Dr. Barr is cochair of the Canadian National Task Force on Adolescent and Young Adult Cancer.
The articles in this supplement represent presentations and discussions at the “International Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada” that was held in Toronto, Ontario, March 11-13, 2010.
Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada, Supplement to Cancer.
With respect to matters pertaining to cancer, childhood is defined as ages 0 to 14 years, and a classification of the malignant diseases affecting this age group has been adopted internationally.1 There is growing acceptance that, for similar purposes, adolescence encompasses the age range from 15 to 19 years,2 but there is much less agreement on the upper age limit for young adults. In Europe, this has been set at age 24 years in the context of Eurocare3; and it has been set at age 29 years in the United States by the Surveillance Epidemiology and End Results (SEER) Program4 and in Canada by the Canadian Cancer Society.5 However, the Progress Review Group, which represents a collaboration between the US National Cancer Institute and the Lance Armstrong Foundation, sets the upper age limit for young adults at 39 years.6 These distinctions have major implications for resource requirements in clinical programs devoted to the special needs of adolescents and young adults (AYA) with cancer, eg, extending the age limit from 24 years to 29 years doubles the number of incident cases (Table 1).
Table 1. Incidence of Cancer in Adolescents and Young Adults
Age Range, y
Rate (per Million per Year)
Data were approximated from the Surveillance, Epidemiology, and End Results (SEER) database (see Bleyer A, O'Leary M, Barr R, Ries LAG, eds. Cancer Epidemiology in Older Adolescents and Young Adults 15-29 Years of Age, Including SEER Incidence and Survival: 1975-2000. NIH Pub. No. 06-5767. Bethesda, MD: National Cancer Institute; 20064).
Taking a global perspective, it has been estimated that there are some 350,000 new diagnoses of cancer annually in the group ages 15 to 29 years and an additional 650,000 diagnoses in the group ages 30 to 39 years (C. Stiller, unpublished results). The international pattern of cancer incidence in adolescents is highly variable,7 and that for young adults also is likely to vary. Furthermore, because the majority of these incident cases occur in low-income countries, many in this group of 1 million probably are never diagnosed, and most receive inadequate therapy. Even in more privileged, industrialized societies, cancer is the commonest cause of death in the group ages 15 to 39 years after homicides, suicides, and unintentional injury (accidents).8
Biology and Survival
The distribution of malignant diseases in AYA is different from that in children and older adults and varies substantially within the AYA age cohort4 and in the same age cohort in different parts of the world.7 A classification system particular to AYA has been proposed.9 In addition, it is increasingly clear that the biology of an individual disease also is distinctive in these different age populations,10 with obvious implications for selecting optimal therapy and for long-term outcomes. In Europe11 and North America,4, 5 5-year survival rates >80% are well recorded in the AYA population—rates that are even higher than those for cancer in childhood. However, this overall statistic is an average of 2 very different circumstances. The survival rates for Hodgkin lymphoma, testicular tumors, thyroid cancer, and melanoma, which together account for >40% of the incident cases among individuals ages 15 to 29 years, exceed 90%; but, for the remaining diagnostic groups, the 5-year survival rates range from 40% to 75%.4, 5, 11 Moreover, differences between countries in survival rates for cancer overall in AYA can be influenced considerably by differences in proportionate disease distribution, as in the phenomenon of “apples, oranges, and melanoma” (Fig. 1). Thus, in tackling the challenge of apparently disappointing improvements in survival rates, measured as the average annual percentage change,12 it will be important to dissect the burden of diseases and compare like with like. The focus of attention should be on those diseases with survival rates <90%.
