yetso
Brad Zebrack, Ph.D.
Heidi Adams
Heidi Adams
Lodovico Balducci, M.D.
Ronald D. Barr, M.B. Ch.B., M.D.
Archie Bleyer, M.D.
Maryann Carousso, F.N.P., R.N.
Maryann Carousso, F.N.P., R.N.
William J. Hicks, M.D.
William J. Hicks, M.D.
Marion Lee, M.P.H., Ph.D.
Steven M. Lipkin, M.D., Ph.D.
Steven M. Lipkin, M.D., Ph.D.
Mary S. McCabe, R.N.
Michael L. Moore, M.D.
Peter Pisters, M.D.
PRG Members
Report of the Adolescent and Young Adult Oncology Progress Review Group
ACKNOWLEDGMENTS
The Adolescent and Young Adult Oncology Progress Review Group (AYAO PRG) process has been a collaborative
effort of the National Cancer Institute (NCI) and the Lance Armstrong Foundation (LAF) involving contributions
from numerous people with different backgrounds, skills, and talents. The AYAO PRG wishes to acknowledge and
extend special thanks to the following groups and individuals:
• The many scientists, clinicians, advocates, and other professionals who generously gave of their time
and knowledge. Without their participation, this report would not have been possible. In particular, we
acknowledge the participants in our AYAO PRG Roundtable meeting and the extraordinary efforts of not only
the PRG members and Co-Chairs but the non-PRG Co-Chairs of our Roundtable Breakout Groups—Marjorie
Kagawa Singer, Kimberly Calder, Smita Bhatia, William Carroll, Robert Comis, Jennifer Ford, Carolyn
Gotay, Brandon Hayes-Lattin, Robert Hiatt, Sandra Horning, Ian Lewis, Joan McClure, Kevin Oeffi nger,
Joseph San Filippo, and Carol Somkin.
• The staff of the NCI Offi ce of Science Planning and Assessment, under the leadership of Cherie Nichols,
who provided ongoing guidance, technical support, and encouragement throughout the process. In particular,
we acknowledge the hard work and dedication of Anne Tatem, Joy Wiszneauckas, Jamelle Banks, and Julie
Mendelsohn.
• The staff at LAF, led by Doug Ulman, who provided coordination and ongoing support in all phases
of the AYAO PRG process. We would like to recognize the hard work of David Lyon, Tina Hamilton,
Claire Neal, Schlonge Dermody, and Devon McGoldrick. We look forward to their efforts in moving the
recommendations into action through the work of the LIVE
STRONG
™ Young Adult Alliance and by
convening the Implementation meeting with experts of the oncology community.
• Beth Mathews-Bradshaw at Science Applications International Corporation (SAIC) for her hard work,
dedication, and meticulous attention to detail while coordinating this effort to keep the PRG focused and on
target.
• The staff of SAIC who assisted in logistics, documentation, and breakout session report preparation: Karen
Rulli and Adeyinka Smith for preparing portfolio analyses and resource materials; Rob Watson for conference
support; Deborah Berlyne, Adam Book, Greg Cole, Maneesha James, Eric Levine, Sabina Robinson, Karen
Rulli, Anita Sabourin, Heather Sansbury, and Pamela Zingeser for serving as science writers; and Jennifer
Secula and Julie Jessup for their expertise related to the design, layout, and editing of the report.
• Suzanne Reuben of Progressive Health Systems, who, as lead science writer, worked steadfastly in crafting
this report.
• Janis Mullaney at the Foundation for the National Institutes of Health (NIH) for her help in establishing the
NCI/LAF public-private partnership.
• NOVA Research, in particular, Ben Neal, for developing and maintaining the AYAO PRG Web site.
• Lynn Ries of the NCI Division of Cancer Control and Population Sciences for her tireless efforts generating
Surveillance, Epidemiology, and End Results (SEER) data for the report.
Report of the Adolescent and Young Adult Oncology Progress Review Group
TABLE OF CONTENTS
Executive Summary
...................................................................................................................................................
i
Introduction
...............................................................................................................................................................
1
Impetus for the Adolescent and Young Adult Oncology Progress Review Group (AYAO PRG)
..........................
1
The PRG Process
................................................................................................................................................
1
The AYAO PRG
...................................................................................................................................................
2
Cancer in the Adolescent and Young Adult (AYA) Population
.............................................................................
3
AYAs Defi ned
.......................................................................................................................................................
3
Cancers Affecting the AYA Population
.................................................................................................................
6
Factors Limiting Progress Against Cancer in the AYA Population
.......................................................................
6
Recommendations
...................................................................................................................................................
11
Conclusion
..............................................................................................................................................................
19
Appendices
Appendix A: Roster of AYAO PRG Participants
..............................................................................................
A-1
Appendix B: Breakout Group Reports
.............................................................................................................
B-1
Appendix C: Charge to the AYAO PRG
..........................................................................................................
C-1
Appendix D: Average Annual Percentage Change in 5-Year Relative Survival of Patients
Diagnosed with Cancer During 1975-1997, Selected Diseases, U.S. SEER
............................
D-1
Appendix E: Glossary of Terms and Acronyms
...............................................................................................
E-1
Report of the Adolescent and Young Adult Oncology Progress Review Group
Executive Summary i
Relatively little is known about biologic, genetic,
epidemiologic, therapeutic, psychosocial, and
economic factors that affect the incidence, disease
outcomes, and quality of life of adolescents and young
adults (AYAs) diagnosed with cancer. However, it
is known that compared with younger and older age
groups, this population—defi ned as those
diagnosed
with cancer at ages 15 through 39
—has seen little or
no improvement in cancer survival rates for decades.
In 2005-2006, the National Cancer Institute (NCI)
partnered with the Lance Armstrong Foundation (LAF)
to conduct a Progress Review Group (PRG) to address
the special research and cancer care needs of the AYA
age group and solicit recommendations for a national
agenda to improve cancer prevention, early detection,
diagnosis, treatment (including survivorship care), and
outcomes among these patients. An Adolescent and
Young Adult Oncology Progress Review Group (AYAO
PRG) was convened, drawing together more than 100
experts from diverse disciplines across the research
enterprise, the cancer control continuum, and the
advocacy and survivor communities. Further, the PRG
leadership sought the input of individuals whose work
in areas not related directly to AYA cancer research
and care might offer important insights for addressing
AYA-specifi c concerns.
Cancers Affecting the Adolescent and
Young Adult Population
Nearly 68,000 people aged 15 to 39 years were
diagnosed with cancer in 2002, approximately 8
times more than children under age 15. These cases
represent about 6 percent of all new cancer diagnoses.
Excluding homicide, suicide, and unintentional injury,
cancer is the leading cause of death among 15 to
39 year-olds. It is the most common cause of death
among females in this age group, and among males
in this group only heart disease claims more lives
annually than cancer.
The most common tumors in 15 to 39 year-olds
(accounting for 86 percent of cancers in the age
range) are breast cancer, lymphoma, germ cell tumors
(including testicular cancer), thyroid carcinoma,
sarcoma (bone and soft tissue), cervical carcinoma,
leukemia, colorectal carcinoma, and central nervous
system tumors. However, the incidence of specifi c
cancer types varies considerably across the AYA age
continuum. For example, among younger AYAs (15
to 19 year-olds), lymphomas, germ cell tumors, and
leukemias account for the largest percentages of all
cancers. Between ages 20 and 39, these and other
cancers decline as a percentage of all cases, while
carcinomas (particularly breast cancer) comprise an
increasing share of cancers in the AYA age cohort.
Non-Hispanic whites in the AYA age group have the
highest incidence of cancer, but also have the highest
overall 5-year survival. American Indians/Alaska
Natives have the lowest cancer incidence, but also have
poor survival rates. African Americans, however, have
the lowest 5-year survival rate across the age range.
Factors Limiting Progress Against
Cancer in Adolescents and Young Adults
Overall, progress in AYA oncology has been hampered
because cancer risk and adverse cancer outcomes have
been under-recognized in this population. Several
closely interrelated factors may have contributed to the
failure to improve the outcomes of AYAs with cancer.
Access to care can be restricted or delayed, in part
because AYAs have the highest uninsured rate of any
age group in the country. Diagnosis can be delayed
because AYAs typically see themselves as invulnerable
to serious disease or injury, causing them to ignore
or minimize symptoms and delay seeking medical
attention. Delayed diagnosis also is common because
providers tend to have a low suspicion of cancer in this
population. Symptoms of cancer may be attributed
to fatigue, stress, or other causes. AYAs with fi rst
symptoms of cancer may see a variety of health care
providers, including pediatricians, internists, family
physicians, emergency room physicians, gynecologists,
dermatologists, gastroenterologists, neurologists,
surgeons, orthopedists, and other specialists.
Once seen, referral patterns for AYAs with suspected
or diagnosed cancers vary widely. These patients too
frequently fall into a “no man’s land” between pediatric
and adult oncology; they may be treated by pediatric,
adult medical, radiation, surgical, or gynecologic
oncologists. Most AYAs are treated in the community
EXECUTIVE SUMMARY
Report of the Adolescent and Young Adult Oncology Progress Review Group
ii
Executive Summary
ii Executive Summary ii
rather than in cancer centers, but a robust community
oncology and primary care infrastructure currently
does not exist to enable patient data collection and
aggregation that would support research efforts. In
addition, contact with many AYA patients is lost
following treatment, complicating collection of
late effects and outcome data in this highly mobile
population.
Research on AYAs has been further constrained by
their exceedingly low participation in the relatively
few clinical trials available to them, in part because
diagnosing physicians seldom refer these patients to
trials. Poor understanding of patient and tumor biology
that distinguishes cancers in this population has
contributed to minimal advances in treatment.
Inconsistency in treatment and follow-up care, coupled
with insuffi cient research data, has prevented the
development of guidelines for treating and monitoring
AYAs with cancer, and few tools exist to measure the
effi cacy of treatment and psychosocial interventions
delivered in diverse settings.
Psychosocial and support services available to AYAs
with cancer (and their families/caregivers) are limited,
although their needs for such services tend to be
broader in scope and intensity than among younger
and older patients because of the many emotional,
developmental, and social changes and transitions
that occur during this stage of life. Lastly, cancer
prevention and early detection receive little emphasis in
health care for the AYA population.
Recommendations
The AYAO PRG identifi ed fi ve imperatives for
improving the outcomes of adolescents and young
adults with cancer.
Recommendation 1: Identify the characteristics
that distinguish the unique cancer burden in the
AYAO patient.
A signifi cantly more robust research effort is needed
to better understand tumor and human factors that
contribute to AYAs’ susceptibility to cancer, their
response to treatment, and their disease outcomes.
Among the cancers affecting AYAs, the PRG identifi ed
as particularly high priorities basic and other biologic
research on aging and patient/host-related factors
in non-Kaposi’s sarcoma, leukemia, lymphoma,
and breast and colorectal carcinomas. Additionally,
increased resources are needed for studies of AYAs’
genetic susceptibility to cancer.
AYA cancer patients and survivors face developmental
challenges that both exceed signifi cantly those faced by
other young people and are distinct from the challenges
faced by other age groups with cancer. Research
is needed to better understand patient and survivor
life stage and developmental characteristics across
six principal domains—intellectual, interpersonal,
emotional, practical, existential/spiritual, and
cultural—that singly or in combination may have
profound effects on individuals’ medical outcomes and
quality of life.
In addition, the factors that characterize and account
for disparities experienced by AYA cancer patients
and survivors are understood only in the broadest
terms and may include human and disease biology,
pharmacogenetics, socioeconomic factors, and the
appropriateness and accessibility of health services
(especially clinical trials). Therefore, research is
needed to elucidate in detail the factors contributing to
under-service and poorer outcomes among AYAs as a
whole and among racial and ethnic subgroups within
the AYA population.
Recommendation 2: Provide education, training,
and communication to improve awareness,
prevention, access, and quality cancer care for
AYAs.
The AYAO PRG recognized an urgent need for a
variety of education, training, and communication
activities to raise awareness and recognition of the AYA
population at both public and professional levels as a
fi rst step toward increasing national focus and resource
allocation to address the AYA cancer problem. To be
effective, all education, training, and communications
must be culturally appropriate and delivered by
individuals who are culturally competent.
Educational and other interventions to modify the
exposure of AYAs in the general population to
potentially modifi able cancer risk factors (e.g., human
papillomavirus, ultraviolet light, poor diet, lack of
physical activity, obesity, tobacco use) offer the
opportunity to reduce cancer risk during the AYA years
as well as risk for cancers in older adulthood. Efforts
Report of the Adolescent and Young Adult Oncology Progress Review Group
Executive Summary iii
also are needed to promote the importance of health
insurance in this population, since neither AYAs nor
their families may place a high priority on maintaining
coverage for young people who typically are healthy.
For those diagnosed with cancer and their families,
targeted education and online resources for cancer
information, insurance resources, peer support, and
other information needs will help empower AYAs to
understand and manage their own care.
Current health care provider training programs
generally do not address AYA-specifi c issues,
resulting in poor recognition of AYAs’ cancer risk and
inadequate response to their medical and psychosocial
needs. Core competency curricula are needed for
inclusion in appropriate initial training and continuing
education programs to ensure that all providers who
work with adolescents and young adults have the
requisite understanding of the cancers that either
peak or occur more commonly in this age group,
post-treatment surveillance for late effects, and the
specifi c psychosocial, economic, educational, and
communication needs of the population. Programs
also are needed to train patient navigators, advocates,
and other lay persons who conduct outreach to and
represent AYA interests. It was the consensus of the
PRG that physician involvement is the key factor in the
patient’s decision to participate in a clinical trial. Thus,
targeted education to raise referring physicians’ and
medical oncologists’ awareness of the potential benefi t
of AYAO relevant trials provides a means to improve
patient outcomes.
Recommendation 3: Create the tools to study the
AYA cancer problem.
The existing research infrastructure is inadequate to
support needed AYA-focused research. Appropriate
research tools to enable such studies must be developed
if they do not exist, and strengthened if potentially
useful infrastructure already is in place.
The most pressing needs are to: (1) create a
prospective database on all AYA cancer patients;
(2) increase the number of annotated AYA tumor,
normal tissue, and other biospecimens; (3) create
or modify assessment tools specifi c to AYA cancer
issues; (4) improve grant coding and search term
standardization; and (5) expand the number of clinical
trials appropriate for and available to AYAs.
Recommendation 4: Ensure excellence in service
delivery across the cancer control continuum
(i.e., prevention, screening, diagnosis, treatment,
survivorship, and end of life).
The AYAO PRG urges the implementation of two
principal strategies to improve service delivery to AYAs
with or at risk for cancer and ensure excellence in care
across the cancer control continuum. First, standards
of care for AYA cancer patients must be developed,
evaluated, and disseminated. This enormous task must
be undertaken with the understanding that standards
are dynamic and must be updated as advances in care
are achieved. Excellence in care may vary not only by
cancer diagnosis but by multiple other variables (e.g.,
age and gender, race/ethnicity/culture, socioeconomic
status, access to/source of care, insurance status) that
must be addressed to meet the complete spectrum of
patient needs.
Second, establishing, disseminating, and reinforcing
standards of cancer care for AYAs will require the
ongoing and concerted collaboration of a diverse
array of stakeholders. Health care providers, research
sponsors, investigators, regulators, insurers, and patient
advocates should expand existing collaborations and
establish a national network or coalition committed to
improving the quality of life and outcomes for AYAs
with cancer.
Recommendation 5: Strengthen and promote
advocacy and support of the AYA cancer patient.
In addition to raising public and professional awareness
of AYAs as a distinct understudied and underserved
age group, advocacy and support services for AYA
cancer patients and survivors need to be strengthened.
Such effective support of AYAs with cancer must
be predicated on an understanding of how cancer
may affect young peoples’ self-identity, self-esteem,
spiritual perspectives, body image, perception of
their future possible life goals, distress levels, need
for information and communication, and numerous
other subjective components of experiencing a life-
threatening disease. Empirical research is needed to
explore these aspects of the cancer experience among
AYAs and inform intervention development and health
care provider training.
Report of the Adolescent and Young Adult Oncology Progress Review Group
iv
Executive Summary
iv Executive Summary iv
Numerous advocacy, patient support, social service,
religious, fraternal, social, and health professional
organizations currently have some focus on AYA
cancer patients and survivors. Training and fi scal
support are needed to expand the capacity of these
established entities to address the psychosocial needs
of this population. In addition to building the capacity
of existing resources to address the psychosocial needs
of AYAs, evaluation is needed to assess the effi cacy
(i.e., effect on outcomes) of existing programs. These
evaluations should be used to inform the development
of new AYA-specifi c interventions.
Conclusion
Cancer in adolescents and young adults is an important
problem that has gone unrecognized or is only a
peripheral concern among numerous research, medical,
health services payor, patient support and advocacy,
funding, and cancer surveillance constituencies, as
well as healthy teenagers and young adults who do
not know they are at risk for cancer. This limited
focus has had severe consequences—a lack of cancer
survival progress spanning more than two decades
and persistent diminution of young cancer survivors’
quality of life.
The AYAO PRG believes that a major, ongoing
AYAO-specifi c research initiative emphasizing AYA
clinical trials and outcomes research is urgently
needed. Collaboration and support from numerous
governmental, academic, public health, community-
based, and other private sector entities will be essential
to its success. The AYAO PRG offers this report as
a blueprint for a focused and structured approach to
improving cancer prevention, cancer care, and the
duration and quality of life for this vital segment of our
society.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Introduction 1
Impetus for the Adolescent and Young Adult
Oncology Progress Review Group (AYAO PRG)
In recent years, the research, clinical care, and patient
advocacy communities increasingly have recognized
a signifi cant lack of attention and resources directed
to adolescent and young adult (AYA) cancer patients
and survivors. Compared with other age groups,
relatively little is known about basic biologic, genetic,
epidemiologic, therapeutic, psychosocial, and
economic factors that affect the incidence, disease
outcomes, and cancer-related quality of life in this
population. It is known, however, that compared with
younger patients, AYAs with cancer have seen little or
no improvement in their survival rates for decades.
In 2005-2006, the National Cancer Institute (NCI)
partnered with the Lance Armstrong Foundation (LAF)
to conduct a PRG to address the special research and
cancer care needs of the AYA age group and solicit
recommendations for a national agenda to improve
cancer prevention, early detection, diagnosis, treatment
(including survivorship care), and outcomes among
these patients. Previous PRGs have addressed specifi c
tumor types and cancer-related health disparities
experienced by people of all ages with any form of
cancer.
The AYAO PRG’s principal focus was to identify
priorities for improving the outcomes of people
diagnosed with cancer as adolescents and young adults.
The survivorship care needs of adolescents and young
adults who were diagnosed and treated as children,
while important, were not the PRG’s central focus.
The PRG Process
As Figure 1 illustrates, the PRG process entails a
comprehensive, collaborative, and integrated approach
with three phases: (1) developing recommendations
with input from the clinical care, research, and
advocacy communities; (2) planning for and
implementing strategies to achieve scientifi c advances
based on PRG recommendations; and (3) reporting on
progress made in addressing PRG recommendations.
Thus, the PRG process offers the opportunity to
continually evaluate progress by tracking current and
future research trends and provides a framework for a
national effort to control and eliminate disease. This
report documents Phase I of the AYAO PRG process.
INTRODUCTION
Figure 1. PRG Three-phase Approach
Phase I Recommendation
Appoint PRG Leadership Team
Hold PRG Leadership Meeting
Recruit PRG Members and
Prepare for Planning Meeting
Hold PRG Planning Meeting
Prepare for Roundtable Meeting
Hold PRG Roundtable Meeting
Prepare PRG Report
Present PRG Report to
Sponsoring Agency Leaders and
Release Report
Phase II Implementation
Establish Implementation Group
Map Ongoing Initiatives
and Projects to PRG
Recommendations
Hold Implementation Meeting
Prepare Proposal for
Implementing PRG
Recommendations
Prepare Implementation Strategy
and Timeline
Identify Measures of Progress
Phase III Reporting
Collect and Analyze Data
Prepare Progress Report
Discuss Progress with
Sponsoring Agency Leaders and
Advisors
Make Course Corrections
as Needed and Adjust
Implementation Strategy
Report of the Adolescent and Young Adult Oncology Progress Review Group
The AYAO PRG
Following selection of the AYAO PRG leadership
group, individuals were nominated to become PRG
members and/or to participate in the Roundtable
meeting at which the recommendations for AYA
research and cancer care priorities contained in this
report were developed. The PRG and Roundtable
participants were drawn from diverse disciplines across
the research enterprise, the cancer control continuum,
and the advocacy community. Further, the PRG
leadership sought the input of individuals whose work
in areas not related directly to AYA cancer research and
care might offer important insights for addressing AYA
concerns.
On December 6-7, 2005, the PRG leadership and
22 PRG members met in Austin, Texas to plan the
Roundtable meeting and identify key issues to be
explored in Breakout Group sessions. The Roundtable
meeting was held on April 24-26, 2006 in Denver,
Colorado. Appendix A provides a roster of all AYAO
PRG participants. Appendix B includes the reports of
the 11 Roundtable Breakout Groups, and Appendix C
specifi es the charge to the PRG. Additional appendices
(D and E, respectively) include survival rates by
selected cancer type and a glossary of terms and
acronyms used in this report.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Cancer in the Adolescent and Young Adult Population 3
AYAs Defi ned
Empirical and observational research to date indicates
that AYAs with cancer are distinguished by physiologic,
developmental, and societal characteristics and less
improvement in survival that set them apart from
younger and older age groups. In prioritizing research
and health care needs of adolescents and young adults
with cancer, the AYAO PRG chose to defi ne the AYA
population by upper and lower age limits to facilitate
clarity, consensus, and data collection and comparison.
After considerable discussion and with some caveats,
the PRG defi ned the AYA population as comprising
individuals aged
15 through 39 years at cancer
diagnosis
. Ideally, the population should be defi ned
as narrowly as possible by tumor biology, physiologic
characteristics, psychodevelopmental stage of life, and
cancer-related challenges. The AYAO PRG sought a
range that was inclusive rather than exclusive, since the
entire age range continues to experience a relative lack
of improvement in survival and because a chief concern
of AYAs with cancer is the lack of a “home” in research
and health care.
Physiologic Characteristics and Possible
Biologic Infl uences on Cancers in AYAs
Clearly, post-pubertal adolescents and young adults
are physiologically distinct from younger children.
Their body conformation, hormonal milieu, and
organ function approximate those of a “full-grown”
adult. However, in terms of oncology, the distribution
of tumor types across the AYA age range overlaps
somewhat with both the common list of pediatric
cancers and those commonly occurring in older adults.
Though pediatric embryonal tumors and carcinomas
common to older adults occur in AYAs, neither makes
up a signifi cant percentage of cancers in this age group.
The cancers that span this age range—leukemias,
lymphomas, sarcomas, and brain tumors—vary in
incidence and survival rates by age. It is becoming
increasingly understood that the survival differences
are as much due to variations in tumor biology as to
variations in either patient physiology or the health
services received. For example, acute lymphoblastic
leukemia (ALL) in a 6-year-old may differ with regard
to key biologic factors compared to ALL in a 19-year-
old. Likewise, breast cancer in a 30-year-old woman or
colon cancer in a 35-year-old man may have biologic
characteristics not found in patients with what appear
to be the same diseases at 65 years of age. These
biologic differences likely interact with or may be
due to genetic, metabolic, hormonal, environmental,
pharmacokinetic, social, and other human factors that
affect disease susceptibility, treatment response, and
outcome.
Heterogeneity of the AYA Population
It is crucial to consider more than chronological
age with regard to research and care delivery
recommendations for AYA cancer patients and
survivors and to expect not only some overlap with
both older and younger age groups but also marked
heterogeneity within the age range. In addition
to biologic and physiologic changes, numerous
psychological, developmental, and social changes make
this a signifi cant period of transition for AYAs. AYAs
possess both developmental similarities and important
differences across the 15 to 39 year age range that
often affect their care-seeking patterns, adherence
to recommended treatment and follow-up care, and
ultimately, disease outcomes.
•
Shared Developmental Characteristics
Among the characteristics AYAs share are a sense
of invincibility and a limited awareness of their
own mortality that can make a cancer diagnosis
particularly devastating. For most AYAs, the personal
experience of disease has been limited to brief bouts
of infectious disease, sports-related injuries, or other
non-life-threatening illnesses. Individuals in the lower
range of this age group are reaching important social
milestones and achieving some measure of autonomy
from parents—getting a driver’s license, living on their
own, establishing fi nancial independence, graduating
from high school or college, seeking employment,
and gaining voting privileges and legal independence.
Young adults in their 20s and 30s are seeking and
forming intimate and long-term relationships and
are either planning or establishing their careers and
families. A cancer diagnosis abruptly derails these
important developmental processes, thrusting the
individual back into uncertainty and sometimes an
CANCER IN THE ADOLESCENT AND YOUNG ADULT (AYA) POPULATION
Report of the Adolescent and Young Adult Oncology Progress Review Group
unwelcome or uncomfortable dependent state. At
the same time, an AYA with cancer, particularly an
individual at the younger end of the age range, often
must “grow up” quickly to understand his or her
disease and become an active participant in cancer
treatment. In addition, since the AYA age range
encompasses the reproductive years, family planning
and fertility preservation are key concerns of both
women and men.
•
Developmental Differences
These similarities notwithstanding, AYAs can vary
widely in terms of their emotional age and maturity
and in their life stage and related needs, and these
differences may not correlate with chronologic age.
The psychosocial needs of a 20-year-old living at home
while attending college are very different from those
of a 35-year-old with two young children. However,
there are 35-year-olds living at home with parents and
there are 20-year-olds with young children. Likewise,
cultural differences may infl uence attitudes about
disease and health, customary life tasks during this
period, or other factors that may contribute directly
or indirectly to cancer risk, disease management, and
outcome. Just as pediatric providers must adapt to the
developmental stage of the child from infancy through
early adolescence and the adult practitioner must
provide age-appropriate care to individuals over a span
of many decades, the provider of oncology services to
AYAs must adapt to and meet both the medical and the
psychosocial needs of the patients in this age range.
Rationale for Selecting the Lower Age Limit
Some AYA cancer patients may be undergoing some
of the life transitions described previously in early
adolescence and will feel out of place in a pediatric
setting. Others do not start these transitions until
after the teenage years but may fi nd themselves in
adult-oriented settings that do not recognize their
psychosocial immaturity. Our health care system is
split in a binary fashion between pediatric and adult
medicine, particularly among the subspecialties and
certainly in oncology. But the point of transition
between the two is blurry—no rules dictate where
AYA patients should receive care. Pediatric hospitals
increasingly have upper age limits of 21 and beyond
and non-pediatric hospitals often accept patients as
young as 15. Studies of care patterns for adolescent
cancer patients show that provision of care at pediatric
hospitals begins to drop at age 14, and by ages 16 to
17 is less than 50 percent. Therefore, the PRG felt
an inclusive lower age limit of 15 was reasonable in
considering the research and care needs of AYAs.
Rationale for Selecting the Upper Age Limit
The biologic and physiologic maturity that occurs
around the time of puberty and achievement of full
stature remains relatively stable during the 20s and 30s.
Between ages 15 and 39, patients have passed puberty
but have not yet experienced the effects of hormonal
decline (menopause for females) or immune response
decline. Few have developed the chronic medical
conditions (e.g., atherosclerosis, hypertension, type
II diabetes, alcoholism) that cause organ dysfunction
and the need for concomitant medications that can
infl uence oncologic decision-making and the care
of older patients. The PRG concluded that from a
psychosocial perspective, the majority of patients up
to age 40 are more likely to feel they have more in
common with other younger patients than with middle
aged or older patients. For these reasons and other
important similarities across the age range described,
the PRG determined that individuals through age 39
should be considered part of the AYA population.
The AYA Cancer Survival Improvement Gap
In addition to the reasons noted for classifying this
group as a distinct, understudied—and underserved—
population, further support for the distinction is found
in an analysis of data from the NCI’s Surveillance,
Epidemiology, and End Results (SEER) program.
These data reveal that improvement in overall 5-year
cancer survival in this age cohort has lagged far behind
that achieved in other age groups. While dramatic
survival improvements (expressed as average annual
percent change, or AAPC) have been achieved in
patients diagnosed at age 15 or younger and steady
improvement has been made against a number of
cancers common among those over age 40, little or
no progress has been seen in the AYA population
(Figure 2). In fact, among those aged 25 to 35
years, survival has not improved in more than two
decades. As Figure 3 illustrates, 15 to 39 year-olds
diagnosed with cancer in 1975-1980 had dramatically
better survival than most other age groups; however,
survival rates for this population have stagnated while
survival improvements achieved in younger and older
age groups have now—or will soon—eclipse AYAs’
Report of the Adolescent and Young Adult Oncology Progress Review Group
Cancer in the Adolescent and Young Adult Population 5
Figure 2. Improvement in 5-Year Relative Survival, Invasive Cancer, SEER 1975-1997
Figure 3. 5-Year Survival of Patients with Cancer by Era, SEER, 1975-1998
-0.5
0.0
0.5
1.0
1.5
2.0
Average Annual Percentage Change
<5
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
1.43
1.53
1.63
0.90
0.59
0.03
-0.18
0.23
0.53
1.04
1.26
1.43
1.61
1.87
1.99
1.83
1.59
1.14
Age at Diagnosis (Years)
Survival %
<5
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
Age at Diagnosis (Years)
40
55
70
85
Diagnosed
1975-1980
Diagnosed
1993-1998
Improvement in survival for
0-14 year-olds between
1975 and 1998
Improvement in survival for
15-39 year-olds between
1975 and 1998
Improvement in survival for
≥40 year-olds between
1975 and 1998
Report of the Adolescent and Young Adult Oncology Progress Review Group
previously superior survival rates. Given the variability
in survival rates by diagnosis (and the very high
survival rates in some cancers common in the AYA
age range), these data have been further analyzed for
selected diagnoses (see Appendix D). The two HIV-
related cancers (Kaposi’s sarcoma and non-Hodgkin’s
lymphoma) in this era certainly contributed to the
declining trend; conversely, survival rates for several
diagnoses increased (especially ALL). However, most
of the other cancers showed the same pattern of lack of
survival improvement as the overall trend.
Cancers Affecting the AYA Population
Excluding homicide, suicide, and unintentional injury,
cancer is the leading cause of death among those aged
15 to 39 years. It is the most common cause of death
due to disease among females in this age group, and
among males in this group only heart disease claims
more lives annually than cancer.
1
Other statistics illustrate the generally underappreciated
cancer problem in the AYA population:
• Nearly 68,000 people aged 15 to 39 years were
diagnosed with cancer in 2002, approximately 8
times more than children under age 15.
2
These
cases represent about 6 percent of all new cancer
diagnoses.
• Cancer incidence among males aged 15 to 19
years is slightly higher than among females of
the same age, but from ages 20 to 39, incidence
is higher among females. At each 5-year
interval, the incidence gap between the genders
increases; by ages 35 to 39, cancer incidence
among females is more than 80 percent higher
than among males.
3
However, after age 40, this
trend reverses (in large part due to increasing
numbers of prostate cancer diagnoses) and
overall cancer incidence among men exceeds
that of women.
• The average annual increase in the incidence rate
of invasive cancer is higher in people aged 25 to
29 years and 30 to 34 years than for other 5-year
age intervals under age 45.
4
The most common tumors in 15 to 39 year-olds
(accounting for 86 percent of cancers in the age
range) are breast cancer, lymphoma, germ cell tumors
(including testicular cancer), thyroid carcinoma,
sarcoma (bone and soft tissue), cervical carcinoma,
leukemia, colorectal carcinoma, and central nervous
system tumors.
5
As Figure 4 illustrates, the incidence
of specifi c cancer types varies across the AYA age
continuum. For example, among younger AYAs (15
to 19 year-olds), lymphomas, germ cell tumors, and
leukemias account for the largest percentages of all
AYA cancers. Between ages 20 and 39, these and other
cancers decline as a percentage of all cases, while
carcinomas (particularly breast cancer) comprise an
increasing share of cancers in the AYA age cohort.
Non-Hispanic whites in the AYA age group have the
highest incidence of cancer, but also have the highest
overall 5-year survival (Figures 5 and 6). American
Indians/Alaska Natives have the lowest cancer
incidence, but also have poor survival rates. Blacks
have intermediate incidence rates, but the lowest 5-year
survival rate across the age range.
