1240 - Prospective Evaluation of Daily Online Adaptive Radiotherapy with 1mm PTV Margins in High Risk HPV Negative Head and Neck Cancer

Purpose/Objective(s): Margin reduction in HPV-negative head and neck squamous cell carcinoma (HNSCC) raises legitimate concerns regarding target coverage and oncologic safety, particularly in biologically aggressive, locally advanced disease. While the DARTBOARD trial demonstrated reduced acute toxicity with adaptive radiotherapy, it did not evaluate ultra-reduced 1-mm margins in a uniformly high-risk HPV-negative population nor report early disease control outcomes. We conducted a prospective phase II trial to evaluate feasibility, dosimetric impact, toxicity, oncologic outcomes, and longitudinal quality of life (QOL) using daily CBCT-based online adaptive radiotherapy (DART) with surface guidance in high-risk HPV-negative HNSCC

Materials/Methods: Patients with HPV-negative HNSCC receiving definitive or adjuvant radiotherapy were prospectively enrolled. Treatments were delivered on the ETHOS online adaptive platform with IDENTIFY surface guidance. CTV-to-PTV margins were 1 mm isotropic and 2 mm craniocaudal. Adaptive plans were generated and selected daily. The primary endpoint was acute toxicity. The secondary endpoints included dosimetric differences, local control, and QOL (EORTC QLQ-H&N35)

Results: Fifteen patients were treated between February 2024 and October 2025 with reduced PTV margin and daily online adaptive radiotherapy. 80% had AJCC stage IVA–B disease. Eight patients received definitive RT (66 Gy/30 fractions) and seven adjuvant RT (60 Gy/30 fractions). Concurrent chemotherapy was delivered in 10 patients. Adaptive replanning was utilized in 99% of fractions due to better coverage and / or reduced OAR doses. Mean adaptive session duration was 19 minutes. The mean deviation from the reference surface was 1mm (0-2mm) during treatment delivery and SGRT monitoring. The mean doses delivered to the ipsilateral parotid and constrictors were 17.7Gy and 30Gy respectively. Acute grade 2 dermatitis and dysphagia occurred in 13% and 20%, respectively, with no grade =3 toxicities. At 18-month median follow-up, the local control was 94%. QOL scores normalized by 6–12 months; persistent xerostomia at 12 months was limited to two patients

Conclusion: In high-risk HPV-negative HNSCC, daily online adaptive RT with 1-mm margins is feasible, enables significant organ-at-risk sparing, and maintains excellent early local control. These data extend beyond DARTBOARD by demonstrating oncologic safety and operational feasibility of ultra-margin reduction in a biologically aggressive population