An analysis of factors affecting survival in adolescents and young adults with cancer


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David Thomas
Peter MacCallum Cancer Centre, Melbourne, Australia

Abstract

Adolescents and young adults (AYA) with some cancers fare substantially worse than children or older adults with the same diseases. These diseases include the bone sarcomas, Ewing sarcoma, Hodgkin lymphoma, rhabdomyosarcoma, some epithelial cancers, and acute lymphoblastic leukemia. This effect may be due to differences in stage at presentation, the type and effectiveness of treatment, or in cancer biology. I will discuss evidence supporting substantial differences in cytotoxic pharmacology that occur with increasing age, which may account in part for these survival differences. There is additional indirect evidence that participation in clinical trials may account for some of the survival gap, through the necessity for clinicians to extrapolate inappropriately from the findings from clinical studies conducted in non-AYA populations. However, the contributing factors appear to vary by cancer subtype. For example, in colorectal cancer there is evidence that advanced stage at presentation may account for differences in outcomes for AYA compared to older patients. By contrast, the efficacy of chemotherapy in either adjuvant or advanced colorectal cancer appears comparable in younger and older populations, and participation of AYA in clinical trials appears at least proportionate to colorectal cancer incidence in this group. In other cancer types, such as rhabdomyosarcoma and ALL, cancer biology clearly changes with age, and it is doubtful whether these cancers merit the same name in AYA as in children. The role of inherited cancer risk has not sufficiently discussed in AYA oncology, and has implications for both long-term survival as well as reproductive choices and treatment options. Taken together, these findings strongly suggest opportunities for clinical intervention which may relatively simply contribute to improved survival, as well as setting challenges to unlock the biological differences across the AYA cancer spectrum.