Factors Limiting Progress Against
Cancer in the AYA Population
Several closely interrelated factors may have
contributed to the failure to improve the outcomes of
AYAs with cancer.
•
Access and Limited Insurance Coverage
Young adults have the highest percentage of uninsured
or underinsured individuals of any age group. In 2004,
13.7 million young adults aged 19 to 29 years lacked
coverage, an increase of 2.5 million since 2000.
6
Lack
of insurance is a major cause of access limitations
1
Total U.S. Deaths 2003, ages 15-39, data from SEER and the
National Center for Health Statistics.
2
American Cancer Society data for 2002.
3
Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA,
Clegg L, Mariotto A, Feuer EJ, Edwards BK (eds). SEER
Cancer Statistics Review, 1975-2002. National Cancer Institute,
Bethesda, MD; at: http://seer.cancer.gov/csr/1975_2002/, based
on November 2004 SEER data submission, posted to the SEER
Web site 2005.
4
Bleyer A, O’Leary M, Barr R, Ries LAG (eds). Cancer
Epidemiology in Older Adolescents and Young Adults 15 to
29 Years of Age, including SEER Incidence and Survival,
1975-2000. National Cancer Institute, NIH Pub. No. 06-5767,
Bethesda, MD, June 2006; at: www.seer.cancer.gov/publications/
aya.
5
SEER 17, 2000-2003.
6
Collins SR, Schoen C, Kriss JL, et al. Rite of Passage? Why
Young Adults Become Uninsured and How New Policies Can
Help. The Commonwealth Fund, updated May 24, 2006.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Cancer in the Adolescent and Young Adult Population 7
Figure 4. Types of Cancer in Older Adolescents and Young Adults (% cases/disease)
Figure 5. Incidence of All Invasive Cancer by Race/Ethnicity SEER, 1994-2003
Age at Diagnosis
0
25
50
75
100
Percent
15-19 20-24 25-29 30-34 35-39
Other
Cervix
Colon & Rectum
Thyroid
Breast
Melanoma
Germ Cell
Soft Tissue
Kaposi’s
Sarcoma
Malignant
Bone Tumors
CNS
Lymphomas
Leukemias
SEER 17, 2000-2003, Ages 15-39
White
non-Hispanic
Hispanic
Black/African
American
Asian/Pacific
Islander
American
Indian/Alaska
Native
0
500
1000
1500
2000
2500
Age at Diagnosis
Percent
<5 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44
NCI SEER Program, SEER 12, November 2005 Submission.
Hispanic is independent of race and can overlap with black, Asian/Pacific Islander, or
American Indian/Alaska Native. White is limited to non-Hispanic white.
Report of the Adolescent and Young Adult Oncology Progress Review Group
in this population. Unless they are disabled, young
adults rarely are covered by their parents’ health
insurance policies after age 23, and many policies
cease covering dependents at age 19 or when they no
longer are full-time students. Medicaid and its state
child health insurance component, SCHIP, also cease
coverage at age 19. Many of the jobs held by AYAs
offer either limited or no health benefi ts. Those in jobs
that offer health coverage may decline it or choose high
deductible, narrow benefi t plans due to cost. If cancer
subsequently is diagnosed, AYAs may fi nd themselves
with limited access to care and may incur high levels
of debt for the cost of care not covered by insurance.
Even those with relatively comprehensive insurance
may be liable for substantial out-of-pocket treatment
and non-treatment costs and may forgo recommended
follow-up testing due to cost. Further, a cancer
diagnosis affects the AYA’s insurability and insurance
rates (for health, life, and disability coverage) for the
rest of his or her life and may cause individuals to
remain in unsatisfactory jobs or choose jobs because of
their health benefi ts.
•
Delayed Diagnosis
Anecdotes abound among AYA cancer survivors who
describe the misdiagnosis of their cancer symptoms
and the months—in some cases years—that elapsed
before a correct diagnosis of cancer was made. Both
provider and patient factors may contribute to late
diagnosis. Health care providers’ level of suspicion
of cancer as a cause of symptoms in this population
generally is low, contributing to delayed diagnosis of
primary cancers, second cancers, and late effects due
to cancer treatment. Cancer symptoms in AYAs may
be attributed to fatigue, stress, or other causes. In
addition, many primary care providers lack the unique
skills and/or are unwilling to care for adolescents.
American and Canadian studies of pediatric and
adolescent cancer patients have shown that the number
of days from symptom onset to diagnosis increases
with patient age, as much as double the number of
days for older adolescents compared with patients 14
and under.
7,8
Diagnosis also is delayed because AYAs
typically see themselves as invulnerable to serious
disease or injury, causing them to ignore or minimize
symptoms and delay seeking medical attention. Some
also may be embarrassed or afraid to seek treatment
for symptoms that involve the genitalia or bowel
function. Personal preferences and cultural taboos may
prevent some patients from receiving needed routine
examinations (e.g., pelvic or breast examinations, in
some cases particularly if performed by male health
care providers). Many AYAs have no primary care
provider and do not receive routine care; they may
delay seeking care because they do not know where
to go (e.g., clinic, private physician, emergency room)
for help. When they do seek care, they may give
incomplete health histories because they are unaware
7
Pollock B, Krischer JP, Vietti TJ. Interval between symptom
onset and diagnosis of pediatric solid tumors.
Journal of
Pediatrics
1991;119(5):725-732.
8
Klein-Geltink J, Pogany L, Mery LS, Barr RD, Greenberg ML.
Impact of age and diagnosis on waiting times between important
treatment events among children 0 to 19 years cared for in
pediatric units: The Canadian Childhood Cancer Surveillance and
Control Program.
Journal of Pediatric Hematology Oncology
2006;28(7):433-439.
Figure 6. Survival, All Invasive Cancer Sites Combined, Aged 15-39 Years, Both Sexes, All Races, SEER 13 Areas, 1992-2002
% Surviving
Years After Diagnosis
0
70
85
100
0 1 2 3 4 5
Hispanic is independent of race and can overlap with black, Asian/Pacific Islander, or
American Indian/Alaska Native. White is limited to non-Hispanic white.
Cause-specific based on any cancer death was used for this analysis.
White
non-Hispanic
Hispanic
Asian/Pacific
Islander
American
Indian/Alaska Native
Black/African
American
Report of the Adolescent and Young Adult Oncology Progress Review Group
Cancer in the Adolescent and Young Adult Population 9
of (or not asked about) relevant personal or family
history or because they choose to withhold information.
In addition, for some AYA women, an obstetrician/
gynecologist may be their only primary care provider;
these providers may have a lower level of suspicion
about non-gynecologic cancers in their AYA patients.
•
Treatment Practices and Treatment Setting
AYAs with fi rst symptoms of cancer may see
a variety of health care providers, including
pediatricians, internists, family physicians, emergency
room physicians, gynecologists, dermatologists,
gastroenterologists, neurologists, surgeons,
orthopedists, and other specialists. As a result,
referral patterns for AYAs with suspected or diagnosed
cancers vary widely. AYAs with cancer too frequently
fall into a “no man’s land” between pediatric and
adult oncology. They may be treated by pediatric,
adult medical, radiation, surgical, or gynecologic
oncologists. Little comparative outcome data exist
to guide the cancer care of these patients with respect
to treatment setting, treatment provider, or treatment
regimen. For younger AYAs and those with tumors
also seen in the pediatric population, it often is unclear
whether pediatric or adult dosages or dosing schedules
of chemotherapeutic agents or radiotherapy are most
appropriate for AYAs with cancer. Differences in
biology and physiology may affect AYAs’ tolerance
of therapy but are poorly understood. Treatment of
AYAs can be complicated by their treatment regimen
adherence issues, which may contribute to their poorer
outcomes.
•
Understudied Population
Research on AYAO has been limited in part
because cancer risk and adverse cancer outcomes
have been under-recognized in this population.
Poor understanding of patient and tumor biology
distinguishing cancers in this population (e.g., ALL
cytogenetics, breast cancer hormone status, colorectal
cancer microsatellite instability) has contributed
to limited advances in treatment. In addition, the
percentage of AYA cancers that are due to hereditary
predisposition is unknown. However, several
environmental risk factors have been identifi ed, such
as human papillomavirus (HPV) infection for cervical
cancer, sun exposure for melanoma, HIV for AIDS-
related malignancies, hepatitis B for liver cancer, and
other linkages to malignancy have been hypothesized
(e.g., Epstein-Barr virus for some cases of Hodgkin’s
disease and nasopharyngeal carcinoma).
•
Capture of Patients and Patient Data
Most AYAs are treated in the community rather than
in cancer centers. A robust community oncology and
primary care infrastructure currently does not exist
to enable patient data collection and aggregation
that would support research efforts. In addition,
contact with many AYAs is lost following treatment,
complicating collection of late effects and outcome
data. The AYA population is highly mobile and
patients may leave the geographic area in which they
were initially treated to pursue educational or career
opportunities. Further, some AYAs shun continued
contact with their treatment providers and the health
care system in general as they attempt to move on with
their lives after cancer.
•
Number of Clinical Trials/Participation Levels
Unlike pediatric cancer patients, few AYAs participate
in treatment clinical trials. More than 90 percent
of patients with cancer under age 15 are treated at
institutions that participate in NCI-sponsored clinical
trials, and as many as two-thirds of these children
are enrolled in clinical trials. This high level of trial
participation has been a principal reason for the
dramatic improvements in cancer survival among
children. By contrast, only 20 to 35 percent of
older adolescents (15 to 19 years old) are treated at
institutions that participate in NCI-sponsored treatment
clinical trials, and only 10 percent of this group is
enrolled in trials.
9,10
Only 1 to 2 percent of 20 to 39
year-olds are entered into clinical trials of pediatric
or adult NCI Cooperative Groups.
11
This low level of
participation may occur because few clinical trials are
available for AYA patients or because physicians fail
9
Bleyer WA, Tejeda H, Murphy SM, Robison LL, Ross JA,
Pollock BH, Severson RK, Brawley OW, Smith MA, Ungerleider
RS. National cancer clinical trials: children have equal access;
adolescents do not.
Journal of Adolescent Health
1997;21:366-
373.
10
Albritton K, Bleyer A. The management of cancer in the older
adolescent.
European Journal of Cancer
2003;39:2548-2548; at:
European Journal of Cancer 2003;39:2548-2548; at: European Journal of Cancer
http://authors.elsevier.com/sd/article/S0959804903008098.
11
Bleyer WA, Barr R. Highlights and challenges. In: Bleyer WA,
O’Leary M, Barr R, Reis LAG (eds). Cancer Epidemiology
in Older Adolescents and Young Adults 15 to 29 Years of Age,
including SEER Incidence and Survival 1975-2000. National
Cancer Institute, NIH Pub. No. 06-5767, Bethesda, MD, June
2006; at: www.seer.cancer.gov/publications/aya.
Report of the Adolescent and Young Adult Oncology Progress Review Group
10
Cancer in the Adolescent and Young Adult Population
10 Cancer in the Adolescent and Young Adult Population 10
to enroll patients in trials for which they are eligible.
Patients aged 15 to 18 years are unlikely to have tumor
biology or host physiology that is different from those
over age 18, yet they usually are excluded from fi rst-
line adult drug development studies. Further, while
nearly all pediatric cancer treatment trials include
patients at least to age 18, a 15-year-old may have a
disease that is not covered by pediatric trials but is
ineligible for adult trials focused on his or her disease.
Similarly, a 35-year-old may have a disease not covered
by adult trials.
•
Psychosocial and Supportive Care
The psychosocial and supportive care needs of AYAs
with cancer tend to be broader in scope and intensity
than such needs in younger and older patients because
of the many emotional, developmental, and social
changes and transitions that occur during this stage of
life. For example, because adolescents and individuals
in their 20s often are self-consciousness (e.g.,
concerned about body changes and body image), these
patients may experience greater diffi culty than younger
or older patients in coping with treatment side effects
such as hair loss, weight gain or loss, acne, and growth
disturbances. For most AYAs, a cancer diagnosis is the
fi rst time they have confronted their mortality. Many
AYA patients also experience feelings of isolation and
have diffi culty fi nding peers among other patients.
AYAs may want or need to maintain work, school,
and social aspects of their lives during treatment.
Moreover, some AYAs, including but not limited
to those at the older end of the age range, may be
responsible for young children of their own. Lingering
cognitive effects may make it diffi cult for AYAs to
return to school or work following treatment, and
educational or career plans may have to be altered.
School systems and employers may not recognize these
treatment effects as real or may resist accommodating
them. Though health provider awareness of potential
treatment-related fertility damage may be improving,
these issues still are not discussed routinely with
patients prior to treatment. Younger AYAs and their
families may experience confl icts concerning who
should be responsible for medical decisions and AYAs
of all ages may experience diffi culties navigating
the health care system. Because of the complexity
and intensity of their emotional and other needs,
AYA patients would benefi t from psychosocial and
supportive care. Services available in pediatric-
oriented settings (which tend to be more numerous) or
adult-oriented settings (where they are more scarce)
still may not be appropriately focused on the needs of
this age group. Lack of psychosocial support during
and after treatment may be a factor in AYAs’ decreased
adherence to treatment and follow-up care regimens
compared with other age groups.
•
Treatment/Follow-up Care Guidelines
Inconsistency in treatment and follow-up and
insuffi cient research data have prevented the
development of guidelines for treating and monitoring
AYAs with cancer, and few tools exist to measure the
effi cacy of treatment and psychosocial interventions.
Guidelines for fertility preservation, a vital concern of
the AYA population, recently were published and will
be disseminated to the oncology community.
12
•
Prevention and Early Detection Emphasis
Cancer prevention and early detection in the AYA
population usually are limited to Papanicolaou testing
(Pap smear) for precancerous cervical abnormalities
and cervical cancer. Physicians do not consistently
recommend that AYA patients perform regular skin
self-examination for early detection of melanoma,
or breast or testicular self-examination, in part due
to controversy about the effi cacy of the latter two
examinations. Similarly, these topics typically are
not discussed in school health education programs.
Adherence levels among patients whose physicians do
recommend self-examination for breast or testicular
cancer or malignant melanoma are unknown.
Because many physicians are unaware of specifi c
cancer risks in AYAs, they may not recommend early
surveillance when it is warranted (e.g., for individuals
with strong family histories of cancer). Of note, a
new test for HPV now is available and covered by
insurance (including nearly all Medicaid programs) in
conjunction with a Pap smear for those over 30 or at
high risk for cervical cancer (such as women of any
age with an abnormal Pap smear), and an HPV vaccine
recently was approved by the U.S. Food and Drug
Administration.
12
Lee SJ, Schover LR, Partridge AH, et al. American Society of
Clinical Oncology recommendations on fertility preservation in
cancer patients.
Journal of Clinical Oncology
2006;24(18):2917-
2931; at: http://www.jco.org/cgi/doi/10.1200/JCO.2006.06.5888.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Recommendations 11
This section describes fi ve imperatives for improving
the outcomes of adolescents and young adults
with cancer. These overarching recommendations
encompass the chief concerns expressed in the
research and care priorities identifi ed by the 11 AYAO
PRG Roundtable Breakout Groups (Table 1). In
addition, the AYAO PRG strongly emphasizes that
the detailed Breakout Group reports provided in
Appendix B are integral components of this report
and urges that those responsible for implementing the
PRG’s recommendations give these documents full
consideration in developing implementation strategies.
Recommendation 1: Identify the characteristics
that distinguish the unique cancer burden in the
AYAO patient.
The limited research to date on older adolescents
and young adults with cancer has only just begun
to elucidate distinguishing biologic and life stage/
developmental characteristics of this population
and, further, to reveal the disparities in cancer care
and outcomes that mark AYAs as an underserved
population.
Elucidate unique biologic characteristics of AYA
cancers and AYA patients that affect disease outcome
in this population.
A signifi cantly more robust
research effort is needed to better understand tumor
and human factors (e.g., the tumor microenvironment)
that contribute to AYAs’ susceptibility to cancer, their
response to treatment, and their disease outcomes. For
RECOMMENDATIONS
example, the correlation between poorer prognosis
and older age in ALL has been established (more
than 80 percent survival in young children compared
with survival below 40 percent in 20 to 39 year-olds).
However, little is known about genotypic variability by
age for other cancers affecting AYAs or the role of the
gene environment in the etiology of malignancies or
late effects. Similarly, the effect of age-related physical
and hormonal changes on drug metabolism and
adverse treatment effects (e.g., neuropathies, glucose
intolerance, avascular necrosis of bone, toxicity-related
death) is poorly understood. Among the cancers
affecting AYAs, the PRG identifi ed as particularly
high priorities basic and other biologic research on
aging and patient/host-related factors in non-Kaposi’s
sarcoma, leukemias, lymphomas, and breast and
colorectal carcinomas. In addition, increased resources
are needed for studies of AYAs’ genetic susceptibility
to cancer, including both malignancies common to this
age cohort and cancers most common in older adults
that occasionally occur in AYAs (e.g., lung cancer in an
18-year-old).
Elucidate AYA life stage/developmental
characteristics that infl uence care seeking, adherence
to treatment, and medical and psychosocial
outcomes.
Adolescence and young adulthood are
times of increased vulnerability to stress under normal
circumstances. AYA cancer patients and survivors face
developmental challenges that both signifi cantly exceed
those faced by other young people and are distinct
from other age groups with cancer. The empirical
literature, however, is limited with respect to the causes
Table 1. Adolescent and Young Adult Oncology Progress Review Group Roundtable Meeting Breakout Groups
Core Topics Cross-cutting Areas
Biology
Prevention/Cancer Control/
Epidemiology/Risk
Insurance
Clinical Care Models
Psychosocial/Behavioral
Factors
Long-term Effects
Access
Clinical Trials/Research
Health-related Quality of
Life
Special Populations
Awareness
Report of the Adolescent and Young Adult Oncology Progress Review Group
12
Recommendations
12 Recommendations 12
and correlates of specifi c psychosocial outcomes.
Previous psychosocial research has combined the
AYA population with either pediatric or adult patients
and survivors, which has obscured the unique needs
of this population. In addition, researchers typically
do not have access to a representative population of
AYAs due to small numbers of cases, gatekeepers’
(e.g., referring physicians) lack of knowledge that their
referral choices may affect outcomes, limited research
resources in community centers where most AYAs
are treated, and limited research funding to support
this area of behavioral research. Research is needed
to better understand patient and survivor life stage
and developmental
characteristics
across six principal
domains—intellectual,
interpersonal,
emotional, practical,
existential/spiritual,
and cultural—that
singly or in combination may have profound effects on
individuals’ medical outcomes and quality of life.
I
dentify and ameliorate health disparities experienced
Identify and ameliorate health disparities experienced I
by AYA cancer patients and survivors.
Numerous
factors (e.g., age, gender, race/ethnicity/culture,
geographic location, education), singly or in
combination characterize specifi c populations affected
by cancer health disparities (see inset, for defi nition).
The type and severity of disparities may result from
inequalities in access to health care, receipt of quality
health care, and/or differences in co-morbidities,
including psychosocial morbidities. Little data exist
to explain outcome disparities by race/ethnicity even
for the most common pediatric cancers. In the adult
literature, particularly regarding breast and prostate
cancers, non-Caucasians appear to have markedly
worse outcomes. However, ongoing research is
clarifying that race often is a proxy measure for
disparities such as socioeconomic position, geographic
access to care, health insurance status, education, and
living conditions. These fi ndings are instructive for
research on AYA cancer disparities, which likewise are
infl uenced by factors other than patient age.
The factors that characterize and account for disparities
experienced by AYA cancer patients and survivors
are understood only in the broadest terms and may
include human and disease biology, pharmacogenetics,
socioeconomic factors, and the appropriateness and
accessibility of health services (especially clinical
trials). Therefore, research is needed to elucidate
in detail the factors contributing to under-service
and poorer outcomes among AYAs as a group and
among racial and ethnic subgroups within the AYA
population. Community involvement and partnership
(including the oncology/medical community and
community-based organizations) in research design and
implementation should be sought to develop and test
hypotheses to ascertain the critical factors infl uencing
AYA cancer disparities, their relative impact, and
possible potentiating interrelationships. Such studies
are essential to designing
and implementing
treatment and other
interventions with a high
likelihood of success.
Efforts to eliminate
disparities also may
benefi t from studies
of the military model for AYA oncology care. All
AYAs in the military have equal access to primary and
tertiary care, longitudinal care throughout treatment
and requisite follow-up care, and either continued
employment after treatment or continued health
benefi ts as veterans. This model effectively eliminates
many of the access and insurance barriers to care
experienced in the civilian population.
Recommendation 2: Provide education, training,
and communication to improve awareness,
prevention, access, and quality cancer care for
AYAs.
The AYAO PRG recognized an urgent need for a
variety of education, training, and communication
activities to raise awareness and recognition of the
AYA population at both public and professional
levels. To be effective, all education, training, and
communications must be culturally appropriate and
delivered by individuals who are culturally competent.
Raise awareness of AYA cancer issues as a fi rst
step toward increasing national focus and resource
allocation to address the AYA cancer problem.
Limited awareness of the AYA population as one
having specifi c cancer risk, treatment, and other care
Cancer health disparities are differences in the incidence,
prevalence, mortality, and burden of cancer and related adverse
health conditions that exist among specifi c population groups in
the United States. These population groups may be characterized
by gender, age, ethnicity, education, income, social class,
disability, geographic location, or sexual orientation.
– National Cancer Institute, Division of Cancer Control and Population Sciences
Report of the Adolescent and Young Adult Oncology Progress Review Group
Recommendations 13
needs distinct from younger and older age groups
has hampered targeted research and education,
training, and communication activities designed for
this population. Raising awareness of these needs
and achieving broad acceptance of AYAs as a distinct
demographic group are crucial steps toward addressing
them. Efforts to raise awareness of the AYA population
have been complicated by its heterogeneity, varying
perceptions of the group by different stakeholders
depending on their relationship to the population, and
diffi culty establishing standard descriptive terminology
among government agencies, funding organizations,
and professional groups.
Further, it is not widely known among the general
public, policy makers, the news and entertainment
media, the military, educational institutions,
philanthropic and other funding organizations, and
the business world that cancer is the leading cause of
disease-related death among adolescents and young
adults. Each of these components of the non-clinical
public requires tailored messaging and focused
outreach to improve awareness of cancer risk among
AYAs and encourage funding for AYA oncology
research and resources. Awareness of the AYA cancer
problem also has been limited by a relative lack of
spokespersons/champions for this population in the
public and professional arenas.
Provide targeted education to patients, families/
caregivers, and the public about AYA cancer issues.
Educational and other interventions to modify
the exposure of AYAs in the general population
to potentially modifi able cancer risk factors (e.g.,
HPV, hepatitis B virus, ultraviolet light, poor diet,
lack of physical activity, obesity, tobacco use, other
environmental carcinogens) offer the opportunity to
reduce cancer risk during the adolescent and young
adult years as well as risk for future cancers in older
adulthood. In addition, efforts are needed to promote
the importance of health insurance in this population,
since neither AYAs nor their families may place a high
priority on maintaining coverage for young people
who typically are healthy. Greater public awareness of
AYA cancer risk and care may be expected to increase
enrollment in health insurance plans and reduce delays
in diagnosis.
For those diagnosed with cancer and their families,
online resources for cancer information, insurance
resources, peer support, and other information needs
will help to empower AYAs to understand and manage
their own care. Educational programs developed
and led by advocacy groups and patient support
organizations that specifi cally focus on AYA issues
across the spectrum of care are needed for patients and
their families and caregivers.
Educate multidisciplinary providers who work
with AYAs to improve referrals and services to
this population.
In general, current health care
provider training programs do not address AYA-
specifi c issues, resulting in poor recognition of
AYAs’ cancer risk and an inadequate response to
their medical and psychosocial needs. Subsequently,
AYAs often experience delayed diagnosis that may
contribute to the population’s lack of survival rate
improvement. Core competency curricula must be
developed and incorporated into appropriate initial
training and continuing education programs to ensure
that all providers who work with adolescents and
young adults—including but not limited to primary
care practitioners, oncology and other medical
specialists, nurses, rehabilitative care providers, other
allied health professionals, and mental health and
social workers—have the requisite understanding of
characteristics unique to or of particular importance
to AYAs. Curricula should address the cancers that
either peak or occur more commonly in this age group,
post-treatment surveillance for late effects, and the
specifi c psychosocial, economic, educational, and
communication needs of the population. Similarly,
programs are needed to train “expert” patients
(including patient navigators) and advocates who
conduct outreach to and represent AYA interests.
Based on data from recent surveys,
13
it was the
consensus of the PRG that physician involvement is
the key factor in the patient’s decision to participate
in a clinical trial. Therefore, targeted education to
raise referring physicians’ and medical oncologists’
awareness of the potential benefi t of AYAO-relevant
trials may be an effective strategy to improve outcomes
for these patients.
13
Comis RL, Colaizzi DD, Miller JD. Cancer Clinical Trials
Awareness and Attitudes in Cancer Survivors. Coalition of
Cancer Cooperative Groups, poster presentation, American
Society of Clinical Oncology Annual Meeting, June 5, 2006.
Report of the Adolescent and Young Adult Oncology Progress Review Group
14
Recommendations
Recommendation 3: Create the tools to study the
AYA cancer problem.
The existing research infrastructure is inadequate to
support needed AYA-focused research. Research tools
to enable AYA-specifi c studies must be developed if
they do not exist and strengthened if potentially useful
infrastructure already is in place.
Create a large prospective database of AYA cancer
patients to facilitate research on this age group.
Although several sources of data exist on this
population, each has signifi cant shortcomings. SEER
and population-based cancer registries are well
suited for studies of incidence, survival, and second
cancers but are limited by a lack of detailed treatment
exposure data. The NCI Cooperative Groups provide
an established data collection infrastructure; however,
most AYAO patients are not enrolled in these protocols,
survivor studies are a lower priority, and many patients
are lost to follow-up. Some AYA-specifi c data may
exist at individual institutions. Neither clinical trial
groups nor individual institutions have the resources
to track patients who are geographically mobile. The
Childhood Cancer Survivor Study (CCSS) describes
late effects in AYA patients treated as children and
adolescents, but it is not known to what extent these
fi ndings are relevant to adolescents treated outside
of a pediatric setting, to young adults (over age 21
at diagnosis), or to people with cancers not included
in the CCSS because they typically are young adult
or adult cancers (e.g., testicular, cervical, and breast
cancers; melanoma).
The Medicaid database should be explored for the
applicability and feasibility of its use in developing
an AYA prospective database. Further, the well-
established active military and veterans health
databases, which include a comprehensive electronic
medical record for each individual, allow easy access
and transfer of data. Because of the skewed age of its
population, approximately 2.3 percent of all new AYA
cancers in the United States are diagnosed within the
military.
Whether a new database is created or existing data
sources are enhanced, standardized, linked, and
aggregated, establishing the necessary data resources
for AYA research is a long-term project that will
require substantial ongoing funding. Privacy concerns
(including restrictions related to Health Insurance
Portability and Accountability Act provisions) must be
addressed, and professional/advocacy partnerships will
be needed to promote participation by health providers
and patients.
Increase the number of annotated specimens to
support research progress.
A signifi cant lack of
infrastructure limits the acquisition and distribution
of AYA tumor samples. Specimens of tumors that
occur in adolescents and young adults are scarce, in
part because some of these cancers are rare and also
because most AYAs are treated in the community and
preserved specimens are not centrally collected or
documented. Even those specimens that exist may lack
suffi cient clinical annotation to make them useful for
many research purposes. As is true in other age groups
and for specifi c cancers, few samples of normal tissue
are available to support research aimed at improving
understanding of cancer etiology, the role of the
tumor microenvironment, mechanisms of progression
and metastasis, and other infl uences that may affect
treatment and outcome. Efforts should be undertaken
to optimize the effectiveness of existing infrastructure
(e.g., Cooperative Human Tissue Network) and to
establish standard operating procedures for tissue
collection, preservation, storage, and distribution that
will help improve AYA tumor, normal tissue, and other
biospecimen resources.
Create/modify needed assessment tools specifi c to
AYA cancer issues.
The AYAO PRG noted the paucity
of assessment and other measurement tools relevant
to AYA cancer patients and survivors. For example,
numerous instruments for assessing health-related
quality of life (HRQL) are available for use in adult
respondents. Only a few such measures have been
developed more or less specifi cally for adolescents,
and few of these have been employed in assessing
HRQL in young adults with cancer. HRQL measures
may be used to distinguish the burden of morbidity
among groups or individuals at a particular point in
time, to assess changes in morbidity over time, in
longitudinal/prospective studies such as clinical trials,
to predict the score on another measure, or to predict
clinical outcome. The need for appropriate HRQL
measures for AYAs with cancer is great and should be
a subject of increased research. Such measures should
Report of the Adolescent and Young Adult Oncology Progress Review Group
Recommendations 15
span the survivorship continuum, be developmentally
appropriate, include co-morbidity assessment and
family well-being, and be usable with patients with
varying literacy levels and cultural identities.
Improve grant coding and search term
standardization to enable evaluation of research
efforts and progress.
Consistent research award
coding across Federal and non-Federal funding
organizations and standardized keyword search
terminology are essential to enable researchers and
funding organizations to adequately evaluate the
type and extent of research on a population. AYAs
lack recognition as a defi ned population, making
it extremely diffi cult, except in obvious cases, to
determine whether and to what extent many National
Institutes of Health (NIH) and other research awards
include AYA subjects, address research questions
relevant to them, or conduct separate data analyses
on this age group. The AYAO PRG encountered this
problem fi rst hand in attempting to assess the NCI
research portfolio on AYA oncology.
Expand clinical trials for AYAs to increase treatment
choices and accelerate treatment advances.
More
clinical trials designed specifi cally for AYAs are
needed, as are more trials that include AYAs in the
accepted patient age range. Young adults diagnosed
with cancers that most commonly occur in younger
children should not be excluded from pediatric
trials that address those malignancies, nor should
adolescents diagnosed with cancers more commonly
occurring in older adults routinely be excluded
from trials of treatments for those diseases. New or
expanded existing clinical trial networks, particularly
community-based networks, are needed to enhance
AYAs’ access to appropriate clinical trials and to
aggregate data on AYAs with specifi c cancers to better
understand their treatment responses and outcomes.
When AYAs are enrolled in trials that include a wide
age range, separate analyses, and reporting of outcomes
by age cohort should be conducted whenever possible.
The AYAO PRG recommends that expanded cancer
treatment trials for AYAs should focus on malignancies
in which treatment improvements will have the greatest
potential impact on the AYA cancer problem: sarcoma,
lymphoma, early breast cancer, early colorectal
carcinoma, germ cell tumors, and leukemia. Further,
increased research is needed on interventions to prevent
or ameliorate the sequelae of cancer therapy (e.g.,
second cancers, infertility, cardiotoxicity, hearing
loss, cognitive dysfunction, obesity) in the AYA
population. HRQL should be routinely incorporated
as a primary outcome measure in clinical trials, as
well as in health services research focused on models
of care, prospective studies of late effects, and studies
of palliative and end of life care. Trial designs that
accommodate factors such as work, school, and child
care demands may improve AYAs’ ability to adhere to
treatment protocols.
Recommendation 4: Ensure excellence in service
delivery across the cancer control continuum
(i.e., prevention, screening, diagnosis, treatment,
survivorship, and end of life).
The AYAO PRG urges the implementation of two
principal strategies to improve service delivery to AYAs
with or at risk for cancer and ensure excellence in care
across the cancer control continuum.
Develop, evaluate, and disseminate standards of care
for AYA cancer patients and survivors to improve
outcomes.
No consistent standards exist for delivery
of cancer-related care to AYAs, and the evidence base
needed to establish standards across the continuum
of care is weak. The inconsistent approach to cancer
diagnosis and treatment delivery among AYAs often
results in poor patient experiences in many aspects
of care and may be a factor in the lack of survival
improvements seen in this population compared with
pediatric and older adult counterparts. Excellence
in care may vary not only by cancer diagnosis, but
by multiple other variables (e.g., age and gender,
race/ethnicity/culture, socioeconomic status, source
of care) that must be addressed to meet the complete
spectrum of patient needs. Developing, disseminating,
and evaluating clinical care guidelines are complex
endeavors. Standards of care are dynamic; they
must be continually evaluated and updated to refl ect
advances in screening, diagnostic techniques and
technologies, treatment, and supportive and palliative
care.
