Palma David A, Prisman Eitan, Berthelet Eric, Tran Eric, Hamilton Sarah, Wu Jonn, Eskander Antoine, Higgins Kevin, Karam Irene, Poon Ian, Husain Zain, Enepekides Danny, Hier Michael, Richardson Keith, Mlynarek Alex, Johnson-Obaseki Stephanie, Gaudet Marc, Bayley Andrew, Dowthwaite Samuel, Jackson James E, Dzienis Marcin, O'Neil John, Chandarana Shamir, Banerjee Robyn, Hart Robert, Chung Jeffson, Tenenholtz Todd, Le Hien, Yoo John, Mendez Adrian, Winquist Eric, Kuruvilla Sara, Stewart Paul, Warner Andrew, Mitchell Sylvia, Chen Jeff, Parker Christina, Kwan Keith, Theurer Julie, Bahig Houda, Christopoulos Apostolos, Mendez Lucas C, Sathya Jinka, Hammond J Alex, Read Nancy, Venkatesan Varagur, Fung Kevin, Nichols Anthony C
Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
Eur J Cancer. 2025 May 2;220:115343. doi: 10.1016/j.ejca.2025.115343. Epub 2025 Mar 10.
The optimal treatment de-escalation approach for HPV-related oropharyngeal squamous cell carcinomas (OPSCC) is unknown. The objective was to assess two de-escalation approaches: primary radiotherapy (RT) vs. transoral surgical (TOS).
Patients with T1-T2 N0-2 HPV-related OPSCC were randomly assigned to primary RT (60 Gy with concurrent weekly cisplatin in node-positive) vs. TOS + neck dissection (ND) (and adjuvant reduced-dose RT depending on pathology). The primary endpoint was 2-year OS (hypothesized to be 94 % in each arm, compared to 84 %). Secondary endpoints included comparisons of survival and quality of life between arms. The trial was stopped early due to two treatment related deaths in the surgical arm.
Sixty-one patients were randomized (n = 30 in RT arm and n = 31 in TOS+ND arm), with a median age of 62 years (IQR: 57-68). The majority were male (n = 51) and never-smokers (n = 31). Median follow-up was 3.7 years (IQR: 3.1-4.5 years). In the RT arm, the primary endpoint for acceptability was met (p = 0.008), and two-year OS was 100 % (95 % confidence interval [CI]: 100-100 %). In the TOS+ND arm, the primary endpoint was not met (p = 0.296) and two-year OS was 90 % (95 % CI: 71-97 %), significantly worse than the RT arm (p = 0.041). Two-year progression-free survival (PFS) were 100 % (95 % CI: 100-100 %) vs. 86 % (95 % CI: 67-95 %) respectively (p = 0.012). Mean (± SD) 2-year MDADI total scores were 89 ± 13 vs. 83 ± 11, respectively (p = 0.11), and grade 2-5 toxicity rates were similar (n = 21 vs. n = 24 respectively, p = 0.51), with no additional grade 5 events.
For treatment de-escalation, a primary RT approach achieved excellent oncologic and functional outcomes and should be tested in phase III de-escalation trials.
Clinicaltrials.gov NCT03210103.
人乳头瘤病毒（HPV）相关的口咽鳞状细胞癌（OPSCC）的最佳治疗降级方法尚不清楚。目的是评估两种降级方法：原发性放疗（RT）与经口手术（TOS）。
T1-T2 N0-2 HPV相关OPSCC患者被随机分配至原发性RT组（淋巴结阳性患者给予60 Gy放疗并同步每周一次顺铂）与TOS +颈部清扫术（ND）组（根据病理结果给予辅助性减量放疗）。主要终点为2年总生存率（假设每组为94%，而之前为84%）。次要终点包括两组之间生存率和生活质量的比较。由于手术组出现两例与治疗相关的死亡，该试验提前终止。
61例患者被随机分组（RT组30例，TOS + ND组31例），中位年龄为62岁（四分位间距：57 - 68岁）。大多数为男性（51例）且从不吸烟（31例）。中位随访时间为3.7年（四分位间距：3.1 - 4.5年）。RT组达到了可接受性的主要终点（p = 0.008），2年总生存率为100%（95%置信区间[CI]：100 - 100%）。TOS + ND组未达到主要终点（p = 0.296），2年总生存率为90%（95% CI：71 - 97%），显著低于RT组（p = 0.041）。2年无进展生存率分别为100%（95% CI：100 - 100%）和86%（95% CI：67 - 95%）（p = 0.012）。2年MDADI总分的均值（±标准差）分别为89 ± 13和83 ± 11（p = 0.11），2 - 5级毒性发生率相似（分别为21例和24例，p = 0.51），无额外的5级事件。
对于治疗降级，原发性RT方法取得了优异的肿瘤学和功能学结果，应在III期降级试验中进行测试。
Clinicaltrials.gov NCT03210103。
