Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institution, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):104-109. doi: 10.1016/j.ijrobp.2019.03.011. Epub 2019 Mar 14.
The early results of a phase 1 study of stereotactic ablative radiation therapy for early-stage glottis cancer were previously reported. However, additional late adverse events occurred in the second arm during the follow-up period. In this study, the dose-limiting toxicities and premature closure of the clinical trial are reported.
Thirteen patients with cT1-2N0M0 squamous cell carcinoma of the glottis were enrolled between May 2015 and July 2018. Seven patients in the first arm received 59.5 Gy to the gross tumor volume and 47.6 Gy to the remaining larynx, delivered in 17 fractions. The second arm dose was 55 Gy and 40.7 Gy in 11 fractions to the gross tumor volume and the remaining larynx, respectively. Patients were treated according to the simultaneous integrated boost approach with volumetric modulated arc therapy.
The median follow-up was 37 months (range, 6-41.4) for the first arm and 14.5 months (range, 4.8-21.5) for the second arm. Maximum acute toxicity was grade 2 laryngeal mucositis for each arm. Maximum chronic toxicity was grade 3 laryngeal inflammation, occurring in 2 patients (33.3%) in the second arm. One patient underwent a laryngomicrosurgical biopsy for a vocal cord ulcer, and another patient underwent supraglottic laryngectomy because of arytenoid cartilage necrosis. In the first arm, chronic toxicity was not observed, except for grade 1 laryngeal edema in 1 patient.
The phase 1 dose escalation study was terminated early because of the unexpected dose-limiting toxicities occurring in patients in the second arm. It was concluded that stereotactic ablative radiation therapy is not feasible for early-stage glottic cancer owing to treatment-related toxicity.
先前报道了立体定向消融放疗治疗早期声门型癌症的 1 期研究的早期结果。然而，在随访期间，第二组中出现了其他晚期不良事件。在这项研究中，报告了剂量限制毒性和临床试验的过早关闭。
2015 年 5 月至 2018 年 7 月期间共招募了 13 例声门区 T1-2N0M0 期的鳞状细胞癌患者。第一组的 7 例患者接受 59.5Gy 的大体肿瘤体积和 47.6Gy 的剩余喉部照射，共 17 个分次。第二组的剂量分别为 55Gy 和 40.7Gy，用于大体肿瘤体积和剩余喉部，共 11 个分次。采用容积调强弧形治疗的同时整合升压方法对患者进行治疗。
第一组的中位随访时间为 37 个月（范围，6-41.4），第二组为 14.5 个月（范围，4.8-21.5）。两组的最大急性毒性均为 2 级喉粘膜炎。第二组有 2 例（33.3%）患者发生 3 级慢性喉炎，为最严重的毒性。1 例患者因声带溃疡行喉显微活检，另 1 例患者因杓状软骨坏死行喉上切除术。第一组除 1 例患者出现 1 级喉水肿外，未观察到慢性毒性。
由于第二组患者出现了意外的剂量限制毒性，1 期剂量递增研究提前终止。研究得出结论，由于与治疗相关的毒性，立体定向消融放疗不适用于早期声门型癌症。
