3455 - Hypoxia Region Dose Escalation in Head and Neck Cancer - Early Clinical Results of Multicenter Study

Purpose/Objective(s): Hypoxia is commonly observed in head and neck cancers and is associated with an increased risk of local and regional recurrence. On the other hand, it can serve as an area for personalized treatment, particularly through dose escalation in image-guided adaptive radiotherapy. This study aims to evaluate the feasibility of personalized dose escalation (10–15%) to hypoxic regions identified using FMISO PET/CT within a nonrandomized clinical trial (NCT05348486). Following dosimetry and acute toxicity, we now present early clinical results.

Materials/Methods: Between May 2022 and February 2025, 68 patients underwent hypoxia-targeted radiotherapy, with target volume delineation based on FMISO PET/CT imaging before treatment initiation and subsequent adaptation after the 11th fraction. A dose escalation up to 79.2 Gy in 33 fractions was administered to the hypoxic planning target volume (hPTV).

Inclusion criteria included a histologically confirmed diagnosis of oropharyngeal p16-negative or laryngeal/hypopharyngeal/oral cavity squamous cell carcinoma (regardless of p16 status) at clinical stage III or IV, eligibility for definitive chemoradiotherapy and exclusion from primary surgical treatment based on multidisciplinary tumor board assessment. Additionally, all patients had an ECOG performance status of 0 or 1.

The outcomes of patients treated with dose escalation using FMISO were compared with FMISO negative patients who received conventional chemoradiotherapy and retrospective cohort of 227 patients without known hypoxia status also treated with conventional chemoradiotherapy without dose escalation, focusing on toxicity, local control and OS. Major toxicity was defined as CTCAE G3 and higher.

Results: Hypoxic regions were detected in 44 patients (65%), with a median hPTV of 3.9 ml (IQR 0.97–11.93). In accordance with the adaptive protocol, 20 of 68 patients (30%) underwent treatment replanning after the 11th fraction. Median and maximum doses delivered to hPTV were 79.2 Gy (IQR 76.2–79.2) and 80.4 Gy (IQR 77.7–81.4), respectively. The median of follow up was 20.2 month (6-42).

The analysis of early late toxicity showed a comparable incidence of major xerostomia (2.2% vs. 0 %) between FMISO positive patients undergoing adaptive RT and FMISO negative cohort. While major dysphagia appeared more frequent in FMISO+ patients (42.5% vs. 23%, P=0.11), the difference was not statistically significant.

Locoregional relapse at 2 years was observed in the FMISO+ group, FMISO- group, and retrospective cohort in 30%, 29%, and 33% of patients, respectively (p=0.9). Median OS was 27.9, 27.4 and 23.1 months.

Conclusion: Personalized dose escalation to hypoxic regions based on FMISO PET/CT imaging is a feasible approach, achieving locoregional control in FMISO+ patients comparable to that seen in FMISO- patients. Further follow-up is necessary to confirm this promising trend.