Department of Radiation Oncology, SUNY Downstate Health Sciences University, Brooklyn, New York.
Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick.
JAMA Netw Open. 2022 Nov 1;5(11):e2241538. doi: 10.1001/jamanetworkopen.2022.41538.
Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT.
To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021.
IMPT or IMRT with or without chemotherapy.
The main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ2 tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups.
The study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16-positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16-positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P < .001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P < .001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P < .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P < .001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P < .001). There were no significant differences in chronic toxic effects of grade 3 or greater, although there was a significant difference for chronic xerostomia of grade 2 or greater (6 IMPT [11%] vs 22 IMRT [10%]; P < .001). Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months.
In this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.
接受放射治疗的口咽癌（OPC）患者经常经历大量的毒性作用，即使采用现代技术如强度调制放射治疗（IMRT）也是如此。与 IMRT 相比，调强质子治疗（IMPT）具有降低周围危及器官剂量的潜在优势；然而，由于 IMPT 的可用性和使用有限，数据仍然很少。
比较新诊断的非转移性 OPC 患者接受 IMPT 与接受 IMRT 联合或不联合化疗的毒性作用和肿瘤学结果。
设计、地点和参与者：这项回顾性队列研究纳入了 2018 年 1 月 1 日至 2021 年 12 月 31 日期间在一家单机构三级学术癌症中心接受根治性放疗的年龄在 18 岁或以上的新诊断为非转移性 OPC 且无远处转移的患者，随访至 2021 年 12 月 31 日。
IMPT 或 IMRT 联合或不联合化疗。
主要结局是急性和慢性（≥6 个月后出现）治疗相关不良事件（AE）的发生率和肿瘤学结果，包括局部区域复发（LRR）、无进展生存期（PFS）和总生存期（OS）。采用 Fisher 确切检验和 χ2 检验评估毒性作用与治疗方式（IMPT 与 IMRT）之间的关系，采用 Kaplan-Meier 法比较两组间 LRR、PFS 和 OS。
研究纳入了 292 例 OPC 患者（272 例 HPV-p16 阳性肿瘤；93%）；254 例（87%）为男性，38 例（13%）为女性，中位年龄为 64 岁（IQR，58-71 岁）。58 例（20%）接受 IMPT 治疗，234 例（80%）接受 IMRT 治疗。中位随访时间为 26 个月（IQR，17-36 个月）。大多数患者（283 例；97%）接受了原发肿瘤 70 Gy 的剂量。57 例接受 IMPT 治疗的患者（98%）和 215 例接受 IMRT 治疗的患者（92%）的疾病为 HPV-p16 阳性。3 年 OS（97% IMPT 与 91% IMRT；P = .18）、PFS（82% IMPT 与 85% IMRT；P = .62）或 LRR（5% IMPT 与 4% IMRT；P = .59）均无显著差异。与 IMPT 相比，IMRT 的急性毒性作用发生率显著更高，包括 2 级或更高级别的口腔疼痛（42 例[72%]与 217 例[93%]；P < .001）、2 级或更高级别的口干症（12 例[21%]与 68 例[29%]；P < .001）、2 级或更高级别的味觉障碍（16 例[28%]与 134 例[57%]；P < .001）、3 级吞咽困难（4 例[7%]与 29 例[12%]；P < .001）、3 级黏膜炎（10 例[53%]与 13 例[70%]；P = .003）、2 级或更高级别的恶心（0 例[0%]与 18 例[8%]；P = .04）和 2 级或更高级别的体重减轻（22 例[37%]与 138 例[59%]；P < .001）。尽管慢性 2 级或更高级别的口干症有显著差异（6 例 IMPT [11%]与 22 例 IMRT [10%]；P < .001），但 3 级或更高级别的慢性毒性作用无显著差异。4 例接受 IMRT（2%）的患者需要经皮内镜胃造口术治疗的时间超过 6 个月，而接受 IMPT 的患者中没有。
在这项研究中，与 IMRT 相比，新诊断的非转移性 OPC 患者接受 IMPT 治疗的急性毒性作用负担明显减轻，慢性毒性作用较少，肿瘤学结果良好，2 年局部区域复发率仅为 5%。需要进行比较这两种技术和患者报告结果的前瞻性随机临床试验。
