2737 - Hypoxia Region Dose Escalation in Head and Neck Cancer: Dosimetric Analysis and Acute Toxicity

Purpose/Objective(s): Hypoxia is commonly observed in head and neck cancers and is associated with an increased risk of local/regional recurrence. It represents a promising target for dose escalation in adaptive IGRT. 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.

Materials/Methods: Between May 2022 and September 2024, 43 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 of 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 or hyperfractionated accelerated radiotherapy, and exclusion from primary surgical treatment based on multidisciplinary tumor board assessment. The outcomes of patients treated with metabolic adaptive radiotherapy were compared with a cohort of 65 patients who received conventional chemoradiotherapy, focusing on dosimetric parameters and acute toxicity. Major acute toxicity was defined as CTCAE G3 and higher.

Results: Hypoxic regions were detected in 33 patients (77%), with a median hPTV of 1.6 ml (IQR 0.2–7.1). In accordance with the adaptive protocol, 13 of 43 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 dose escalation did not affect the planned dose to the boost PTV (bPTV) or elective PTV (ePTV), with D95% for bPTV remaining at 96.2% (IQR 95.3–98.2).

Median doses to critical organs, including the brainstem (25.2 Gy, IQR 21.8–31.3), spinal cord (32.0 Gy, IQR 22.9–41.0), spinal canal (40.0 Gy, IQR 33.0–47.2), and parotid glands (25.3 Gy, IQR 23.2–33.6), demonstrated no statistically significant differences between adaptive and conventional protocols. The analysis of acute toxicity showed a comparable incidence of major dermatitis (25% vs. 20%) and xerostomia (2.5% vs. 3.1%) between FMISO patients undergoing adaptive RT and the retrospective cohort. While mucositis appeared more frequent in FMISO patients (32.5% vs. 23%, P=0.14), the difference was not statistically significant. However, dysphagia was significantly more prevalent in the dose escalation group (37.5% vs. 20%, p = 0.03). Hematological toxicity remained similar across the cohorts.

Conclusion: Personalized dose escalation (10–15%) to hypoxic regions based on FMISO PET/CT imaging is a feasible approach, achieving effective dose distribution without negatively impacting surrounding organs with a slight increase in acute toxicity. Clinical Trial number: NCT05348486.