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Where Adolescents and Young Adults With Cancer Receive Their Care: Does It Matter?

Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio; and San Antonio Cancer Institute, San Antonio, TX

During the last 25 years, improvement in survival for young children with cancer has been striking. Survival has also increased for older adults; however, 5-year survival rates have fallen for older adolescent and young adult (AYA) cancer patients.¹ Reasons for this decline, termed the "AYA Cancer Survival Gap," remain unknown. Bleyer et al² suggested that a lower participation rate on clinical trials in this age group may partially account for poorer survival, but the reasons why remain unclear. The type of practice where cancer care is delivered may also influence clinical trial participation and outcome.

Two articles in this issue of the Journal of Clinical Oncology analyzed where older adolescents and young adults received their cancer care.^3,4 Both utilized statewide, population-based cancer registries to describe the referral patterns for older AYAs with cancer. Newly diagnosed AYAs with cancer were categorized by whether or not they received their care at institutions that participate in the Children's Oncology Group (COG).

Albritton et al³ identified characteristics predictive of receiving care at a pediatric oncology versus medical oncology treatment program. Whether care was delivered at Utah's only pediatric cancer treatment program, the Primary Children's Medical Center (PCMC; Salt Lake City), was determined for all incident cancer cases aged 0 to 24 years from the Utah Cancer Registry. Overall, 34% of older adolescents aged 15 to 19 years were seen at PCMC, whereas 97% of children age 0 to 9 years and 82% of children 10 to 14 years were seen at PCMC. The rate at which older adolescents were cared for at a pediatric center varied by diagnosis: 29% for lymphoma, 34% for brain tumors, and 53% for leukemias.

Howell et al⁴ found that 87% of young patients 0 to 14 years in Georgia were seen at one of the five COG-affiliated institutions in the state. Compared with younger patients, only 36% of 15- to 19-year-olds were seen at COG institutions. In an earlier analysis of Surveillance, Epidemiology, and End Results (SEER) cases from 1992 to 1997, Liu et al⁵ reported that only 24.4% (723 of 2968) of 15- to 19-year-olds were seen at former legacy Children's Cancer Group or Pediatric Oncology Group institutions.

For younger children with cancer, clinical trial participation is associated with a survival advantage.^6,7 Large-scale outcome evaluations for AYAs have not been performed. Historically, although younger patients seen at pediatric oncology centers were more likely to be enrolled onto clinical trials, fewer trials may be available for AYA patients. In an evaluation of available National Cancer Institute–sponsored clinical trials, 677 of 703 active protocols had age eligibility restrictions that excluded a portion of the AYA population.⁸

It is extremely difficult to identify major barriers to participation on clinical trials for AYAs from registry information alone, and strong evidence linking improved survival with clinical trial participation for AYAs is missing. Howell et al⁴ reported that 5-year survival rates in Georgia were not significantly associated with sites where care was delivered, although there was a nonsignificant trend toward better survival at COG institutions for all malignancies except non-Hodgkin's lymphoma, germ cell tumors, and carcinomas. Unfortunately, retrospective reviews using secondary data sources limit the availability of critical data elements needed to accurately characterize the specific treatment regimens and outcomes. Thus, we are limited to correlational comparisons to infer a cause-and-effect relationship between site of care, participation on trials, and outcome for AYAs with cancer.

A combination of factors is likely to contribute to the AYA gap, including limited access to state-of-the-art therapy, lower participation on clinical trials, unfavorable tumor biology, variation in response to therapy, and differences in supportive care practices. Most importantly, pediatric oncologists tend to use more aggressive treatment plans with almost universal curative intent. Triage to risk-based treatment regimens requires sophisticated and rapid diagnostic biologic characterization of the tumor at diagnosis, a typical feature of pediatric oncology treatment programs. If AYAs are not treated at such programs, access to biologically targeted treatment may be restricted.

The analyses by Albritton et al³ and Howell et al⁴ relied exclusively on existing registry data. The use of population-based registries minimizes potential referral bias common in studies from individual centers or from clinical trials consortia. The population-based registry infrastructure in North America varies from state to state and province to province, although all belong to the North American Association of Central Cancer Registries, which sets minimum data collection standards. Data from the SEER program were used to identify the AYA gap.² However, population-based registries typically do not include the important biologic information needed to fully characterize malignancies. Although outcome data are collected from a number of states including those participating in SEER program, it is not routinely collected by most state registries.

The COG has created the Children's Cancer Research Network (CCRN), which may someday provide a mechanism to link records for patients treated at COG centers to North American population-based registry information.⁹ This CCRN initiative would bring together well-characterized COG clinical patient data on outcome, tumor biology information derived from biorepositories, and regimen-specific treatment information with existing population-based cancer registry information.

