Collaborative Research in Childhood Cancer Survivorship: The Current Landscape

Abstract

Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk for premature death. Furthermore, clear associations exist between specific therapeutic exposures and the risk for a variety of long-term complications. The entire landscape of health issues encountered for decades after successful completion of treatment is currently being explored in various collaborative research settings. These settings include large population-based or multi-institutional cohorts and single-institution studies. The ascertainment of outcomes has depended on self-reporting, linkage to registries, or clinical assessments. Survivorship research in the cooperative group setting, such as the Children's Oncology Group, has leveraged the clinical trials infrastructure to explore the molecular underpinnings of treatment-related adverse events, and to understand specific complications in the setting of randomized risk-reduction strategies. This review highlights the salient findings from these large collaborative initiatives, emphasizing the need for life-long follow-up of survivors of childhood cancer, and describing the development of several guidelines and efforts toward harmonization. Finally, the review reinforces the need to identify populations at highest risk, facilitating the development of risk prediction models that would allow for targeted interventions across the entire trajectory of survivorship.

Fig 1.

Cumulative prevalence of health conditions in 1,713 adults from the St Jude Lifetime Cohort.

Fig 2.

Risk of subsequent malignant neoplasms by radiation dose for (A) brain tumors and (B) breast cancer.

Fig 3.

All-cause mortality among 5-year survivors from the Childhood Cancer Survivor Study.

Fig 4.

Genetic susceptibility to anthracycline-related cardiotoxicity: (A) CBR3 genotype and risk of cardiomyopathy after exposure to low-to-moderate dose anthracyclines and (B) HAS3 genotype and risk of cardiomyopathy after exposure to high-dose anthracyclines.