Department of Radiation Oncology.
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Am J Clin Oncol. 2023 Jul 1;46(7):293-299. doi: 10.1097/COC.0000000000001007. Epub 2023 Apr 24.
The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT).
Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529.
Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment.
Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.
本试验旨在评估接受强度调制质子治疗（IMPT）的肛门癌患者接受根治性放化疗的患者和医生报告的毒性。
患有 II 期和 III 期肛门癌的患者接受 IMPT 治疗。所有患者均接受 2 个周期的 5-氟尿嘧啶和顺铂与放射治疗同时进行。在基线、放化疗期间每周以及使用医生分级的不良事件通用术语标准（CTCAE）v4.0 和 PRO-CTCAE 进行随访时评估毒性。主要终点是定义急性≥2/3 级胃肠道（GI）、泌尿生殖系统（GU）、皮肤和血液学毒性的点估计值和 95%置信区间。比较每个域的 PRO-CTCAE 问题得分≥3 的比例与基线相比。将≥2 级和≥3 级毒性的比例与接受 RTOG 0529 治疗的历史强度调制放疗患者进行比较。
2017 年至 2020 年期间共招募了 14 名患者。与接受强度调制放疗的患者相比，接受 IMPT 治疗的患者的医生报告的 GI、GU、皮肤和血液学毒性发生率没有显着差异。基线时患者报告的皮肤和 GU 毒性发生率较低，第 6 周达到峰值（分别为 91%和 58%的 PRO-CTCAE 项目≥3 级），并在 IMPT 后 3 个月恢复正常。相比之下，基线时高等级 PRO-CTCAE GI 评分的比例为 40%，在治疗后 12 个月仍持续存在。
在这项效力不足的试验中，与 IMPT 相比，临床医生报告的毒性并未得到改善。高等级 GI 症状持续 12 个月，与基线相似。需要采取额外措施来最大程度地减少与放化疗相关的急性和慢性毒性。
