Dynamics-Adapted Radiotherapy Dose (DARD) for Head and Neck Cancer Radiotherapy Dose Personalization

Standard of care radiotherapy (RT) doses have been developed as a one-size-fits all approach designed to maximize tumor control rates across a population. Although this has led to high control rates for head and neck cancer with 66–70 Gy, this is done without considering patient heterogeneity. We present a framework to estimate a personalized RT dose for individual patients, based on pre- and early on-treatment tumor volume dynamics—a dynamics-adapted radiotherapy dose (D(DARD)). We also present the results of an in silico trial of this dose personalization using retrospective data from a combined cohort of n = 39 head and neck cancer patients from the Moffitt and MD Anderson Cancer Centers that received 66–70 Gy RT in 2–2.12 Gy weekday fractions. This trial was repeated constraining D(DARD) between (54, 82) Gy to test more moderate dose adjustment. D(DARD) was estimated to range from 8 to 186 Gy, and our in silico trial estimated that 77% of patients treated with standard of care were overdosed by an average dose of 39 Gy, and 23% underdosed by an average dose of 32 Gy. The in silico trial with constrained dose adjustment estimated that locoregional control could be improved by >10%. We demonstrated the feasibility of using early treatment tumor volume dynamics to inform dose personalization and stratification for dose escalation and de-escalation. These results demonstrate the potential to both de-escalate most patients, while still improving population-level control rates.