Long-term effects of radiation exposure among adult survivors of childhood cancer: results from the childhood cancer survivor study

Abstract

In the last four decades, advances in therapies for primary cancers have improved overall survival for childhood cancer. Currently, almost 80% of children will survive beyond 5 years from diagnosis of their primary malignancy. These improved outcomes have resulted in a growing population of childhood cancer survivors. Radiation therapy, while an essential component of primary treatment for many childhood malignancies, has been associated with risk of long-term adverse outcomes. The Childhood Cancer Survivor Study (CCSS), a retrospective cohort of over 14,000 survivors of childhood cancer diagnosed between 1970 and 1986, has been an important resource to quantify associations between radiation therapy and risk of long-term adverse health and quality of life outcomes. Radiation therapy has been associated with increased risk for late mortality, development of second neoplasms, obesity, and pulmonary, cardiac and thyroid dysfunction as well as an increased overall risk for chronic health conditions. Importantly, the CCSS has provided more precise estimates for a number of dose-response relationships, including those for radiation therapy and development of subsequent malignant neoplasms of the central nervous system, thyroid and breast. Ongoing study of childhood cancer survivors is needed to establish long-term risks and to evaluate the impact of newer techniques such as conformal radiation therapy or proton-beam therapy.

FIG. 1

Relative risk with 95% confidence intervals of subsequent glioma, meningioma (open boxes, mean observed relative risk for meningioma; closed boxes, mean observed relative risk for glioma; solid line, fitted line for meningioma risk; hatched line, fitted line for glioma risk), and thyroid neoplasms (solid line represents linear dose–response model for relative risk, hatched line represents linear exponential dose–response model for relative risk) within the Childhood Cancer Survivor Study by radiation dose. Reprinted with permission from J. Natl. Cancer Inst. 98, 1528–1537 (2006) and from Lancet 356, 2014–2023 (2005).

FIG. 2

Fitted breast cancer risk by radiation dose to the breast and ovary. Reprinted with permission from J. Clin. Oncol. 27, 3901–3901 (2009).

FIG. 3

Model-based estimates of linear changes in mean body mass index (BMI) at baseline and follow-up for 706 survivors of acute lymphoblastic leukemia treated with >20 Gy cranial radiation compared to siblings. Reprinted with permission from J. Clin. Oncol. 26, 4639–4645 (2008).

FIG. 4

Cumulative incidence of lung fibrosis, chronic cough, and exercise induced shortness of breath in the CCSS cohort with increasing time from diagnosis based on exposure to chest radiation (XRT), pulmonary-toxic chemotherapy, both or neither. Reprinted with permission from Cancer 95, 2431–2441 (2002).

FIG. 5

Probability of developing an underactive thyroid after diagnosis of Hodgkin lymphoma according to dose of thyroid radiation (RT).

FIG. 6

Relative risk with 95% confidence intervals of developing a chronic medical condition (grade 1–4, grade 3 or 4, ≥2 conditions) based on radiation exposure (RT) compared to siblings.