低剂量放疗治疗人乳头瘤病毒相关口咽鳞癌的单臂、2 期研究。
Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study.
机构信息
Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
出版信息
Lancet Oncol. 2017 Jun;18(6):803-811. doi: 10.1016/S1470-2045(17)30246-2. Epub 2017 Apr 20.
BACKGROUND
Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma.
METHODS
We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195.
FINDINGS
Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment.
INTERPRETATION
Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients.
FUNDING
University of California.
背景
人乳头瘤病毒（HPV）阳性的头颈部癌症对放射治疗非常敏感。我们研究了对于 HPV 阳性口咽癌患者，减少剂量的放化疗是否可以在保持生存结果的同时提高耐受性。
方法
我们在美国的两家学术医院进行了一项单臂、2 期试验，纳入了新诊断的、经活检证实的 III 或 IV 期口咽鳞状细胞癌患者，通过 p16 检测 HPV 阳性，Zubrod 表现状态评分为 0 或 1。患者接受两个周期的诱导化疗，每 21 天给予紫杉醇 175mg/m 和卡铂（目标区域曲线下面积 6），随后进行每日图像引导的调强放疗，并同时给予每周 30mg/m 的紫杉醇。对诱导化疗有完全或部分反应的患者接受 54Gy/27 次，对反应不完全或无反应的患者接受 60Gy/30 次。主要终点是所有完成方案治疗的合格患者的 2 年无进展生存率。这项研究在 ClinicalTrials.gov 注册，编号为 NCT02048020 和 NCT01716195。
结果
2012 年 10 月 4 日至 2015 年 3 月 3 日，共纳入了 45 名患者，中位年龄为 60 岁（IQR 54-67）。1 名患者未接受治疗，44 名患者纳入分析。24 名（55%）对诱导化疗有完全或部分反应的患者接受 54Gy 放疗，20 名（45%）反应不完全或无反应的患者接受 60Gy 放疗。中位随访时间为 30 个月（IQR 26-37）。3 名（7%）患者出现局部区域复发，1 名（2%）患者出现远处转移；2 年无进展生存率为 92%（95%CI 77-97）。44 名患者中有 26 名（39%）发生 3 级不良事件，但无 4 级事件报告。诱导化疗期间最常见的 3 级事件是白细胞减少（17 [39%]）和中性粒细胞减少（5 [11%]），化疗放疗期间最常见的是吞咽困难（4 [9%]）和粘膜炎（4 [9%]）。44 名患者中有 1 名（2%）在 3 个月时依赖胃造口管，6 个月后没有患者依赖。
结论
与使用标准剂量的历史方案相比，减少 15-20%剂量的放化疗联合治疗与较高的无进展生存率和改善的毒性特征相关。放疗的降级有可能提高这些患者的治疗效果比和长期功能。
资金来源
加利福尼亚大学。
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