ImportanceIntensity-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).ObjectiveTo investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation.Design, Setting, and ParticipantsIn 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.InterventionSixty- 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.Main Outcomes and MeasuresThe 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.ResultsA 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.Conclusions and RelevanceThis 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.Trial RegistrationClinicalTrials.gov Identifier: NCT03521570

中文翻译：

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纳武单抗调强再放疗治疗复发性或继发性头颈鳞状细胞癌


重要性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。目的探讨其耐受性、PFS、OS、设计、设置和参与者在这项多中心非随机 2 期单臂试验中，复发性或第二原发性 HNSCC 患者的治疗结果对满足递归划分分析 1 类和 2 类定义的人进行了评估。 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 月之间进行评估。 干预 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，持续 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。主要结果和措施主要终点是 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。 结果 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%] 接受了颈部清扫术； ）。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1 臂对数秩检验小于 43.8%磷= 。002 在一年的时间内。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——癌症治疗的一般和功能评估——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。 结论和相关性 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，与历史数据相比，PFS 有希望改善控制。该治疗耐受性良好，值得进一步评估。试验注册临床试验。政府标识符： NCT03521570