The AYAO PRG believes steps toward establishing
standards of excellence in AYA cancer care must be
taken now. The standards should be based on available
evidence, best practices, and expert opinion, with the
expectation that they will evolve as the evidence base
Report of the Adolescent and Young Adult Oncology Progress Review Group
16
Recommendations
16 Recommendations 16
matures. Assessment of HRQL should be routinely
incorporated as a part of the standard of quality cancer
care. Existing clinical practice guidelines for cancers
common in AYAs (e.g., leukemia, Hodgkin’s disease),
supportive care (e.g., pain and distress management),
and post-treatment surveillance such as those
developed by the National Cancer Comprehensive
Network and the Children’s Oncology Group provide a
starting point for this work. In addition, the American
Society of Clinical Oncology is developing evidence-
based guidelines for the long-term care of adult
survivors, including AYAs.
Likewise, new AYA-specifi c clinical programs
should be developed based on current knowledge and
successful existing programs. These AYA programs
should be evaluated rigorously through a program of
health services research to strengthen the evidence base
and guide future program development. Specifi cally,
research is needed to investigate the benefi ts and
drawbacks of treating AYAs as a distinct group with
special clinical and psychosocial care needs, the
value of creating organizational structures to support
these needs, and the impact of such programs on
patient outcomes. Despite the need for research, the
PRG concurs with the consensus that has emerged
among health professionals, health care organizations,
patients, and advocates that services for AYAs should
be based on a patient-centered model of care. Such
a model includes system-related elements (e.g., rapid
access, competent assessment, timely and accurate
diagnosis, evidence-based treatment, access to clinical
trials, minimal treatment and late treatment effects,
psychosocial and other support) and other patient-
valued elements (e.g., clear, accurate, and empathetic
communication; expertise specifi c to young people and
disease; appropriate facilities; peer support).
In addition, the impact of access to care on the ability
of AYAs to receive quality care must be considered
across the care continuum. As the age group most
likely to be uninsured or underinsured, the lack of or
insuffi cient medical insurance coverage is a signifi cant
impediment to AYAs developing a primary care
relationship, obtaining appropriate referrals and second
opinions, and receiving the best possible care. For
the best possible outcomes, AYA patients need access
to oncology centers of excellence, access to clinical
trials, and a means to obtain appropriate counseling,
peer support, and patient navigation/health coaching.
Moreover, some services (e.g., patient navigation,
psychosocial care) may not be reimbursed, creating
a further barrier to access. Establishing standards
of care/treatment guidelines for AYA oncology will
provide the basis for insurance coverage determinations
and should secure or improve reimbursements for
needed services.
Establish a national network or coalition of providers
and advocates seeking to achieve a standard of
excellence in AYA cancer care.
Establishing,
disseminating, and reinforcing standards of cancer
care for AYAs will require the ongoing and concerted
collaboration of a diverse array of stakeholders
including health care providers, research sponsors,
investigators, regulators, insurers, and patient advocates
who are committed to improving the quality of life
and outcomes for AYAs with cancer. Currently,
limited collaborative agreements exist among specifi c
stakeholders to advance a particular aspect of AYA
care or to fulfi ll individual organizational missions. To
achieve excellence in care across the cancer control
continuum, ways must be found to better coordinate
the activities of these numerous stakeholders toward
common goals and to measure and communicate
progress.
Recommendation 5: Strengthen and promote
advocacy and support of the AYA cancer patient.
In addition to raising public and professional awareness
of AYAs as a distinct understudied and underserved
age group (see also Recommendation 2), advocacy and
support services for AYA cancer patients and survivors
need to be strengthened. To do so, it will be necessary
to better understand and address the subjective
experience of AYA patients, expand the capacity of
existing resources to address AYA psychosocial needs,
and develop new resources and interventions designed
to meet these needs.
Address the subjective experience of AYA patients.
Effective support of AYAs with cancer must be
predicated on an understanding of how cancer may
affect young peoples’ self-identity, self-esteem,
spiritual perspectives, body image, perception of
their future possible life goals, distress levels, peer
relationships, family dynamics, need for information
and communication, and numerous other subjective
Report of the Adolescent and Young Adult Oncology Progress Review Group
Recommendations 17
components of experiencing a life-threatening disease.
Empirical research is needed to explore these aspects
of the cancer experience among AYAs and inform
intervention development and health care provider
training.
Build the capacity of existing resources to address
AYA psychosocial needs.
Some resources exist to
address psychosocial needs of AYA cancer patients/
survivors and their caregivers. For example, a small
number of online communities (such as Planet Cancer)
have been started with limited resources by young
adult survivors; these communities are serving a
substantial number of AYAs but need more support
to evaluate, refi ne, and expand their programs. Other
existing AYA-specifi c resources include print materials,
telephone information services, and in-person
counseling/educational activities. Many general and
disease-oriented patient support organizations are in
place but have a variable level of focus on the AYA
population. Community clinical oncology practices
and other medical, social service, and rehabilitative
care providers could be more effective providers of
AYA psychosocial care or could be assisted to become
more effective in making appropriate referrals. These
providers also could become involved in developing,
testing, and evaluating AYA-specifi c psychosocial
interventions in various community settings.
Social, professional, religious, and fraternal
organizations with established ties to their communities
also could build their capacity to assist AYAs
with cancer and their families and caregivers. In
addition, such organizations offer the possibility of
community partnerships to better design, test, and
evaluate psychosocial interventions targeting defi ned
subgroups of AYAs. Further, with appropriate training,
community organizations can be an important resource
for addressing AYA psychosocial needs outside of
the traditional insurance system until reimbursement
policies more fully cover these services.
Evaluate existing programs and develop new
interventions.
In addition to building the capacity of
existing resources to address the psychosocial needs of
AYAs, evaluation is needed to assess the effi cacy (i.e.,
effect on outcomes) of existing interventions. These
evaluations should be used to inform the development
of new AYA-specifi c interventions. For example,
funding should be obtained to support efforts such as
testing and refi ning existing peer navigation models
and developing new AYA-specifi c navigation programs,
conducting longitudinal and/or multi-method theory-
based approaches to evaluating peer support and
family-based interventions, and developing and testing
interventions (e.g., to reduce social isolation, improve
family communication, increase health promoting
behaviors) to ameliorate negative psychosocial
outcomes.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Conclusion 19
Cancer in adolescents and young adults is an important
problem that has gone unrecognized or is only a
peripheral concern among numerous constituencies,
including but not limited to healthy teenagers and
young adults who do not know they are at risk;
primary care providers; pediatric and adult medical,
radiation, and gynecologic oncologists; basic
scientists; psychosocial, behavioral, and health services
researchers; many cancer patient support providers
and advocates; cancer registries; and funding sources
for research and cancer-related care. The unfortunate
results of this lack of focus have been severe—a lack
of cancer survival progress spanning more than two
decades and persistent diminution of young cancer
survivors’ quality of life.
The Adolescent and Young Adult Oncology Progress
Review Group (AYAO PRG) drew together more than
CONCLUSION
100 researchers, health care providers, advocates,
insurers, industry representatives, and health services
and health policy experts to consider the state of
cancer-related science and care for this population and
develop recommendations to accelerate progress and
improve outcomes across the research and cancer care
continuum. The AYAO PRG believes that a major,
ongoing AYAO-specifi c research initiative emphasizing
AYA clinical trials and outcomes research is urgently
needed. Collaboration and support from numerous
governmental, academic, public health, community-
based, and other private sector entities will be essential
to its success. The AYAO PRG offers this report as
a blueprint for a focused and structured approach to
improving cancer prevention, cancer care, and the
duration and quality of life for this vital segment of our
society.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix A: Roster A-1
APPENDIX A
ROSTER OF AYAO PRG PARTICIPANTS
Leadership
Karen Albritton, M.D.,
PRG Co-Chair
Dana Farber Cancer Institute
Michael Caligiuri, M.D.,
PRG Co-Chair
Ohio State University
Barry Anderson, M.D., Ph.D.,
PRG Executive
Director
Cancer Therapy Evaluation Program, National Cancer
Institute
Cherie Nichols, M.B.A.,
NCI Representative
Offi ce of Science Planning and Assessment, National
Cancer Institute
Doug Ulman
LAF Representative
, Lance Armstrong Foundation
Members
Heidi Adams
Planet Cancer
Lodovico Balducci, M.D.
H. Lee Moffi tt Cancer Center
Ronald Barr, M.B. Ch.B., M.D.
McMaster University
Archie Bleyer, M.D.
St. Charles Medical Center
Maryann Carousso, F.N.P., R.N.
Memorial Sloan-Kettering Cancer Center
William Hicks, M.D.
Ohio State University
Marion Lee, M.P.H., Ph.D.
University of California, San Francisco
Steven Lipkin, M.D., Ph.D.
University of California, Irvine
Mary McCabe, R.N.
Memorial Sloan-Kettering Cancer Center
Michael Moore, M.D.
Nationwide Insurance
Peter Pisters, M.D.
M.D. Anderson Cancer Center
Brad Pollock, M.P.H., Ph.D.
University of Texas Health Science Center
Amelie Ramirez, Dr.P.H.
Baylor College of Medicine
Lynn Ries, M.S.
SEER Program, National Cancer Institute
Lorna Rodriguez-Rodriguez, M.D., Ph.D.
Cancer Institute of New Jersey
Lydia Shrier, M.P.H., M.D.
Children’s Hospital Boston
Muneesh Tewari, M.D., Ph.D.
Fred Hutchinson Cancer Center
Beth Virnig, M.P.H., Ph.D.
University of Minnesota School of Public Health
Karen Weiss, M.D.
U.S. Food and Drug Administration
Bruce Williams
Enzon Pharmaceuticals
Brock Yetso
The Ulman Cancer Fund for Young Adults
Brad Zebrack, Ph.D.
University of Southern California
AYAO PRG MEMBERS
Report of the Adolescent and Young Adult Oncology Progress Review Group
A-2 Appendix A: Roster
BREAKOUT GROUPS AND CO-CHAIRS
Awareness
Heidi Adams
Planet Cancer
Brandon Hayes-Lattin, M.D.
Oregon Health & Science University
Sandra Horning, M.D.
Stanford University
Prevention
Brad Pollock, M.P.H., Ph.D.
University of Texas Health Science Center
Marion Lee, M.P.H., Ph.D.
University of California, San Francisco
Robert Hiatt, M.D., Ph.D.
University of California, San Francisco
Biology
Muneesh Tewari, M.D., Ph.D.
Fred Hutchinson Cancer Center
William Carroll, M.D.
New York University
Access
Karen Albritton, M.D.
Dana Farber Cancer Institute
Mary McCabe, R.N.
Memorial Sloan-Kettering Cancer Center
Joan McClure, M.S.
National Comprehensive Cancer Network
Insurance
Michael Moore, M.D.
Nationwide Insurance
Joseph San Filippo
Nationwide Insurance
Kimberly Calder, M.P.S.
National Multiple Sclerosis Society
Clinical Care Models
Lorna Rodriguez-Rodriguez, M.D., Ph.D.
Cancer Institute of New Jersey
Ian Lewis, M.B. Ch.B., F.R.C.P., F.R.C.P.C.H.
St. James’ University Hospital
Carol Somkin, Ph.D.
Kaiser Permanente
Clinical Trials/Research
Barry Anderson, M.D., Ph.D.
National Cancer Institute
Archie Bleyer, M.D.
St. Charles Medical Center
Robert Comis, M.D.
Coalition of Cancer Cooperative Groups
Special Populations
William Hicks, M.D.
Ohio State University
Marjorie Kagawa Singer, Ph.D., R.N.
University of California, Los Angeles
Smita Bhatia, M.D., Ph.D.
City of Hope
Psychosocial/Behavioral Factors
Brad Zebrack, Ph.D.
University of Southern California
Amelie Ramirez, Dr.P.H.
Baylor College of Medicine
Jennifer Ford, Ph.D.
Memorial Sloan-Kettering Cancer Center
Health-related Quality of Life
Ronald Barr, M.B. Ch.B., M.D.
McMaster University
Carolyn Gotay, Ph.D.
Cancer Research Center of Hawaii
Long-term Effects
Beth Virnig, M.P.H., Ph.D.
University of Minnesota School of Public Health
Kevin Oeffi nger, M.D.
Memorial Sloan-Kettering Cancer Center
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix A: Roster A-3
Lucile Adams-Campbell, Ph.D.
Howard University Cancer Center
H. Nelson Aguila, D.V.M.
Offi ce of Centers, Training and Resources, National
Cancer Institute
Daniel Armstrong, Ph.D.
Miami University
Kimlin Ashing-Giwa, Ph.D.
University of California, Los Angeles
Noreen Aziz, M.P.H., M.D., Ph.D.
Division of Cancer Control and Population Sciences,
National Cancer Institute
Deborah Banker, Ph.D.
The Leukemia & Lymphoma Society
Smita Bhatia, M.D., Ph.D.
City of Hope
Clara Bloomfi eld, M.D.
Ohio State University Medical Center
Cheryl Boyce, M.S.
Ohio Commission on Minority Health
Kimberly Calder, M.P.S.
National Multiple Sclerosis Society
William Carroll, M.D.
New York University
Jacqueline Casillas, M.D.
University of California, Los Angeles
Diane Colaizzi
Coalition of Cancer Cooperative Groups
Robert Comis, M.D.
Coalition of Cancer Cooperative Groups
David Coronado, M.P.A.
Independent Health Care Consultant
Gina D’Amato, M.D.
H. Lee Moffi tt Cancer Center and Research Institute
Stella Davies, M.B.B.S., Ph.D., M.R.C.P.
Cincinnati Children’s Hospital Medical Center
Dennis Deapen, Dr.P.H.
University of Southern California
Craig Earle, M.D.
Dana Farber Cancer Institute
David Feeny, Ph.D.
Institute of Health Economics
Jennifer Ford, Ph.D.
Memorial Sloan-Kettering Cancer Center
Margaret Foti, M.D. (h.c.), Ph.D.
American Association for Cancer Research
Darlene Gibbon, M.D.
The Cancer Institute of New Jersey
John Goldberg, M.D.
Dana Farber Cancer Institute
Lia Gore, M.D., F.A.A.P.
University of Colorado Cancer Center
Carolyn Gotay, Ph.D.
Cancer Research Center of Hawaii
Brooke Hamilton
Offi ce of Liaison Activities, National Cancer Institute
Douglas Hawkins, M.D.
Seattle Children’s Hospital and Regional Medical
Center
Brandon Hayes-Lattin, M.D.
Oregon Health & Science University
Pamela Haylock, R.N., M.A.
Cancer Care Consultant
Susan Hedlund, M.S.W.
Cancer Care Resources
Robert Hiatt, M.D., Ph.D.
University of California, San Francisco
Sandra Horning, M.D.
Stanford University
Marjorie Kagawa Singer, Ph.D., R.N.
University of California, Los Angeles
Ernest Katz, Ph.D.
Children’s Hospital Los Angeles
Mary Louise Keohan, M.D.
Memorial Sloan-Kettering Cancer Center
Ian Lewis, M.B. Ch.B., F.R.C.P., F.R.C.P.C.H.
St. James’ University Hospital
ROUNDTABLE ATTENDEES
Report of the Adolescent and Young Adult Oncology Progress Review Group
A-4 Appendix A: Roster
Michael Link, M.D.
Stanford University
Henri Lipmanowicz
Plexus Institute
Joseph Lipscomb, Ph.D.
Emory University
Cynthia Love, R.N., B.S.N.
Pediatric Oncology Branch, National Cancer Institute
Kevin Lucia, M.H.P., J.D.
Georgetown University
Craig Lustig
Children’s Cause for Cancer Advocacy
David Lyon
Lance Armstrong Foundation
Ralph Manchester, M.D.
University of Rochester
Joan McClure, M.S.
National Comprehensive Cancer Network
Gail McGrath
National Patient Advocate Foundation
Craig Nichols, M.D.
Oregon Health & Science University
Kevin Oeffi nger, M.D.
Memorial Sloan-Kettering Cancer Center
Kutluck Oktay, M.D.
Weill Medical College of Cornell University
Ann O’Mara, Ph.D., R.N.
Division of Cancer Prevention, National Cancer
Institute
David Osoba, B.S.C., M.D.
Quality of Life Consultant
Grace Powers-Monaco, J.D.
Medical Care Ombudsman Volunteer Program
Randi Rosenberg
Young Survival Coalition
Brian Rubin, M.D., Ph.D.
University of Washington Medical Center
Kathleen Ruccione, M.P.H., R.N., C.P.O.N.,
F.A.A.N.
Children’s Hospital Los Angeles
Joseph San Filippo
Nationwide Insurance
Leslie Schover, Ph.D.
M.D. Anderson Cancer Center
Barbara Ullman Schwerin, J.D.
Disability Rights Legal Center
Leonard Sender, M.D.
University of California, Irvine Medical Center
Peter Shaw, M.D.
Children’s Hospital of Pittsburgh
Susan Matsuko Shinagawa, Ph.D.
Intercultural Cancer Council
Stuart Siegel, M.D.
Children’s Hospital Los Angeles
Carol Sienche
Offi ce of Education and Special Initiatives, National
Cancer Institute
William Small Jr., M.D.
Northwestern Memorial Hospital
Carol Somkin, Ph.D.
Kaiser Permanente
Wendy Stock, M.D.
University of Chicago
Jeffrey Summers, M.D.
U.S. Food and Drug Administration
Daniel Sussman, Ph.D.
Division of Cancer Biology, National Cancer Institute
Gail Tomlinson, M.D., Ph.D.
University of Texas Southwestern Medical Center
Carmina Valle, M.P.H.
Offi ce of Cancer Survivorship, National Cancer
Institute
Samuel Wells, M.D.
Duke University
Jeremy Whelan, M.D.
University College Hospital
Elizabeth Williams, Ph.D.
Meharry Medical Arts Center, Vanderbilt University
ROUNDTABLE ATTENDEES (CONT.)
Table of Contents
Awa
reness
..............................................................................................................................................................
B-
3
Prevention/Cancer Contr
ol/Epidemiology/Risk
.......................................................................................................
B-
7
Biol
ogy
...................................................................................................................................................................
B-
1
1
Acce
ss
..................................................................................................................................................................
B-
1
5
Insu
rance
..............................................................................................................................................................
B-
1
9
Clinical Care Mode
ls
.............................................................................................................................................
B-
2
3
Clinical Tria
ls/Research
........................................................................................................................................
B-
2
7
Special Popu
lations
..............................................................................................................................................
B-
3
5
Psych
osocial/Behavioral Factors
..........................................................................................................................
B-
4
1
Health-related Quality of Life
................................................................................................................................
B-
4
7
Long-term Effe
cts
.................................................................................................................................................
B-
5
1
APPENDIX B
BREAKOUT GROUP REPORTS
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix B: Breakout Group Reports B-1
Report of the Adolescent and Young Adult Oncology Progress Review Group
Co-Chairs
Heidi Adams
Brandon Hayes-Lattin
Sandra Horning
Participants
Deborah Banker
Michael Moore
Kimberly Calder
Craig Nichols
Maryann Carousso
Amelie Ramirez
David Coronado
Randi Rosenberg
Darlene Gibbon
Leslie Schover
Brooke Hamilton
Stuart Siegel
Pamela Haylock
Carol Sienche
David Lyon
Brock Yetso
Gail McGrath
Background
Adolescents and young adults (AYAs) with cancer have
“fallen through the cracks” when it comes to treatment,
clinical research, resources, and support services.
The Adolescent and Young Adult Oncology Progress
Review Group (AYAO PRG) has defi ned the AYA age
group as those 15 to 39 years old. This defi nition was
based on data showing a “gap” that occurs in this age
range: In the past 30 years, improvement in survival
rates for AYAs has not kept pace with that experienced
by their older and younger counterparts.
For AYA issues to be addressed effectively, the fi rst,
critical step is broad acceptance of AYAs as a distinct
demographic group with unique needs related to their
age and stage of life. Awareness and acceptance
of AYAs as a unique group must increase among
AYA stakeholders, including clinicians, researchers,
advocates, and patients and their families/caregivers
to achieve the goal of increasing awareness among
funding agencies, policy makers, publishers, medical
societies, and the general public.
An initial step toward achieving this goal will be
identifying key groups among these stakeholders that
can signifi cantly effect change for AYAs. Messages
and outreach strategies then must be developed
to increase awareness about AYAs as a separate
population with unique characteristics.
Another key to defi ning AYAs as a distinct group
will be highlighting those points in the cancer care
continuum where AYAs fall through the cracks. For
example, compared to the general population, AYAs are
more likely to experience delayed diagnoses, they are
the least represented population in clinical trials, and
they are the most likely non-elderly group to be under-
or uninsured. Increased awareness that problems such
as these exist is essential to begin addressing them.
Descriptions of the unique epidemiology of AYA
cancer patients have only begun to appear in the
past decade. Only this year (2006) was the fi rst-ever
Surveillance, Epidemiology, and End Results (SEER)
program monograph on AYAs published. Little
published research exists that pertains specifi cally to
AYA patients. The current state of the AYA oncology
literature remains largely descriptive; research projects
and publications may involve patients in the AYA age
range, but questions directly relating biologic and
psychosocial AYA factors to outcomes rarely have been
addressed.
AYA research is diffi cult to identify because it lacks
standardized language for keyword searches. The
lack of recognition of AYAs as a distinct group was
illustrated by the diffi culty in extracting relevant
information from the National Cancer Institute’s
(NCI’s) research portfolio for the purposes of this
PRG. An initial keyword search for “young,” “teen,”
or “adolescent” retrieved 585 studies; however,
the majority of the studies were not focused on
AYA cancers and were therefore eliminated from
consideration. In addition, projects that focused
specifi cally on cancers that predominately strike AYAs
(e.g., testicular cancer) were not retrieved by this
search strategy unless the abstract specifi cally included
the previously noted keywords. NCI’s indexing
and coding systems need to be adapted to recognize
AYAs as a distinct group for the purposes of effective
research and data compilation.
With AYAs established as a discrete demographic
group, the essential prospective research specifi cally
designed or stratifi ed for AYAs can be conducted.
AWARENESS
Appendix B: Breakout Group Reports - Awareness B-3
Report of the Adolescent and Young Adult Oncology Progress Review Group
Well-designed studies addressing AYA-specifi c
biologic and psychosocial factors will require
identifi cation of programs with adequate numbers
of AYA patients in treatment and follow-up and
dedicated, funded researchers.
Priority 1
Establish AYA as a distinct group of cancer patients
based on unique needs and issues, institutionalize
the defi nition, and gain broad acceptance among
stakeholders in AYA care.
Rationale
The AYA group shares common needs and issues
that differentiate them from other cancer cohorts. To
effectively and appropriately address these needs,
they must be accorded recognition as a separate
demographic group. The lack of recognition of AYAs
as a distinct group is illustrated by the diffi culty in
extracting relevant information from the NCI research
portfolio so that neither a specifi c nor sensitive search
for AYA investigations was possible in preparation
for this PRG as detailed earlier. Education, research,
career development, clinical care, and support
services focused on the distinct AYA group cannot
occur without appropriate, broad recognition of their
defi nition.
Implementation Barriers
• AYAs are a previously undefi ned,
heterogeneous group of patients.
• AYAs may be viewed differently by various
stakeholders according to their relationship to
the group.
• The term “adolescent” may have a negative
connotation for older adolescent patients.
• Limited data exist to support the current
defi nition of AYAs as comprising patients aged
15 to 39 years.
• Establishing standardized terminology among
government agencies, funding organizations,
and professional societies is diffi cult.
Potential Partnerships and Resources
• Funding agencies
• Health care professional organizations
• Advocacy groups
• Federal agencies
• National Library of Medicine
• International Committee of Medical Journal
Editors
• International Cancer Research Portfolio
Concrete Actions in the Next Three Years
• NCI should establish/coordinate search terms,
keywords, and coding specifi c to AYAs.
• Key stakeholders should be convened
at the November 2006 meeting of the
LIVE
STRONG
™ Young Adult Alliance to
demonstrate unifi ed acceptance of the AYA
defi nition.
Priority 2
Increase awareness in the clinical sphere (e.g.,
patients, caregivers, providers) regarding the
signifi cance and unique aspects of AYA oncology.
Rationale
To this point, AYA cancer patients have fallen through
the cracks in medical, psychosocial, and support
services, resulting in a relative lack of improvement
in survival rates. Because the prevalence of cancer
in this age group is not widely appreciated, clinical
suspicion in AYA patients, caregivers, and providers is
low. Once diagnosed, there is a lack of awareness as to
the elements of appropriate care for AYA patients. In
addition to the greater likelihood of delayed diagnoses,
AYAs face unique issues with regard to their education,
fi nancial, and insurance status; fertility; social support;
and psychological issues. Spotlighting these issues and
the under-representation of AYAs in clinical trials are
the fi rst steps toward addressing them.
Implementation Barriers
• Getting the attention of stakeholders is diffi cult.
• AYAs are a previously undefi ned cohort.
• Clinical care providers are fragmented between
pediatric and adult oncology and between
academic and community centers.
• AYAs lack spokespeople/champions.
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Feelings of invincibility among AYAs contribute
to awareness problems.
• Different messages will be required to effectively
reach different segments in the clinical care
sphere: health care professionals, patients, and
caregivers.
Potential Partnerships and Resources
• Professional organizations
• Academic institutions
• Community cancer centers
• Advocacy organizations
• Medical journals
• Mass media
• American Medical Writers Association
• Military and educational institutions
Concrete Actions in the Next Three Years
• Encourage professional societies and
publications to develop AYA-specifi c forums.
• Stimulate development of AYA-specifi c curricula
in oncology professional training programs.
• Encourage the Lance Armstrong Foundation
(LAF), CancerCare, and other partner
organizations to host teleconferences for
patients/caregivers on AYA issues.
• Encourage the LIVE
STRONG
™ Young Adult
Alliance to coordinate a comprehensive public
relations campaign on AYA needs and issues.
• Encourage NCI to develop AYA-specifi c patient,
provider, and caregiver materials.
Priority 3
Increase awareness in the non-clinical sphere (e.g.,
public, media, corporations, and policy makers)
regarding the signifi cance and unique aspects of
AYA oncology.
Rationale
The general public, funding organizations, policy
makers, and the business world are largely unaware that
cancer is a leading cause of death among adolescents
and young adults. Increased awareness about the
prevalence and burden of AYA cancer may increase
enrollment in health insurance plans, promote timely
diagnoses, and encourage funding of research and
resources for AYA oncology, thereby reducing AYAs’
suffering and improving outcomes.
Implementation Barriers
• Signifi cant competition with other health-related
messages targeting AYAs, such as drunk driving
and drug abuse.
• Lack of high-profi le spokespeople to champion
AYA cause.
• Lack of messaging and focus.
• Small size and political weakness of AYAs as a
group.
• Competition for funding.
• AYA sense of invincibility.
Potential Partnerships and Resources
• Large corporations/employers
• Military
• Educational institutions
• Community organizations
• Advocacy groups
• Insurance industry
• Youth-oriented media outlets
• Professional organizations
• Government policy makers
• Celebrities, entertainment industry
Concrete Actions in the Next Three Years
• Identify and recruit high-profi le, credible AYA
spokespeople.
• Approach Health in Hollywood and other youth-
oriented media to encourage them to highlight
this problem.
• Schedule briefi ngs for policy makers on Capitol
Hill.
• Encourage the LIVE
STRONG
™ Young Adult
Alliance to coordinate a comprehensive public
relations campaign on AYA needs and issues.
• Approach the Ad Council for a national media
campaign highlighting AYAs.
Appendix B: Breakout Group Reports - Awareness B-5
Report of the Adolescent and Young Adult Oncology Progress Review Group
Conclusion
A lack of awareness exists among all stakeholders and
the general public about the signifi cance of cancer in
the AYA population and the unique needs and issues
of AYA patients related to their age and stage of life.
Until now, the AYA population has not been offi cially
defi ned. Broad recognition and acceptance of the AYA
defi nition are critical fi rst steps to improving outcomes
and quality of life for AYA patients.
Awareness must increase in both the clinical and non-
clinical arenas. Within these spheres of infl uence, key
stakeholders who can signifi cantly effect change for
AYAs must be identifi ed and, through appropriately
tailored messaging and outreach, these stakeholders
must be energized to recognize and promote AYAs as a
distinct demographic population.
Report of the Adolescent and Young Adult Oncology Progress Review Group
PREVENTION/CANCER CONTROL/EPIDEMIOLOGY/RISK
Co-Chairs
Brad Pollock
Marion Lee
Robert Hiatt
Participants
Lucile Adams-Campbell
Ralph Manchester
John Goldberg
Gail McGrath
Carolyn Gotay
Ann O’Mara
Steven Lipkin
Lynn Ries
Cynthia Love
Gail Tomlinson
David Lyon
Carmina Valle
Background
Etiology
The etiology of AYA cancers remains largely
understudied. Without an understanding of the etiology
of these malignancies, developing effective cancer
preventive interventions is challenging. Substantial
resources have been directed at studying the causes of
childhood cancer, which collectively represent less than
1 percent of all new cancer cases annually. Cancer
incidence in the 15 to 39 year-old age group is 4.3
times higher than for children under age 15. Six types
of cancer account for 67 percent of all cancers in the
AYA population: breast (15.4 percent), lymphoma
(12.1 percent), melanoma (11.0 percent), thyroid (10.7
percent), female genital system (9.9 percent), and male
genital system (8.1 percent).
1
Little research has focused on the etiology of
malignancies that occur primarily in AYAs. The
research that has been done indicates that cancer family
syndromes (e.g., germline mutations) account for less
than 5 percent of the overall incidence of cancers in
this age group. Environmental factors are thought to
play a minimal but undefi ned role in the etiology of
childhood malignancies. The etiologies of cancers in
the adolescent and young adult years represent a mix of
the genetic and environmental factors.
Adolescents and young adults in the general population
often are exposed to known risk factors for adult
malignancies (e.g., human papillomavirus, hepatitis
B virus, poor diet, lack of physical activity, obesity,
tobacco use). Therefore, an important opportunity
exists in this age group to develop and implement
interventions that can reduce the risk of future adult
malignancies. In addition, the occurrence of treatment-
related sequelae in AYA survivors may be modifi ed
by interventions during or after cancer therapy.
Currently, little evidence is available to indicate that
these interventions alter long-term outcomes. A
number of intervention strategies for adult cancer
involve altering exposure to potentially modifi able risk
factors. It is likely that understanding the interplay
between environmental exposures and genetic factors,
or gene-environment interactions, will guide the way to
developing effective preventive interventions for AYAs.
Prevention
Very little prevention research has been targeted at this
age group because the AYA cancer problem is under-
appreciated and because researchers may anticipate
problems with AYAs’ adherence to research protocols.
AYAs with cancer also are unlikely to be treated in
research centers. Because of these barriers and those
imposed by gaps in health care use and insurance, few
preventive interventions have been aimed at this age
group.
Cancer prevention strategies are aimed at reducing
the incidence of new cancers. These strategies can
be grouped into those aimed at blocking the initial
onset of disease (primary prevention), those aimed at
detecting disease in the earliest stages of development
(secondary prevention), and interventions targeting the
post-diagnosis period (tertiary prevention).
An overall prevention strategy should focus on
identifying etiologic factors for cancers that affect
AYAs. However, primary prevention focused on the
AYA population will also affect cancer incidence
later in life, given the long latency of most cancers
following exposure. For example, tobacco use is not
likely to signifi cantly increase the burden of cancers
in the adolescent and young adult years, but will do
so later in life. Likewise, sun exposure at early ages
is strongly associated with skin cancers, including
malignant melanomas, that occur most frequently later
1
SEER 17, 2000-2003.
Appendix B: Breakout Group Reports - Prevention/Cancer Control/Epidemiology/Risk B-7
Report of the Adolescent and Young Adult Oncology Progress Review Group
in adulthood. Reduced exposure to direct sunlight and
increased use of sun block decrease cancer incidence
later in life. Infectious agents are strongly implicated
in the etiology of some adult malignancies, such
as cervical cancer. Human papillomavirus (HPV)
vaccines have been shown to be extremely effective
at blocking new HPV infection in adolescent girls,
thus reducing cervical cancer incidence later in
life. Other AYA cancer preventive strategies might
focus on increasing physical activity and maintaining
appropriate energy balance.
Secondary preventive methods in early detection are
non-existent in this population with the exception of
Pap smears for cervical cancer. The low incidence of
common adult cancers (e.g., breast, colon, prostate) in
AYAs make effi cacy trials of established early detection
procedures such as mammography and colonoscopy
impractical. However, identifying high-risk AYAs
based on their genetic predisposition may provide an
acceptable and cost-effective strategy for targeted early
detection interventions. Improved access to and use of
diagnostic imaging and screening tests that use highly
sensitive biomarker assays may also reduce the cancer
burden.
