Feasibility study of manual dose escalation method with normal tissue complication probability in radiation dose escalation for prostate cancer

This study aimed to investigate the feasibility of the manual expansion method with normal tissue complication probability (NTCP) for dose escalation. The dose-volume histogram (DVH) of the previously published data from proton and photon therapy plans was used to evaluate the effect of NTCP on dose escalation. The escalated DVH was manually obtained by increasing dose up to 1.8-times based on previously published data. Various NTCP calculation models have been applied to the DVH of patients with prostate cancer. The feasibility of the manual expansion plan method was verified by comparing it with an optimized plan using a treatment planning system (TPS). The risk ratio was investigated to determine the possible dose escalation ratio according to a rectal radiation therapy oncology group (RTOG) toxicity of ≥ grade 2. In addition, the relative biological effectiveness (RBE) uncertainty of NTCP was investigated using a linear-quadratic (LQ)-model-based equivalent dose of 2 Gy. Manual dose expansion, up to 1.8-times for rectum and bladder, showed acceptable DVH compared to the DVH optimized by TPS for both proton pencil-beam scanning (PBS) and photon volumetric modulated arc therapy (VMAT) plans. The risk ratio can provide information for toxicity-related dose escalation range for analysis of the risk ratio of proton therapy to photon therapy for the rectum even though the NTCP of proton therapy is higher than that of photon therapy. In the hypo-fractionated scheme, RBE uncertainty results in severe late toxicity for the rectum for the dose escalation ratio of up to 1.3-times. The manual expansion method is feasible with a specific treatment modality and can be a useful tool for dose escalation studies.