Machtay Mitchell, Torres-Saavedra Pedro A, Thorstad Wade, Nguyen-Tân Phuc Felix, Siu Lillian L, Holsinger F Christopher, El-Naggar Adel, Chung Christine, Cmelak Anthony, Burtness Barbara, Bednarz Greg, Quon Harry, Breen Stephen L, Gwede Clement K, Dicker Adam P, Yao Min, Jordan Richard C, Dorth Jennifer, Lee Nancy, Chan Jason W, Dunlap Neal, Bar-Ad Voichita, Stokes William A, Chakravarti Arnab, Sher David, Rao Shyam, Harris Jonathan, Yom Sue S, Le Quynh-Thu
Penn State Milton S Hershey Medical Center, Hershey, PA.
Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD.
J Clin Oncol. 2025 Apr 20;43(12):1474-1487. doi: 10.1200/JCO-24-01829. Epub 2025 Jan 22.
Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer.
Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)-negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test.
We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided = .0747; 5-year OS 76.5% 68.7%), but DFS was (HR, 0.75; one-sided = .0168; 5-year DFS 71.7% 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided = .3101). There were no grade 5 toxicities in either arm.
RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.
对于局部晚期头颈部鳞状细胞癌，放疗（RT）联合西妥昔单抗（C）已显示出优于单纯放疗的效果。我们在完全切除的中危癌症患者中对此进行了验证。
患者患有口腔、口咽或喉的头颈部鳞状细胞癌（SCCHN），伴有一项或多项需要术后放疗的危险因素。患者按1:1随机分配至每周一次使用C的调强放疗（60 - 66 Gy）组或单纯放疗组。主要假设是，对于随机分配/符合条件的患者，RT + C将改善总生存期（OS），并制定了预先设定的次要计划，以在人乳头瘤病毒（HPV）阴性亚组中进行验证。无病生存期（DFS）和毒性反应为次要终点。通过分层对数秩检验评估OS和DFS；通过Fisher精确检验比较毒性反应。
2009年11月至2018年3月，我们共纳入702例患者；577例被随机分配/符合条件。大多数（63.6%）患有口腔癌，大多数（84.6%）具有高表皮生长因子受体表达。死亡人数（184例）少于预期。OS（中位随访7.2年）未得到显著改善（风险比[HR]，0.81；单侧P = 0.0747；5年OS 76.5%对68.7%），但DFS得到改善（HR，0.75；单侧P = 0.0168；5年DFS 71.7%对63.6%）。RT + C的益处仅在HPV阴性亚组中观察到（占试验患者的80.2%）。3 - 4级急性毒性发生率为70.3%（RT + C）对39.7%（RT；双侧P < 0.0001），主要为皮肤和/或黏膜反应。≥3级晚期毒性发生率为33.2%（RT + C）对29.0%（RT；双侧P = 0.3101）。两组均无5级毒性反应。
对于切除的中危SCCHN患者，与单纯放疗相比，RT + C显著改善了DFS，但未改善OS，且未增加长期毒性。对于精心挑选的HPV阴性疾病患者，RT + C是一个合适的选择。