Tertiary prevention is aimed at reducing subsequent
cancer risk and adverse treatment effects following a
primary cancer diagnosis. Survivors of AYA cancer are
at risk for many treatment-related, long-term sequelae,
such as second primary cancers, heart failure, hearing
loss, and cognitive dysfunction. Prognostic factors
for these outcomes must be elucidated to formulate
strategies for reducing their incidence. Relevant
interventions may involve manipulations of primary
cancer therapies, such as using continuous instead
of bolus infusion of anthracyclines to decrease the
risk of cardiotoxicity, chemoprotectants designed to
decrease myocardial damage during anthracycline
administration, or otoprotectants during platinum
administration. Other interventions may be targeted
at survivors, such as increasing physical exercise to
prevent obesity among AYAs who are completing their
cancer therapy.
Identifi ed Action Areas
The Prevention/Cancer Control/Epidemiology/Risk
Breakout Group identifi ed the need for action in 10
areas:
1. Tobacco control: postponement of smoking
initiation; potential long-term health effects
of environmental tobacco smoke exposure;
adverse effects on offspring of tobacco smoke
exposure during pregnancy; genetic variation
in addiction susceptibility; cessation efforts in
AYAs.
2. Cancer prevention vaccines: HPV vaccine
implementation issues; hepatitis B vaccine;
Epstein-Barr virus vaccine.
3. Genetic susceptibility: importance in AYA
cancer etiology; potential use of genetic
screening to identify high-risk populations and
in monitoring for second cancers; privacy and
data access concerns; use of genetic testing
to identify populations for chemoprevention;
possibility of including an AYA cancer in The
Cancer Genome Atlas (TCGA).
4. Sequelae of cancer treatment in AYAs: second
primary cancers; ototoxicity; cardiotoxicity;
social integration and educational reentry;
fertility issues; dietary interventions to modify
risk of sequelae.
5. Sun exposure risk (increased education for
prevention and early detection of malignant
melanoma, squamous cell carcinoma):
awareness of risk among AYAs, educators, and
parents; possible viable screening alternatives;
access to early detection services.
6. Surveillance of AYA cancer patterns: greater
depth and breadth of traditional surveillance
activities; more detailed information on risk
behaviors, treatment/tumor characterization,
quality of care, economic factors, and patient-
centered outcomes.
7. Early-onset breast cancer: research on
epidemiology; chemoprevention (e.g.,
raloxifene, COX-2 inhibitors); special
population issues including higher incidence in
African American and Asian women; relation
of risk to diet, obesity, and energy balance.
8. Chemoprevention
9. Lifestyle interventions: behavior modifi cation
to improve diet (e.g., 5-A-Day); education on
benefi ts of healthy lifestyle; healthy lifestyle
interventions in AYA survivors.
Report of the Adolescent and Young Adult Oncology Progress Review Group
10. Early detection of AYA cancers: effi cacy of
using genetic susceptibility markers to identify
high-risk populations with special attention
to testicular cancer, breast cancer, cervical
dysplasia, and melanoma.
The top three priorities were selected based on these
criteria:
• Importance with respect to the level of cancer
burden in the AYA population or to the potential
for intervening with AYAs to reduce adult cancer
risk
• Lack of resources currently devoted to the issue
• Potential for actual implementation
Priority 1
Increase research on interventions to prevent or
ameliorate the sequelae of cancer therapy in the
AYA population.
Rationale
AYA survivors suffer from a broad spectrum of
treatment-related sequelae (e.g., second malignancies,
infertility, cardiotoxicity, hearing loss, cognitive
dysfunction, obesity). Although adolescents and young
adults have a sense of immortality prior to having
cancer, awareness of their vulnerability and motivation
to participate in prevention research may be heightened
after being treated. Opportunities therefore exist to
conduct effective research aimed at improving survival
and preventing or ameliorating the late effects of cancer
therapy.
Implementation Barriers
• More than 75 percent of adolescents aged 15
to 19 years are not seen at a cooperative group
institution.
• People in this age range often have diffi culty in
adhering to prescribed regimens.
• Funding in this area is inadequate.
• Researcher interest is low due to lack of
awareness of the AYA cancer problem.
• This population often falls through the cracks
with respect to access to health services,
including prevention services.
Potential Partnerships and Resources
• Expanded biospecimen repositories to facilitate
research
• New and enhanced infrastructure for conducting
longitudinal studies and interventions and
tracking long-term outcomes
• Potential partners: National Institutes of Health
(NIH), Lance Armstrong Foundation (LAF),
college health groups, American Cancer Society
(ACS), American Society of Clinical Oncology
(ASCO), Centers for Disease Control and
Prevention (CDC)
Concrete Actions in the Next Three Years
• Fund sequelae prevention research.
• Increase awareness of need for research in this
area (e.g., conferences, publications, workshops).
Priority 2
Increase resources for studies of genetic
susceptibility in AYA cancers, including
designation of an AYA cancer-specifi c component
in The Cancer Genome Atlas (TCGA).
Rationale
Cancers that occur in younger persons (children
and adolescents) are thought to be related more to
genetic etiologies than to environmental etiologies.
In the general AYA population, opportunities exist
to identify subsets at high risk of adult cancers using
genetic screening and new technologies, such as high-
throughput genomic and proteomic assessments. The
new TCGA needs to include at least one cancer that is
common in the AYA population.
Implementation Barriers
• Privacy, medicolegal, and insurability issues
may restrict more widespread use of genetic
screening.
Potential Partnerships and Resources
• Genetic counselors
• Biotechnology industry
• NIH/NCI
Appendix B: Breakout Group Reports - Prevention/Cancer Control/Epidemiology/Risk B-9
Report of the Adolescent and Young Adult Oncology Progress Review Group
Concrete Actions in the Next Three Years
• Sponsor conferences and workshops focused
on genetic susceptibility and the use of genetic
markers to identify high-risk subsets of AYAs.
• Increase research funding (e.g., through Requests
for Applications and Program Announcements)
to assess the use of genetic screening to reduce
the cancer burden.
Priority 3
Increase education in the AYA population on
the risks of sun exposure to reduce the risk of
malignant melanoma.
Rationale
It is known that sun exposure at younger ages greatly
increases the risk of malignant melanoma and other
skin cancers in adulthood. Melanoma accounts for 93
percent of invasive skin cancers (excluding basal and
squamous cell carcinoma and Kaposi’s sarcoma) in the
15 to 39 year-old age group.
Implementation Barriers
• Adolescents and young adults consider
themselves at minimum risk of disease and
therefore feel that they do not need to protect
themselves from sun exposure.
• Even though AYAs have some knowledge about
the effects of sun exposure, physical appearance
in this population remains an overriding high
priority. Being sun tanned is considered
attractive among most Caucasians, who are at
highest risk for melanoma.
Potential Partnerships and Resources
• Cosmetic industry
• Pharmaceutical industry
• Schools and health educators
• NCI, ACS, CDC
Concrete Actions in the Next Three Years
• Develop and implement school curricula
(elementary through college) on the dangers of
sun exposure and on practices that can reduce
skin cancer risk.
• Support behavioral research to develop more
effective interventions to reduce sun exposure.
• Identify AYAs in the general population who
are at relatively high risk of skin cancers due to
genetic predisposition.
Conclusion
There are many prevention opportunities to
dramatically reduce the burden of cancer in both the
AYA population and older adult populations. Some of
the common barriers to achieving prevention goals are
related to the sense of invulnerability and immortality
common among adolescents and young adults, the lack
of scientifi c interest in developing preventive measures
for this population, and providers’ lack of concern
about the need to recommend preventive measures. In
addition, it is not clear which health care specialists
should be responsible for implementing preventive
measures. By implementing the three top priorities
described along with the research and programs listed
in the Breakout Group’s other identifi ed action areas,
the incidence of cancer and cancer-related morbidity
among AYAs would be markedly decreased.
B-10
Appendix B: Breakout Group Reports - Prevention/Cancer Control/Epidemiology/Risk
B-10 Appendix B: Breakout Group Reports - Prevention/Cancer Control/Epidemiology/Risk B-10
Report of the Adolescent and Young Adult Oncology Progress Review Group
BIOLOGY
Co-Chairs
Muneesh Tewari
William Carroll
Participants
Deborah Banker
Michael Link
Clara Bloomfi eld
Brian Rubin
Gina D’Amato
Wendy Stock
Stella Davies
Jeffrey Summers
Margaret Foti
Daniel Sussman
Douglas Hawkins
Bruce Williams
Background
The stark lack of improvement in survival outcomes
for adolescent and young adult cancer patients over
the past few decades contrasts sharply with dramatic
improvements in childhood cancer cure rates and the
recent, steady improvement in overall cancer survival
rates for adults. Many of the advances in cancer
survival in children and adults have been achieved
through an integrated understanding of tumor biology
and the normal biology of the patient, which has far
outpaced the state of this knowledge about the AYA
population, even for cancers with a high prevalence
in adults (e.g., breast and colon cancers). To improve
outcomes for AYA cancer patients, this knowledge gap
must be closed.
The lack of progress in AYA cancer biology research is
partly explained by the relative rarity of AYA cancers,
the small number of AYA patients entering clinical
trials, and the scarcity of normal and tumor tissue
samples. Therefore, the many AYA cancer research
stakeholders must pool their resources and cooperate to
more effectively study normal and tumor biology in the
AYA population.
Sequencing of the human genome and new
technologies for global molecular analysis (e.g., global
gene expression
1
) are creating opportunities to study
molecular differences among AYA, childhood, and
adult cancers in greater detail than previously has been
possible. Much of the data showing that age-related
biologic factors probably do play a role in cancer
outcomes result from studies comparing the genetics
of acute lymphoblastic leukemia (ALL) in children and
adults.
Researchers know that different age groups tend to
develop characteristic genetic subtypes of ALL, and
the relationship of ALL subtype to prognosis is well
established. For example, children with ALL blast
cells
2
having a genetic mutation known as the TEL-
AML1 fusion transcript have an unusually good
prognosis. In contrast, patients with a particular
BCR-ABL mutation
3
have an unfavorable prognosis.
Researchers have found that up to 50 percent of
children between 1 and 9 years of age, but only 10
percent or fewer of children ages 10 or older, have blast
cells harboring a favorable genotype such as TEL-
AML1. Less than 2 percent of younger children have
the unfavorable BCR-ABL genotype, compared with
approximately 12 percent of young adult ALL patients.
Less is known about age-related genetic differences in
other tumor types. However, one study showed that
gastrointestinal stromal tumors in children tend not to
have a c-kit mutation that is commonly seen in adults
with this disease. Other research suggests that the type
of genetic mutations found in Ewing’s sarcoma tumors
may differ considerably between children and adult
patient populations.
Some studies point to the role of epigenetics, including
methylation of cancer-causing genes, in age-related
differences in cancer outcomes. In one study for
example, several key cancer-causing genes, including
LATS-1, CDH1, p57, p14, and p15, were more likely
to be methylated in adults than in children. Age-related
changes in epigenetic regulation also may affect the
expression of genes involved in drug metabolism and
account for some of the characteristic differences
in outcome and drug toxicity documented in AYAs.
Side effects that AYA patients experience more than
other populations include higher induction death
1
Global gene expression measures the patterns of expression of up
to thousands of genes in a sample.
2
Immature cells that normally comprise 5 percent of the bone
marrow.
3
t(9;22) BCR-ABL translocation.
Appendix B: Breakout Group Reports - Biology B-11
Report of the Adolescent and Young Adult Oncology Progress Review Group
rate,
4
pancreatitis, treatment-related neuropathy,
5
and
glucose intolerance. An understanding of the biologic
mechanisms underlying treatment toxicities will help
researchers design equally effective but less toxic
treatment regimens for AYA patients. For example,
one group of researchers found that the maturing bone
of AYA patients treated with dexamethasone may be
particularly susceptible to osteonecrosis. This fi nding
led to a modifi ed dexamethasone dosage schedule for
adolescents 13 years and older.
Further, developmental and hormonal differences may
infl uence drug metabolism and increase the risk of
drug toxicity and relapse. The increased incidence
of obesity in AYA patients compared with younger
patients has been associated with poorer outcomes.
Data from another study suggest that obese patients
can tolerate therapy, although an acute myeloid
leukemia (AML) study reported increased side effects
in obese AML patients. Further research is needed to
elucidate the relationship among obesity, drug toxicity,
and outcomes. The effects of pregnancy on cancer
development and response to therapy in AYAs also are
not well understood.
In summary, emerging data, much of it from ALL
studies, indicate that differences in host/patient and
tumor biology play a role in the poorer prognosis of
AYA patients. Further studies in ALL and other tumors
are likely to lead to important observations that can be
translated into better therapies and improved outcomes
for the AYA population.
Major Challenges in Studying Tumor Biology in
the AYA Population
• The biology of tumors in AYAs is poorly
understood.
• Host/patient differences as a function of age are
understudied.
• Infrastructure to support acquisition and
distribution of samples is lacking.
Priority 1
Improve basic biologic research in AYA non-
Kaposi’s sarcomas.
Rationale
Although sarcomas are an important group of diseases
in the AYA population, the basic biology of AYA
non-Kaposi’s sarcomas is poorly understood. In
many respects sarcomas are an orphan disease, but the
opportunity exists to signifi cantly enhance knowledge
about AYA sarcoma biology. Although some
investigators already are collecting biological samples
for AYA sarcoma research, establishing a network to
share samples is the top priority. Building on existing
infrastructure, such as the Cooperative Human Tissue
Network (CHTN), to obtain more AYA sarcoma
samples would be an expedient way to accomplish this
goal.
Implementation Barriers
• Sarcoma is a relatively rare disease.
• Limited funding is available to study sarcoma
biology.
• The number, size, and quality of annotated AYA
non-Kaposi’s sarcoma biological samples are
limited.
• AYA sarcoma patients are diagnosed and treated
by a diverse group of providers, mostly in
community medical settings where collection of
fresh tissue samples is not valued.
• The incentive for investigators to collect
samples is low. There is no mandatory sample
collection, best practice collection guidelines, or
infrastructure for accessing samples. Regulatory
barriers to sample collection also exist.
Potential Partnerships and Resources
• Sarcoma Alliance for Research through
Collaboration (SARC)
• National Cancer Institute (NCI) Cooperative
Groups and Cancer Centers
• American Association for Cancer Research
(AACR)
• CHTN—infrastructure for sample collection,
maintenance, and distribution
4
The rate of patient death due to toxic effects of chemotherapy
given to treat the tumor.
5
Functional disturbance or pathologic changes in the peripheral
nervous system.
B-12
Appendix B: Breakout Group Reports - Biology
B-12 Appendix B: Breakout Group Reports - Biology B-12
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Lance Armstrong Foundation (LAF)—AYA non-
Kaposi’s sarcoma research advocacy
• American College of Surgeons—partnerships for
tissue collection
Concrete Actions in the Next Three Years
• NCI, SARC, and the cooperative groups should
issue a directive requiring submission of AYA
sarcoma samples to CHTN for sharing with other
investigators. For example, SARC membership
could be made dependent on providing an agreed
upon number of samples for submission. NCI
and/or SARC also should develop and require
compliance with a standard operating procedure
for sample processing, annotation, and access.
Both tumor and normal tissues are needed.
Scientifi c review for proper sample distribution
already exists through CHTN.
• NCI and others should identify funding sources
for and implement collection of tissues with a
required minimum of annotation data, building
on the CHTN infrastructure.
• NCI, AACR, and/or other funders should
issue a Request for Applications (RFA) for
basic biologic research in AYA non-Kaposi’s
sarcomas. Research areas should not be limited
by the RFA; however, important areas include
epigenetics, developmental biology, stem
cell research, and preclinical models. Cross-
disciplinary studies (e.g., stem cell research,
developmental biology) should be encouraged.
Priority 2
Improve understanding of host/patient biology of
aging and cancers, including sarcomas, leukemias,
lymphomas, and breast and colorectal carcinomas,
in the AYA population.
Rationale
The biology of aging in this population has been
understudied yet may have cross-cutting relevance
to many AYA cancers. This population may have
unique genetic and epigenetic differences compared
to either younger or older age groups, as well as
important hormonal and physiologic differences
(e.g., effects of pregnancy, increased prevalence of
obesity in adolescence). An understanding of how
these differences may affect cancer development, drug
metabolism, and response to treatment is needed to
improve survival in AYA cancer patients. Achieving
this understanding will require focused collaboration
and optimal utilization of resources. The availability of
normal tissues is essential.
Implementation Barriers
• Few normal tissue samples are available to
perform this research.
• Collaboration among oncologists studying AYA
cancer and biologists studying aging is limited.
• Funding for host/patient biologic research in the
AYA population is insuffi cient.
Potential Partnerships and Resources
• National Institute on Aging (NIA), LAF,
Leukemia & Lymphoma Society, and AACR—
promote research collaboration and provide
funding
• Cooperative groups, cancer centers, and
CHTN—provide infrastructure for tissue
collection
Concrete Actions in the Next Three Years
• AACR/NCI/NIA should convene a
multidisciplinary meeting of investigators to
discuss hypotheses and experimental approaches
to understanding the effects of AYA development
and aging on cancer. This meeting will serve as
a springboard for creating a network of experts
and potential collaborators interested in this
research topic.
• NCI, NIA, and other funders should issue
an RFA for the study of biologic aging in
the AYA population in both the normal and
cancer contexts. The RFA should encourage
investigation of all AYA cancers, including
sarcomas, leukemias, lymphomas, and
carcinomas.
• NCI, SARC, and/or other research sponsors
should provide funding to create incentives for
banking and sharing normal and all types of
AYA tumor samples using mechanisms similar to
those described in Priority 1.
Appendix B: Breakout Group Reports - Biology B-13
Report of the Adolescent and Young Adult Oncology Progress Review Group
Priority 3
Investigate a potential biologic basis of age-related
differences in outcome for AYA cancers, beginning
with leukemias and lymphomas.
Rationale
Evidence suggests that for certain cancers such as
leukemia and lymphoma, disease biology is different
in AYA patients compared with their younger or
older counterparts. These differences could be due
to variations in host/patient physiology (see Priority
2) or age-related differences in tumor biology.
Understanding how basic aspects of disease biology,
including the role of the tumor microenvironment,
change with aging in AYA individuals is needed.
Leukemias and lymphomas are AYA cancers for which
a substantial body of biologic knowledge already
exists. Furthermore, pediatric and medical oncologists
studying leukemia and lymphoma already have formed
effective collaborative infrastructures. Thus, these
diseases provide a good starting point for implementing
this priority.
Implementation Barriers
• The number and quality of biologic samples in
the AYA population for leukemia and lymphoma
are limited.
• Funding for studies of tumor biology related to
outcomes in the AYA population is limited.
• Because accrual of AYA patients to protocols is
limited, the collection of samples and clinical
information on disease presentation, laboratory
features, stage, and outcome also is limited.
Potential Partnerships and Resources
• NCI, AACR, Leukemia & Lymphoma Society,
LAF—funding
• Cooperative groups—clinical trials, samples, and
annotated data
Concrete Actions in the Next Three Years
NCI and/or other funders should issue an RFA to study
age-related biologic differences in lymphoma and/or
leukemia, focusing on the AYA population. The RFA
should fund examination of samples from both adult
and pediatric clinical trials and address the biologic
basis of outcome differences. Progress in lymphoma
and leukemia studies will serve as a model for
investigating other cancers in this population.
Conclusion
Preliminary research indicates that signifi cant
differences in AYA tumor and host biology
compared with other age groups account for some
of the corresponding differences in outcome for this
population. Researchers are beginning to identify
some differences in biology that will serve as a lead
to more detailed studies. Relevant technical and
scientifi c breakthroughs are being made in fi elds such
as genomics, stem cell research, and aging research.
Investigators increasingly are developing collaborative
networks and encouraging clinical trial participation
and tumor banking. The following will be critical
to the success of research in this area: (1) improved
funding for AYA cancer research (especially in
understudied cancers such as non-Kaposi’s sarcoma),
(2) tissue samples (normal and tumor), and (3)
consideration of both host/patient physiology and
tumor biology in the AYA population.
B-14
Appendix B: Breakout Group Reports - Biology
Report of the Adolescent and Young Adult Oncology Progress Review Group
ACCESS
Co-Chairs
Karen Albritton
Mary McCabe
Joan McClure
Participants
Nelson Aguila
Craig Lustig
Dennis Deapen
Ralph Manchester
Jennifer Ford
Lorna Rodriguez-Rodriguez
Margaret Foti
Joseph San Filippo
Susan Hedlund
Leonard Sender
Henri Lipmanowicz
Lydia Shrier
Joseph Lipscomb
Carmina Valle
Kevin Lucia
Bruce Williams
Background
Access, as defi ned by the Institute of Medicine
Committee on Monitoring Access to Personal Health
Care Services,
1
is the “timely use of personal health
services to achieve the best possible health outcomes.”
An individual with cancer should have access to an
oncologist who offers the most experience and best
survival outcome for a given diagnosis, participation
in clinical trials, and support services appropriate
for the needs of the patient. Adolescents and young
adults (AYAs) with cancer should have the same
opportunity as older or younger patients to achieve
their best possible outcome. Population data document
poorer outcomes in AYA patients compared with
their younger counterparts, and studies in Ewing’s
sarcoma, rhabdomyosarcoma, synovial sarcoma, and
acute lymphoblastic leukemia have shown that this
difference is due in part to health services delivery and
access barriers and not solely to biology. Outcome
differentials such as these are alarming and highlight
the need to identify factors that affect access to therapy
for these different populations.
In assessing access issues of the AYA population,
the entire continuum of care must be considered,
beginning with evaluation of fi rst symptoms, the
diagnostic process, therapy, supportive care, post-
treatment surveillance, and survivorship issues. To
minimize delays in diagnosis and to ensure appropriate
referral, patients should have access, regardless of
fi nancial and insurance status, to a consistent primary
care provider who provides a developmentally
appropriate, welcoming environment that maximizes
adherence and communication. The provider should
be knowledgeable about AYA cancers to have an
appropriate level of suspicion regarding cancer in
these patients and allow referral to the appropriate
oncologist.
Upon diagnosis, a patient should have access to
oncologic professionals who can provide high quality
care based on experience or specialized training. AYAs
also should have access to developmentally appropriate
psychosocial support and counseling regarding issues
such as fertility preservation, education, employment,
disability, insurance, and other fi nancial and legal
concerns. Further, AYAs should have access to peer
support and suffi cient information to make informed
decisions about treatment. To ensure the best quality
of treatment, AYAs should have access to an evidence-
based standard of care (where it exists) and clinical
trials, including biologically appropriate novel agents.
Following completion of therapy, AYA survivors should
be provided with a portable follow-up plan of care that
takes into account their stage of life and mobility and
includes information about long-term and late effects,
insurance, self-advocacy, and health maintenance.
The challenges to optimal access are substantial:
• Practical and Financial Barriers
– Lack of adequate insurance decreases
therapeutic options for patients (e.g., second
opinions, choice of specialists, access to
expensive treatments and medication).
– Lack of a primary care physician may be a
deterrent to seeking timely attention for early
symptoms of cancer.
– Concerns about missing school or work or
getting child care for young children may
1
Millman M (ed). Access to Health Care in America. Committee
on Monitoring Access to Personal Health Care Services, Institute
of Medicine, Washington DC, National Academies Press, 1993.
Appendix B: Breakout Group Reports - Access B-15
Report of the Adolescent and Young Adult Oncology Progress Review Group
keep AYA patients from making or keeping
appointments during normal clinic hours and
otherwise impede access to care.
– Location of treatment may limit access to
clinical trials.
– AYAs may not be willing or able to travel long
distances to centers of AYA excellence for
specialty care.
• Provider Issues
– The clinical suspicion of cancer is low for
patients of this age.
– Because AYAs do not need or receive routine
medical care, physicians may be unaware
of the patients’ baseline medical status and
therefore may miss signs of cancer.
– Coordination of care issues among
multidisciplinary providers is a challenge to
both providers and patients.
– Treatment setting may limit access to clinical
trials.
• Personal Beliefs, Knowledge, and Behavior
– AYAs are a generally healthy population with
a strong sense of immortality and invincibility
that may limit their ability to acknowledge
the possibility of a cancer diagnosis and the
necessity of intervention.
– For AYAs, the rigors of therapy may interfere
with meeting the developmental milestones of
independence and socialization and can lead to
non-adherence with treatment and follow-up
recommendations.
Priority 1
Explore models and pilot programs that use health
coaches/navigators to facilitate full access to and
utilization of optimal AYA oncology care.
Rationale
AYA patients must navigate a complex health
care system composed of multiple specialists and
uncoordinated resources. The health care system is
unfamiliar to this generally healthy population that
previously has not needed to access these services.
In addition, the system is not focused on the special
needs of younger cancer patients and most available
resources are not developmentally appropriate. Many
AYA patients lack the built-in advocacy of family
or community. A patient navigator can provide
information and guidance regarding the treatment
center, clinical trials, and supportive care services.
Implementation Barriers
• Navigator services are not billable and require
institutional or long-term philanthropic support.
• Effi cacy of cancer patient navigators is not yet
established.
• AYAs are relatively few in number and are
scattered throughout the country, making service
programs diffi cult to implement.
Potential Partnerships and Resources
• Potential funding sources—National Cancer
Institute (NCI), including the Cancer Disparities
Research Program/Patient Navigator Research
Program; Lance Armstrong Foundation (LAF);
American Cancer Society (ACS); public and
private payors
• Potential models—Foundation for Informed
Medical Decision Making, Cancer Information
Service (CIS), Ulman Cancer Fund for Young
Adults, NCI Patient Navigator Academy
• Potential implementers—Academic cancer
centers, Community Clinical Oncology
Programs (CCOPs), CIS
Concrete Actions in the Next Three Years
• Evaluate existing models of patient navigation/
health coaching and explore their applicability in
the AYA setting.
• Pilot and assess models of AYAO health
coaching/navigation including virtual navigators
accessed through existing patient information
programs such as CIS and ACS.
B-16
Appendix B: Breakout Group Reports - Access
B-16 Appendix B: Breakout Group Reports - Access B-16
Report of the Adolescent and Young Adult Oncology Progress Review Group
Priority 2
Develop an AYA-specifi c educational portal (Web-
based and CD-ROM/DVD) for patients, caregivers,
and health care providers.
Rationale
Due to the rarity of AYA cancers and limited
evidenced-based care guidelines, no central information
resource exists that is developmentally and clinically
appropriate for AYAs. Such a resource, maintained and
updated for use by diverse groups, is needed to ensure
access to the most up-to-date diagnostic, treatment,
follow-up, and survival information.
Implementation Barriers
• A variety of groups are working to develop such
resources; however, these groups generally have
limited fi nancial resources and personnel to
dedicate to this effort, and duplication of effort
should be avoided.
• Funding is needed to develop and maintain an
integrated Web portal.
Potential Partnerships and Resources
• NCI, including CIS and www.cancer.gov
• ACS
• Patient advocacy groups
• Professional organizations, e.g., American
Society of Clinical Oncology (ASCO), Oncology
Nursing Society (ONS)
• CureSearch
• Association of Cancer Online Resources (www.
acor.org)
• LIVE
STRONG
™ Young Adult Alliance
Concrete Actions in the Next Three Years
• Identify the most appropriate parent organization
or establish a coalition for the Web portal.
• Identify current sources of content and
contributors who will collaborate to develop a
comprehensive and integrated site.
• Build a developmentally appropriate Web-based
user interface.
• Market the portal to user communities.
• Negotiate linkage to and from medical
information Web sites used by primary care
providers.
Priority 3
Develop standards of excellence that document
best practices for access to diagnostic, treatment,
and follow-up care for AYAs.
Rationale
An essential element of providing access to quality
care is defi ning what constitutes that care so that
organizations and institutions can have a standard
by which to develop their programs and by which
to measure success. These standards also will help
empower patients to participate actively in planning
care with their providers. Because AYA oncology
is a relatively new fi eld, it is anticipated that these
standards will begin as a consensus process informed
by current evidence, and the levels of evidence on
which recommendations are based will be identifi ed
explicitly. The limitations of this evidence will inform
future research priorities and standards will evolve as
additional evidence is developed.
Implementation Barriers
• Limited evidence is available to inform best
practices.
• Small numbers of experts are available to
develop and update standards of care.
• The wide age range and the diversity of
diagnoses, many of which are low incidence
cancers, will make it diffi cult to develop
recommendations that apply to the entire AYA
population.
• Compliance with guidelines may not be
achievable by all providers.
Potential Partnerships and Resources
• National Comprehensive Cancer Network
• Professional societies, e.g., ASCO
• Agency for Healthcare Research and Quality
• Coalition of Cooperative Oncology Groups
Appendix B: Breakout Group Reports - Access B-17
Report of the Adolescent and Young Adult Oncology Progress Review Group
Concrete Actions in the Next Three Years
• Review the existing evidence.
• Identify a parent organization for the standards
development process.
• Identify experts who will write the standards.
• Identify groups that will disseminate the
standards.
• Convene a meeting and develop a draft standard.
• Develop an implementation plan including
ongoing updates and expansion.
Conclusion
Because AYA patients appear to be lagging behind
in survival improvements and quality of survival, the
extent to which access issues are barriers to the best
outcome must be assessed and better understood.
Research is needed to analyze and ameliorate the
impact of provider (e.g., site, specialist, treatment
regimen, level of supportive care), logistic, and patient
barriers so that care can be provided equally to all
patients. In the interim, concrete steps can be taken to
improve care provided today: developing guidelines
that establish a standard of care, making this and
other guidance available to AYA patients through
a coordinated Web portal, and providing patient
navigator assistance to AYA cancer patients. These
steps should alleviate some of the disparities that AYAs
suffer in accessing quality cancer care.
B-18
Appendix B: Breakout Group Reports - Access
B-18 Appendix B: Breakout Group Reports - Access B-18
Report of the Adolescent and Young Adult Oncology Progress Review Group
INSURANCE
Co-Chairs
Michael Moore
Joseph San Filippo
Kimberly Calder
Participants
Archie Bleyer
Kevin Lucia
Cheryl Boyce
Grace Powers-Monaco
David Coronado
Barbara Schwerin
Angelina Esparza
Susan Shinagawa
David Feeny
Jeremy Whelan
Brooke Hamilton
Elizabeth Williams
Brandon Hayes-Lattin
Background
Adolescence and young adulthood are periods of great
change for most individuals. The transition from being
a “dependent” to an independent and autonomous
functioning member of the “real world” has important
implications for all aspects of adolescents’ and young
adults’ (AYAs’) lives.
For AYAs with health insurance, this transition
includes an evolution in health insurance as coverage is
transferred from parent or school to a new employer or
spouse. For others, however, the transition is not nearly
so smooth. Lack of health insurance due to “aging
out” of parent’s coverage, the end of full-time student
coverage, unemployment, or an initial job that does not
offer health insurance can be an outcome of the current
employer-based health insurance system that underpins
the health care system in the United States. Young
adults are the most underinsured age group in the
United States. Recent data reveal that over 49 percent
of young adults aged 18 to 24 years were uninsured for
at least 1 month over a 24-month period (2001-2002),
and 29.6 percent were uninsured for an entire year.
1
Even when purchasing health insurance is an option,
many young adults forgo many optional forms of
insurance in favor of other necessities. Unfortunately
for some, when major health problems arise, the lack
of health care coverage becomes a major obstacle to
treatment and recovery. There appear to be multiple
reasons that young adults place such low priority on
health coverage. These include the following:
• A perception of invulnerability and the presence
of good health
• Competing fi nancial priorities such as education,
transportation, housing costs, and entertainment
• The high cost of health insurance premiums
One of the well-worn tenets of insurance is that “you
can’t get fi re insurance on a house when smoke is
coming out of the windows.” The same generally
holds true for health insurance—individual coverage
generally is not available if one has developed a major
health condition prior to application, and if available,
its cost can be prohibitive.
Group health insurance holds more promise for AYAs
with pre-existing conditions because little if any
underwriting is required. Most employer-sponsored
health insurance is of this nature, but rising premiums
have caused many employers to limit this popular
employee benefi t by decreasing the employer’s
contribution and offering less comprehensive plans
with higher employee copayments. Some smaller
employers have discontinued health insurance as a
benefi t and recent surveys indicate a strengthening of
this trend.
