KEY POINTS
- DEHART was a single-centre phase 1 trial enrolling 18 patients with advanced head and neck squamous cell carcinoma who were ineligible for or declined cisplatin, had unresectable oral cavity cancer, postoperative recurrence or de novo metastatic disease. Median age was 74 years, 66% had oral cavity primaries and 78% had human papillomavirus-negative disease.
- Patients received 40 Gy in 15 fractions to elective nodal regions, 45 Gy in 15 fractions to an intermediate-risk volume and escalating doses of 50, 55 or 60 Gy in 15 fractions to gross disease. Magnetic resonance-guided adaptation was performed at fractions 6 and 11, with planning target volume margins of no more than 3 mm.
- The first five patients received atezolizumab 1,680 mg on day 1 of radiotherapy and every four weeks thereafter. Three of five patients developed symptomatic HSV-1 reactivation, and two experienced dose-limiting toxicities, prompting removal of concurrent atezolizumab from the protocol.
- In the concurrent cohort, grade 3 oral mucositis and dysphagia each occurred in 80%, while one patient developed grade 4 aspiration pneumonia and respiratory failure. One patient stopped radiotherapy after 11 of 15 fractions.
- Thirteen subsequently enrolled patients began atezolizumab only after radiotherapy. No dose-limiting toxicity was observed after the amendment, and the maximum tolerated radiation dose was established as 60 Gy in 15 fractions.
- Among the seven patients treated to 60 Gy, no locoregional failures occurred during one year of follow-up, and one-year progression-free survival was 71.4%. Three of four patients with advanced oral cavity cancer treated at this dose achieved complete clinical responses.
- No grade 4 or higher toxicity attributed to treatment occurred at the 60 Gy dose level. Patient-reported swallowing and symptom scores declined during treatment but generally returned toward baseline by one year.
CLINICAL TAKEAWAY
Delivering 60 Gy in 15 adaptive fractions followed by atezolizumab appeared feasible in this small, medically challenging population. Concurrent atezolizumab should not be extrapolated from these data because three of five patients developed HSV-1 reactivation with substantial toxicity; efficacy findings at 60 Gy are promising but based on only seven patients.
SOURCE
International Journal of Radiation Oncology, Biology, Physics