Abstract

Purpose:To examine how much lifetime attributable risk (LAR) as an in silico surrogate marker of radiation‐induced secondary cancer would be lowered by using proton beam therapy (PBT) in place of intensity modulated x‐ray therapy (IMXT) in pediatric patients.Methods:From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: a) brain, head, and neck, b) thoracic, c) abdominal, and d) whole craniospinal (WCNS) irradiation. IMXT was re‐planned using the same computed tomography and region of interest. Using dose volume histogram (DVH) of PBT and IMXT, the LAR of Schneider et al. was calculated for the same patient. The published four dose‐response models for carcinoma induction: i) full model, ii) bell‐shaped model, iii) plateau model, and ix) linear model were tested for organs at risk. In the case that more than one dose‐response model was available, the LAR for this patient was calculated by averaging LAR for each dose‐response model.Results:Calculation of the LARs of PBT and IMXT based on DVH was feasible for all patients. The mean±standard deviation of the cumulative LAR difference between PBT and IMXT for the four categories was a) 0.77±0.44% (n=7, p=0.0037), b) 23.1±17.2%,(n=8, p=0.0067), c) 16.4±19.8% (n=8, p=0.0525), and d) 49.9±21.2% (n=3, p=0.0275, one tailed t‐test), respectively. The LAR was significantly lower by PBT than IMXT for the the brain, head, and neck region, thoracic region, and whole craniospinal irradiation.Conclusion:In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. This method was suggested to be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques.This research was supported by the Translational Research Network Program, JSPS KAKENHI Grant No. 15H04768 and the Global Institution for Collaborative Research and Education (GI‐CoRE), Hokkaido University, founded by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.

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