Most employers who extend coverage to dependents
do so only until age 19, unless the child is enrolled as a
full-time student. Coverage typically ceases at age 23
unless the individual is disabled and remains dependent
upon the parent. In employer and other group health
plans, pre-existing conditions are not covered unless
there has been continuous “creditable” health insurance
coverage prior to application (i.e., no gap in coverage
for more than 63 days). In the AYA age group, breaks
in coverage occur frequently for numerous reasons,
as noted previously. These issues, coupled with the
individual’s (and perhaps family’s) perception that
health insurance for adolescents and young adults is
not a high priority need, may pose major problems
in obtaining health insurance at an affordable rate in
1
Mills R, Bhandari S. Health Insurance Coverage in the United
States: Current Population Reports, U.S. Census Bureau P60-223,
2003; at: http://www.census.gov/prod/2003pubs/p60-223.pdf.
Appendix B: Breakout Group Reports - Insurance B-19
Report of the Adolescent and Young Adult Oncology Progress Review Group
the future, particularly if the young person develops
a major health condition such as cancer that requires
costly extended treatment.
Provisions of Federal laws such as the Consolidated
Omnibus Budget Reconciliation Act (COBRA) and
the Health Insurance Portability and Accountability
Act (HIPAA) provide important legal protections
that guarantee continued insurability provided that
the individual previously was covered under a group
health insurance plan and maintained creditable
coverage without an extended disruption. In addition,
COBRA and HIPAA provide for a transition period
during which alternative coverage can be obtained.
These provisions are particularly important for those
with pre-existing conditions and other “high risks,”
as a signifi cant break in coverage may subject the
individual to a pre-existing condition exemption clause,
higher premiums, or outright declination of coverage.
Although these laws guarantee continuous eligibility
during a transition period, under COBRA, employer
contributions to premiums cease and premiums rise
considerably as the individual assumes both employee
and employer portions of the cost. Further, when
COBRA and HIPAA protections cease, unless group
coverage can be obtained, individual coverage often
is fi nancially out of reach for AYAs with pre-existing
conditions. These principles and scenarios apply
similarly to disability insurance and to a certain extent
to life insurance.
States have served as the nation’s laboratories for
developing and testing insurance programs for
individuals at high risk, yet no standard model exists.
Unaffordable premiums, waiting periods, and other
barriers often place these programs out of reach for
many individuals and families. Nationwide, Medicaid
continues to serve as the insurer of last resort, although
eligibility, benefi ts, and administration vary widely
among the states. Further, many consider state budget
cutbacks and Federal defi cit reduction measures major
threats to meaningful Medicaid coverage.
Priority 1
Develop a public relations campaign using
high-profi le individuals to promote the need for
health insurance.
Rationale
AYAs must be encouraged to take responsibility for
their own health care needs as they enter adulthood.
They must be educated about the fact that they are at
risk for serious illnesses, particularly cancer. Unless
AYAs are covered under a parent’s health insurance as
an eligible dependent, employed with health benefi ts,
or a full-time student, they need to include health
insurance among their high priorities. However,
convincing typically healthy AYAs that health
insurance is an important priority is a challenge. Well-
known public fi gures such as athletes and entertainers
should be enlisted to bring this important issue to light.
This approach has been successful in changing AYA
behavior, as evidenced by public campaigns to reduce
tobacco use and teenage drinking and driving, and
should be employed to promote the need for health care
coverage in this population.
Implementation Barriers
• Persuading young adults to purchase health
insurance is diffi cult because of their perception
of invincibility. In addition, limited income
(if any), fi nishing education, career pursuits,
housing expenses, starting a family, and other
priorities tend to take precedence over health
insurance concerns.
• It is important to recognize that the AYA group
is a heterogeneous population and, therefore,
targeted marketing is necessary. A variety of
media messages and approaches will be needed,
taking into account “language,” cultural, and
ethnic differences in the AYA population.
Further, AYAs must be approached on their level,
using their language, values, and technology.
• AYAs lack an understanding of the complex
health insurance marketplace, particularly
regarding “transition issues,” insurance rating
practices, exclusions for pre-existing conditions,
waiting periods, variation in benefi t packages,
regulatory variation among states, and policy
B-20
Appendix B: Breakout Group Reports - Insurance
B-20 Appendix B: Breakout Group Reports - Insurance B-20
Report of the Adolescent and Young Adult Oncology Progress Review Group
costs. It will be a challenge to convey the
message that insurance is important to a
population with limited knowledge of the
issues and a lack of experience.
Potential Partnerships and Resources
• National Cancer Institute
• Centers for Medicare and Medicaid Services
• Lance Armstrong Foundation
• National Coalition of Cancer for Survivorship
• American Cancer Society (ACS)/cancer
advocacy community (young adults)
• Insurance industry
• America’s Health Insurance Plans
Concrete Actions in the Next Three Years
• Contact insurance industry representatives to
share available information/descriptive data
regarding numbers of uninsured AYAs and
causal factors to document the extent of the
problem and to determine the focus of the
campaign.
• Encourage public-private partnerships
to promote the value and importance of
maintaining continuous health insurance
coverage utilizing marketing plans focused on
the AYA target audience.
• Identify successful health education campaign
models for the AYA population.
• Identify potential spokespeople and
organizations to launch the campaign.
• Determine funding sources.
Priority 2
Convene stakeholders and experts to create and
disseminate a centralized repository of resources
and best practices regarding available health
coverage options.
Rationale
AYAs lack suffi cient knowledge of the issues
associated with obtaining and maintaining insurance
coverage, including rules and regulations governing
guaranteed insurability and the multitude of
potential public and private health insurance/health
care coverage options. It is diffi cult for consumers
generally, and particularly for inexperienced AYAs, to
navigate the complex insurance and health care system
and obtain concise, relevant, and easily understandable
information. A centralized repository of information
on potential sources of coverage, eligibility criteria,
policy options, benefi ts and limitations, premiums and
copayments, insurer contact information, and other
key elements would be extremely useful to consumers
seeking insurance coverage. Such an information
source also would be helpful to AYAs who may be
insured but need assistance in identifying providers
or understanding benefi ts, coverage restrictions, and
reimbursement. The repository also would be available
to benefi ts counselors who provide support to AYAs
and their families.
In concert with this priority, the PRG endorses the
development of a curriculum to train AYA advocates in
identifying sources of health insurance and navigating
the system to make best use of available coverage.
Implementation Barriers
• No centralized source for this information exists
at present; therefore, stakeholder cooperation is
essential for success.
• Stakeholders need to be made aware of the
magnitude of the problem and be willing to
provide and update the relevant data.
• Content must be identifi ed, and information must
be presented in a consistent fashion to enable
meaningful assessment of alternatives.
• Insurance-related information is complex and
may be diffi cult for many to comprehend.
• Sources of leadership and funding for this effort
are unclear.
Potential Partnerships and Resources
• Cancer Information Service
• ACS
• Cancer and insurance advocacy groups
• Academic institutions
• Insurance industry
• Private foundations
Appendix B: Breakout Group Reports - Insurance B-21
Report of the Adolescent and Young Adult Oncology Progress Review Group
Concrete Actions in the Next Three Years
• Identify minimum data set for dissemination.
• Determine strategy for collecting and
disseminating information.
• Identify and convene key stakeholders.
• Obtain information and resources within 12
months.
• Implement information dissemination strategy
within 18 months.
Priority 3
Challenge oncology experts to develop AYA
oncology treatment guidelines upon which
coverage determinations can be made for this
population.
Rationale
No universally accepted payment guidelines exist for
AYA oncology patients. Health plans vary signifi cantly
with regard to benefi t packages and associated
treatment costs. This situation results in patient and
provider frustration, time spent pursuing appeals, and
delays or interruptions in treatment. Establishing
guidelines will support a more consistent approach
to coverage for AYA treatment modalities, including
psychosocial support and rehabilitative services.
Implementation Barriers
• It is diffi cult to arrive at consensus.
• No current guidelines exist upon which to base
coverage.
• Guideline development is a lengthy, complex,
and costly process.
• Technology advances often outpace clinical
guideline development.
Potential Partnerships and Resources
• American Society of Clinical Oncology
• Oncology Nursing Society
• Association of Clinical Oncology Social Workers
• Insurance industry technology assessment groups
• National Association of Insurance
Commissioners
• Advocates
Concrete Actions in the Next Three Years
• Establish consensus regarding the need to
develop coverage guidelines.
• Convene a panel of leaders in oncology practice
and care to draft guidelines.
• Obtain endorsement by nationally recognized
professional cancer organizations.
• Identify funding sources including public,
private, and industry organizations.
• Obtain support of the health insurance industry.
Conclusion
The need for health insurance coverage for AYAs
is generally unappreciated as AYAs typically view
themselves as healthy individuals who are invulnerable.
With limited resources and competing priorities, health
insurance often is not considered a necessity.
Lack of awareness of viable options for insuring
this population group exacerbates the problem of
coverage loss among AYAs. No centralized source of
information exists regarding viable health coverage
options for AYAs. A centralized repository of
health coverage information will improve consumer
information access and enhance decision-making
regarding health care coverage.
It is crucial to help AYAs understand that individual
insurance coverage must be purchased and maintained
when the AYA is in good health so that coverage can be
obtained at a reasonable cost and to ensure that the plan
is in place if and when the need for care arises. Sports
fi gures and popular entertainers have proven most
successful in changing youth behavior and should be
recruited to help communicate the importance of health
coverage for AYAs.
The absence of universal coverage guidelines currently
results in confusion and frustration among providers,
payors, and patients; national coverage guidelines
would provide the basis for agreement about coverage
for AYA cancer care.
B-22
Appendix B: Breakout Group Reports - Insurance
B-22 Appendix B: Breakout Group Reports - Insurance B-22
Report of the Adolescent and Young Adult Oncology Progress Review Group
CLINICAL CARE MODELS
Co-Chairs
Lorna Rodriguez-Rodriguez
Ian Lewis
Carol Somkin
Participants
Nelson Aguila
Joan McClure
Lodovico Balducci
Craig Nichols
Darlene Gibbon
Peter Pisters
William Hicks
Kathleen Ruccione
Henri Lipmanowicz
Leonard Sender
Craig Lustig
Stuart Siegel
Mary McCabe
Background
Adolescents and young adults (AYAs) with cancer have
not benefi ted comparably from the increased survival
and reduced mortality experienced in recent years by
both older and younger cancer patients.
1
Tremendous
gaps in our knowledge exist concerning the factors that
account for poor outcomes in this age group and how
best to treat AYA patients with cancer.
AYAs with cancer face multiple clinical and social
challenges that affect their outcomes and which may
vary not only by cancer site, but also by multiple
other variables, including age, gender, race/ethnicity,
socioeconomic status, and source of care. For example,
concerns about school, work, family, pregnancy,
sexuality, and insurance are likely to affect adherence
to treatment. Yet little data exist to address these
issues.
Considerable interest has emerged recently in
developing innovative specialized programs for
AYAs with cancer. Research is needed to investigate
the benefi ts and drawbacks of treating AYAs as a
distinct group with special needs for clinical care and
psychosocial support services, and the consequent
value of creating organizational structures to support
these needs. Currently, most AYAs are treated by either
pediatric or adult oncologists and few studies have
evaluated how the organization of clinical care affects
an individual’s survival and quality of life. Further,
little is known about what additional specialized
training health professionals need to improve treatment
for AYA patients with cancer.
In the United Kingdom, the fi rst inpatient unit to care
specifi cally for teenagers and young adults with cancer
was established in 1990. Since then, an additional
eight units have been established, with more planned.
AYA-specifi c multidisciplinary teams have started
to evolve alongside the inpatient units, but with no
clearly consistent model of practice. Each unit and
team has responded to local circumstances. Early
indications are that outcomes for patients with cancer
treated in areas with these centers have improved,
but the data are preliminary and the methodology has
not been validated. Recently, a broad consensus has
emerged among health care professionals, health care
organizations, patients, and advocates regarding the key
elements required to deliver a patient-centered model
of care (see fi gure that follows).
KEY ELEMENTS OF PATIENT-CENTERED PATHWAY
What Young People Need What Young People Expect
Rapid Access;
Competent Assessment
Rapid, Accurate Diagnosis
Evidence-based
Treatment
Best Chance of Survival
Least Possible
Physical Cost
Support
Psychological, Social,
Educational, Vocational
Clear, Accurate,
Empathetic Information
Expertise in Disease;
Expertise in Young People
Good Facilities;
Peer Support
Choices
As Close to Home as
Possible, When Possible
Access to Clinical Trial
(If Available)
Adapted from Lewis I. Patterns of care for teenagers and young adults with cancer; is there a single blue-
print? In: Eden TOB, Barr TD, Bleyer A, Whiteson M (eds). Cancer and the Adolescent (2nd edition),
pp. 241-258, BMS Books, Blackwell Publishing, 2005.
1
Bleyer A, O’Leary M, Barr R, Ries LAG (eds). Cancer
Epidemiology in Older Adolescents and Young Adults 15 to
29 Years of Age, including SEER Incidence and Survival:
1975-2000. National Cancer Institute, NIH Pub. No. 06-5767,
Bethesda, MD, 2006.
Appendix B: Breakout Group Reports - Clinical Care Models B-23
Report of the Adolescent and Young Adult Oncology Progress Review Group
These elements now have been incorporated into
formal national guidelines for improving outcomes
in children and young people with cancer in the
United Kingdom.
2
This model is conceptual and
implementation requires practical elements such as
AYA-specifi c multidisciplinary teams, dedicated units,
navigators (called key workers in the United Kingdom),
good informatics, a registry system, appropriate clinical
trials and protocols, and the development of local and
national networks. These developments have specifi c
implications for training and research.
The AYAO PRG Clinical Care Models Breakout
Group agreed that the core elements of this model
were relevant to the United States health care system
but required local modifi cation. Key aspects of the
AYA clinical cancer care problem in the United States
include the following:
• AYAs are an underserved population.
• Underservice to AYAs with cancer is poorly
recognized. Delayed diagnosis occurs
frequently.
• AYA patients are treated disparately; no agreed
upon standards/protocols of care exist.
• Access to clinical trials is poor.
• Recognition of the need for peer and
psychosocial support is limited, and little such
support is provided.
• Knowledge about AYA clinical care needs is
limited.
• Service development in the United States is
embryonic.
The Breakout Group recommends the following
priorities.
Priority 1
Develop patient-centered and needs-led AYA
programs after fi rst defi ning core elements and
standards.
Rationale
To improve care for AYA cancer patients, it is
necessary to establish protocols, to improve recognition
of the population, clinical trial access, peer and
psychosocial support, and knowledge of AYA clinical
care needs.
Implementation Barriers
• Lack of clarity and defi nition of the population
(15 to 39 years of age).
• Multiple cancer sites.
• Lack of advocacy.
• Lack of recognition by many oncology
professionals that AYAs need both site-specifi c
and age-specifi c care, leading to treatment and
patient “ownership” confl icts.
• Existing National Cancer Institute (NCI)
Cooperative Group self-interest.
• Lack of funding.
Potential Partnerships and Resources
• Patient advocacy organizations, e.g., Lance
Armstrong Foundation (LAF)
• National Institutes of Health (NIH), e.g., NCI,
National Heart, Lung, and Blood Institute
(NHLBI)
• Health care organizations
• American Society of Clinical Oncology (ASCO)
and other professional societies
• American Cancer Society (ACS)
• International partners
• NCI Cooperative Groups
• Department of Defense (DoD)
• National Comprehensive Cancer Network
(NCCN)
• Academic institutions
• Robert Wood Johnson Foundation (RWJF)
Concrete Actions in the Next Three Years
• Create a national network of stakeholders to
deliver this agenda.
• Develop agreed upon service standards with
NCCN.
• Identify champions to develop and promote local
multidisciplinary networks to share practice and
develop local responses to national guidelines.
2
National Institute of Health and Clinical Excellence—Improving
Outcomes Guidance, United Kingdom.
B-24
Appendix B: Breakout Group Reports - Clinical Care Models
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Issue a Request for Applications (RFA) for
service development and evaluation programs.
• Convene a national patient meeting to collect
feedback.
Priority 2
Develop core competency-based curricula to
incorporate appropriate training programs for
multidisciplinary professionals and develop expert
patient and advocate programs.
Rationale
Current training programs do not address AYA-
specifi c issues, resulting in poor recognition of
the needs of this group, delayed diagnosis, and no
improvement in outcome for decades. The AYA
population has a specifi c set of cancers that either
peak or occur more commonly in this age range
(e.g., bone sarcomas, germ cell tumors, lymphomas,
leukemias, melanoma, certain less common/early-
onset epithelial tumors). AYAs have specifi c
psychosocial, economic, and educational needs.
The AYA population also does not fi t easily into
either the classic pediatric or the adult paradigms
of communication and interaction with health
professionals. The challenges of working within a
focused multidisciplinary group must be addressed
through training programs for health professionals.
Implementation Barriers
• Lack of recognition by many oncology
professionals that AYAs need both site-specifi c
and age-specifi c care, leading to treatment and
patient “ownership” confl icts.
• Lack of awareness/understanding among
practitioners about why AYA-specifi c
curriculum development and training are
needed.
• Competition for time and funding.
• Lack of awareness of the existence of this
population.
• Scarcity of trainers.
Potential Partnerships and Resources
• Patient advocacy organizations, e.g., LAF
• NIH institutes, e.g., NCI, NHLBI
• Health care organizations
• ASCO and other professional societies
• ACS
• International partners
• NCI Cooperative Groups
• DoD
• NCCN
• Academic institutions
• RWJF
• Accreditation Council for Graduate Medical
Education (ACGME)
• Afl ac
Concrete Actions in the Next Three Years
• Create AYA-specifi c modules or tracks within
existing health professional training programs.
– Identify AYA educators to develop necessary
curricula.
– Discuss with ACGME and the Oncology
Nursing Society the need to incorporate AYA
curricula as a requirement.
– Obtain funding for training through the
following:

NIH K-type training grants specifi c for
AYA

Other organizations such as Afl ac,
RWJF, American Association for Cancer
Research, and ASCO
– Develop educational programs for AYA
patients and families led by advocacy groups.
Priority 3
Develop AYA-focused health services research
capacity to evaluate service delivery programs.
Rationale
(see Background)
Implementation Barriers
• Health Insurance Portability and Accountability
Act privacy provisions
Appendix B: Breakout Group Reports - Clinical Care Models B-25
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Need to identify funding and champions
• Lack of consistent and validated methodologies
Potential Partnerships and Resources
• Patient advocacy organizations, e.g., LAF
• NIH institutes, e.g., NCI, NHLBI
• Health care organizations
• ASCO and other professional societies
• ACS
• International partners
• NCI Cooperative Groups
• DoD
• NCCN
• Academic institutions
• RWJF
Concrete Actions in the Next Three Years
• Convene a working group to develop research
methods and establish collaborations to evaluate
different models of care. It is imperative to
include all relevant stakeholders, including
researchers, providers, patients, advocacy
groups, insurance representatives, and NIH (NCI
and other institutes).
Conclusion
No consistent standard exists for delivery of care to
the AYAO population. This defi cit has resulted in poor
patient experiences and likely is associated with the
lack of recent improvement in survival compared to the
pediatric or adult populations. Similarly, educational
programs are lacking that address directly the needs of
the AYA group and those who provide service to them.
To address these issues, the AYAO PRG Clinical Care
Models Breakout Group recommends the adoption of
patient-centered approaches to care, which requires
the development of a standard of care and AYA-
specifi c programs. These standards and programs will
require evaluation through a program of health service
research. In addition, core competency programs
for professionals, patients, and advocates should be
developed.
B-26
Appendix B: Breakout Group Reports - Clinical Care Models
B-26 Appendix B: Breakout Group Reports - Clinical Care Models B-26
Report of the Adolescent and Young Adult Oncology Progress Review Group
CLINICAL TRIALS/RESEARCH
Co-Chairs
Barry Anderson
Archie Bleyer
Robert Comis
Participants
Lodovico Balducci
Brian Rubin
Clara Bloomfi eld
Peter Shaw
Diane Colaizzi
Carol Somkin
Gina D’Amato
Wendy Stock
John Goldberg
Jeffrey Summers
Mary Louise Keohan
Daniel Sussman
Michael Link
Samuel Wells
Cynthia Love
Jeremy Whelan
Background
The Clinical Trials/Research Breakout Group
considered the following background information in
formulating its priority recommendations:
• Excluding homicide, suicide, and unintentional
injury, cancer is the leading cause of death in
Americans aged 15 to 39 years. In females it
ranks as the number one cause of death, whereas
in males it ranks as number two, following heart
disease.
• The average annual increase in the incidence rate
of invasive cancer is higher in people aged 25
to 29 years and 30 to 34 years than for all other
5-year age groups under 45 years old.
• Among the 703 active, applicable National
Cancer Institute (NCI)-sponsored trials, only 26
Phase III trials do not have age limitations that
exclude a portion of the adolescent and young
adult (AYA) patient population. No Phase III
melanoma, hepatic cancer, or thyroid cancer
trials are accessible to this group.
• The average annual percent change (AAPC) in
5-year survival rate among 15 to 39 year-olds
decreases in correspondence with the rate of
clinical trial participation in this age group.
• It is possible to estimate the impact of a specifi c
cancer type in the AYA patient population by
combining three factors: survival progress
(AAPC in 5-year survival), cancer incidence
rate, and mortality rate.
In preparation for the Breakout Group session, each
group member was asked to complete a survey
of factors that may explain the AYA clinical trial
participation gap. The integrated results of this survey
are shown in Table 1.
Priority 1
Focus on increasing referring physician and
oncologist awareness.
Rationale
More than 60 percent of children with cancer
participate in clinical trials, compared with 3 to 5
percent of adults. Only 1 to 2 percent of adolescent
and young adult oncology (AYAO) patients participate
in clinical trials.
1
Many differences exist between the
pediatric and adult clinical trials environment that may
explain the trial participation dichotomy, including
an integrated clinical trials educational approach in
pediatrics training and the fact that pediatric oncology
is largely academic/medical center-based. Adult
oncology is carried out primarily in the community,
where 80 percent of cancer patients receive their
care. Many excellent community-based oncology
practices exist and approximately 60 percent of adult
patients entered into NCI Cooperative Group studies
are referred from community-based practices. Clinical
trials participation is generally underfunded and takes
signifi cant resources in both time and personnel.
The Breakout Group members agreed that physician
involvement and infl uence are key factors in the
patient’s decision to participate in a clinical trial. This
impression is confi rmed by recent surveys evaluating
the role of the physician, conducted by the Coalition
of Cancer Cooperative Groups (CCCG).
2
According
1
Bleyer A, Budd T, Montello M. Lack of clinical trial
participation and of progress in older adolescents and young
adults with cancer.
Current Problems in Pediatric and
Adolescent Health Care
2005;35(5):186-195.
2
Comis RL, Colaizzi DD, Miller JD. Cancer clinical trials
awareness and attitudes in cancer survivors. Coalition of Cancer
Cooperative Groups, poster presentation, American Society of
Clinical Oncology Annual Meeting, June 5, 2006.
Appendix B: Breakout Group Reports - Clinical Trials/Research B-27
Report of the Adolescent and Young Adult Oncology Progress Review Group
Table 1. Potential Reasons for the AYA Clinical Trials Participation Gap
Health
Professional
(physicians,
nurses,
allied health
professionals)
• Lack of clinical trials for AYAO patients
• Arbitrary clinical trial age criteria excludes AYAs
• Lack of awareness of clinical trials available to the AYAO population
• Referral patterns dictate the centers to which AYAO patients go
• Medical and pediatric oncologists may not be aware of each other’s clinical trials
• Most experienced medical team not providing care to AYAO patients with specifi c diagnoses
• Adult oncologists have few patients with “AYA cancers”
• Lack of access to oncologist/cancer center
• More business-like models of medical oncology practice vs. academic model of pediatric oncology practice
• Money/time commitment to initial and continuing education
• Location/hours not amenable to hours required for clinical trials
• Expected poor patient adherence to protocol
• Loss of patients – turf confl icts, expected good outcome
• Lower reimbursement expected
• Lack of facility conducive to AYA care and clinical trial requisites
• Clinical trial not available via medical oncologist’s practice
• Reluctance of medical oncologists and pharmaceutical companies to develop clinical trials for young patients
Societal/Cultural
(health care
system, socioeco-
nomics, cultural
dynamics)
• Age – denial of disease
• Patient unprepared for illness, much less clinical trials
• Health insurance gap
• Insurance guides referral patterns
• For “emancipated” adolescent or young adult, entry into quality health care system may be a major issue
• Time constraints – school, work, and late or multiple appointments
• Clinic hours not friendly to student or working adult schedules
• Language barrier
• Educational level
• Trial groups not “cross-cutting” for diseases (e.g., Children’s Oncology Group vs. intergroups)
• Lack of social support for transportation, cost of care
• Lack of awareness by employers, school personnel, associates, neighbors, and community
• Clinical trials not a priority
• Financial – physicians want reimbursement for themselves
• Physician ego – can do things as well or better than a trial
• Adolescents may be less compliant than adults
• Lack of clinical niche (e.g., adult vs. child cooperative group)
to the surveys, 6 percent of Americans rely exclusively
on their physician in health care decision-making, and
an additional 53 percent rely on both their physician
and their own research into their health problem.
Physicians and/or organizations of physicians and
researchers are the most trusted information sources
concerning health issues in general, and clinical trials
in particular. Approximately 20 percent of Americans
indicate that they would be very willing to participate
in clinical trials, but would rely on their physician for
guidance.
Only 10 percent of cancer survivors report being aware
that they could have participated in a clinical trial as
part of their cancer treatment. Among the survivors
who know about clinical trials, over 70 percent were
made aware of this opportunity through a physician;
no other information source category had a signifi cant
impact on patients’ awareness of clinical trials. Three
percent of survivors participated in a clinical trial and
an identical proportion declined to participate, primarily
because they were not sure that the clinical trial would
provide an outcome at least equivalent to standard care.
Lastly, there was a direct and statistically signifi cant
relationship between patient clinical trial participation
and the physician’s encouragement to participate, the
oncology team’s efforts to educate the patient about
clinical trials, and the oncology team’s assistance to the
patient to fi nd a trial.
B-28
Appendix B: Breakout Group Reports - Clinical Trials/Research
B-28 Appendix B: Breakout Group Reports - Clinical Trials/Research B-28
Report of the Adolescent and Young Adult Oncology Progress Review Group
Personal/Patient
(older adolescents
and young adults)
15 to 19 year-olds:
• Dependency on parents/system – lack of independence
• Parental lack of education
• Age group least expected to take ownership of their own health care
• Not wishing to assume responsibility
• Unsure of best treatment setting (medical vs. pediatric oncology center)
20 to 29 year-olds:
• Access – not offered
• Intermediate likelihood of taking ownership of own health care
• School/work/family responsibilities
30 to 39 year-olds:
• Access – not offered
• Group most expected to take ownership of own health care
• Work/family responsibilities
All three AYA age groups:
• Lack of awareness of trials or their importance
• Not advocates for themselves
• Health insurance; fi nancial burden of premiums and out-of-pocket costs
• Body image
• Transportation/housing
• Financial limitations
• Travel restrictions
• Distrust – “guinea pig” issues (afraid of being experimented on)
• Distrust – delays in diagnosis
• Adherence
• Independence/autonomy
• Concern about time commitment and extra tests/studies associated with trial participation for young adults with
job/family concerns
• Preference to stay close to home and peers
• Less motivated
Family/
Community
(family members,
colleagues/
friends, educa-
tors, employers,
politicians, legisla-
tors, knowledge
workers)
• Family – distance, responsibilities
• Want patients close to home/family
• Colleagues – isolation
• Educators – home schooling
• Employees – lost hours
• Politicians – lack of knowledge of impact
• Lack of awareness of clinical trial importance
• Lack of education
• Lack of guidance
• Inadequate community resources
• Lack of advocate within health care system
• Too much input from too many people
• Confl icting opinions offered by family members and/or others
• Isolation – lack of knowledgeable support group
• Afraid of experimental nature of trials
• Diffi cult dynamics – patients have both parents and children
Table 1. Potential Reasons for the AYA Clinical Trials Participation Gap (cont.)
Appendix B: Breakout Group Reports - Clinical Trials/Research B-29
Report of the Adolescent and Young Adult Oncology Progress Review Group
3
Ages 15 to 39 years, inclusive.
4
Hampton T. Cancer treatment’s trade-off.
Journal of the
American Medical Association
2005;294:167-168.
Therefore, since most AYAO patients are cared for in
the community medical oncology system, increasing
referring physician and oncologist awareness of the
availability and potential value of clinical trials to AYA
cancer patients should be a top priority to increase AYA
participation in trials.
Implementation Barriers
• Need to change referring physician and
oncologist attitudes about AYA participation in
clinical trials and the most appropriate treatment
setting for AYAO patients.
• Lack of health provider education regarding
clinical trials in general and trials available for
AYAO patients.
• Need to address barriers to the transition
of primary cancer treatment responsibility
for AYAO patients from a predominantly
academically based, clinical research-oriented
pediatric oncology environment to the more
private practice-oriented adult oncology
environment.
• Need to overcome barriers to AYAO patient
referral from practice-oriented adult oncology
environments to tertiary cancer center programs.
Potential Partnerships and Resources
• CCCG, representing the various components
of the publicly funded clinical trials structure,
and the individual NCI-supported Cooperative
Groups
• Community and academic cancer organizations,
networks, and societies that refl ect the spectrum
of providers involved in caring for AYA cancer
patients
• General medical societies, including family
practice, internal medicine, surgery and surgical
specialties, gynecology, dermatology, and local/
state medical societies
• Nursing societies, which represent an integral
and indispensable component of the health care
and clinical trials continuum
Concrete Actions in the Next Three Years
• Develop a syllabus on AYAO for presentations
by oncology experts to professional societies.
• Develop syllabi (slide libraries) on AYAO
adapted for local/regional presentations.
• Have professional societies endorse the AYAO
clinical trials awareness concept.
• Request that the American Society of Clinical
Oncology (ASCO) conduct a targeted
educational session at its annual meeting.
• Disseminate a “Dear Physician” letter from NCI.
Priority 2
Target malignancies that have the greatest potential
impact on the AYA
3
cancer problem for increased
clinical trial involvement: sarcomas, lymphomas,
breast cancer, colorectal carcinoma, germ cell
tumors, leukemia, malignant melanoma, bone
sarcomas, and brain tumors.
Rationale
The AAPC in 5-year survival rate for all invasive
cancers shows the least amount of progress in patients
between 15 and 39 years of age at diagnosis.
4
The AYA
survival improvement defi cit is a general AYA cancer
problem, with 18 of 26 cancers/cancer groups evaluated
demonstrating a defi cit. By equally considering the
AAPC in 5-year survival rate, the absolute survival
rate during 1975-1998, and the proportion of all
malignancies that the cancer represents, a list of the
cancers that could provide the greatest potential impact
on AYA outcome can be estimated and would include
non-Kaposi’s soft-tissue sarcoma, non-Hodgkin’s
lymphoma, hepatic cancer, germ cell tumors (males
and females combined), colorectal carcinoma, breast
cancer, malignant melanoma, and brain tumors. If
one weights the AAPC more than the absolute 5-
year survival rate and cancer prevalence, the cancer
priority list changes to include non-Kaposi’s soft-tissue
sarcomas, non-Hodgkin’s lymphomas, hepatic cancer,
germ cell tumors, colorectal carcinoma, breast cancer,
Hodgkin’s lymphoma, and bone sarcoma (see Table 2).
The least common of these cancers is hepatocellular
carcinoma and is therefore not considered a high
priority. Although leukemia does not appear in the list,
the AYAO PRG opted to include leukemia as a second
B-30
Appendix B: Breakout Group Reports - Clinical Trials/Research
B-30 Appendix B: Breakout Group Reports - Clinical Trials/Research B-30
Report of the Adolescent and Young Adult Oncology Progress Review Group
Source: SEER 1975-1998.
5
Stock W, Sather H, Dodge RK, Bloomfi eld CD, Larson A,
Nachman J. Outcome of adolescents and young adults with
ALL: a comparison of Children’s Cancer Group and Cancer and
Leukemia Group B regimens.
Blood
2000;96:467a (Abstract).
Blood 2000;96:467a (Abstract).Blood
6
Boissel N, Auclerc MF, Lheritier V, et al. Should adolescents
with acute lymphoblastic leukemia be treated as old children
or young adults? Comparison of the French FRALLE-93 and
LALA-94 trials.
