Variable-Interval Temporal Feathering to Optimize Organ-at-Risk Repair for Head and Neck Adaptive Radiotherapy

PurposeTemporally feathered radiation therapy (TFRT) for head-and-neck cancer (HNC) radiotherapy combines variable-dose daily subplans to increase the rest time of organs-at-risk (OARs) as sought in intensity modulated radiation therapy (IMRT). While the standard TFRT recommends uniform rest time for each OAR, improved toxicity outcomes may be achieved through variable rest time for OARs by incorporating the OARs variable radiosensitivity profiles. Methods and MaterialsA decision-making model was constructed to maximize the combined recovery of OARs by determining OARs optimal rest times. Two main components were incorporated: the cumulative biologically effective dose based on the linear-quadratic model; and a dynamical model capturing the adjusted recovery of OARs as a function of delivered dose. Further, variable radiosensitivity profiles were allowed across the OARs to capture their variable recovery time. Individual recoveries of each OAR under IMRT and the standard TFRT (sTFRT) was compared against optimized TFRT (oTFRT). ResultsFive OARs (larynx, esophagus, parotid, spinal cord, brainstem) were considered. When the cumulative dose delivered under TFRT and IMRT remains the same, three OARs exhibited higher recovery under oTFRT compared to the second-best approach (larynx (81.8% vs. 74.1%), esophagus (95.9% vs. 93.9%), parotid (85.6% vs. 83.5%), while the recovery of spinal cord (90.5% vs. 90.8%) and brainstem (96.2% vs. 96.6%) remained comparable under TFRT and IMRT approaches. With different cumulative dose under TFRT and IMRT, oTFRT achieved significantly higher recovery for larynx (95.5% vs. 81.8%) and parotid (92.9% vs. 85.6%), while it is slightly outperformed by IMRT for esophagus (93.4% vs. 95.9%), spinal cord (87.1% vs. 90.5%), and brainstem (90.2% vs. 96.6%). When considering the minimum end-of-treatment recovery, oTFRT always achieved higher recovery among the other two approaches. ConclusionsBy considering non-identical radiosensitivity profiles of OARs in HNC radiotherapy, TFRT can optimize their rest time to enhance recovery at the end of treatment, potentially reducing patient toxicities.