OPTIMA 研究：人乳头瘤病毒阳性口咽癌的 II 期剂量和体积递减试验。
OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer.
机构信息
Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, USA.
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, USA.
出版信息
Ann Oncol. 2019 Feb 1;30(2):297-302. doi: 10.1093/annonc/mdy522.
BACKGROUND
Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy.
PATIENTS AND METHODS
Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity.
RESULTS
Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001).
CONCLUSIONS
Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified.
CLINICAL TRIAL REGISTRATION
Clinical trials.gov identifier: NCT02258659.
背景
HPV+口咽鳞状细胞癌患者根据诱导化疗的反应被分配接受剂量和体积降低的放疗（RT）或放化疗（CRT），以限制治疗相关毒性，同时保持疗效。
方法
患者被分为低危（≤T3，≤N2B，≤10 包年吸烟史）或高危（T4 或≥N2C 或>10 PYH）。在三个周期的卡铂/紫杉醇 Nab 后，使用实体瘤反应评估标准 1.1 评估反应。≥50%应答的低危患者接受 50 戈瑞（Gy）RT（RT50），而 30%-50%应答的低危患者或≥50%应答的高危患者接受 45 Gy CRT（CRT45）。应答较少的患者接受标准的 75 Gy CRT（CRT75）。RT/CRT 仅限于第一组未受累淋巴结。主要终点是与 85%的历史对照相比的 2 年无进展生存率。次要终点包括总生存率和毒性。
结果
共纳入 62 例患者（28 例低危/34 例高危）。低危患者中，71%接受 RT50，21%接受 CRT45。高危患者中，71%接受 CRT45。中位随访 29 个月，低危患者 2 年 PFS 和 OS 分别为 95%和 100%，高危患者分别为 94%和 97%。总体 2 年 PFS 为 94.5%，在历史对照的 11%非劣效性边界内。3 级以上粘膜炎分别发生在 RT50、CRT45 和 CRT75 组的 30%、63%和 91%（P=0.004）。RT50、CRT45 和 CRT75 组的任何 PEG 管使用率分别为 0%、31%和 82%（P<0.0001）。
结论
HPV+ OPSCC 的诱导化疗联合反应和风险分层的剂量和体积降低的 RT/CRT 与良好的肿瘤学结果和降低的急性和慢性毒性相关。在大型多中心研究中进一步评估基于诱导的降级是合理的。
临床试验注册
ClinicalTrials.gov 标识符：NCT02258659。
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