Journal of Clinical Oncology
2003;21:774-780.
7
Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C,
Vora A, Rowe J, Webb D. Adolescents with acute lymphoblastic
leukaemia: outcome on UK national paediatric (ALL97) and
adult (UKALLXII/E2993) trials.
Pediatric Blood Cancers
2006,
in press, online at: http://www3.interscience.wiley.com/cgi-bin/
abstract/112264430.
tier priority because of the now well-known difference
in outcome among 15 to 21 year-olds with acute
lymphoblastic leukemia when treated with adult and
pediatric therapies.
5,6,7
Therefore, the AYAO PRG recommends that the fi rst
tier of high priority cancers should be non-Kaposi’s
soft tissue sarcoma, non-Hodgkin’s lymphoma, germ
cell tumors, colorectal carcinomas, and breast cancer.
The second tier includes Hodgkin’s lymphoma, bone
sarcomas, melanoma, brain tumors, and leukemia.
Implementation Barriers
• Lack of awareness: The cancers with the
greatest potential to address the AYA cancer
survival defi cit are not generally known.
• Inadequate and variable clinical trial availability:
Too few NCI Cancer Therapy Evaluation
Program (CTEP)-sponsored clinical trials are
available to AYA cancer patients, ranging from 0
to 6 for each of the individual cancers targeted.
• Limited focus within the clinical trials enterprise:
The high-impact AYA cancers and the AYA
clinical trials defi cit are underrepresented in the
high-profi le 2006 NCI Clinical Trials Working
Group (CTWG) report.
8
The pharmaceutical
industry has little incentive to focus on this
group of malignancies.
Potential Partnerships and Resources
• NCI and pharmaceutical industry support will be
essential to provide a portfolio of clinical trials
to address these cancers.
• Intergroup mechanisms, e.g., cooperative
groups, cancer centers, and Community Clinical
Oncology Programs (CCOPs), as these cancers
will need CTEP guidance and incentives.
CCOPs can assume responsibility for accruing
patients to these trials.
• Community networks such as U.S. Oncology,
Kaiser Permanente, and Tennessee Oncology
should focus on accruing AYA patients with
these cancers to clinical trials.
• Military medical facilities that treat AYAs with
the high priority cancers should be encouraged to
participate in intergroup trials.
• The U.S. Food and Drug Administration (FDA)
can encourage new agent development for AYA
patients with the selected cancers, including
providing orphan drug status and other incentives
to the pharmaceutical industry.
Table 2. Top 8 Cancers in 15-39 Year-Olds in Order of National Defi cit, with Emphasis on Lack of Progress
5-Yr Sur-
vival AAPC*
Mean 5-Yr
Survival*
% of All
Cancer
+
Impact
Factor
Impact Weighting 50% 25% 25%
Non-Kaposi’s Soft Tissue Sarcoma
5.2% 21%
4%
10.0
Non-Hodgkin’s Lymphoma
2.1% 60%
6%
4.7
Hepatic Cancer
0%
13%
1%
4.6
Germ Cell Tumors
2.1%
87%
10% 3.5
Colorectal Carcinoma
0.6%
58%
5%
3.1
Breast Cancer
0.4%
74% 15% 3.0
Hodgkin’s Lymphoma
1.4%
88%
6% 2.5
Bone Sarcoma
0.1%
74% 11% 2.2
*1975-1998
+In age group
8
Accessed at: http://www.cancer.gov/dctd/report.pdf on April 26,
2006.
Appendix B: Breakout Group Reports - Clinical Trials/Research B-31
Report of the Adolescent and Young Adult Oncology Progress Review Group
9
http://www.fda.gov/cder/pediatric/index.htm.
10
http://www.fda.gov/orphan.
11
Accessed at: http://www.ncrn.org.uk/csg/groups.
asp?groupID=23 on April 26, 2006.
• The National Cancer Comprehensive Network
can both set guidelines for the management
of these cancers in AYA patients and conduct
clinical trials in this age group.
• The Association of Community Cancer Centers
can make clinical trials in these diseases in AYA
patients a priority.
• Advocacy organizations and professional
societies can inform constituents of the age
group and its high priority cancers and identify
programs/resources to address the challenge.
Examples include ASCO, AACR, Lance
Armstrong Foundation (LAF), American Cancer
Society, American Society of Hematology,
Leukemia & Lymphoma Society, Oncology
Nursing Society, and the Association of Pediatric
Oncology Nurses.
• The Cooperative Human Tissue Network and
cancer center tissue repositories can target these
cancers for tissue collection for AYA patients to
facilitate translational research.
Concrete Actions in the Next Three Years
• NCI should designate selected clinical trials
in these cancers in AYA patients as “high
priority” and establish appropriate per-case
reimbursement.
• Through its Pediatric Exclusivity mechanism, the
Best Pharmaceuticals for Children Act,
9
and its
Offi ce of Orphan Products Development,
10
the
FDA should encourage orphan disease status for
high priority AYA cancers that meet the criteria.
• The Cancer Center Support Grant (CCSG)
mechanism should be used to evaluate cancer
center performance in AYA oncology and
thereby promote clinical research in the targeted
cancers in AYA patients.
• Encourage and mentor young investigators in
AYA oncology to focus on the targeted cancers.
Priority 3
Create a NCI Adolescent and Young Adult
Oncology Initiative including a scientifi c/clinical
liaison position, supported through public-private
partnership, to facilitate the development and
implementation of AYA clinical trials and to focus
NCI efforts on AYA cancer-related health care
delivery and outcomes research.
Rationale
NCI-supported cancer clinical trial Cooperative
Groups and Cancer Centers currently lack incentives
to encourage the necessary collaboration among
institutions and investigators to enroll AYA patients on
clinical trials or to generate AYA relevant clinical trials
and related research. NCI lacks personnel to champion
AYA clinical trial implementation and to oversee other
AYA cancer-related research efforts. Developing an
Adolescent and Young Adult Oncology Initiative would
demonstrate NCI’s commitment to the AYA cancer
research effort and provide leverage for advancing
AYA cancer initiatives. The United Kingdom National
Cancer Research Institute’s Teenage and Young Adults
Clinical Studies Development Group,
11
a public-
private partnership, drives clinical trial activity for 15
to 25 year-old cancer patients and has successfully
increased accrual to clinical trials among this group.
The Adolescent and Young Adult Oncology Initiative
and its scientifi c/clinical liaison should be housed in
the Offi ce of the NCI Director to increase the position’s
profi le and authority.
Implementation Barriers
• Insuffi cient personnel for clinical trial support
mechanisms within NCI to accommodate the
additional work necessary to appropriately
address AYA clinical trial and research needs.
• Insuffi cient NCI funds to readily support
personnel for an Adolescent and Young Adult
Oncology Initiative.
• Relatively high cost of implementing clinical
trials affecting small numbers of patients at the
central and local level; lack of non-governmental
resources to conduct these trials successfully.
B-32
Appendix B: Breakout Group Reports - Clinical Trials/Research
B-32 Appendix B: Breakout Group Reports - Clinical Trials/Research B-32
Report of the Adolescent and Young Adult Oncology Progress Review Group
Potential Partnerships and Resources
• NCI Offi ce of the Director, NCI CTEP; National
Institute on Aging; National Center for Child
Health and Human Development; National
Heart, Lung, and Blood Institute
• CCCG, cooperative groups, and CCOPs
• FDA
• Pharmaceutical companies
• Department of Defense
• LAF
Concrete Actions in the Next Three Years
• Devote resources from the NCI Center to Reduce
Cancer Health Disparities to fund an Adolescent
and Young Adult Oncology Initiative.
• Facilitate the access of AYA patients to all
disease-appropriate adult or pediatric cooperative
group trials by actively promoting intergroup
collaboration and increasing awareness of
available studies among medical and surgical
oncologists.
• Increase the number of clinical trials
(cooperative group and cancer center) that target
malignancies diagnosed in AYA patients and
that are designed to answer specifi c biologic,
treatment-related, quality of life, and late effect
questions relevant to the AYA age group.
• Provide incentives for oncologists to enroll AYA
patients in trials by increasing reimbursement
rates for enrolling an AYA patient in the more
complex Phase III trials.
• Increase the overall number of clinical trials
relevant for AYA patients.
• Consider establishing AYA Centers of
Excellence.
Conclusion
Low accrual into clinical trials is a critical factor
affecting the poor rate of improvement in AYA survival.
Because referring physicians and oncologists play a
key role in directing patients into clinical trials, it is
important that they be fully informed of the availability
and potential benefi ts of trials for which AYA patients
are eligible. A key fi nding of the Breakout Group is
that even when AYA patients are aware of and willing
to participate in clinical trials, relatively few trials are
open to them because of age restrictions or the absence
of trials for the cancer types that are diagnosed in this
age group. A public-private partnership, managed
within NCI, can ensure that the AYA patient population
has equal access to clinical trials and the progress in
outcome that results from them.
The cancers that have the highest likelihood of national
impact on AYA outcome are non-Kaposi’s soft tissue
sarcoma, non-Hodgkin’s lymphomas, germ cell tumors,
colorectal carcinomas, and breast cancer. The second
tier of priority includes Hodgkin’s lymphoma, bone
sarcomas, melanoma, brain tumors, and leukemia.
Improving treatment for these targeted malignancies
through clinical trials will have the greatest potential to
reduce cancer-induced death and suffering in the AYA
population.
Appendix B: Breakout Group Reports - Clinical Trials/Research B-33
Report of the Adolescent and Young Adult Oncology Progress Review Group
SPECIAL POPULATIONS
Co-Chairs
William Hicks
Marjorie Kagawa Singer
Smita Bhatia*
Participants
Lucile Adams-Campbell
Marion Lee
Kimlin Ashing-Giwa
Steven Lipkin
Cheryl Boyce
Kevin Oeffi nger
William Carroll
Grace Powers-Monaco
Jacqueline Casillas
Lynn Ries
Stella Davies
Barbara Schwerin
Robert Hiatt
Susan Shinagawa
*Named co-chair but unable to attend Roundtable
Background
Signifi cant disparities in cancer incidence, prevalence,
and mortality exist among specifi c populations in the
United States. These populations, often referred to as
“special populations,” can be defi ned by gender, age,
ethnicity, race, culture, education, income, and social
class, among other parameters.
1
Historically, special
populations, particularly racial and ethnic minority
groups, have been understudied and underserved.
In recent years, the U.S. Department of Health and
Human Services (HHS) has launched several initiatives
to address and eliminate health disparities among
population subsets, such as Healthy People 2010 and
the Cancer Health Disparities Progress Review Group.
Because our nation is still faced with and committed
to eliminating the unequal burden of cancer among
different racial and ethnic minority groups, the Special
Populations Breakout Group focused primarily on
cancer disparities that exist among racial and ethnic
groups within the AYA population, while recognizing
that our strategies need to be explored across all of the
special populations.
The statistics are daunting—among 15 to 39 year-
olds, non-Hispanic whites have the highest risk of
developing cancer, while Asians, American Indians,
and Native Alaskans have lower risk. African
Americans and American Indian/Alaska Natives,
however, have worse outcomes compared with non-
Hispanic whites and Asians. Data are extremely
scarce, however, on outcome by race/ethnicity within
the AYA population for individual cancer types.
Disparities may result from inequalities in access to
health care, in receipt of quality health care, and/or
from differences in co-morbidities. Other factors
known to contribute to racial disparities in cancer
mortality include differences in exposure (e.g.,
Helicobacter pylori
for stomach cancer), access to
high-quality regular screening (for breast, cervical, and
colorectal cancers), and timely treatment. The extent
to which these factors individually or collectively
contribute to overall differential survival is unclear.
However, limited fi ndings suggest that blacks who
receive cancer treatment and medical care equivalent to
whites experience similar outcomes.
2
In 1993, Congress responded to concerns about
unequal access to clinical trials and enacted the
National Institutes of Health (NIH) Revitalization
Act, which encouraged representation of women and
minority patients in NIH-sponsored research.
3
HHS
has responded to this call to enhance the heterogeneity
of trial populations through multiple mechanisms,
including creating the National Cancer Institute (NCI)
Minority Community Clinical Oncology Programs,
developing focused initiatives in partnership with the
Centers for Disease Control and Prevention (CDC) and
academic and medical centers, and emphasizing trials
that focus specifi cally on the elderly.
4
Investigations of race- and sex-based disparities
in cancer treatment trial participation have yielded
confl icting results. A study of black, Hispanic, and
white participation in NCI cancer treatment trials
between 1991 and 1994 concluded that these groups
1
Trans-HHS Cancer Health Disparities Progress Review Group.
Making Cancer Health Disparities History, a Report of the
Trans-HHS Cancer Health Disparities Progress Review Group,
Department of Health and Human Services, March 2004.
2
Bach PB, Schrag D, Brawley OW, et al. Survival of blacks and
whites after a cancer diagnosis.
Journal of the American Medical
Association
2002;287:2106-2112.
3
NIH Revitalization Act of 1993, P.L. 103-43.
4
Stallings FL, Ford ME, Simpson NK, et al. Black participation
in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer
Screening Trial.
Controlled Clinical Trials
2000;21:379s-389s.
Appendix B: Breakout Group Reports - Special Populations B-35
Report of the Adolescent and Young Adult Oncology Progress Review Group
were represented in trial populations in proportions
parallel to the incident burden of disease in these
groups and suggested that there is equal access to NCI
trials.
5
This report was confi rmed by a subsequent
analysis of enrollment by the Southwest Oncology
Group that compared the proportion of blacks and
Hispanics enrolled in trials for 15 cancer types with
their share of the U.S. cancer population between 1993
and 1996.
6
The authors found that representation of
minorities varied substantially by type of cancer. Of
the patients with leukemia, head and neck cancer, or
prostate cancer, black patients were more likely than
white patients to enroll; however, of the lymphoma
or ovarian cancer patients, blacks were less likely
than whites to enroll. Murthy, et al. characterized
the representation of racial and ethnic minorities
in cancer trials sponsored by NCI, using a cross-
sectional population-based analysis of all participants
in therapeutic non-surgical NCI Cooperative Group
clinical trials in breast, colorectal, lung, and prostate
cancer from 2000 through 2002.
7
In a separate
analysis, the ethnic distribution of patients enrolled in
2000 through 2002 was compared with those enrolled
in 1996 through 1998, using logistic regression models
to estimate the relative risk ratio of enrollment for
racial and ethnic minorities to that of white patients
during these time periods. The authors concluded that:
(1) enrollment in cancer trials is low for all patient
groups, (2) racial and ethnic minorities were less likely
to enroll in cooperative group cancer trials than were
whites, and (3) the proportion of black trial participants
has declined in recent years. Again, data specifi c to the
AYA population by race/ethnicity are not available and
need to be collected.
The Special Populations Breakout Group
examined available data on three of the cancers
that signifi cantly affect the AYA population: acute
lymphoblastic leukemia (ALL), breast cancer, and
rhabdomyosarcoma. The striking variability in
outcomes in the AYA population, and more specifi cally
in minorities and other disadvantaged groups within
this population, is summarized in the subsequent
discussion.
ALL
ALL is the most common childhood malignancy, and
children with ALL treated with contemporary therapy
have a 5-year survival rate of 80 percent.
8
Several
studies have shown highly signifi cant differences in
survival among ethnic and racial groups.
9
Remission
rates were comparable among the four ethnic and racial
groups studied (97 to 99 percent), but relapse rates
were signifi cantly different, resulting in the observed
differences in event-free survival (EFS). African
American children had the poorest outcome and
Asian Americans the best outcome. The outcome for
Hispanics was intermediate between that of Caucasians
and African Americans. Multivariate analysis revealed
ethnic background to be independently associated
with decreased EFS, even after controlling for known
adverse risk factors including age at diagnosis.
Differences in disease biology and clinical presenting
features in childhood ALL between whites and
African Americans have been examined. African
American children present with features indicative of
a larger tumor burden including elevated white cell
count, adenopathy, and organomegaly; have a higher
frequency of T-cell disease (associated with poorer
outcome); and display a paucity of hyperdiploid
disease (associated with more favorable outcome).
However, multivariate analysis demonstrated that
neither clinical features nor biologic prognostic
factors could explain the poor outcome among African
Americans. The literature contains no data examining
differences in disease biology among other ethnic and
racial groups, let alone in the AYA population.
Breast Cancer
Age-specifi c breast cancer rates for black women
under age 35 are twice that of white women of similar
age, and mortality rates are three times higher than
among whites. A recent study using SEER data
5
Tejeda HA, Green SB, Trimble EL, et al. Representation of
African-Americans, Hispanics, and whites in National Cancer
Institute cancer treatment trials.
Journal of the National Cancer
Institute
1996;88(12):812-816.
6
Hutchins L, Unger J, et al. Underrepresentation of patients 65
years of age or older in cancer treatment trials.
New England
Journal of Medicine
1999;341:2061-2067.
7
Murthy VH, Krumholz HM, Gross CP. Participation in cancer
clinical trials—race-, sex-, and age-based disparities.
Journal of
the American Medical Association
2004;291:2720-2726.
8
See note 3.
9
Clegg LX, Li FP, Hankey BF, et al. Cancer survival among US
whites and minorities: a SEER (Surveillance, Epidemiology,
and End Results) program population-based study.
Archives of
Internal Medicine
2002;162:1985-1993.
B-36
Appendix B: Breakout Group Reports - Special Populations
B-36 Appendix B: Breakout Group Reports - Special Populations B-36
Report of the Adolescent and Young Adult Oncology Progress Review Group
found racial/ethnic variation in clinical presentation,
treatment, and survival. Both African American
and Hispanic women presented with higher disease
stage and a higher prevalence of adverse prognostic
indicators compared with white women.
10
African
American and Hispanic women were less likely than
non-Hispanic white women to receive cancer-directed
surgery of any kind and to receive radiation following
breast conserving surgery. Racial/ethnic differences
in clinical presentation and treatment were associated
with poorer overall survival. Native American women
included in this study (from the Southwest, Detroit,
and Seattle) had the lowest incidence of breast cancer
in this age group. In terms of screening, data from
the 2000 National Health Interview Survey were
analyzed in 2004 to determine the degree to which
race/ethnicity remains a predictor of the receipt of
mammography screening after adjusting for personal
and health characteristics, socioeconomic status, and
access to and utilization of care variables.
11
This study
found that blacks and Hispanics were signifi cantly
less likely to report receipt of nearly all preventive
services examined. Among whites, 67 percent
reported mammographic screening, as did 60 percent
of English-speaking Hispanics. However, only 52
percent of Spanish-speaking Hispanics reported
mammographic screening. These fi ndings suggest that
some of the differences in socioeconomic status (SES)
are indicators of racial/ethnic disparities seen in breast
screening, but few studies have been conducted on the
racialized aspects of access and care and the interactive
effect of race and SES.
Rhabdomyosarcoma
A retrospective analysis of children with
rhabdomyosarcoma who were treated on International
Rhabdomyosarcoma Group protocols between 1994
and 1997 revealed that African Americans, other ethnic
minority groups, and whites experienced similar 5-year
EFS despite an exponential increase in non-Kaposi’s
sarcomas. In addition, African Americans aged 5 to
45 years had the highest incidence of non-Kaposi’s
sarcoma and Kaposi’s sarcoma of any group. Non-
white children more often had invasive, larger, stage 2
or 3 tumors, or tumors with positive regional nodes.
12
Eliminating cancer health disparities is a formidable
task that will require multifaceted, multidisciplinary
approaches and an understanding of biologic and
non-biologic factors that infl uence clinical outcomes
and quality of life. Based upon the current literature,
disease biology; pharmacogenetic differences; social,
cultural, and economic factors; and participation in
clinical trials will likely be key factors in incidence and
survival disparities among racial and ethnic groups,
particularly with respect to the AYA population. The
following three recommendations were developed to
eliminate health disparities in cancer care in adolescent
and young adult populations across the cancer care
continuum (prevention, screening, diagnosis, treatment,
survivorship, and end of life). In some instances, the
recommendations will extend to subgroups other than
ethnic/racial minorities within the AYA population,
such as legal immigrants.
Priority 1
Identify specifi c biologic mechanisms that
contribute to variations in cancer incidence and
outcomes in racial/ethnic groups within the AYA
population.
Rationale
Differences in incidence and outcomes between
different racial and ethnic groups have been observed
(see Background section).
Implementation Barriers
• Inaccuracy of race/ethnicity designation by both
patients and providers.
• Low accrual of clinical trial participants
(aversion to clinical trials both in minority and
AYA populations).
• Population heterogeneity (e.g., age, gender, SES,
race/ethnicity, high variation within the OMB
Directive 15 categories for race/ethnicity).
10
Shavers VL, Harian LC, Stevens JL. Racial/ethnic variation in
clinical presentation, treatment, and survival among breast cancer
patients under age 35.
Cancer
2003;97:134-137.
11
Lees KA, Wortely PM, Coughlin SS. Comparison of racial/
ethnic disparities in adult immunizations and cancer screening.
American Journal of Preventive Medicine
2005;29:404-411.
12
Baker KS, Anderson JA, Lobe TE, et al. Children from ethnic
minorities have benefi ted equally as other children from
contemporary therapy for rhabdomyosarcoma: a report from
the Intergroup Rhabdomyosarcoma Study Group.
Journal of
Clinical Oncology
2002;20(22):4428-4433.
Appendix B: Breakout Group Reports - Special Populations B-37
Report of the Adolescent and Young Adult Oncology Progress Review Group
Potential Partnerships and Resources
• Ethnic medical associations—e.g., National
Medical Association (NMA)
• Community and cancer advocacy groups,
including children’s cancer advocates
• Urban/regional hospitals
• NIH/NCI/CDC
• Community nonmedical professional
organizations
• Churches/minority-based organizations
• State cancer plans
• Historically Black Colleges and Universities
(HBCU)/minority-serving institutions (MI),
tribal colleges, Hispanic educational institutions,
Asian American and Pacifi c Islander Health
Forum
• State offi ces of minority health
• NCI-designated Comprehensive Cancer Centers
(CCCs)
• NCI Community Network Programs (CNPs)
• AYA survivors
Concrete Actions in the Next Three Years
• Encourage funding organizations to develop
and release specifi c Requests for Applications
(RFAs) and Program Announcements that focus
on underlying biologic mechanisms of ethnic
differences in the AYA cancer population.
• Promote the use of existing biorepositories
(e.g., NCI-designated CCC and Veterans
Administration repositories) by the research
community to explore racial/ethnic differences.
Priority 2
Improve access and quality of care across the cancer
care continuum (i.e., standard of care, prevention,
screening, diagnosis, treatment, survivorship, and
end of life) for the AYA population.
Rationale
A more comprehensive, integrated approach to cancer
care is needed. Many minority groups do not have
the same access and quality of care as whites, thereby
affecting their cancer outcomes adversely. The AYA
population must have access to comprehensive,
integrated state-of-the-art health care, including
insurance coverage.
Implementation Barriers
• Lack of insurance.
• Dearth of education/awareness among patients
and health care professionals about the cultural
needs of diverse racial/ethnic groups.
• Lack of cultural competency.
• Paucity of minority providers that can provide
and model appropriate and acceptable care for
patients from diverse cultural groups.
Potential Partnerships and Resources
• Ethnic medical associations (e.g., NMA)
• Community and cancer advocacy groups
• Urban/regional hospitals
• NIH/NCI/CDC
• Community nonmedical professional
organizations
• Churches/minority-based organizations
• State cancer plans
• HBCU/MI, tribal colleges, Hispanic educational
institutions, Asian American and Pacifi c Islander
Health Forum
• State offi ces of minority health
• CCCs
• CNPs
• AYA survivors
Concrete Actions in the Next Three Years
• Encourage meaningful partnerships between
cancer centers and community physicians/
hospitals/other community providers to evaluate
the standard of care for AYAs from diverse race/
ethnic/cultural/socioeconomic groups.
• Implement patient navigator programs for
racial/ethnic/cultural/socioeconomic subgroups
within the AYA population (see also other
Breakout Group recommendations that focus on
navigators/coaches).
B-38
Appendix B: Breakout Group Reports - Special Populations
B-38 Appendix B: Breakout Group Reports - Special Populations B-38
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Provide community incentives for recruiting
patients to clinical and cancer control trials
(i.e., funded resources within the community
to focus on the AYA population, including
media promotion). Examples may include
establishing centers of learning and developing
and implementing school curricula (beginning
in elementary school and continuing through
college) to improve understanding among AYAs
of cancer risk and appropriate cancer screening
and care.
• Require cancer centers to adhere to established
and emerging culturally and linguistically
appropriate standards and skills and integrate
them into education and practice.
• Develop programs for AYA survivors to
serve as health care informants, providers,
and researchers (e.g., National Breast Cancer
Coalition’s Project LEAD).
Priority 3
Integrate existing community assets (religious,
social, professional, and fraternal organizations) to
decrease disparities in AYA populations.
Rationale
The most straightforward and practical approach to
gaining the necessary knowledge and confi dence
of the community is by joining forces with existing
community assets and organizations. The positive
impact of community support and collaborative
efforts has been demonstrated (e.g., the NCI-funded,
ethnic-specifi c Community Partners Network). This
recommendation is intended to engage and expand
community participation and develop sustainable
infrastructure within communities. Similar
recommendations were made by the Trans-HHS
Cancer Health Disparities Progress Review Group and
can be cross-referenced in its report.
13
Implementation Barriers
• Lack of community education.
• Awareness defi cits.
• Acceptance of the status quo; lack of
age-appropriate innovative outreach efforts that
are culturally relevant and acceptable.
• Nascent stage of scientifi c inquiry into the actual
effects of culture variation and the racialization
of our society and its impact on practice.
Potential Partnerships and Resources
• Ethnic medical associations (e.g., NMA)
• Community and cancer advocacy groups
• Urban/regional hospitals
• NIH/NCI/CDC
• Community nonmedical professional
organizations
• Churches/minority-based organizations
• State cancer plans
• HBCU/MI, tribal colleges, Hispanic educational
institutions, Asian American and Pacifi c Islander
Health Forum
• State offi ces of minority health
• CCCs
• CNPs
• AYA survivors
Concrete Actions in the Next Three Years
• Encourage funding organizations to prepare
and release RFAs that develop and sustain
community-based participatory education and
research (e.g., Continuing Medical Education
accreditation for professionals involved in AYAO
care) in which investigators will work with the
community across the cancer care continuum.
• Promote cooperation and networks between
existing AYA advocacy groups and the
community.
• Advocate for more sophisticated social and
behavioral scientifi c paradigms that are inclusive
of cultural differences beyond the crude distal
measures of race/ethnicity currently used.
13
See note 1.
Appendix B: Breakout Group Reports - Special Populations B-39
Report of the Adolescent and Young Adult Oncology Progress Review Group
Conclusion
The AYA oncology population is an understudied
group. Within this group, special populations as
defi ned by gender, age, ethnicity, race, education,
income, social class, and other parameters are even
less well studied. By implementing these priorities, a
substantial improvement in racial and ethnic disparities
within the AYA population will be achieved. A
multifaceted approach is necessary, including the
participation of communities of affected individuals.
Individuals and communities must be empowered to
undertake and solve the problem together. Included in
this approach is a better understanding of the biologic
and nonbiologic factors that contribute to cancer
disparities in the AYA population.
B-40
Appendix B: Breakout Group Reports - Special Populations
B-40 Appendix B: Breakout Group Reports - Special Populations B-40
Report of the Adolescent and Young Adult Oncology Progress Review Group
PSYCHOSOCIAL/BEHAVIORAL FACTORS
Co-Chairs
Brad Zebrack
Amelie Ramirez
Jennifer Ford
Participants
Heidi Adams
Ernie Katz
Daniel Armstrong
David Osoba
Kimlin Ashing-Giwa
Randi Rosenberg
Pamela Haylock
Lydia Shrier
Susan Hedlund
Carol Sienche
Marjorie Kagawa Singer
Background
Adolescence and young adulthood are times
of increased vulnerability to stress, presenting
adolescent and young adult (AYA) cancer patients
and survivors with major developmental challenges
beyond those faced by other young people.
1
Thus,
they have unique health and psychosocial needs
when compared with childhood cancer patients or
older adults diagnosed and treated for cancer during
later stages of life. Yet empirical literature is limited
regarding specifi c psychosocial outcomes, causes,
and correlates for patients and survivors diagnosed as
older adolescents and young adults.
Contemporary research trends in pediatric
psychosocial oncology are relevant to an AYA
population. These trends encompass: (1) a stress-
coping model/framework, recently amended with
a focus on post-traumatic effects; (2) a family
systems approach emphasizing interactive responses
and interpersonal infl uences within families; and
(3) a developmental approach in which the issues
experienced by children of various ages are treated
in the context of their normative physical and
psychosocial maturation. Assessing psychosocial
and behavioral issues across six dimensions will
help identify patient and survivor needs and inform
the development of interventions that address both
psychopathologic disease prevention and health
promotion.
Intellectual Issues
Often, adolescents and young adults with cancer
lack critical information regarding their disease and
its treatment, including information about types
and dosages of treatment and in some cases, even
the type of cancer they have, along with knowledge
about potential long-term late physical effects.
2,3
As
a result, many patients/survivors seek educational
and support resources that are relevant to their age
group. Communicating information about diagnosis,
prognosis, treatment, and long-term effects to AYA
cancer patients can be a sensitive issue and it is crucial
that information is targeted toward each patient’s age
and cognitive abilities. Furthermore, these resources
must be culturally relevant and disseminated with a
high level of cultural competence (i.e., communicating
with messages of hope and compassion relative to each
unique culture).
Interpersonal Issues
Relating with family, peers, and health professionals is
an important aspect of life for AYAs with cancer. As
young people try to deal with or discuss cancer with
their parents they sometimes discover that they have
quite different coping strategies. For instance, parents
may want to discuss issues with their child that the
child does not wish to discuss, or vice versa. Family
member support is a critical component of health, well-
being, and adjustment to cancer, and studies suggest
that most young adult survivors report improved
family relationships. With regard to peer relations,
it is not uncommon for adolescents and young adults
with cancer to experience changes in friendships
and/or a sense of isolation from friends due to lengthy
periods away from home, school, or work during
treatment. Some friendships may founder over time.
1
Hobbie WL, Stuber M, Meeske K, Wissler K, Rourke MT,
Ruccione K, et al. Symptoms of posttraumatic stress in young
adult survivors of childhood cancer.
Journal of Clinical
Oncology
2000;18(24):4060-4066.
2
Bashore L. Childhood and adolescent cancer survivors’
knowledge of their disease and effects of treatment.
Journal of
Pediatric Oncology Nursing
2004;21(2):98-102.
3
Kadan-Lottick NS, Robison LL, Gurney JG, Neglia JP, Yasui
Y, Hayashi R, et al. Childhood cancer survivors’ knowledge
about their past diagnosis and treatment: Childhood Cancer
Survivor Study.
Journal of the American Medical Association
2002;287:1832-1839.
Appendix B: Breakout Group Reports - Psychosocial/Behavioral Factors B-41
Report of the Adolescent and Young Adult Oncology Progress Review Group
The impact of cancer treatment on sexuality, intimacy,
and formation of mature, committed relationships is
particularly salient to this population. Finally, while a
trusting and therapeutic relationship between a doctor
and a patient is an important component of care, health
care professionals and young adults may fi nd it diffi cult
or intimidating to communicate with one another and
poor communication of important clinically relevant
information may result.
Emotional Issues
Though varying substantially in their theoretical
frames, inquiry methods, and samples of informants,
studies of AYAs suggest the following: (1) some
patients and survivors have managed to grow in
positive ways as a result of their cancer experience,
(2) most patients and survivors are probably
relatively average in psychosocial terms and on most
psychosocial/quality of life measures, and (3) some
patients experience ongoing psychological and/or
social adjustment problems, including depression and
other mood disorders, and anxiety, including post-
traumatic stress symptoms. Risk factors for these
and other associated psychosocial stressors identifi ed
in the research literature include but are not limited
to temporal clustering of stressful medical and life
events, poverty, prior experiences with poor coping
resources, pre-existing emotional problems or family
discord, extent of disease and treatment severity, degree
of distress or residual disability, and lack of social
support. Additionally, cancer requires individuals to
renegotiate their identity.
4
Changes in body image,
disruption of normal activities, and adverse reactions
to the effects of cancer and its treatment may affect
the sense of self in adolescents and young adults with
cancer.
