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Elective para-aortic (PAO) radiotherapy (RT) has been the standard adjuvant therapy after local surgery in stage I seminoma for many years, using photons and an APPA field setup. In the past decade this policy is however shifting towards watchful waiting, since several cohort studies demonstrated that this young patient category with excellent overall survival is at considerable risk for late effects including second primary cancer (SPC) risks related to the radiation exposure of organs at risk (OAR), in particular the stomach, pancreas, and kidneys. Current developments in RT offer more advanced options with VMAT and proton therapy, with the potential to reduce OAR dose levels and therefore SPC risks. In the current study we compared dose to the OARs between VMAT, proton therapy and an APPA reference group. Mean dose was considered as a suitable proxy for SPC risks, since a linear dose-response is assumed in the observed OAR dose range of ≈0.1-15 Gy, causing cell damage but not cell kill, according to the theoretical models (linear, linear plateau, linear exponential). 

In six recent clinical treatment plans we added delineations of pancreas and stomach and re-optimized the VMAT plan (13x2 Gy, single-ARC, 10 MV, clinical constraints) applying a uniform 7 mm PTV-CTV margin and created an additional proton plan. All received RT to the PAO lymph nodes and two had additional RT to para-iliacal (PAI) lymph nodes. Proton therapy plans were optimized using in-house developed software for the prioritized multi-criteria optimization of RT treatment plans. A standard setup of 2 posterior beams at gantry angles of 165 and 195 degrees were used. Scenario-based robust optimization with 7mm setup error and 3% relative stopping power prediction error (range) robustness was used.

Mean dose to OARs and the total scanned volume (proton vs VMAT) showed relevant OAR dose reductions for the majority of patients and for all OARs, with largest absolute reductions for pancreas and right kidney (4-6 Gy), and largest relative reductions for stomach and right kidney (90%-96%); see Figure & Table. The total sum of mean dose reductions (kidney L + kidney R + stomach + pancreas) was in the range of 15-20 Gy in 4 patients (all PAO), 10 Gy in 1 patient and 3 Gy in 1 patient (both PAO+PAI: case nr 5 & 6 in Figure). Compared to the historical APPA group, we observed that with VMAT dose levels to the stomach decreased and dose to the kidneys increased. With proton therapy, low dose levels to both kidney and stomach can be achieved.

We demonstrated that with proton therapy clinically meaningful OAR dose reductions can be achieved with respect to SPC risks in a proportion of the seminoma patient group, compared to modern RT with VMAT. Risk reductions of other late effects (e.g. diabetes) can be expected as well. For young seminoma patients with unfavorable dose distributions to OARs with a VMAT plan, proton therapy would therefore be a superior treatment option.