Why the lack of Progress in Older Adolescents and Young adults with cancer

Absolute differences in survival between younger patients and adolescent and young adult patients are probably due to a combination of biologic and therapeutic differences, some immutable. However, the marked disparity in survival improvement over time suggests mutable changes disproportionably rendered.

Proposed explanations apply to the patient, healthcare profession, family/community, and society/culture in general [24]. The patient category can be subdivided further into biologic/physical, psychologic/emotional

Figure 5.5

Comparison in males and females with invasive cancer of average annual percent change from 1975 to 1997 in the 5-year survival rate (United States SEER program). Modified from Bleyer [26]

Figure 5.6

Correlation of national cancer mortality rate reduction in the United States as a function of age at death, with the rate of improvement in survival duration as a function of age at diagnosis (data from the United States Census Bureau and United States SEER program)

spiritual, economic/financial, and social factors. Biologic factors include the unique physiologic and pharmacologic characteristics of adolescent and young adult patients and their cancers. The health-care profession explanation includes a lack of awareness by general healthcare providers and of training, knowledge, and experience by oncology specialists. There is no other age during which the time to diagnosis is longer, fewer tumor specimens are available for transla-tional research, or clinical trial participation is lower [11]. The family/community category involves family members and knowledge workers who lack awareness of the problem. Societal issues consist of the challenges societies face in providing for adolescent and young adult healthcare needs. Institutions of higher learning do not have cancer awareness as an essential educational or health evaluation component.

The issue of clinical trial participation seems paramount, since failure to investigate a disease in an age group in which it is prevalent or different is likely to limit the progress that can be made in that group. "No research, no gain" is the explanation. In the United States, the pace of improvement in the 5-year survival rates from sarcoma over the past quarter century has been far less above age 15 years than in younger patients, and this age-dependent pattern is statistically correlated with the rate of clinical trial activity [8]. A report from Australia documented a sharp falloff in bone sarcoma patients entered onto clinical trials above age 15 years, in association with a drop in survival rate [25].

Although the correlation of outcome improvement with clinical trial participation is not proof of a cause-and-effect relationship, there are reasons to believe that failure to study cancer therapies in specific age subgroups does explain, at least in part, why progress in the age group has fallen behind that achieved in other age groups that have had higher rates of clinical trial participation. The correlation of outcome improvement with clinical trial participation underscores the value of clinical trials in cancer research.

The above considerations suggest several solutions:

1. Societal/cultural: improve awareness of the adolescent and young adult cancer problem.

2. Family/community: improve awareness and healthcare insurance to reduce delays in diagnosis and permit participation in clinical trials.

3. Professional: increase awareness and training, and the availability, importance and utilization of clinical trials [15].

4. Personal/patient: overcome invincibility ideation and emphasize importance of health-care and health-care insurance. Another conceptual approach to overcoming the barriers to clinical trial participation faced by adolescent and young adult patients is provided in Table 5.1.

Reversing the trend and allowing older adolescents and young adults to catch up with the progress made in younger and older patients will require a comprehensive effort by multiple organizations, including the federal government, the insurance industry, service groups, the clinical trials cooperative groups, the pedi-atric academic societies, community agencies, and health-care providers. A multipronged approach to problem solving will be required, beginning with public and professional awareness initiatives such as this report.

In 2000, the Adolescent and Young Adult Initiative of the Children's Oncology Group and the NCI was established as a means to increase the enrollment of adolescents and young adults in cancer clinical trials. This initiative aims to bring advances in cancer education, prevention, and treatment - including educational, social, and emotional development - to this segment of the North American population, and to member sites in Australia, New Zealand, and Europe, whose progress in cancer outcome has fallen behind that achieved in younger and older patients.

The initiative includes several strategies. In all of the pediatric group protocols for malignancies that sub-stantively overlap young adult patients, such as leukemia, Hodgkin lymphoma and the sarcomas, the upper age limit has been raised to 30, 40, or 50 years, depending on the disease. The pediatric group has also opened adult cooperative group trials in melanoma. Reciprocally, an adult cooperative group has opened the pedi-atric cooperative group trial in Ewing sarcoma. Plans are underway for the pediatric and adult groups to develop and open trials together in other sarcomas.

Other targets for mutual development include ALL, Hodgkin lymphoma, non-Hodgkin lymphoma, and hepatic cancer.

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