5
Some AYA survivors actively seek to improve or adjust
their physical, psychological, and social status and
view themselves as involved in a process of accepting
their cancer and getting back to normal. Yet even these
young people may still worry about their physical
health status and bodies, their self-esteem and identity,
their immediate family’s welfare, relating with the
social world and being “different,” re-integrating with
the school system or work environment, possibilities
for the future (including access to life and health
insurance, jobs and career options, understanding
genetic compromises stemming from treatment), and
ensuring continued care from a skilled and attentive
medical system. Opportunities for peer involvement
often provide adolescents and young adults a chance to
address these areas of concern.
Practical Issues
AYA patients often are subject to painful procedures
and treatments. They also experience a lack of “fi t”
in a health care system that distinguishes pediatric
from adult care. As a direct result of cancer diagnosis
and treatment, they confront myriad disruptions in
their lives, particularly with regard to school, work,
and family life. Many families lack resources to pay
for increased needs for transportation, child care,
copayments for health care and drugs, and food or
housing expenses. After treatment ends, AYAs face a
complex system of health care delivery and fi nancing,
and they may have diffi culty locating and accessing
primary care providers. As maturing and developing
young people, they remain challenged by peer and
other pressures regarding tobacco, alcohol, or drug
use, and these challenges may be more pronounced in
underserved groups. All of these factors may infl uence
AYAs’ adherence to treatment protocols and their sense
of independence or control over their lives.
Existential/Spiritual Issues
Young people with cancer defi ne uncertainty both as
living with the unknown and as not knowing what to
expect. Survivors in their teens and young adult years
further suggest that while uncertainty can be a source
of distress, it also can be a catalyst for personal growth,
a deepened appreciation for life, greater awareness of
life purpose, development of confi dence and resilience,
and optimism. A signifi cant proportion of people with
cancer acknowledge the support they receive through
God, faith, religious practices, and involvement in their
place of worship, although some young people indicate
that having cancer challenges their current religious
beliefs and values.
4
Mathieson CM, Stam HJ. Renegotiating identity: cancer
narratives.
Sociology of Health and Illness
1995;17(3):283-306.
5
Zebrack BJ. Cancer survivor identity and quality of life.
Cancer
Practice
2000;8(5):238-242.
B-42
Appendix B: Breakout Group Reports - Psychosocial/Behavioral Factors
B-42 Appendix B: Breakout Group Reports - Psychosocial/Behavioral Factors B-42
Report of the Adolescent and Young Adult Oncology Progress Review Group
Cultural Relevance
Understanding the needs, risks, and lifestyles of
adolescent and young adult cancer patients and
survivors necessitates an awareness of the strong,
often covert infl uences of culture, race/ethnicity,
and socioeconomic status in shaping reactions and
responses to health problems. Literature suggests
that culturally different views of the meanings of
health, illness, and treatment exert strong infl uence on
both patients’ and care providers’ behaviors. At the
same time, unintentional and often institutionalized
forms of discrimination in the provision of care (e.g.,
unconscious bias; poverty; and racial inequalities in
education, fi nancial resources, transportation facilities,
insurance) often determine the level of care available
to whole groups of patients and families. As a result,
neither equitable nor adequate access to quality cancer
care is ensured for everyone in today’s health care
environment.
Methodologic Considerations
The majority of research combines adolescents and
young adults into a single or more heterogeneous
sample. This is true in many studies of patients
on treatment as well as in studies of off-treatment
survivors. Literature searches utilizing the keywords
“cancer” and “young adults” or “cancer” and
“adolescents” most often turn up research studies that
include AYA survivors of childhood cancer, and young
adults as part of samples consisting of a wide range
of ages. For example, less than 1 percent of cancer-
related citations in the National Library of Medicine’s
PubMed database between 1993 and 2003 were
specifi c to survivorship issues among the adolescent
and young adult population.
6
Since data on adolescents
and young adults often are not reported separately,
little is known about the specifi c needs, concerns, and
psychosocial development of AYA cancer patients and
survivors.
7
Priority 1
Develop and apply appropriate methodologic
approaches to better understand AYA health care
and psychosocial needs.
Rationale
AYAs share a set of universal needs with cancer
patients of all ages, including the need for
evidence-based clinical care and family/social
support. In addition, AYAs have unique health
care and psychosocial needs that are infl uenced by
developmental, sociocultural, and cancer-specifi c
contexts. Existing methods for assessing psychosocial
outcomes in either pediatric or adult populations may
not be suffi cient for capturing the full AYA experience.
Appropriate approaches for assessing AYA health care
and psychosocial needs must be founded on methods of
investigation that address the impacts of cancer as they
are infl uenced by normative developmental challenges
(e.g., peer involvement, establishing a world view,
identity development) and sociocultural factors (e.g.,
values and beliefs about cancer/illness, socioeconomic
status, education). Current research limits our ability
to draw specifi c conclusions about the unique needs of
AYAs.
Implementation Barriers
• AYAs currently are not recognized as a distinct
or diverse population.
• Researchers typically do not have access to a
representative population of AYAs, due in part
to small numbers, lack of recognition among
gatekeepers (e.g., providers) that AYAs are a
unique and understudied cohort, and limited
research resources in community centers where
most AYAs are treated.
• Few researchers possess training in both
developmental psychology and research
methodologies that could advance our
understanding of the unique needs of
this population. In addition, few funding
mechanisms exist to support this area of
behavioral research.
6
Bleyer A, O’Leary M, Barr RD, Ries LAG (eds). Cancer
Epidemiology in Older Adolescents and Young Adults 15 to 29
Years of Age, including SEER Incidence and Survival:1975-
2000. Bethesda, MD, National Cancer Institute, 2006.
7
Reuben SH.
Living Beyond Cancer: Finding a New Balance,
President’s Cancer Panel, 2003-2004 Annual Report. National
Institutes of Health, National Cancer Institute, May 2004.
Appendix B: Breakout Group Reports - Psychosocial/Behavioral Factors B-43
Report of the Adolescent and Young Adult Oncology Progress Review Group
Potential Partnerships and Resources
• Collaborative research between academia and
community-based treatment facilities
• Collaboration among investigators utilizing
multiple methods of data collection and analysis
(i.e., quantitative and qualitative methods)
• Collaboration with other community-based
organizations or bodies that may provide
access to adolescents and young adults (e.g.,
professional societies, social and/or service
organizations, educational/vocational training
institutions, faith-based institutions)
• Collaboration with cancer-specifi c advocacy
groups (e.g., Planet Cancer, Ulman Cancer Fund
for Young Adults) and professional organizations
(e.g., Society of Adolescent Medicine, National
Comprehensive Cancer Network) serving AYAs
• Partnership between the National Cancer
Institute (NCI) and foundations to create specifi c
funding mechanisms for psychosocial research
on AYAs
Concrete Actions in the Next Three Years
• Identify gaps in the literature and evidence-based
psychosocial intervention models (e.g., from
other disease groups) that may apply to AYAs.
• Identify and secure funding from foundations
whose missions may be in concert with
psychosocial needs of AYAs.
• Convene psychosocial experts and AYA
stakeholders to develop needs assessment tools
and other methods.
• Sponsor a consensus conference on assessment
of AYA psychosocial needs.
Priority 2
Improve training/education to enhance health care
professionals’ abilities to deliver developmentally
appropriate care and to enhance AYAs’ and family
members’ abilities to be proactive in their health
care.
Rationale
Few health care providers possess the requisite
knowledge, skill, or comfort levels to address the
specifi c needs and challenges of AYAs. In our
fragmented health care system, AYA patients and their
families need targeted, tailored, and culturally relevant
resources to participate effectively in their health care
decision-making.
Implementation Barriers
• Current medical education models do not train
health care providers to work with AYAs.
• Clinical education and training are limited in
their developmental and cultural relevance and
biopsychosocial approach to care.
• AYA families and patients do not routinely have
access to developmentally appropriate resources
or support agencies.
Potential Partnerships and Resources
• Collaborations among public health,
psychology, social work, medicine, and health
communication experts
• Health and medical education systems
• Involvement of advocacy groups and
stakeholders in developing education and
training programs
Concrete Actions in the Next Three Years
• Assess the needs of health care providers (e.g.,
oncology, primary care, mental health) to
enhance AYA psychosocial outcomes.
• Develop Special Interest Groups within the
American Society of Clinical Oncology, the
American Association for Cancer Research,
and other health care professional societies to
promote education across the continuum of AYA
health care and psychosocial needs.
• Develop multidisciplinary care models and
incorporate psychosocial training of AYAs into
specialty certifi cation processes.
• Identify factors that promote AYA engagement
in their health care and enhance psychosocial
outcomes.
B-44
Appendix B: Breakout Group Reports - Psychosocial/Behavioral Factors
Report of the Adolescent and Young Adult Oncology Progress Review Group
Priority 3
Identify, implement, and evaluate innovative peer
and family support intervention models throughout
the continuum of care (i.e., from diagnosis through
treatment, off-treatment survival, and/or end of
life).
Rationale
Few evidenced-based peer and family support
psychosocial interventions are available for AYAs.
Existing peer support models (e.g., AYA support
groups, retreats, uses of technology) are being initiated
through community-based agencies and some medical
centers. These programs have potential for enhancing
outcomes (e.g., reducing social isolation, improving
psychosocial functioning, promoting successful
adjustment) but have yet to be tested empirically.
Family-based intervention models from pediatrics (e.g.,
parent support groups, Impact of Traumatic Stressors
Interview Schedule) also may have utility for AYAs.
Implementation Barriers
• Understanding of the most effective types and
methods of peer and family support is limited,
including types of interventions that are most
appropriate for specifi c subgroups of the AYA
population (as defi ned by age/developmental
stage, ethnicity/race, and socioeconomic status).
• Conceptual, nonconventional, and innovative
models that may be more effective, appropriate,
and culturally relevant for AYAs (e.g., use of
media technology for intervention delivery) must
be developed and tested; however, this has not
been completed to date.
• Limited resources exist to support longitudinal
studies to assess the impact and durability
of interventions on psychosocial functioning
changes over time.
Potential Partnerships and Resources
• Corporate foundations and philanthropic
organizations (e.g., Microsoft, Dell,
pharmaceutical companies, community service
organizations)
• NCI, Lance Armstrong Foundation, American
Cancer Society, etc.
• AYA advocacy groups (e.g., Young Survival
Coalition, Planet Cancer)
Concrete Actions in the Next Three Years
• Achieve consensus as to key psychosocial
outcomes (e.g., reduce social isolation,
enhance family communication, increase health
promoting behaviors) associated with peer- and
family-based intervention participation.
• Develop and evaluate a peer navigator model.
• Develop Requests for Applications/Program
Announcements for longitudinal and/or
multimethod theory-based approaches to test
the effi cacy of peer support and family-based
psychosocial interventions.
• Evaluate or test existing peer or grassroots
interventions.
• Develop a directory of psychosocial care
resources.
• Sponsor a consensus conference for psychosocial
intervention in AYAs with cancer.
• Develop a network (listserv) of AYA researchers.
Conclusion
AYAs are faced with multiple developmental and
psychosocial challenges that can be exacerbated
by the experience of cancer. These challenges
span several domains, but little is known about the
specifi c psychosocial needs of AYA patients and
survivors across these multiple domains. Enhancing
the life experiences of AYA cancer patients and
survivors requires assessment studies of AYA-specifi c
psychosocial needs, health professional education/
training on AYA-specifi c psychosocial issues, and
evidence-based intervention development.
Appendix B: Breakout Group Reports - Psychosocial/Behavioral Factors B-45
Report of the Adolescent and Young Adult Oncology Progress Review Group
HEALTH-RELATED QUALITY OF LIFE
Co-Chairs
Ronald Barr
Carolyn Gotay
Participants
Daniel Armstrong
David Osoba
Craig Earle
Peter Pisters
David Feeny
Brad Pollock
Douglas Hawkins
Kathleen Ruccione
Ernie Katz
William Small
Ian Lewis
Beth Virnig
Kutluck Oktay
Brock Yetso
Ann O’Mara
Brad Zebrack
Background
The rationale for measuring health-related quality of
life (HRQL) has been reviewed in detail by Feeny, et
al.
1
Purposes for which such measurement can be used
include those defi ned by Guyatt, et al.,
2,3
Lipscomb et
al.,
4
and Osoba.
5
These fall into three categories:
• Discrimination – distinguishing the burden of
morbidity among groups or individuals at a point
in time
• Evaluation – assessing changes in morbidity over
time, in longitudinal/prospective studies such as
clinical trials
• Prediction – using an HRQL measure to predict
the score on another measure or to predict
clinical outcome (prognostication)
A plethora of instruments is available for use in adult
respondents. Far fewer have been designed for use
in children and an even smaller number have been
assessed by Eiser and Morse
6
as sound. A limited
number of measures have been developed more or
less specifi cally for adolescents,
7
and a few of these
have been employed in the assessment of HRQL in
young people with cancer.
8,9
Measures of HRQL can
be classifi ed as health profi les, which may or may not
provide a single summary score, and preference-based
measures, which may measure preferences either
directly (e.g., by the standard gamble technique) or by
the use of multi-attribute health status classifi cation
systems and associated preference functions. Health
profi les may be specifi c (applicable to a particular
population), generic, or both (modular, e.g., the Peds
QL
10
).
HRQL instruments have been designed for self-
administration (proxy or self-assessment), including
mailed questionnaires, administration by interviews
(face-to-face or by telephone), or by computer. Some
HRQL instruments have been adapted to multiple
cultural/linguistic needs. The challenges posed by
HRQL measurement in pre-school age children (e.g.,
the need for proxy ratings) are well recognized.
11
Such
hurdles are less diffi cult to surmount in adolescents and
young adults (AYAs).
Opportunities for research in this area pertinent to
adolescent and young adult oncology (AYAO) include
the following:
1
Feeny D, Furlong W, Mulhern RK, Barr RD, Hudson M. A
framework for assessing health-related quality of life among
children with cancer.
International Journal of Cancer
1999;
International Journal of Cancer 1999; International Journal of Cancer
Supplement,12:2-9.
2
Guyatt GH, Feeny DH, Patrick DL. Measuring health-related
quality of life.
Annals of Internal Medicine
1993;118:622-629.
3
Guyatt GH, Jaeschke R, Feeny DH, Patrick DL. Measurements
in clinical trials: choosing the right approach. In: Spilker B (ed).
Quality of Life and Pharmacoeconomics in Clinical Trials, 2nd
edition. Philadelphia, Lippincott-Raven, 1996, pp. 41-48.
4
Lipscomb J, Gotay CC, Snyder C. Outcomes Assessment in
Cancer. Cambridge: Cambridge University Press, 2005.
5
Osoba DE. Measuring the effects of cancer on health-related
quality of life.
PharmacoEconomics
1995;7:308-319.
6
Eiser C, Morse R. The measurement of quality of life in
children: past and future perspectives.
Developmental and
Behavioral Pediatrics
2001;22:248-256.
7
Grant J, Cranston A, Horsman J, et al. Health status and
health-related quality of life in adolescent survivors of cancer in
childhood.
Journal of Adolescent Health
2006;38:504-510.
8
Patrick D, Edwards T, Topolski T, et al. Youth quality of life: a
new measure incorporating the voices of adolescents.
Quality of
Life Newsletter
2002;28:7-8.
Life Newsletter 2002;28:7-8.Life Newsletter
9
Varni JW, Burwinkle TM, Katz ET, et al. The Peds QL in
pediatric cancer: reliability and validity of the Pediatric Quality
of Life Inventory Generic Core Scales, Multidimensional Fatigue
Scale, and Cancer Module.
Cancer
2002;94:2090-2106.
Cancer 2002;94:2090-2106.Cancer
10
See note 9.
11
Nathan PC, Furlong W, Barr RD. Challenges to the measurement
of health-related quality of life in children receiving cancer
therapy.
Pediatric Blood Cancer
2004;43:215-223.
Pediatric Blood Cancer 2004;43:215-223.Pediatric Blood Cancer
Appendix B: Breakout Group Reports - Health-related Quality of Life B-47
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Inclusion of HRQL measures in clinical trials—
While this is increasingly common in the adult
context and has been essentially mandated by
some funding agencies (e.g., the National Cancer
Institute of Canada
12
), lamentably few examples
involve younger age groups.
• Impact of measurement on treatment decisions
and compliance—As yet this opportunity has
been addressed largely in theory,
13
but it is
especially apposite to the age range encompassed
by the AYAO PRG, in which issues of decision-
making and adherence/compliance loom large.
• Linkage of HRQL data to a central registry of
adolescents and young adults with cancer—So
far this registry is a pipe dream, but such a
linkage would provide additional grist to the
argument for its establishment. A case for
quality-adjusted survival has been made
14
and
a fl edgling example of linking HRQL data to
a national registry has been described, in the
context of “late effects,” with the Canadian
Childhood Cancer Surveillance and Control
Program.
15
Priority 1
Identify and/or develop instruments for assessing
HRQL appropriate to the AYA population.
Rationale
A paucity of information exists on the HRQL
domains that are relevant to the AYA age groups.
Appropriate ways to measure these domains also are
needed. Important concerns include measurements
that: (1) span the survivorship continuum, (2) are
developmentally appropriate, (3) include co-morbidity
assessment and family well-being, and (4) are
appropriate to the patients’ literacy level.
Implementation Barriers
• Lack of validated measures that span the
developmental trajectory.
• Limited attention to the AYA age groups in
HRQL assessments to date.
• Vested interests in available instruments.
• Lack of a conceptual model of HRQL in AYAs.
Potential Partnerships and Resources
• National Cancer Institute (NCI) Cooperative
Groups and Cancer Centers
• Professional organizations, e.g., Oncology
Nursing Society (ONS), American Society
of Clinical Oncology (ASCO), International
Society for Quality of Life Research (ISOQOL)
• National Institutes of Health (NIH), NCI
• Military medical organizations that treat AYA
cancer patients
• Advocacy organizations, e.g., Lance Armstrong
Foundation (LAF)
• Others, e.g., American Cancer Society (ACS)
Concrete Actions in the Next Three Years
• Develop strategies for communication and
collaboration among researchers, e.g., an AYA
network.
• Explore collaborations with relevant projects,
e.g., Patient Reported Outcomes Measurement
Information System (PROMIS), Patient Reported
Outcomes and Quality of Life Instruments
Database (PROQOLID).
• Convene a consensus conference to assess the
state of the science and identify future directions
for HRQL instrument development relevant to
the AYA population, with leadership provided by
NCI, LAF, and other stakeholders.
12
Ganz PA, Moinpour CM, Cella DF et al. Quality-of-life
assessment in cancer clinical trials: a status report.
Journal of
the National Cancer Institute (USA)
1992;84:994-995.
13
Gesundheit B, Greenberg ML, Kapelushnik Y, Koren G. Drug
compliance by adolescent cancer patients. In: Bleyer WA, Barr
RD (eds). Cancer in Adolescents and Young Adults. Heidelberg,
Springer-Verlag (in press).
14
Barr RD, Sala A. Quality-adjusted survival: a rigorous
assessment of cure after cancer during childhood and
adolescence.
Pediatric Blood Cancer
2005;44:201-204.
Pediatric Blood Cancer 2005;44:201-204.Pediatric Blood Cancer
15
Pogany L, Barr RD, Shaw A, Speechley KN, Barrera M,
Maunsell E. Health status in survivors of cancer in childhood
and adolescence.
Quality of Life Research
2006;15:143-157.
B-48
Appendix B: Breakout Group Reports - Health-related Quality of Life
B-48 Appendix B: Breakout Group Reports - Health-related Quality of Life B-48
Report of the Adolescent and Young Adult Oncology Progress Review Group
Priority 2
Apply HRQL assessments in clinical care.
Rationale
HRQL assessments have the potential to enhance
participation of AYA patients in their own clinical care,
including communication, adherence, and
decision-making. These assessments also may
contribute to improved clinical management by health
care providers.
Implementation Barriers
• Lack of solid evidence that HRQL assessments
contribute to clinical care.
• A perceived added burden to consumers and
providers.
• Perceptions that patients are unable to make
autonomous decisions.
• Insuffi cient information about how to interpret
HRQL assessments in clinical care.
• Limited marketing to clinicians by the HRQL
community so that potential contributions of the
assessments are unrealized.
Potential Partnerships and Resources
• Advocacy organizations
• ASCO
• Cancer centers and children’s hospitals
• Department of Defense (DoD), given the age
distribution of military personnel
• Health Maintenance Organization (HMO)
research networks, e.g., Cancer Research
Network
• HRQL professional organizations, e.g., ISOQOL
Concrete Actions in the Next Three Years
• Funding agencies should develop a Request for
Applications to support this effort, which could
include conducting focus groups with patients
and providers.
• Form partnerships with organizations with
relevant interests to pilot test promising models.
Interventions utilizing new technologies, e.g.,
linkage with electronic medical records, touch
screens, Personal Digital Assistants (PDAs), and
devices such as iPods, are particularly ripe for
development.
Priority 3
Use HRQL as a primary outcome in research
applications.
Rationale
HRQL measures can be used to identify previously
unknown, under-appreciated, and under-reported
morbidity and prognostic factors. Examples include
clinical trials, health services research focused on
investigating models of care, prospective studies of late
effects, and palliative and end of life care.
Implementation Barriers
• Low priority for funding.
• Need for additional infrastructure for HRQL
questionnaire administration and analysis.
• Lack of clear evidence for clinically meaningful
differences in HRQL scores.
• Limited training opportunities for physicians
and other health care providers in HRQL
measurement and application.
Potential Partnerships and Resources
• NCI, Surveillance, Epidemiology, and End
Results Program; NCI QOL Intergroup
• ASCO, American Association for Cancer
Research
• Cancer centers
• Pharmaceutical companies
• Cooperative groups
• Advocacy organizations
• Academic institutions (e.g., medical schools)
• DoD
Concrete Actions in the Next Three Years
• Include HRQL assessments in studies of
survivorship care plans.
• Develop criteria for successful implementation
of HRQL assessments in protocols applicable to
AYA populations. It is recommended that this
action be completed by NCI.
Appendix B: Breakout Group Reports - Health-related Quality of Life B-49
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Convene a consensus conference to assess the
state of the science and future directions for
work in this area.
Conclusion
HRQL for the AYA population needs to be defi ned and
measured, and the results applied. This will require
developing appropriate instruments and identifying
uses for them in both clinical treatment and clinical
trials. Numerous barriers must be overcome before
this goal can be attained. Collaborative relationships
involving government agencies, advocacy and
professional organizations, academic institutions,
cancer centers, cooperative groups, HMO research
networks, pharmaceutical companies, and established
partnerships (e.g., the NCI QOL Intergroup) will
greatly facilitate the achievement of this goal. The
strategies for communication and collaboration among
researchers, development of appropriate assessment
tools, and other priorities outlined in this report offer
signifi cant opportunities for increasing understanding
of HRQL in the AYA population.
B-50
Appendix B: Breakout Group Reports - Health-related Quality of Life
B-50 Appendix B: Breakout Group Reports - Health-related Quality of Life B-50
Report of the Adolescent and Young Adult Oncology Progress Review Group
LONG-TERM EFFECTS
Co-Chairs
Beth Virnig
Kevin Oeffi nger
Participants
Noreen Aziz
Joseph Lipscomb
Ronald Barr
Kutluk Oktay
Maryann Carousso
Leslie Schover
Jacqueline Casillas
Peter Shaw
Craig Earle
William Small
Sandra Horning
Samuel Wells
Mary Louise Keohan
Background
An understanding of the long-term health outcomes
associated with adolescent and young adult
(AYA) cancer and cancer therapy is essential for
providing anticipatory risk-based care for survivors.
Furthermore, an appreciation of the long-term
morbidity and mortality associated with specifi c
therapies is important when developing or refi ning
new cancer treatment strategies. Though the body
of knowledge is growing regarding long-term health
outcomes in survivors of adolescent cancer and some
young adult cancers (e.g., testicular cancer), many
signifi cant knowledge gaps impede the care of this
high-risk population.
Terminology
The National Cancer Institute (NCI) defi nes long-
term effects as those conditions that develop during
therapy and persist after the completion of therapy.
1
Late effects refers to conditions that develop after the
completion of therapy. Though some late effects may
occur within months after therapy ends, many will
not become evident for 10 to 20 years. Ascertaining
whether a condition is a long-term or late effect can
be diffi cult, so some researchers group all outcomes
together and refer to them as late effects. It also is
important, though sometimes diffi cult, to ascertain
whether a late effect is related to previous cancer
therapy or is simply due to the normal aging process
and the genetic/lifestyle predispositions of the
individual. Thus, it is important methodologically to
determine the excess risks attributable to various cancer
treatment exposures. For the purposes of this report,
the term “late effects” is intended to include both long-
term and late effects.
Mechanisms of Late Effects in AYA
Cancer Survivors
When considering the nature and likelihood of late
effects, a fi rst step is to identify the mechanisms
leading to such outcomes. Effects due to treatment
can be caused either individually or in combination by
surgery (e.g., small bowel obstruction, oophorectomy),
radiation therapy (e.g., damage to bones, second
cancers), chemotherapy, other adjuvant therapies
(e.g., secondary leukemia, cardiac damage), and
underlying genetic propensity. In addition, growing
evidence suggests that the age of cancer onset, or the
age at which an individual receives treatment, may
differentially affect the likelihood of experiencing an
adverse long-term outcome. This latter observation is
particularly important because it raises questions about
the applicability of knowledge gained from studies of
one age group (e.g., the Childhood Cancer Survivor
Study–CCSS) to people in other age groups (the AYA
population). For example, the cognitive damage
seen in children may not occur in adults treated with
similar chemotherapies, perhaps due to differences in
development-related sensitivity of the brain. Finally,
some late effects may refl ect the cancer experience
rather than any particular treatment. Frequent reports
of depression, post-traumatic stress disorder, and risk-
taking behavior among survivors are examples of such
manifestations.
1
Aziz NM, Rowland JH. Trends and advances in cancer
survivorship research: challenge and opportunity.
Seminars in
Radiation Oncology
2003;13(3):248-266.
Appendix B: Breakout Group Reports - Long-term Effects B-51
Report of the Adolescent and Young Adult Oncology Progress Review Group
Increased Risk of Late Mortality and Morbidity
Compared with age- and sex-specifi c mortality rates
in the general U.S. population, long-term survivors
of adolescent cancer face an increased risk of death
beyond 5 years from their cancer diagnosis.
2,3
Though
less well studied, similar effects have been reported in
young adult cancer survivors. The excess mortality is
due to late recurrences of the original cancer, second
cancers, and heart and lung disease as a consequence of
the therapy of the original cancer.
4
The long-term morbidity associated with AYA cancer
therapy likely varies by cancer exposure and age at
treatment. Serious effects include second cancers,
infertility, gonadal dysfunction and premature gonadal
failure, cardiovascular disease, and psychological
problems. Depending upon treatment exposure, all
organ systems can be affected.
Much of what is known about late mortality and
morbidity has been learned from studies focusing
on pediatric cancer survivors, including adolescent
cancer survivors treated in pediatric settings. The
CCSS, an NCI-supported 26-institution cohort study
that is tracking the health outcomes of over 14,000
long-term pediatric cancer survivors diagnosed 1970-
1986, has been a major contributor to understanding
the long-term health outcomes of survivors.
5
We
expect that some of this information is applicable to
survivors of young adult cancers with similar treatment
exposures, such as survivors of Hodgkin’s disease, soft
tissue sarcoma, and bone tumors. However, further
study is needed to determine the differential effect of
various treatment exposures based on age at therapy.
Moreover, large gaps exist in the understanding of
morbidity in survivors of young adult cancers.
Health Care of AYA Cancer Survivors
Recognizing the long-term risks of cancer survivors,
NCI
6
and the Institute of Medicine (IOM)
7,8
recommend lifelong follow-up care for all cancer
survivors. Adolescent cancer survivors treated in the
pediatric oncology setting usually are followed in
pediatric-based long-term follow-up (LTFU) programs.
These programs provide risk-based health care that
is anticipatory and proactive and that includes a
systematic plan of prevention and surveillance based
on risks associated with the cancer therapy, genetic
predispositions, lifestyle behaviors, and co-morbid
health conditions.
9
Recommendations for surveillance
are based on the Children’s Oncology Group (COG)
evidence-based guidelines.
10
The greatest challenge in
these programs is transitioning the adolescent cancer
survivor to adult-based providers in their young adult
years.
In the last 5 years, several programs have been
developed for survivors of young adult cancer. These
are either cancer-specifi c (e.g., testicular cancer
survivor program), treatment modality-specifi c (e.g.,
stem cell transplant survivor program), or more
comprehensive, including all age groups of cancer
survivors. The American Society of Clinical Oncology
(ASCO) recently has undertaken an extensive effort
to develop evidence-based guidelines for the long-
term care of adult survivors, including AYA survivors.
However, most AYA survivors are not followed in a
survivor-type program, but by primary care physicians
who often are unfamiliar with the risks associated with
AYA cancer therapy.
11
6
Rowland JH, Aziz N, Tesauro G, et al. The changing face
of cancer survivorship.
Seminars in Oncology Nursing
2001;17:236-240.
7
Hewitt M, Weiner SL, Simone JV (eds). Childhood Cancer
Survivorship: Improving Care and Quality of Life. Washington,
DC, National Academies Press, 2003.
8
Hewitt M, Greenfi eld S, Stovall E. (eds). From Cancer Patient to
Cancer Survivor: Lost in Transition. Washington, DC, National
Academies Press, 2006.
9
Aziz NM, Oeffi nger KC, Brooks S, Turoff AJ. Comprehensive
long-term follow-up programs (LTFU) for pediatric cancer
survivors.
Cancer,
in press, 2006.
10
Landier W, Bhatia S, Eshelman DA, et al. Development of
risk-based guidelines for childhood cancer survivors: the
Children’s Oncology Group Long-Term Follow-Up Guidelines.
Journal of Clinical Oncology
2004;22:4979-4990; at: www.
survivorshipguidelines.org
11
Oeffi nger KC, McCabe MS. Models for delivering survivorship
care.
Journal of Clinical Oncology
, in press, 2006.
2
Mertens AC, Yasui Y, Neglia JP, et al. Late mortality experience
in fi ve-year survivors of childhood and adolescent cancer: the
Childhood Cancer Survivor Study.
Journal of Clinical Oncology
2001;19(13):3163-3172.
3
Moller TR, Garwicz S, Barlow L, et al. Decreasing late
mortality among fi ve-year survivors of cancer in childhood and
adolescence: a population-based study in the Nordic countries.
Journal of Clinical Oncology
2001;19(13):3173-3181.
4
Fossa SD, Aass N, Harvei S, Tretli S. Increased mortality rates
in young and middle-aged patients with malignant germ cell
tumours.
British Journal of Cancer
2004;90(3):607-612.
British Journal of Cancer 2004;90(3):607-612.British Journal of Cancer
5
Robison LL, Mertens AC, Boice JD, et al. Study design and
cohort characteristics of the Childhood Cancer Survivor Study: a
multi-institutional collaborative project.
Medical and Pediatric
Oncology
2002;38(4):229-239.
B-52
Appendix B: Breakout Group Reports - Long-term Effects
B-52 Appendix B: Breakout Group Reports - Long-term Effects B-52
Report of the Adolescent and Young Adult Oncology Progress Review Group
Challenges in AYA Survivorship Research
Four broad types of studies are needed to fi ll the gaps
in our understanding of AYA survivors:
• Observational epidemiologic studies to identify
risk factors for long-term health outcomes and
potential modifying factors
• Biologic studies to assess the infl uence of the
gene environment on late effects
• Intervention studies aimed at preventing late
effects, reducing morbidity and mortality, and
enhancing quality of life
• Studies to compare different methods of caring
for AYA survivors
Perhaps the most signifi cant challenge in AYA
survivorship research is identifying a population
of survivors that is of adequate size to conduct
hypothesis-driven studies while minimizing selection
and participation biases. Several potential populations
for AYA survivorship studies exist, each with
different strengths and limitations. The Surveillance,
Epidemiology, and End Results (SEER) program
registries and state-based cancer registries are well
suited for second cancer and late mortality studies
but are limited by a lack of treatment exposure data
including chemotherapy agent and dose. In addition,
the SEER data cannot be used to study long-term
morbidity associated with cancer care. Linking SEER
with Medicaid databases may increase their usability
for some AYA studies. The NCI Cooperative Groups
(e.g., COG, Southwest Oncology Group [SWOG],
Cancer and Leukemia Group B [CALGB]) provide
large and diverse populations, including minorities,
an existing infrastructure for research, and readily
available detailed treatment exposure data. However,
most AYAO patients are not enrolled in cooperative
group protocols, survivor studies are a lower priority,
and the loss to follow-up rate is high. The CCSS
provides a unique opportunity to study survivors of
adolescent cancer (diagnosed at 15 to 20 years of
age) but does not include any young adults. Finally,
populations at single institutions are sometimes of
adequate size to conduct AYA survivorship studies.
