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Purpose  To investigate the role of intensity modulated proton therapy (IMPT) for advanced hepatocellular carcinoma in comparison with volumetric modulated arc therapy (VMAT).    Methods  An in-silico planning study was performed on 20 patients. The prescription dose was 60Gy in 6 fractions. Patients were planned with abdominal compression. IMPT plans were optimized with or without the inclusion of CT calibration (3%) and isocenter positioning (2,4,6mm) uncertainties. Plan robustness was appraised comparing rubust optimized plans vs standard plans and also in terms of the worst-case scenario. VMAT plans were optimized for 10FFF photon beams using 2 partial arcs.    Results  Target coverage was fully achieved by both VMAT and IMPT plans with a significant improvement in homogeneity (~25%) with IMPT. Integral dose was reduced of ~60% with IMPT while the conformality of the dose distributions was similar among techniques. The sparing of the organs at risk was strongly improved with IMPT although all clinical objectives were met for both techniques. The inclusion of the uncertainties in the optimization lead to some deterioration in the target dose homogeneity (from 40 to 80% worse with 4 or 6mm position uncertainty) while none of the coverage parameters or OAR objective was violated. The worst-case scenario analysis demonstrated the risk of a major target underdosage only in the case of the most extreme errors (6mm) with D 98%  in average ~12% lower than the threshold.    Conclusion  IMPT with the support of abdominal compression, can be considered a viable solution also for advanced hepatocellular carcinoma patients. Great care shall be put in the minimization of the residual respiration and positioning uncertainties but the dosimetric advantage for organs at risk and the relative robustness on target coverage are promising factors.

Critical appraisal of the potential role of intensity modulated proton therapy in the hypofractionated treatment of advanced hepatocellular carcinoma