Phase 1 Dose Escalation of Stereotactic Body Radiation Therapy and Concurrent Cisplatin for Reirradiation of Unresectable, Recurrent Squamous Cell Carcinoma of the Head and Neck

• DOI: 10.1016/j.ijrobp.2023.04.007
• Publication Date: 2023-04-26T00:03:18Z
• Authors: Michelle I. Echev...; George Q. Yang; Dung-Tsa Chen; Kedar Kirtane; Jeffery Russell; Julie Kish; Jameel Muzaffar; Kristen Otto; Tapan Padhya; Caitlin McMullen; Krupal Patel; Christine H. Chung; Jimmy J. Caudell
• Keywords: Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Humans; Cisplatin; Neoplasm Recurrence, Local; Radiosurgery; 3. Good health; Re-Irradiation

Patients with locoregional recurrence of squamous cell carcinoma of the head and neck (SCCHN) have relatively poor outcomes; therefore, stereotactic body radiation therapy (SBRT) has been investigated for this patient population. We performed a phase 1 clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin in previously irradiated locoregional SCCHN.Patients with recurrent SCCHN who had previously undergone radiation therapy to doses ≥45 Gy to the area of recurrence ≥6 months before enrollment and who were not surgical candidates or refused surgery were eligible. SBRT was delivered every other day for 5 fractions. Starting dose level was 6 Gy × 5 fractions, followed by 7 Gy × 5 fractions and 8 Gy × 5 fractions. Chemotherapy consisted of cisplatin given before every SBRT fraction at a dose of 15 mg/m2. Patients were monitored for dose-limiting toxicities (DLT) that occurred within 3 months from the start of SBRT. Secondary endpoints included locoregional failure, distant metastasis, and overall survival.Twenty patients were enrolled, with 18 patients evaluable for endpoints. One patient at dose level 1 (30 Gy) died of unknown causes 2 weeks following completion of treatment. Therefore, an additional 3 patients were accrued to the 30-Gy dose level, with no further DLTs observed. Three patients were then accrued at dose level 2 (35 Gy) and 9 patients at dose level 3 (40 Gy) without DLTs. At a median follow-up of 9.5 months, cumulative incidence of locoregional failure at 2 years was 61% (95% confidence interval [CI], 12%-66%), cumulative incidence of distant metastasis was 11% (95% CI, 74%-100%) at 2 years, and overall survival was 22% (95% CI, 9%-53%) at 2 years.Concurrent cisplatin and reirradiation with an SBRT dose of ≤40 Gy was safe and feasible in patients with locoregionally recurrent or second primary SCCHN.