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

DEHART：针对头颈癌的剂量递增大分割适应性放射治疗

• 批准号: 10323293
• 负责人: Musaddiq Awan
• 金额: $ 18.23万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323293
• 关键词: Acute; Area; Conformal Radiotherapy; Cytotoxic Chemotherapy; Data; Deglutition; Development; Disease; Disease Management; Distant Metastasis; Dose; Ensure; Event; External Beam Radiation Therapy; Failure; Functional Imaging; Future; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Immunotherapy; Intensity-Modulated Radiotherapy; Magnetic Resonance; Malignant Neoplasms; Maximum Tolerated Dose; Methodology; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Outcome; PD-1/PD-L1; Patients; Phase I Clinical Trials; Quality of life; Radiation; Radiation Dose Unit; Radiation therapy; Regimen; Regional Disease; Residual Tumors; Residual state; Resistance; Safety; Signal Transduction; Speech; Techniques; Technology; Testing; Therapeutic; Time; Toxic effect; Treatment Failure; anatomic imaging; base; chemoradiation; comparative efficacy; disorder control; efficacy trial; functional outcomes; image guided; improved; improved outcome; mortality; new technology; novel; optimal treatments; patient population; phase 1 designs; phase I trial; phase II trial; radiation delivery; response; standard of care; therapy outcome; treatment strategy; tumor

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.

摘要