Can future reirradiation justify upfront proton therapy? An extension of model-based proton therapy selection beyond primary-course NTCP benefit

Objective: Current model-based proton therapy selection values normal tissue sparing only through its immediate reduction in normal tissue complication probability (NTCP). If reirradiation later adds further dose to the normal tissue, sparing achieved during primary treatment may become more clinically valuable. We investigated whether, and under which conditions, this contingent benefit could justify upfront proton therapy. Approach: We formulated a reirradiation-aware criterion that weights the NTCP benefits of upfront proton therapy after primary treatment alone or followed by reirradiation by their respective probabilities. Proton therapy is recommended when the expected benefit reaches a referral threshold T. Assuming a common logistic NTCP model for both scenarios, we derived screening conditions from the paired primary photon and proton plans to identify patients for whom future reirradiation could justify additional referral. We then quantified the minimum reirradiation probability and admissible added risk-score contributions for additional referral, and mapped referral patterns across primary profiles and reirradiation scenarios. Main results: Additional referral occurred for patients with substantial primary normal tissue sparing but a small immediate NTCP reduction because both plans lay on a flat region of the NTCP curve. In these cases, reirradiation could add sufficient normal tissue dose for the retained sparing to yield a larger NTCP benefit. Higher reirradiation probability expanded eligibility, whereas greater exposure could reduce the NTCP benefit as both predictions approached saturation. Significance: The proposed framework identifies well-defined patient profiles for which upfront proton therapy may be justified even if the NTCP benefit of proton therapy in the first treatment is below the threshold T.