Risk of Subsequent Neoplasms in Childhood Cancer Survivors After Radiation Therapy: A PENTEC Comprehensive Review

Area of Science:

• Radiation oncology
• Pediatric oncology
• Cancer epidemiology

Background:

• Childhood cancer survivors treated with radiation therapy (RT) face an increased risk of developing subsequent neoplasms (SNs).
• Understanding the dose-response relationship and modifying factors is crucial for mitigating long-term risks.

Purpose of the Study:

• To analyze the effect of RT dose on the risk of central nervous system (CNS) SNs, sarcomas, and lung cancers in childhood cancer survivors.
• To investigate how host and treatment factors modify the risk of developing these subsequent neoplasms.

Main Methods:

• A systematic literature review (1975-2022) identified 83 studies for CNS SNs, 118 for sarcomas, and 10 for lung SNs.
• Quantitative and qualitative data on SN incidence, RT dose, age, sex, chemotherapy, and latent time were extracted.
• Inverse-variance weighted linear regression was used to estimate the excess relative ratio (ERR) per Gray (Gy).

Main Results:

• Significant dose-response relationships were found for subsequent meningiomas (ERR/Gy = 0.44), malignant CNS neoplasms (ERR/Gy = 0.15), sarcomas (ERR/Gy = 0.045), and lung cancer (ERR/Gy = 0.068).
• Younger age at diagnosis and female sex were associated with increased risk for meningioma; chemotherapy (alkylating agents, anthracyclines) increased sarcoma risk.
• No significant effect of age was observed for malignant CNS neoplasms, and data were insufficient for lung cancer age effects.

Conclusions:

• A clear dose-response relationship exists between RT and the risk of CNS SNs, sarcomas, and lung SNs in childhood cancer survivors.
• Strategies limiting high-dose radiation volume, alongside consideration of age and chemotherapy, are vital for reducing SN risk.
• This Pediatric Normal Tissue Effects in the Clinic (PENTEC) analysis underscores the long-term risks associated with pediatric RT.