Impact of daily adaptive head and neck radiotherapy on toxicity and quality-of-life: results of the DARTBOARD phase II randomized trial

Background The utility of adaptive radiotherapy (ART) for head and neck squamous cell carcinoma (HNSCC) remains poorly defined. Daily ART (DART) promises both anatomic adaptation and planning target volume (PTV) reduction. In this prospective trial using cone-beam computed tomography-based ART, patients with HNSCC undergoing definitive radiotherapy (RT) or chemoradiotherapy (CRT) were randomized to DART with reduced PTV margins or no ART with standard margins (image-guided RT [IGRT]). Methods Eligibility criteria included a diagnosis of oropharynx, larynx, or hypopharynx HNSCC receiving definitive radiotherapy. All individuals received involved nodal radiotherapy per previous institutional study. The PTV margins were 1 mm (2 mm craniocaudal) versus 5 mm in the DART and IGRT arms, respectively. The primary endpoint was patient-reported xerostomia at one year, assessed with the Xerostomia Questionnaire (XQ). Results Fifty patients were enrolled (26 IGRT, 24 DART) between March 2022 and June 2023. The cohort consisted of 38 oropharynx and 12 larynx/hypopharynx patients. The mean ipsilateral parotid gland, ipsilateral and contralateral submandibular gland doses were significantly lower with DART. There was significantly less acute dermatitis in the DART arm (Grade 0/1/2 0%/69%/31% vs. 17%/75%/8% DART, p = 0.01) but no significant difference in any patient-reported outcome at one year. The adjusted difference in XQ score at one year was 10.0 (95% CI -4.7-24.7, p = 0.58). Conclusion Online DART for HNSCC is oncologically sound and improved acute toxicity profiles, but it did not reduce patient-reported xerostomia, the primary endpoint. Additional evidence is needed to understand the potential benefits and limitations of this paradigm, including its cost-effectiveness. Trial registration Clinicaltrials.gov identifier, NCT04883281