Importantly, none of these population databases
are ideal in their current state to be used for AYA
survivorship studies. An additional challenge to this
area of study is identifying an appropriate control
group for comparison.
Priority 1
Establish a prospective database of AYA cancer
patients.
Rationale
Without prospective studies of AYA survivors, the
late effects they experience and how these relate
to treatment and individual differences will remain
unknown. The database would be used in connection
with patient-supplied follow-up information to better
understand currently recognized late effects and
those yet to be identifi ed. Specifi c treatment and
other patient information is best recorded at time
of treatment. The database must contain detailed
treatment information and include information to
permit long-term follow-up so that impact of treatment,
common risk factors, and underlying propensity
can be linked to the development of late effects
including second cancers, cardiovascular problems,
musculoskeletal problems, and fertility/gonadal
dysfunction.
Implementation Considerations/Barriers
• Suffi cient funding will be essential to support
the development and maintenance of a national
shared database with common data elements.
This effort will require a long-term commitment
of funds; the time frame for this activity will be
longer than the typical grant. Funds are needed
for shared infrastructure and to support local data
collection efforts.
• Physicians who treat AYA cancer patients,
particularly those in community settings, must
be willing to enroll patients. Some may cite
privacy concerns, others may worry that the
quality of care they provide will be critiqued. It
is likely that the participation levels of pediatric
and adult oncologists will vary. Professional
societies (e.g., ASCO) and the NCI Cooperative
Groups will be essential for building physician
willingness to participate.
• Patients must be willing to allow the recording
of initial treatment data and agree to provide
information on their long-term health status.
Several potential barriers to patient participation
exist, as well as an equal number of reasons why
Appendix B: Breakout Group Reports - Long-term Effects B-53
Report of the Adolescent and Young Adult Oncology Progress Review Group
this population might be unusually cooperative.
For example, physicians who are unwilling or
uncomfortable with participation might do a
poorer job of enrolling their patients in the study.
Conversely, AYAs’ sense of isolation and feeling
that they are unique may lead to increased
participation as a way to feel that they are part
of a community. Advocacy groups, particularly
those with an AYA focus, will be important
partners as they can encourage both patients and
providers to support this effort.
• For this effort to be successful, patients
not treated in major cancer centers must
be included. While it is easiest to enroll
patients of providers who are active research
participants and/or oncologists who are active
in national organizations such as cancer centers
or cooperative groups, late effects need to be
assessed in all patients including community
providers not involved in research. Reaching
those providers (and patients) will take extra
effort. Population-based registries such as SEER
and state registries will be important resources in
this activity.
Concrete Actions in the Next Three Years
• Convene a consensus panel to identify data
elements to be included regarding initial
treatment—chemotherapy, radiotherapy, surgery,
and other treatments. The conference also
should identify existing assessments of late
effects experienced by AYA survivors.
• Work on strategies to bring patients treated in
community settings into this partnership; explore
how population-based registries can help identify
patients treated by providers who are not active
participants in cooperative groups.
• Pilot test the system to assess ease of data
collection and feasibility of short- and long-term
follow-up.
Priority 2
Improve the long-term health care of AYA cancer
survivors.
Rationale
Most AYA cancer survivors are not followed by
clinicians familiar with cancer survivors. Risk-based
health care for AYA cancer survivors is associated with
reduced morbidity and mortality and improved quality
of life.
Implementation Considerations/Barriers
• Study design issues for risk-stratifi ed survivor
care model development and assessment.
• Lack of consensus on a standard set of outcome
measures.
• Issues in integrating innovative technology (e.g.,
cross-platform electronic health record) into care
model development and assessment.
• Relative lack of evidence-based guidelines for
survivors of young adult cancers that may lead to
premature recommendations.
Concrete Actions in the Next
Three Years/Partnerships
• Issue an NCI/Lance Armstrong Foundation
(LAF)-sponsored Request for Applications
(RFA) for “Best Practice Models for AYA
Cancer Survivors” that will fund the testing
and comparison of risk-stratifi ed models of
survivor care, incorporating methods of formal
knowledge transfer from oncology to primary
care, and using a common set of measurements
across studies. Potential partners include the
Robert Wood Johnson Foundation (chronic
disease management program), Community
Clinical Oncology Programs, and Agency for
Healthcare Research and Quality-supported
primary care practice-based research networks.
• Develop and disseminate a monograph on AYAO
survivorship. Potential partners on this project
include ASCO, American Academy of Family
Physicians, American Academy of Pediatrics,
American College of Physicians, and American
College of Obstetricians and Gynecologists.
B-54
Appendix B: Breakout Group Reports - Long-term Effects
Report of the Adolescent and Young Adult Oncology Progress Review Group
• Support initiatives to enhance the development
and dissemination of survivorship care plans.
Existing models include the IOM Implementing
Survivorship Care Planning initiative, the
Ontario Passport for Health, and LAF
LIVE
STRONG
™ notebook.
• Enhance the LIVE
STRONG
™ Web site with
dynamic question-and-answer capability and a
list of AYA LTFU programs.
• Partner with insurance companies to develop
an AYA survivor chronic disease management
program.
Priority 3
Conduct studies of AYA cancer survivors
to understand the late effects of cancer care
experienced by persons who completed cancer
treatment.
Rationale
Many gaps remain in our knowledge of the late effects
experienced by current cancer survivors. Some gaps
are due to the paucity of specifi c treatment information.
For example, SEER does not routinely collect and/
or disseminate to the research community detailed
treatment information such as chemotherapy agent
and dose, radiotherapy dose and target, or surgery.
Other gaps are due to incomplete information on
treatments received (e.g., indication that radiotherapy
was received, but no information about fi elds and
dose) or a lack of focus on the AYA population
despite available data. Obtaining knowledge about
the late effects experienced by current survivors will
inform recommendations for ongoing clinical care for
survivors and may lead to changes in primary treatment
of newly diagnosed cancer patients.
Implementation Considerations/Barriers
• Recovering suffi cient detail about primary (and
secondary) treatment may require access to
original patient charts. Depending on provider
record retention policies, this may not be
possible. At best, it will be time consuming
and diffi cult. For this reason, studies that rely
on data collection from chart-based resources
should be focused and well thought out. Much
of the cost of these studies is associated with
retrieving the original chart so it is important that
data collection be complete and accurate.
• Ideally, these studies will include controls to
enable researchers to differentiate between late
effects of cancer treatment and the normal aging
process. Options for controls include general
population controls, siblings or other close
relatives as controls, using controls from within
the cancer population but treated differently
(e.g., received radiotherapy vs. did not) and
allowing people to serve as their own controls
(e.g., sarcoma within radiation fi elds vs. outside
of radiation fi elds). Each study type has its own
strengths and weaknesses. It is important that
these studies be of high quality.
• Although the Health Insurance Portability and
Accountability Act (HIPAA) privacy provisions
do not necessarily preclude access to medical
records for research, HIPAA will increase
access barriers and may necessitate obtaining
primary consent for access. This access might
include both primary treatment information
and information on late effects. While most
follow-up studies will require patient contact,
information on patients who are lost to follow-
up will assist with the assessment of bias.
Obtaining next-of-kin consent for deceased
patients may be diffi cult, but these patients are
of high importance since non-cancer mortality
is the most extreme of late effects. Advocacy
groups will be an essential partner to help
facilitate patient willingness to participate, which
is necessary to achieve a high response rate.
• One option for conducting follow-up studies
will be to partner with cooperative groups and
assess late effects experienced by participants
in trials in which the trial contains suffi cient
numbers of people in the AYA age range.
One challenge is the lack of overlap between
COG and adult oncology trials. An additional
problem is the low participation rate in trials for
AYA populations, particularly by racially and
economically diverse populations.
• Many existing population-based data sources
that are easily accessed by researchers are
de-identifi ed (e.g., SEER, American College of
Surgeons National Cancer Data Base – NCDB);
Appendix B: Breakout Group Reports - Long-term Effects B-55
Report of the Adolescent and Young Adult Oncology Progress Review Group
these data sources would be more valuable for
studies of late effects if they were linked with
other data sources that contain information about
long-term outcomes. Depending on the source,
retrieving identifi able data will require obtaining
consent from the entities that contain the
identifi ers (e.g., individual registries including
individual hospitals that contributed to the
NCDB).
• AYA survivors tend to be mobile, both switching
providers and moving from where they lived
while undergoing treatment. Collecting high
quality patient identifi ers will facilitate follow-
up, but loss to follow-up will likely remain a
signifi cant problem. The CCSS may provide
insight into effective ways to locate those
who are lost to follow-up and methods to
enhance continued contact. Advocacy groups
will be essential to help develop methods for
maintaining long-term contact and for helping to
leverage existing technology such as the Internet
to facilitate data collection and bi-directional
information transfer.
Concrete Actions in the Next Three Years
• Issue a focused AYAO RFA for high quality
studies of late effects including second cancers,
cardiovascular morbidity/mortality, and fertility.
These studies will have to balance the need
for highly detailed information on treatment
with more general treatment information that is
population-based.
• Conduct methodologic pilot studies for
qualitative research on cancer survivors.
Qualitative approaches will give survivors
a chance to inform the research/clinical
community about the effects they attribute to
their cancer treatment. It is likely that many of
these will prove to be previously unrecognized or
under-reported effects.
• Develop a roster or repository of data sources
that can serve as a baseline for follow-up and
facilitate the use of common data elements and
methodologies while also ensuring that the
research effort is spread across the range of
issues facing long-term survivors of AYA cancer.
Conclusion
Many late effects of cancer and cancer treatment
experienced by AYA survivors have not been
characterized and are not well understood.
Mechanisms for follow-up care and education of
survivors with respect to late effects are not well
established. The fi rst and third priorities recommended
earlier are designed to create means for identifying
late effects and better understanding their causative
mechanisms. The second priority addresses strategies
for incorporating knowledge of late effects into follow-
up care of AYA cancer survivors. These strategies
include raising awareness of late effects among
survivors and caregivers, maintaining survivors’
treatment records, and developing and evaluating
evidence-based standards for survivor health care.
B-56
Appendix B: Breakout Group Reports - Long-term Effects
B-56 Appendix B: Breakout Group Reports - Long-term Effects B-56
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix C: Charge to the AYAO PRG C-1
APPENDIX C
CHARGE TO THE AYAO PRG
Background
The National Cancer Institute (NCI) supports basic, clinical, and population-based research to study the causes,
biology, prevention, early detection, diagnosis, prognosis, control, survivorship, outcomes, and treatment of cancer.
NCI’s vision for the oncology community is “a nation free from the suffering and death due to cancer by 2015
and dramatic reductions in cancer incidence.” NCI’s mission is to “reduce the burden and eliminate the adverse
outcomes of cancer by leading an integrated effort to advance fundamental knowledge about cancer across a
dynamic continuum of discovery, development, and delivery.” In an unprecedented partnership, NCI is collaborating
with the Lance Armstrong Foundation (LAF) to review the state of research on cancers that primarily affect
adolescents and young adults. LAF’s mission is to inspire and empower people affected by cancer.
The NCI, in collaboration with LAF, has established the Adolescent and Young Adult Oncology Progress Review
Group (AYAO PRG), composed of prominent members of the scientifi c, medical, and advocacy communities, to
develop a national agenda for adolescent/young adult oncology. In developing this agenda, the AYAO PRG will
solicit input from the research, clinical, and advocacy communities.
A written report describing the group’s fi ndings and recommendations will be presented to the Advisory Committee
to the Director. The PRG report will be widely disseminated, and the PRG will meet with oncology community
leaders to discuss a plan of action that will ensure that the priority areas of the PRG are well addressed.
Charge
• Assess the state of research in adolescent and young adult oncology. The primary focus will be on prevention,
diagnosis, and treatment of cancer in young adults and includes second cancers in pediatric cancer survivors
and survivorship issues related to treatment.
– Comprehensively defi ne and describe issues facing adolescents and young adults with cancer.
– Identify areas of strength, gaps, and opportunities.
• Defi ne and prioritize investment areas; compare and contrast these priorities with the NCI research portfolio.
• Prepare a written report that describes fi ndings and recommendations for meeting unmet opportunities and
needs within the construct of discovery, development, and delivery.
• Discuss a plan of action with NCI leaders and key stakeholders and funders to ensure that the priority areas
are well addressed.
• Identify and act on collaborative strategic implementation initiatives.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix D: Average Annual Percentage Change in 5-Year Relative Survival, Selected Diseases D-1
APPENDIX D
AVERAGE ANNUAL PERCENTAGE CHANGE IN 5-YEAR
RELATIVE SURVIVAL OF PATIENTS DIAGNOSED WITH CANCER
DURING 1975-1997, SELECTED DISEASES, U.S. SEER
Report of the Adolescent and Young Adult Oncology Progress Review Group
1.7%
1.6%
0.5%
1.2%
1.0%
0.5%
0.6%
0.8%
1.2%
1.6%
2.3%
2.6%
3.6%
4.1%
4.4%
3.8%
5.1%
2.1%
0%
1%
2%
3%
4%
5%
6%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Germ Cell, Trophoblastic, Other Gonadal Neoplasms
0.6%
1.6%
0.8%
-0.9%
-0.7%
-3.2%
-4.0%
-4.7%
-3.5%
-2.5%
-0.5%
0.1%
0.8%
1.0%
1.8%
1
.9%
1.0%
0.5%
-5%
-4%
-3%
-2%
-1%
0%
1
%
2%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Soft Tissue Sarcoma (includes Kaposi’s Sarcoma)
0.6%
1.6%
0.8%
-0.9%
0.6%
0.8%
1.1%
0.0%
0.3%
0.2%
0.8%
1.0%
1.2%
1.4%
2.2%
2.2%
1.1%
0.4%
-1%
0%
1%
2%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Soft Tissue Sarcoma (excluding Kaposi’s Sarcoma)
1.2%
0.8%
0.8%
0.4%
0.5%
0.4%
0.6%
0.4%
0.4%
0.5%
1.7%
1.5%
2.1%
3.0%
2.2%
2.7%
0%
4%
2%
6%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+*
Age at Diagnosis (Years)
AAPC
Hodgkin’s Lymphoma
6.3%
4.1%
2.8%
3.5%
2.5%
1.0%
-0.3%
-2.1%
-1.3%
-0.8%
0.3%
1.0%
0.7%
1.6%
1.2%
1.7%
2.4%
1.7%
1.5%
-1%
-2%
1%
0%
3%
2%
4%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Non-Hodgkin’s Lymphoma
1.7%
1.9%
3.2%
3.8%
4.8%
4.6%
0.9%
0.5%
-2.7%
0.6%
-1.0%
-0.7%
-1.1%
-2.4%
-3.2%
-1.6%
-4%
-2%
0%
2%
4%
6%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79*
80-
84
85+*
Age at Diagnosis (Years)
AAPC
Acute Lymphoblastic Leukemia
1.9%
2.0%
3.8%
3.8%
6.3%
5.2%
4.0%
2.5%
2.5%
2.0%
1.2%
1.3%
0.8%
1.2%
1.3%
1.7%
1.4%
0.2%
0%
2%
4%
6%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Leukemia
2.9%
2.1%
2.0%
1.8%
2.0%
0.7%
0.6%
0.3%
1.5%
0.7%
1.1%
1.0%
0.7%
4.1%
3.6%
3.4%
0.7%
3.2%
0%
1%
2%
3%
4%
5%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Malignant Bone Tumors
* Incomplete data.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix D: Average Annual Percentage Change in 5-Year Relative Survival, Selected Diseases D-3
0.3%
0.4%
0.3%
0.3%
0.2%
0.4%
0.7%
0.8%
1.2%
1.3%
1.4%
1.6%
1.9%
2.0%
1.8%
1.6%
1.4%
0%
0.5%
1%
1.5%
2%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Carcinomas
0.0% 0.0%
-0.2%
0.1%
0.0%
0.0%
0.0%
0.0%
0.0%
0.1%
0.2%
0.1%
0.3%
0.9%
1.0%
1.8%
2.5%
0.6%
-0.3%
0.3%
0.8%
1.3%
1.8%
2.3%
2.8%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Thyroid Cancer
0
.
6%
0.3%
0.6%
0.6%
0.6%
0.6%
0.9%
1.0%
1.0%
0.9%
1.0%
0.9%
1.0%
1.0%
0.0%
0.3%
0.6%
0.9%
1.2%
<5* 5-9* 10-
14*
15-
19*
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Breast Cancer
1.1%
1.3%
1.3%
1.4%
1.5%
1.7%
2.1%
2.2%
2.7%
1.9%
2.0%
2.7%
3.7%
4.8%
3.1%
-2.8%
-2.3%
1.6%
-3%
-2%
-1%
1%
0%
2%
3%
4%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Central Nervous System Cancer
0.9%
1.1%
3.1%
1.8%
2.2%
1.7%
0.7%
1.4%
1.4%
1.6%
1.0%
1.6%
1.2%
1.9%
2.4%
2.3%
3.7%
0.5%
0%
1%
2%
3%
4%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Renal Cancer
-0.7%
0.0%
0.3%
0.9%
0.6%
0.4%
0.5%
0.4%
0.5%
0.5%
0.4%
0.4%
0.9%
0.5%
1.0%
1.6%
0.9%
2.1%
-1.0%
-0.5%
0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Malignant Melanoma
2.4%
2.7%
0.7%
-1.2%
2.5%
4.1%
-1.4%
-1.8%
-4.8%
-0.3%
-0.7%
3.0%
1.9%
5.1%
3.8%
-2.8%
-3.9%
-6%
-7%
-5%
-3%
-2%
0%
2%
4%
3%
5%
6%
<5 5-9 10-
14
15-
19
20-
24
25-
29
30-
34
35-
39
40-
44
45-
49
50-
54
55-
59
60-
64
65-
69
70-
74
75-
79
80-
84
85+
Age at Diagnosis (Years)
AAPC
Hepatic Cancer
1%
-1%
-4%
-7.0%
* Incomplete data.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix E: Glossary of Terms and Acronyms E-1
APPENDIX E
GLOSSARY OF TERMS AND ACRONYMS
AACR American Association for Cancer Research
AAFP American Academy of Family Physicians
AAP American Academy of Pediatrics
AAPC Average annual percent change
ACCC Association of Community Cancer Centers
ACGME Accreditation Council for Graduate Medical Education
ACOG American College of Obstetricians and Gynecologists
ACoS American College of Surgeons
ACOSW Association of Clinical Oncology Social Workers
ACP American College of Physicians
ACS American Cancer Society
“aging out” When a dependent child reaches a designated age and is no longer eligible for coverage under
his/her parents’ health insurance policy.
AHIP America’s Health Insurance Plans
AHRQ Agency for Healthcare Research and Quality (HHS)
AI/AN American Indian/Alaska Native
ALL Acute lymphoblastic leukemia
AML Acute myeloid leukemia
API Asian/Pacifi c Islander
ASCO American Society of Clinical Oncology
Avascular Necrosis/ Cellular death of the components of bone, including bone marrow, due to impaired blood supply.
Osteonecrosis
AYA Adolescents and young adults; individuals 15 through 39 years of age
AYAO Adolescent and young adult oncology
Behavioral Research Research into what motivates people to act as they do. The results of such research can be
used, for example, to help persuade people to adopt healthy lifestyles and to follow screening
and treatment guidelines.
Biomarker A substance sometimes found in the blood, other body fl uids, or tissues. A high level of a
biomarker may indicate the presence of a certain type of cancer.
Biospecimen Annotation Clinical data related to the specimen and patient necessary to optimize the usefulness of the
specimen for research purposes.
Blast Cells Immature cells that normally comprise 5 percent of the bone marrow.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Bolus Infusion A dose of medication injected at one time rather than spread out in smaller doses over a period
of time.
CALGB Cancer and Leukemia Group B
Cancer Advocacy Organizations and individuals dedicated to or with an interest in communicating and stimulating
Community activities and fi scal support to benefi t individuals with cancer or at risk for cancer.
Cancer Burden The sum of the tangible and intangible costs of cancer borne by individuals, families, a specifi c
population or group, or the nation.
Cancer Care Continuum The medical and nonmedical services associated with cancer prevention, detection, diagnosis,
treatment, survivorship, and end of life care.
Cancer Health Disparities Differences in the incidence, prevalence, mortality, and burden of cancer and related adverse
health conditions that exist among specifi c population groups in the United States. These
population groups may be characterized by gender, age, ethnicity, education, income, social
class, disability, geographic location, or sexual orientation.
Carcinoma Cancer that begins in tissues that line or cover internal organs or in the skin.
Cardiotoxicity Cardiovascular damage or dysfunction that may occur as a side effect of some chemotherapy
drugs.
Caregiver A family member, signifi cant other, or other lay person who provides care and assistance to a
person with cancer.
CCC (NCI-designated) Comprehensive Cancer Center
CCCG Coalition of Cancer cooperative groups
CCOP Community Clinical Oncology Program (NCI)
CCSG Cancer Center Support Grant
CCSS Childhood Cancer Survivor Study
CDC Centers for Disease Control and Prevention (HHS)
Cervical Dysplasia Precancerous changes of the cervix. Also called cervical intraepithelial neoplasia (CIN).
Chemoprevention Use of a drug or agent to prevent a disease or medical condition.
Chemoprotectant Medications administered to patients prior to or in conjunction with chemotherapy to reduce the
risk of adverse side effects from anti-cancer drugs.
CHTN Cooperative Human Tissue Network
CIS Cancer Information Service (NCI)
CMS Centers for Medicare and Medicaid Services (HHS)
CNP Community Network Program (NCI)
COBRA Consolidated Omnibus Budget Reconciliation Act
COG Children’s Oncology Group
Consensus Panel/ A group of medical or technical experts convened to clarify issues involving the application of
Conference medical technology or research fi ndings to clinical practice.
Co-morbidities Other medical or psychosocial conditions experienced by a person with cancer.
Cooperative Groups Networks of academic biomedical institutions and physicians funded by NCI to conduct clinical
research.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix E: Glossary of Terms and Acronyms E-3
Copayment Portion of the cost of a health service for which the patient is liable; may be a fi xed dollar amount
or a percentage of the total cost.
Creditable Coverage Generally includes periods of coverage under an individual or group health plan not followed by
a break in coverage of 63 or more days.
CTEP Cancer Therapy Evaluation Program (NCI)
CTWG Clinical Trials Working Group (NCI)
Cultural and Linguistic Respect for and responsiveness to cultural and linguistic needs. “Culture” refers to integrated
Appropriateness patterns of human behavior that include the language, thoughts, communications, actions,
customs, beliefs, values, and institutions of racial, ethnic, religious, or social groups.
Cytogenetics The study of chromosomes and chromosomal abnormalities.
DoD Department of Defense
EBV Epstein-Barr virus
Embryonal Tumor A mass of rapidly growing cells that begins in embryonic (fetal) tissue. Embryonal tumors may
be benign or malignant and include neuroblastomas and Wilms’ tumors.
Empirical Research Research that uses direct or indirect observation as its test of reality.
Epigenetics The study of changes in gene silencing that occur without changes in the genes themselves.
Many genes in the body are permanently turned off as part of normal development. But
sometimes that process goes awry, turning off genes that should otherwise remain active.
This fi eld of study and its associated therapies aims to switch these genes back on as a new
approach to the treatment of aging, inherited diseases, and cancer.
Etiology The cause or origin of disease.
FDA U.S. Food and Drug Administration (HHS)
Genetic Predisposition Having one or more altered genes that increase the likelihood of developing a particular medical
or Susceptibility condition.
Genotype The genetic makeup, as distinguished from the physical appearance, of an organism or a group
of organisms.
Glucose Intolerance Several distinct disorders, of which diabetes mellitus is the most common.
Gonadal Failure Inadequate functioning of the testes or ovaries as manifested by defi ciencies in the production of
sperm or eggs or the secretion of gonadal hormones.
HBCU Historically Black Colleges and Universities
Health Services Research A multidisciplinary fi eld of inquiry, both basic and applied, that examines the use, costs, quality,
accessibility, delivery, organization, fi nancing, and outcomes of health care services to increase
knowledge and understand the structure, processes, and effects of health services for individuals
and populations.
Heterogeneity (population) A group of individuals having similarities that are strong enough to consider them a discrete
population, but also having distinct, important differences among individuals within the
population.
HHS Department of Health and Human Services
HIPAA Health Insurance Portability and Accountability Act
HPV Human papillomavirus
Report of the Adolescent and Young Adult Oncology Progress Review Group
HRQL Health-related quality of life
ICMJE International Committee of Medical Journal Editors
Incidence Number of new cases of a disease that occur in a population over a period of time.
Insurance Rating The setting of premium price classes to which an insurance company assigns individuals or
groups based on its assessment of the risk of insuring them.
IOM Institute of Medicine
ISOQOL International Society for Quality of Life Research
LAF Lance Armstrong Foundation
Late Effects Conditions that develop after the completion of cancer therapy.
Late Mortality The total number of deaths in the late stages of an ongoing treatment, or a signifi cant length of
time after treatment of an acute condition.
Long-term Effects Conditions that develop during therapy and persist after the completion of therapy.
LTFU Long-term follow-up
Medicaid A program that uses Federal and state funds to pay for medical services for low-income
individuals (Centers for Medicare and Medicaid Services, HHS).
MI Minority-serving institutions
Microsatellite Instability A change that occurs in the DNA of certain cells (such as tumor cells) in which the number of
repeats of microsatellites (short, repeated sequences of DNA) is different than the number of
repeats that was in the DNA when it was inherited. The cause of microsatellite instability may be
a defect in the ability to repair mistakes made when DNA is copied in the cell.
NAIC National Association of Insurance Commissioners
NCCN National Cancer Comprehensive Network
NCCS National Coalition for Cancer Survivorship
NCDB National Cancer Data Base
NCI National Cancer Institute (NIH)
Neuropathy Functional disturbances or pathologic changes in the peripheral nervous system.
NHLBI National Heart, Lung, and Blood Institute (NIH)
NIA National Institute on Aging (NIH)
NIH National Institutes of Health
Observational Research A type of study in which individuals are observed or certain outcomes are measured. No attempt
/Study is made to affect the outcome (for example, no treatment is given).
ONS Oncology Nursing Society
Oophorectomy Surgical removal of one or both ovaries.
Osteonecrosis See:
Avascular Necrosis
Ototoxicity Damage to auditory function that may occur as a side effect of some chemotherapy agents.
Outcome Referring to the medical, psychosocial, socioeconomic, or other result of cancer or cancer
treatment.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix E: Glossary of Terms and Acronyms E-5
PA/PAR Program Announcement
Palliative Care Care that does not have curative intent, but is focused on symptom control and patient quality of
life.
Pathogenesis The development of disease; specifi cally the cellular events, reactions, and mechanisms
occurring in the development of disease.
Patient-centered Care A system and philosophy of care that includes: (1) respect for patients’ values, preferences, and
expressed needs; (2) coordination and integration of care; (3) information, communication, and
education; (4) physical comfort; (5) emotional support—relieving fear and anxiety; and
(6) involvement of family and friends.
Patient Navigator/Coach A trained individual, often a cancer survivor or other layperson, who assists newly diagnosed
patients and their caregivers. This assistance generally begins at the point of an abnormal
fi nding and continues throughout diagnosis and the treatment process. Navigators assist
patients in fi nding needed information, making and keeping appointments, arranging supportive
services, and facilitating patient communication with the treatment team, among other duties.
Peer Review A system for evaluating research applications that uses reviewers who are the professional
equals of the applicant.
Pharmacogenetics The convergence of pharmacology and genetics dealing with genetically determined responses
to drugs.
Pharmacokinetics The activity of drugs in the body over a period of time, including the processes by which drugs
are absorbed, distributed in the body, localized in the tissues, and excreted.
Prevalence The number of all new and old cases of a disease in a defi ned population at a particular point in
time.
Prevention, primary Interventions aimed at blocking the initial onset of disease.
Prevention, secondary Interventions aimed at detecting disease in its earliest stages of development.
Prevention, tertiary Interventions targeting the post-diagnosis period.
PRG Progress Review Group
PROMIS Patient Reported Outcomes Measurement Information System
PROQOLID Patient Reported Outcomes and Quality of Life Instruments Database
Psychodevelopmental Time in life at which individuals are concerned primarily with personality, social knowledge and
Stage skills, and emotions.
PTSD Post-traumatic stress disorder
Quality of Life The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment
on the quality of life. These studies measure aspects of an individual’s sense of well-being and
ability to carry out various tasks.
Randomized Controlled A prospective study in which participants are randomly assigned to one or more groups exposed
Trial to an experimental intervention and a control group that is not exposed to the experimental
intervention.
RFA Request for Applications
RWJF Robert Wood Johnson Foundation
SARC Sarcoma Alliance for Research through Collaboration
SCHIP State Child Health Insurance Program (Medicaid)
Report of the Adolescent and Young Adult Oncology Progress Review Group
Second Cancer A second primary tumor occurring in an individual that may or may not be related to previous
cancer therapy; not a metastasis (spread) of the original tumor.
SEER Surveillance, Epidemiology, and End Results Program (NCI)
Sequelae Undesirable physical or psychosocial after-effects of disease or disease treatment.
SES Socioeconomic status. A measure of access to social and economic resources, most commonly
indicated by income, level of education, or type of occupation. Similar: socioeconomic position.
Sociocultural Referring to a highly variable complex of factors including but not limited to values, beliefs,
customs, language, communications, institutions, socioeconomic status, and education.
Stakeholder An organization, agency, individual, or group of individuals having an interest in a particular
issue, disease, or other matter.
Standard of Care Treatment that experts agree is appropriate, accepted, and widely used. Health care providers
are obligated to provide patients with the standard of care. May also be called standard therapy
or best practice.
Supportive Care Any of a broad range of medical, psychosocial, and practical interventions provided to a cancer
patient/survivor. The goal of supportive care is to prevent or treat as early as possible the
symptoms of the disease, side effects caused by treatment of the disease, and psychological,
social, and spiritual issues related to the disease or its treatment. Also called palliative care,
comfort care, and symptom management. Caregivers also may receive supportive services,
such as counseling.
Surveillance Monitoring of disease incidence, prevalence, survival, mortality, and trends. Also, monitoring of
an individual after cancer treatment for late or long-term effects, including second cancers.
Survival The period of time from cancer diagnosis until death.
Survival, disease-free/ The period of time following cancer treatment during which there is no evidence of recurrence or
event-free residual disease.
Survival, overall The percentage of people in a study, a treatment group, or a defi ned population who are alive for
a defi ned period of time, usually 5 years. Usually reported as time since diagnosis or treatment.
Individuals may still have evidence of active disease or may be disease free. Also called the
survival rate.
Survival, relative A specifi c measurement of survival. For cancer, the rate is calculated by adjusting the survival
rate to remove all causes of death except cancer. The rate is determined at specifi c time
intervals, such as 2 years and 5 years after diagnosis.
Survivorship In cancer, survivorship covers the physical, psychosocial, and economic issues of cancer, from
diagnosis until the end of life. It includes issues related to the ability to get health care and follow-
up treatment, late effects of treatment, second cancers, and quality of life. It also may include
fi nancial and legal issues.
SWOG Southwest Oncology Group
TCGA The Cancer Genome Atlas
Toxicity-related Death Mortality due to toxic effects of chemotherapy or other cancer treatment.
Translational Research Research that advances fi ndings from basic research studies into interventions or technologies
intended for use in clinical practice.
Report of the Adolescent and Young Adult Oncology Progress Review Group
Appendix E: Glossary of Terms and Acronyms E-7
Tumor Microenvironment The cells surrounding a tumor, also called the stroma, that infl uence the growth of the tumor and
its ability to progress and metastasize. The stroma also can limit the ability of therapeutics to
reach the tumor, alter drug metabolism, and contribute to the development of drug resistance.
Manipulating human/host-tumor interactions may be important in preventing or reversing
the conversion of a normal cell to a malignant one and in re-establishing normal control
mechanisms.
Underwriting The process of evaluating applications for insurance based on an established set of guidelines.
Underwriting determines the risk associated with an applicant and either assigns the applicant to
a rating class or declines to offer a policy.