Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients

To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose–volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose–response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means ± standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 ± 0.52% (n = 7, P = 0.0021), (ii) 23.3 ± 17.2% (n = 8, P = 0.0065), (iii) 16.6 ± 19.9% (n = 8, P = 0.0497) and (iv) 50.0 ± 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques.