University of California San Francisco, San Francisco, CA.
NRG Oncology Statistics and Data Management Center, Philadelphia, PA.
J Clin Oncol. 2021 Mar 20;39(9):956-965. doi: 10.1200/JCO.20.03128. Epub 2021 Jan 28.
Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.
In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).
Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( = .04). For IMRT, 2-year PFS was 87.6% ( = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% 52.4%; < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( = .56).
The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.
降低放射治疗剂量可以提高低危人乳头瘤病毒相关口咽鳞状细胞癌（OPSCC）患者的生活质量（QOL）。减少剂量的放射治疗是否能达到与标准放化疗相当的疾病控制和 QOL 尚不清楚。
在这项随机、二期试验中，p16 阳性、T1-T2 N1-N2b M0 或 T3 N0-N2b M0 OPSCC（第 7 版分期）的患者，吸烟史≤10 包年，接受 60 Gy 强度调制放射治疗（IMRT），6 周内每周给予顺铂（C），或 5 周内给予 60 Gy IMRT。为了进入三期研究，一个治疗组必须达到 2 年无进展生存率（PFS）率高于 85%的历史对照率，且 MD 安德森吞咽障碍量表（MDADI）的 1 年平均综合评分≥60。
306 例患者被随机分配并符合条件。IMRT + C 的 2 年 PFS 为 90.5%，拒绝了 2 年 PFS≤85%的零假设（=0.04）。IMRT 的 2 年 PFS 为 87.6%（=0.23）。IMRT + C 和 IMRT 的 1 年 MDADI 平均评分分别为 85.30 和 81.76。IMRT + C 和 IMRT 的 2 年总生存率分别为 96.7%和 97.3%。急性不良反应（AE）定义为治疗结束后 180 天内发生的不良反应。IMRT + C 组的 3-4 级急性 AE 更多（79.6%比 52.4%；<0.001）。3-4 级晚期 AE 的发生率分别为 21.3%和 18.1%（=0.56）。
IMRT + C 组达到了预先设定的终点，证明可以推进到三期研究。IMRT + C 组报告的 3-4 级急性 AE 发生率更高。
