Abstract
BACKGROUND: This single-arm phase II trial aimed to assess the effectiveness and safety of incorporating hyperthermia into salvage concurrent chemoradiotherapy (CCRT) for previously irradiated unresectable recurrent head and neck cancer. METHODS: We enrolled patients with non-metastatic recurrent head and neck cancer who had previously undergone radiotherapy (RT) and were unfit for salvage surgery. Eligible patients received hyperthermia during salvage CCRT. RT consisted of an upfront boost with 10 Gy in 2 fractions to gross tumor volume, followed by 40 Gy in 20 fractions to clinical target volume, for a total of 50 Gy in 22 fractions. Weekly hyperthermia for 6 sessions started after RT initiation; each session lasted for 40 min, beginning within 2 h after RT and maintaining a maximum temperature of 42 ± 0.5 °C. Concurrent chemotherapy included weekly cisplatin 20 mg/m(2) and docetaxel 10-12 mg/m(2) for 6 weeks. Primary endpoint was overall response rate (ORR). Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. RESULTS: Among 35 eligible patients, ORR was 82.9%, with complete response in 54.3%, partial response in 28.6%, stable disease in 11.4%, and progressive disease in 5.7%. After a median follow-up of 2.7 years, median OS was 32.8 months (95% confidence interval [CI], 16.7-48.9), and 2-year OS was 57.1% (95% CI, 40.6-73.6). Median PFS was 14.9 months (95% CI, 5.7-24.1), and 2-year PFS was 34.3% (95% CI, 18.6-50.0). Acute mucositis was grade 0-1 in 68.6%, grade 2 in 25.7%, and grade 3 in 5.7%. Acute dermatitis was grade 0-1 in 85.7% and grade 2 in 14.3%. No definite burn injury occurred. Grade 3-4 leucopenia, anemia, thrombocytopenia accounted for 14.3%, 14.3%, and 8.6%, respectively. Osteonecrosis was noted in 12 patients. No grade 5 toxicity was observed. CONCLUSIONS: Adding hyperthermia to salvage CCRT greatly enhances tumor response and survival rates compared to historical re-irradiation outcomes for previously irradiated unresectable recurrent head and neck cancer, with manageable toxicities. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02567383 ), Registered October 1 , 201 5 - https://www. CLINICALTRIALS: gov/study/NCT02567383.