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.
JAMA Oncol. 2022 Jun 1;8(6):1-7. doi: 10.1001/jamaoncol.2022.0615.
The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown.
To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC.
DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up.
Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings).
The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects.
Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively).
In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes.
Clinicaltrials.gov Identifier: NCT03210103.
人乳头瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）治疗降级的最佳方法尚不清楚。
评估原发放疗（RT）与原发经口手术（TOS）在 HPV 相关 OPSCC 治疗降级中的作用。
设计、地点和参与者：这是一项在加拿大和澳大利亚的 9 个三级学术癌症中心进行的国际、多中心、开放标签、平行组 2 期随机临床试验，纳入了 2018 年 2 月 13 日至 2020 年 11 月 17 日期间 T1-T2N0-2 p16 阳性 OPSCC 的患者。患者的随访时间长达 3 年。
原发 RT（包括 60Gy RT 联合阳性淋巴结患者每周顺铂）与 TOS 和颈清扫术（ND）（根据病理发现进行辅助低剂量 RT）。
主要终点是与历史对照相比的总生存（OS）。次要终点包括无进展生存期（PFS）、生活质量和毒性。
共有 61 名患者被随机分组（RT 组 30 例[49.2%]，TOS 和 ND 组 31 例[50.8%]；中位[IQR]年龄 61.9[57.2-67.9]岁；8 名女性[13.6%]和 51 名男性[86.4%]；31 名从未吸烟者[50.8%]）。试验于 2018 年 2 月开始，由于 TOS 和 ND 臂毒性作用过大，于 2020 年 11 月停止入组。中位随访时间为 17 个月（IQR，15-20 个月）。OS 终点有 3 例死亡事件，均发生在 TOS 和 ND 臂，包括 2 例与治疗相关的死亡（分别在随机分组后 0.7 个月和 4.3 个月）和 1 例心肌梗死（8.5 个月）。PFS 终点有 4 例事件，也均发生在 TOS 和 ND 臂，包括 3 例死亡事件和 1 例局部复发。因此，OS 和 PFS 数据仍不成熟。RT 组有 20 例（67%）和 TOS 和 ND 组有 22 例（71%）患者发生 2-5 级毒性反应。两组患者在 1 年时的 MD 安德森吞咽困难指数平均（SD）评分相似（分别为 85.7[15.6]和 84.7[14.5]）。
在这项随机临床试验中，TOS 与 5 级毒性反应的不可接受风险相关，但试验组中患者在 1 年内均获得了良好的吞咽功能。需要进行长期随访以评估 OS 和 PFS 结局。
Clinicaltrials.gov 标识符：NCT03210103。
