Proton beam therapy for oropharyngeal cancer (TORPEdO): a phase 3, randomised controlled trial.

We aimed to compare late functional, patient-reported, disease control, and survival outcomes between IMPT and IMRT.

我们的目标是比较IMPT与IMRT在晚期功能、患者报告、疾病控制和生存结果方面的差异。

Methods

We did a phase 3 trial (TORPEdO) in 20 UK National Health Service hospitals.

我们在20家英国国家医疗服务体系医院进行了TORPEdO III期临床试验。

We randomly assigned (2:1) patients with locally advanced oropharyngeal squamous cell carcinoma to IMPT or IMRT (70 Gy in 33 fractions, for 6·5 weeks) with two cycles of high-dose cisplatin (100 mg/m2, every 3 weeks).

我们按照2:1的比例随机分配了局部晚期口咽鳞状细胞癌患者接受质子束治疗（IMPT）或调强放疗（IMRT，总剂量70 Gy，分33次照射，持续6.5周），并接受两个周期的高剂量顺铂治疗（每3周100 mg/m2）。

Co-primary endpoints at 12 months were gastrostomy-tube dependence (use of feeding tube for nutrition) or severe weight loss (≥20% from baseline) and University of Washington quality of life (UW-QoL) mean physical composite score for saliva, taste, chewing, swallowing, speech and appearance.

12个月的主要共研究终点是胃造口管依赖（使用喂食管进行营养）或严重体重减轻（从基线起≥20%）以及华盛顿大学生活质量（UW-QoL）平均身体综合评分，包括唾液、味觉、咀嚼、吞咽、言语和外观。

The study was registered with the ISRCTN registry, ISRCTN16424014; recruitment is complete and follow-up is ongoing.

该研究已在ISRCTN注册，注册号为ISRCTN16424014；招募工作已完成，随访正在进行中。

Results

Between Feb 25, 2020, and June 13, 2023, we randomly assigned 205 patients (99 [48%] with T3 or T4 disease and 44 [22%] with bilateral neck lymph node involvement (N2[c]); 136 [66%] to IMPT and 69 [34%] to IMRT). 163 (80%) patients were male and 42 (20%) were female.

在2020年2月25日至2023年6月13日期间，我们随机分配了205名患者（其中99名[48%]患有T3或T4期疾病，44名[22%]双侧颈部淋巴结受累（N2[c]）；136名[66%]接受IMPT治疗，69名[34%]接受IMRT治疗）。163名（80%）患者为男性，42名（20%）为女性。

Ethnicity data were self-reported by 177 (86%) patients; most were White British (167 [94%]).

177名（86%）患者自我报告了种族数据；其中大多数为白种英国人（167名[94%]）。

At 12 months, gastrostomy-tube dependence occurred in two (2%) of 119 patients in the IMPT group and in one (2%) of 59 patients in the IMRT group and severe weight loss occurred in 20 (18% [97·5% CI 11 to 28]) of 110 patients in the IMPT group and in three (6% [1 to 17]) of 53 patients in the IMRT group (combined odds ratio 2·80 [97·5% CI 0·75 to 10·4]; p=0·079).

在12个月时，IMPT组的119名患者中有2名（2%）和IMRT组的59名患者中有1名（2%）依赖胃造口管，IMPT组的110名患者中有20名（18% [97.5% CI 11至28]）和IMRT组的53名患者中有3名（6% [1至17]）出现严重体重减轻（综合比值比为2.80 [97.5% CI 0.75至10.4]；p=0.079）。

Mean UW-QoL physical composite scores at 12 months were 78·3 in the IMPT group versus 77·1 in the IMRT group (difference 1·3 [97·5% CI -3·7 to 6·2]; p=0·56).

12个月时，IMPT组的UW-QoL身体综合评分平均为78.3，而IMRT组为77.1（差异1.3 [97.5% CI -3.7至6.2]；p=0.56）。

There were 14 serious adverse events in 12 patients (nine assessed as unrelated to the study treatment [four in the IMPT group and five in the IMRT group] and five study treatment-related [one IMPT vs four IMRT]); the most common events were acute kidney injury (five [36%]) and thromboembolism (four [29%]).

在12名患者中发生了14起严重不良事件（其中九起被认为与研究治疗无关[IMPT组四起，IMRT组五起]，五起与研究治疗相关[IMPT组一起，IMRT组四起]）；最常见的事件是急性肾损伤（五起[36%]）和血栓栓塞（四起[29%]）。

There were no treatment-related deaths.

没有与治疗相关的死亡事件。

At a median follow-up of 28·3 months (IQR 26·5 to 39·3), 24-month freedom from loco-regional recurrence rates were 94% (99% CI 86-98) in the IMPT group versus 97% (82-100) in the IMRT group (hazard ratio[HR] 2·6 [99% CI 0·3 to 20·3; 95% CI 0·5-12·4]; p=0·24), and overall survivalrates were 95% (86 to 98) in the IMPT group versus 95% (81-99) in the IMRT group (HR 1·6 [99% CI 0·3 to 8·8; 95% CI 0·4 to 5·9; p=0·47).

在中位随访时间为28.3个月（四分位数间距26.5至39.3）时，IMPT组的24个月局部区域无复发生存率为94%（99%置信区间86-98），而IMRT组为97%（82-100）（风险比[HR]为2.6 [99%置信区间0.3至20.3；95%置信区间0.5-12.4]；p=0.24），总生存率在IMPT组为95%（86至98），IMRT组为95%（81-99）（HR为1.6 [99%置信区间0.3至8.8；95%置信区间0.4至5.9；p=0.47）。

interpretation

IMPT and IMRT had similar late physical quality of life scores, gastrostomy-tube dependence, local control, and overall survival. In health-care settings where IMPT is not used routinely for oropharyngeal squamous cell carcinoma, IMRT remains the standard of care.

IMPT和IMRT在晚期生活质量评分、胃造口管依赖性、局部控制和总生存方面相似。在不常规使用IMPT治疗口咽鳞状细胞癌的医疗环境中，IMRT仍然是标准治疗方法。

funding

Cancer Research UK.

英国癌症研究