非转移性复发性或第二原发性头颈鳞状细胞癌（HNSCC）的调强放射治疗（IMRT）再照射导致无进展生存期（PFS）和总生存期（OS）较差。为了研究耐受性、PFS、OS、以及IMRT再放疗期间和之后患者报告的纳武单抗（已批准的HNSCC患者护理标准）结果。在这项多中心非随机2期单臂试验中，满足递归分区分析的复发性或第二原发性HNSCC患者的治疗结果评估了 1 类和 2 类定义。 2018年7月11日至2021年8月12日期间，有62名患者获得同意并进行了筛查。数据在 2023 年 6 月至 12 月期间进行评估。在 6 至 6.5 周内，每天 30 至 33 次进行 60 至 66 Gy 的 IMRT，使用纳武单抗 240 mg，在 IMRT 期间于 2 周前静脉注射，每 2 周一次，共 5 个周期，然后使用纳武单抗， 480 mg，每 4 周静脉注射一次，纳武单抗总持续时间为 52 周。主要终点是 PFS。次要终点包括 OS、发生率和毒性反应类型，包括长期治疗相关的毒性反应、患者报告的结果以及组织和血液生物标志物的相关性。总共筛选了 62 名患者，其中 51 名患者可评估（中位[范围]年龄为 62 [56-67] 岁；42 [82%] 为男性；6 [12%] 患有 p16 疾病；38 [75%] 接受过颈部清扫术； ）。中位随访时间为 24.5 个月（95% CI，19.0-25.0），估计的 1 年 PFS 为 61.7%（95% CI，49.2%-77.4%），拒绝了 1 年 PFS 率的零假设在 1 年时间范围内，采用 1 臂对数秩检验 P = .002，低于 43.8%。最常见的与治疗相关的 3 级或以上不良事件 (6 例 [12%]) 是淋巴细胞减少症，其中 2 名患者 (4%) 和各 1 名患者 (2%) 表现出结肠炎、腹泻、肌炎、恶心、粘膜炎和重症肌无力。癌症治疗的功能评估 - 一般和癌症治疗的功能评估 - 头颈问卷生活质量评分在所有时间点保持稳定和一致。观察到血液 PD1、KI67 和 CD4 T 细胞增加的患者存在有利于 PFS 和 OS 恶化的假设生成趋势。这项 IMRT 再放射治疗和纳武单抗的多中心非随机 2 期试验表明，与历史对照相比，PFS 有希望改善。该治疗耐受性良好，值得进一步评估。ClinicalTrials.gov 标识符：NCT03521570。

Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS).To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation.In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023.Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks.The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers.A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed.This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation.ClinicalTrials.gov Identifier: NCT03521570.