Assessment of the risk of developing second tumors after pediatric craniospinal irradiation.
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INTRODUCTION/BACKGROUND: Pediatric craniospinal irradiation is associated with a potential long-term risk of radiation-induced second malignancies because of the greater radiosensitivity and life expectancy of pediatric patients. This study aimed to estimate the incidence and mortality risk of second tumors after pediatric craniospinal radiotherapy, comparing Three-Dimensional Conformal Radiotherapy (3DCRT) and Volumetric Modulated Arc Therapy (VMAT). METHODS: A structured literature review with systematic search and study selection was conducted following Preferred Reporting Items for Systematic and Meta-Analyses Search (PRISMA-S) principles to identify published dosimetric studies on pediatric craniospinal irradiation. Mean absorbed dose values for organs at risk were extracted from the included studies and used to estimate lifetime attributable risk (LAR) of cancer incidence and mortality based on the Biological Effects of Ionizing Radiation VII (BEIR VII) report, according to organ, sex, and age at exposure. Deterministic sensitivity analyses were performed using the original and redistributed BEIR VII coefficients for the residual category "other cancers," as well as dose variability scenarios based on Dmean - SD, Dmean, and Dmean + SD. RESULTS: Two studies were included in the final review. VMAT was associated with lower mean absorbed doses for the thyroid, esophagus, heart, liver, lungs, pancreas, bladder, rectum, and eyes, whereas 3DCRT showed lower absorbed doses for the kidneys, intestine, gonads, breast, and lenses. For both techniques, the thyroid, lungs, esophagus, and breast showed the highest estimated incidence and mortality risks, whereas the lowest risks were generally observed for the gonads, rectum, bladder, and kidneys. Estimated risk decreased with increasing age at exposure and was generally higher in females. Sensitivity analyses showed that redistribution of the pooled BEIR VII "other cancers" coefficient substantially reduced absolute LAR values for residual-category organs without materially changing the overall comparative pattern between 3DCRT and VMAT. DISCUSSION: These findings suggest that VMAT may reduce estimated long-term risk for several organs, although not uniformly across all organs at risk. The results should be interpreted as comparative model-based estimates, because they were derived from literature-based dose data and BEIR VII risk modelling rather than patient-specific dosimetry. CONCLUSION: This study provides a comparative and exploratory model-based assessment of second cancer risk after pediatric craniospinal radiotherapy. The findings support the importance of treatment technique selection in pediatric radiotherapy, while indicating that future studies should incorporate individualized treatment planning data and, when feasible, Monte Carlo-based dose reconstruction to improve the precision of absolute risk estimates. PLAIN LANGUAGE SUMMARY: Radiation treatment in children can sometimes increase the risk of developing a second cancer later in life. This study reviewed published research and used dose data to estimate longterm cancer risks from two different radiation therapy techniques used for treating the brain and spine in children. This study found that one technique often gave lower doses to several organs, while the other gave lower doses to some different areas, and risk varied by organ, age, and sex. This matters because understanding these differences can help clinicians choose treatment approaches that may reduce longterm risks for children.