BACKGROUND A phase I-II study to evaluate the feasibility and efficacy of intensified, primary radiotherapy (RT) for Locally Advanced Head and Neck Squamous Cell Carcinoma (LAHNSCC) employing dose escalation by hyperfractionation, acceleration of treatment time, concomitant chemotherapy and hypoxic modification. METHODS Patients with HPV/p16- LAHNSCC receiving primary hyperfractionated, accelerated RT, 76 Gy/56 fx, 10 fx/week for 5½ weeks, concomitant weekly cisplatin (40 mg/m2) and nimorazole (HART-CN) were included. Primary endpoint was locoregional failure (LRF). Secondary endpoints were overall survival (OS) and toxicity. RESULTS 50 patients received HART-CN from 2013 to 2017. Median age was 60 years. Most patients had stage IV hypo- or oropharynx cancer with a heavy smoking history. All oropharyngeal cancers were HPV/p16-negative. Ninety-eight percent of patients completed RT, but compliance to cisplatin and nimorazole was lower. Median observation time was 44 months. LRF was diagnosed in 10 patients. All LRFs were in the high-dose CTV. The 3-year actuarial LRF was 21%, and OS was 74%. The peak incidence of acute toxicity showed that 67% of patients experienced severe dysphagia, 61% severe mucositis, and 78% were equipped with feeding tubes. Late severe morbidity was seen in 7 of 29 recurrence-free patients with at least 3 years of followup, who presented with either severe dysphagia (n = 2), severe xerostomia (n = 1), severe fibrosis of the neck (n = 3) or osteoradionecrosis (n = 1). Three were still tube dependent. CONCLUSION HART-CN is feasible in patients with HPV/p16- LAHNSCC in good health. Although acute toxicity was pronounced, the proportion of patients with late toxicity was acceptable and outcome at 3 years encouraging.

中文翻译：

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DAHANCA 28：针对局部晚期、HPV/p16 阴性口咽、下咽、喉和口腔鳞状细胞癌患者进行超分割加速放疗联合顺铂和尼莫唑 (HART-CN) 的 I/II 期可行性研究

背景 一项 I-II 期研究，旨在评估局部晚期头颈部鳞状细胞癌 (LAHNSCC) 的强化初级放疗 (RT) 的可行性和疗效，该疗法通过超分割、加速治疗时间、伴随化疗和低氧调整来增加剂量。方法 HPV/p16-LAHNSCC 患者接受初级超分割加速放疗，76 Gy/56 fx，10 fx/周，持续 5½ 周，同时每周使用顺铂 (40 mg/m2) 和尼莫唑 (HART-CN)。主要终点是局部失败（LRF）。次要终点是总生存期（OS）和毒性。结果 2013 年至 2017 年有 50 名患者接受了 HART-CN。中位年龄为 60 岁。大多数患者患有 IV 期下咽癌或口咽癌，并有大量吸烟史。所有口咽癌均为 HPV/p16 阴性。98% 的患者完成了放疗，但顺铂和尼莫唑的依从性较低。中位观察时间为 44 个月。10 名患者被诊断为 LRF。所有 LRF 均在高剂量 CTV 中。3 年精算 LRF 为 21%，OS 为 74%。急性毒性峰值发生率显示，67% 的患者出现严重吞咽困难，61% 的患者出现严重的粘膜炎，78% 的患者配备了饲管。在至少 3 年随访的 29 名无复发患者中，有 7 名出现晚期严重并发症，表现为严重吞咽困难 (n = 2)、严重口腔干燥症 (n = 1)、严重颈部纤维化 (n = 3) ) 或放射性骨坏死 (n = 1)。三个仍然依赖管。结论 HART-CN 在健康状况良好的 HPV/p16-LAHNSCC 患者中是可行的。虽然急性毒性很明显，