Optimizing allocation of limited proton fractions via NTCP-optimized combined proton-photon radiotherapy

Compared to photon radiotherapy (RT), proton RT is less widely available and more costly. To maximize the normal-tissue complication probability (NTCP) benefit of limited proton resources at a population level, this work introduces a novel NTCP-optimized combined proton-photon treatment (NTCP-CPPT) approach that can achieve the OAR-sparing benefits in terms of reaching desired NTCP thresholds with the minimal proton fraction. NTCP-optimized intensity-modulated proton therapy (NTCP-IMPT) and NTCP-optimized intensity-modulated radiation therapy (NTCP-IMRT) plans are generated via the NTCP-optimized treatment planning based on physical dose and NTCP objectives. For each patient, a minimal proton fraction is determined for the NTCP-CPPT plan as a combination of NTCP-IMPT and NTCP-IMRT plans, while still retaining the sum-NTCP threshold for the patient to be justified for the proton access. For comparison, conventional CPPT (CONV-CPPT) plans are obtained by a combination of conventional IMRT (CONV-IMRT) and conventional IMPT (CONV-IMPT) plans that are solely optimized based on physical dose optimization. Compared to CONV-CPPT, NTCP-CPPT reduced the average proton fractions from 18 to 3 without compromising physical dose objectives, while both NTCP-CPPT and CONV-CPPT plans maintained a sum-NTCP below 20% relative to CONV-IMRT. Additionally, NTCP-CPPT, using an average of 22 proton fractions out of 35, maintained the same sum-NTCP as CONV-IMPT required 35 proton fractions. To increase patient access to proton RT, a novel combined proton-photon treatment called NTCP-CPPT is proposed that can provide a minimal number of proton fractions while still retaining sufficient OAR-sparing benefits to justify the proton access.