To address the unique aspects of cancer in the adolescent and young adult, the COG formed the Adolescent and Young Adult Committee in 2000. Research priorities include gaining a better understanding of the unique biologic characteristics of cancers that affect the AYA population. The AYA Committee is enhancing opportunities for participation on clinical trials by increasing the number of new trials available for this age group, including new combined therapeutic protocols with the adult cooperative groups; so far, combined protocols have been developed for sarcoma, melanoma, acute lymphoblastic leukemia, and Hodgkin's lymphoma. However, the likelihood of continued cooperative development of combined protocols is threatened with the current severe decrease in research funding for the all NCI-sponsored cooperative groups. The AYA Committee seeks to identify and reduce barriers to enrollment onto protocol therapy as well as improve adherence to prescribed regimen (a particularly difficult challenge in this age group). Interventions administered during adolescence can have dramatic effects on survival and quality of life across the life span. The AYA Committee has developed research aimed at improving psychosocial support during therapy, preventing treatment-related sequelae, increasing the continuity of health care as adolescents transition into adulthood, and increasing knowledge and practice of healthy dietary and physical exercise lifestyle habits.

Many of the special research and care needs for AYAs with cancer were identified by the Adolescent and Young Adult Oncology Progress Review Group (PRG),⁸ cosponsored by the NCI and the Lance Armstrong Foundation (Austin, TX). They include development of resources to better identify AYA cases in the population; characterization of biologic differences between AYAs and other age groups that may predict outcome disparities; and provision of services to support the long-term psychosocial, preventive, and surveillance needs of survivors. In November 2006, the Lance Armstrong Foundation sponsored a follow-up meeting with scientists and community leaders to develop an implementation plan for the PRG recommendations. Teaming with a major advocacy organization like the Lance Armstrong Foundation will increase the likelihood that this PRG will have a tangible impact.

Ensuring that AYAs with cancer receive the best available care is a first step aimed at eliminating the AYA gap. Referral to pediatric treatment programs or to emerging AYA oncology programs is likely to improve access to state-of-the-art therapies and increase clinical trials participation. The articles in this issue of the Journal show that a substantial proportion of AYAs with malignancies are not seen at pediatric treatment centers, programs that have traditionally placed a great emphasis on enrolling all eligible patients onto clinical trials. At present, given our research infrastructure deficiencies, we cannot fully explain why AYAs are not enrolled onto clinical trials or whether increased participation will actually result in improved outcome. To avoid reliance on correlative comparisons of limited registry data, large population-based cohorts of well-characterized AYAs with cancer should be prospectively tracked from diagnosis through treatment and into long-term survivorship. However, given the increasingly limited federal funding environment for cancer cooperative group research, it is difficult to imagine this happening unless other research support mechanisms can be involved.

The crisis of having 45 million uninsured Americans is compounded for AYAs with cancer, many of whom are no longer covered by their parents' health care insurance policies, and the majority of whom will be large consumers of health care services to manage cancer- and treatment-related late effects over many decades of survivorship. We are in our infancy in understanding the unique characteristics that distinguish adolescent and young adult malignancies from cancers that occur in younger children and older adults. Developing the appropriate research infrastructure is the key to accelerating our understanding of cancers in the AYA population. Reducing outcome disparities for AYAs with cancer should be a national priority.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Bleyer A, O'Leary M, Barr R, et al: Cancer Epidemiology in Older Adolescents and Young Adults 15 to 29 Years of Age, Including SEER Incidence and Survival: 1975-2000. Bethesda, MD, National Institutes of Health, 2006

2. Bleyer A: Older adolescents with cancer in North America deficits in outcome and research. Pediatr Clin North Am 49:1027-1042, 2002[CrossRef][Medline]

3. Albritton KH, Wiggins CH, Nelson HE, et al: Site of oncologic specialty care for older adolescents in Utah. J Clin Oncol 25:4616-4621, 2007[Abstract/Free Full Text]

4. Howell DL, Ward KC, Austin HD, et al: Access to pediatric cancer care by age, race, and diagnosis, and outcomes of cancer treatment in pediatric and adolescent patients in the state of Georgia. J Clin Oncol 25:4610-4615, 2007[Abstract/Free Full Text]

5. Liu L, Krailo M, Reaman GH, et al: Childhood cancer patients' access to cooperative group cancer programs: A population-based study. Cancer 97:1339-1345, 2003[CrossRef][Medline]

6. Meadows AT, Kramer S, Hopson R, et al: Survival in childhood acute lymphocytic leukemia: Effect of protocol and place of treatment. Cancer Invest 1:49-55, 1983[Medline]

7. Wagner HP, Dingeldein-Bettler I, Berchthold W, et al: Childhood NHL in Switzerland: Incidence and survival of 120 study and 42 non-study patients. Med Pediatr Oncol 24:281-286, 1995[Medline]

8. Adolescent and Young Adult Oncology Progress Review Group: 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. Bethesda, MD, National Cancer Institute, 2006

9. Ross JA, Severson RK, Pollock BH, et al: Childhood cancer in the United States: A geographical analysis of cases from the Pediatric Cooperative Clinical Trials groups. Cancer 77:201-207, 1996[CrossRef][Medline]

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