Optimal Timing of Organs-at-Risk-Sparing Adaptive Radiation Therapy for Head- and-Neck Cancer under Re-planning Resource Constraints.

Background and Purpose: Prior work on adaptive organ-at-risk (OAR)-sparing radiation therapy has typically reported outcomes based on fixed-number or fixed-interval re-planning, which represent one-size-fits-all approaches and do not account for the variable progression of individual patients' toxicities. The purpose of this study was to determine the personalized optimal timing for re-planning in adaptive OAR-sparing radiation therapy, considering limited re-planning resources, for patients with head and neck cancer (HNC). Materials and Methods: A novel Markov decision process (MDP) model was developed to determine optimal timing of re-planning based on the patient's expected toxicity, characterized by normal tissue complication probability (NTCP), for four toxicities. The MDP parameters were derived from a dataset comprising 52 HNC patients treated at the University of Texas MD Anderson Cancer Center between 2007 and 2013. Kernel density estimation was used to smooth the sample distributions. Optimal re-planning strategies were obtained when the permissible number of re-plans throughout the treatment was limited to 1, 2, and 3, respectively. Results: The MDP (optimal) solution recommended re-planning when the difference between planned and actual NTCPs (ΔNTCP) was greater than or equal to 1%, 2%, 2%, and 4% at treatment fractions 10, 15, 20, and 25, respectively, exhibiting a temporally increasing pattern. The ΔNTCP thresholds remained constant across the number of re-planning allowances (1, 2, and 3). Conclusion: In limited-resource settings that impeded high-frequency adaptations, ΔNTCP thresholds obtained from an MDP model could derive optimal timing of re-planning to minimize the likelihood of treatment toxicities.