Risk of Subsequent Neoplasms in Childhood Cancer Survivors After Radiation Therapy: A PENTEC Comprehensive Review.
Level 3 - non-randomized controlled study
Systematic review of observational cohort and case-control studies
PubMed 37777927 · doi:10.1016/j.ijrobp.2023.07.025
What was done
A Pediatric Normal Tissue Effects in the Clinic (PENTEC) systematic review evaluated studies published from 1975 to 2022 on subsequent neoplasms in childhood cancer survivors who received radiation therapy. Quantitative and qualitative data were extracted from 86 studies for central nervous system (CNS) neoplasms, 118 for sarcomas, and 11 for lung cancer. Inverse-variance weighted linear regression was used to estimate excess relative risk per Gray (ERR/Gy), excess absolute risks, and the modifying effects of age, sex, and chemotherapy.
What was found
Linear dose-response relationships were observed across all evaluated neoplasms. The estimated ERR/Gy was 0.44 (95% CI, 0.19-0.68) for meningiomas, 0.15 (95% CI, 0.11-0.18) for malignant CNS neoplasms, 0.045 (95% CI, 0.023-0.067) for sarcomas, and 0.068 (95% CI, 0.03-0.11) for lung cancer. Younger age at primary diagnosis increased the risk of subsequent meningioma and sarcoma, but not malignant CNS neoplasms (insufficient data for lung cancer). Females had a higher risk of meningioma than males (odds ratio 1.46, 95% CI, 1.22-1.76, P < .0001), with no significant sex differences for the other neoplasms. Alkylating agents and anthracyclines were associated with increased sarcoma risk, but specific chemotherapy associations were not observed for CNS or lung neoplasms.
Why it matters
This review provides quantitative estimates of radiation-induced secondary cancer risk per Gray in pediatric cancer survivors. It supports the importance of conformal radiation delivery to reduce normal tissue exposure and lower long-term secondary cancer risks.
Limits
The analysis relies on heterogeneous observational studies spanning nearly five decades, during which radiation techniques and systemic therapies evolved substantially. Total individual patient counts were not reported in the abstract, and data were insufficient to assess the role of age at exposure for lung cancer risk.