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

Mohammad U. Zahid,Heiko Enderling,Eduardo G. Moros,Abdallah S. R. Mohamed,Clifton D. Fuller,Louis B. Harrison,Jimmy J. Caudell

doi:10.3390/jpm11111124

Mohammad U. Zahid, Heiko Enderling + Show 5 more

Open Access

https://doi.org/10.3390/jpm11111124

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Abstract

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 (DDARD). 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 DDARD between (54, 82) Gy to test more moderate dose adjustment. DDARD 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.

Highlights

Head and neck cancers (HNC) are among the ten most common cancer types worldwide, with an increasing incidence in certain virally driven subtypes [1,2]
Longitudinal tumor volume data were collected for a cohort of 17 head and neck cancer patients from the Moffitt Cancer Center (MCC) treated with 66–70 Gy RT in 2 Gy weekday fractions, and for a cohort of 22 patients from the MD Anderson Cancer Center (MDACC) with 66–70 Gy RT in 2 or 2.12 Gy weekday fractions or with accelerated fractionation with or without chemotherapy (Figure 1A)
We developed a mathematical modeling framework to introduce the concept of a dynamics-adapted radiation therapy dose for individual HNC patients

Summary

Introduction

Head and neck cancers (HNC) are among the ten most common cancer types worldwide, with an increasing incidence in certain virally driven subtypes [1,2]. Established risk factors for HNC include tobacco use, alcohol consumption and infection by the human papillomavirus (HPV). Standard of care treatment options include definitive RT, with or without systemic therapy, or initial surgical resection followed by adjuvant RT, with or without systemic therapy, as needed and based on pathological risk features [3]. With an increasing understanding of inter-patient heterogeneity, RT should be tailored to individual patients [5]. Current efforts to personalize RT mainly adapt the target volume based on response; there have been no trials attempting to individualize radiation dose

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