# DEHART: Dose-Escalated Hypofractionated Adaptive Radiation Therapy for Head and Neck Cancers

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $182,325

## Abstract

Abstract
Locoregional failure remains the principal mode of mortality in head and neck squamous cell carcinomas
(HNSCCs) treated with conventional chemoradiation therapy over 7 weeks. Radiation dose escalation with
hypofractionation has shown unparalleled local control in many other malignancies, such as non-small cell lung
cancer, but has been stymied in HNSCCs due to toxicity concerns. MR-guided radiation therapy (MRgRT)
allows for adaptive radiation dose escalation based on tumor response, which may improve therapeutic
outcomes while limiting toxicities.
Our proposal, titled Dose-Escalated Hypofractionated Adaptive Radiotherapy (DEHART), evaluates a novel
framework for radiation delivery using MRgRT with concurrent PD-1/PD-L1 targeted immunotherapy in patients
with advanced HNSCCs. Unlike conventional radiotherapy, DEHART modifies radiation dose using MRgRT by
adapting the radiation plan weekly during the course of treatment, escalating radiation dose to residual tumor
while deescalating radiation dose to areas of tumor regression. We hypothesize that DEHART will safely
deliver ablative radiation doses in 15 fractions over 3 weeks while limiting both toxicity and the effect of tumor
repopulation by resistant clonogens, thus resulting in an improved therapeutic ratio.
We aim to test this hypothesis through a Phase I clinical trial with the following specific aims: (1) Determine the
maximum tolerated dose (MTD) of the DEHART regimen delivered using MRgRT with concurrent
immunotherapy in a population of patients who are not candidates or unsuitable for definitive chemoradiation
therapy; (2) Evaluate the toxicity and functional outcomes of the DEHART regimen including changes in
baseline speech, swallow and quality of life; and (3) Assess the efficacy of DEHART and obtain volumetric and
functional imaging correlates of efficacy using MRgRT to serve as hypothesis-generating data for future trials
of radiation dose adaptation. To determine the MTD of the DEHART regimen, we propose an 18 patient study
using a modified Time-to Event Continual Reassessment (TITE-CRM) Phase I Design with three radiation
dose levels delivered to regressing disease: 50 Gy in 15 fractions, 55 Gy in 15 fractions and 60 Gy in 15
fractions.
If DEHART is found to be safe and shows a signal of efficacy in this study, we will conduct a future Phase II
trial to compare this novel treatment strategy to standard-of care conventionally fractionated chemoradiation in
patients with locally advanced HNSCCs.

## Key facts

- **NIH application ID:** 10323293
- **Project number:** 5R21CA256144-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Musaddiq Awan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,325
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10323293

## Citation

> US National Institutes of Health, RePORTER application 10323293, DEHART: Dose-Escalated Hypofractionated Adaptive Radiation Therapy for Head and Neck Cancers (5R21CA256144-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10323293. Licensed CC0.

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