Health Care System Determinants of Clinical Outcomes
Among the numerous factors contributing to this debate is the locus of care for AYA with cancer. This is an important determinant of access to age-appropriate and disease-appropriate health care systems and providers; infrastructure, such as physical facilities; and treatment, including clinical trials. Even within the narrow age range of adolescence, as exemplified by a study in Ontario,13 the proportion of newly diagnosed patients who receive care in an institution with expertise in pediatric oncology falls off dramatically with increasing age. A similar phenomenon has been described in Italy14 and in the state of Victoria, Australia,15 with the minority of incident cases in the group ages 15 to 19 years attending institutions in the national pediatric oncology consortium. Why does this matter? Adolescents who receive their cancer care in children's hospitals are an order of magnitude more likely to be enrolled on a clinical trial than those who receive their care elsewhere,14-16 although there appears to be an overall dearth of accrual of AYA to brain tumor trials.15, 17 Because pediatric protocols for some diseases offer survival advantages for AYA over those designed for older patients, eg, acute lymphoblastic leukemia,18 the locus of care for these young patients obviously is a major determinant of clinical outcome. Conversely, health care teams who are more experienced in diseases with greater prevalence among older patients, such as carcinomas, should be engaged in the management of AYA who have these diseases.19 It also must be recognized that the case for survival advantage by enrolment in clinical trials has been subject to challenge.20
Changes to the system and the care of AYA patients are taking place in some countries. The expanding network of centers in the United Kingdom, established by the Teenage Cancer Trust (Fig. 2), now provides care to more than half of the population of AYA with cancer (M. Whiteson, unpublished results ), and the National Cancer Research Institute has established a Teenage and Young Adult Clinical Studies Development Group.21 Furthermore, the accrual of AYA to clinical trials in the United States has increased in recent years, in contrast to the rates for children and older adults,22 likely reflecting the increasing collaboration between the Children's Oncology Group and adult cancer cooperative groups. A similar improvement, particularly with respect to sarcomas, has been observed in Europe.22 The National Institute for Clinical Excellence in the United Kingdom noted that all pediatric and adolescent patients should be offered entry to any clinical trial for which they are eligible.23
Survivorship, Research Commitment, and Advocacy
The burden of morbidity and premature mortality among adult survivors of cancer in childhood has been well reported by investigators of the Childhood Cancer Survivor Study in the United States.24, 25 The Institute of Medicine of the National Academies has addressed the challenges of cancer survivorship in detail.26, 27 In addition, the National Cancer Institute established an Office of Cancer Survivorship in 1996, and its first director was a pediatric oncologist. Attention has been drawn to the need for quality adjustment of survival duration based on measures of health-related quality of life.28 Several of these measures are suitable for use in the AYA population,29, 30 and a few (preference-based measures) can be used for cost-utility analyses in economic evaluation of cancer treatment programs.31 The case for a variable cost per quality-adjusted life year threshold was made recently.32
In October 2009, the Canadian Cancer Research Alliance, consisting of more than 20 member organizations, issued a report on the investment in research on cancer in childhood and adolescence for the period from 2005 to 2007. More than 7000 peer-reviewed projects were included in that analysis.33 The report identified a total of $38 million that had been invested in this area, representing $1 in every $30 of total cancer research support that exceeded $1 billion. This was proportionately double the overall investment based on incidence. It was revealed that the major foci of the investments were cancer biology, treatment, and research, and there was virtually no investment in research on cancer prevention in this age group.
Yet, there are obvious targets for cancer prevention in the AYA population that have been identified for more than a decade. These include limitation of solar exposure34-36; cervical cancer screening,37, 38 especially in populations with high prevalence rates39; vaccines for human papillomavirus (HPV) and hepatitis; and tobacco use, including the oral, smokeless variety.40 Programs aimed at particular populations, such as Native Americans41 and African Americans,42 have been devised. Hepatitis and HPV vaccination provide further effective strategies. Of course, it is especially important to develop secondary prevention programs for AYA cancer survivors.43, 44
There are no more important agents of change than the community of advocacy groups, exemplified by the Teenage Cancer Trust in the United Kingdom, CanTeen in Australia, and the Lance Armstrong Foundation (LAF) based in the United States, and the LAF currently has assumed a global role.45 Collaboration with health care providers, as in the AYA initiative of the International Society of Pediatric Oncology,46 can heighten awareness considerably and lead to cooperative endeavors that will forge meaningful advances in the field of AYA oncology. The Progress Review Group in the United States and the National Task Force in Canada are but 2 examples of collaboration between the various health care providers and other interested stakeholders. We are in the “adolescence of young adult oncology,”47 and much growth and development remains to be accomplished. In that continuing endeavor, we should heed the simple but eloquent mantra that “cure is more than the eradication of cancer…cure is the restoration of health.”48
However they are defined as an age group, a large number of AYA with cancer in the world either do not come to diagnosis or receive inadequate therapy. For those who live in affluent societies, there are common challenges relating to access to optimal care, including therapeutic clinical trials that take into account the biologic distinctions of the malignant diseases that occur in AYA. Beyond the completion of active treatment, provision of appropriate survivorship programs remains highly variable and often inadequate. Research priorities can be defined, but additional resources are required to address them. Improving the future for AYA with cancer will need the combined efforts of survivors, groups of advocates, organizations of health care providers, and other stakeholders in effective interactions with policy makers and administrators to make sustainable change happen.
Funding for the National Task Force on Adolescents and Young Adults with Cancer has been made possible by a financial contribution from Health Canada through the Canadian Partnership Against Cancer. Funding for the workshop was provided by C17; the Advisory Board of the Institute for Cancer Research at the Canadian Institutes for Health Research (CIHR); the Public Health Agency of Canada; the Ontario Institute for Cancer Research; the Meetings, Planning, and Dissemination Grants program of the CIHR; the Terry Fox Research Institute; LIVESTRONG, formerly the Lance Armstrong Foundation; the Canadian Cancer Society Research Institute; Young Adult Cancer Canada; Hope and Cope; and the Comprehensive Cancer Centre at the Hospital for Sick Children, Toronto, in addition to the support provided by the Canadian Partnership Against Cancer to the Task Force on Adolescents and Young Adults with Cancer.