肿瘤电场治疗高级别脑胶质瘤的初步疗效和安全性分析

Efficacy and safety of tumor-treating fields in treatment of high-grade gliomas

目的评价我国真实世界临床实践环境中高级别脑胶质瘤患者使用肿瘤电场治疗(TTFields)的疗效和安全性。方法回顾性分析中山大学肿瘤防治中心自2019年4月至2021年1月收治的15例复发和9例新诊断的高级别脑胶质瘤患者临床资料,所有患者使用TTFields时间均≥1个月。随访5.3个月(范围为2.3~10.7个月),按照神经肿瘤反应评估(RANO)标准判断肿瘤稳定或进展。按照Kaplan-Meier法计算无进展生存时间(PFS)和总生存时间(OS)。按照不良事件通用术语5.0版(CTCAE v5.0)标准和TTFields相关皮肤不良反应(dAE)分级标准记录不良事件。使用欧洲癌症研究和治疗组织生活质量核心问卷30(QLQ-C30)和脑癌模块问卷20(QLQ-BN20)评估患者健康相关生活质量(HRQoL)。治疗依从性通过NovoTTF-200A治疗设备的使用数据进行评估,以每日TTFields使用时间的百分比计算。结果24例患者使用TTFields的中位治疗持续时间为4.2个月(范围为1.0~10.7个月),中位治疗依从性为91.5%(范围为67.0%~97.0%)。TTFields单用2例,联合化疗22例。随访截至2021年4月,24例患者中14例稳定,10例进展(其中8例死亡)。15例复发患者的中位PFS为5.9个月(95%CI:3.3~8.6),中位OS为8.5个月(95%CI:3.2~13.8);9例新诊断患者的中位PFS和OS均为10.7个月(95%CI:无)。主要不良反应为1级(58.3%)和2级(12.5%)dAE,无3~4级dAE,表现为接触性或过敏性皮炎、糜烂、毛囊炎和溃疡。87.5%的患者HRQoL稳定。结论初步结果显示我国复发高级别脑胶质瘤患者接受TTFields的OS与国外文献报道相当,新诊断患者需进一步行生存随访;患者的治疗依从性和安全性高,dAE的发生率高于文献报道,但均为1~2级,毒性可接受。

Objective Tumor-treating fields(TTFields)is a kind of non-invasive anti-mitotic tumor therapy,which has been approved for patients with newly diagnosed and recurrent glioblastoma.This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed.All patients accepted TTFields≥1 month.Follow-up was performed for 5.3 months(ranged from 2.3 to 10.7 months);Response Assessment in Neuro-Oncology Working Group(RANO)criteria was used to evaluate the glioma responses.The progression-free survival(PFS)and overall survival(OS)were calculated according to Kaplan-Meier method.Common Terminology Criteria for Adverse Events v5.0(CTCAE v5.0)and TTFields related skin adverse reaction(dAE)criteria were used to evaluate the adverse events.Quality of life questionnaire-core 30(QLQ-C30)and QLQ-brain cancer module(QLQ-BN20)questionnaires were used to evaluate the health-related quality of life(HRQoL).Treatment compliance was evaluated by data on the use of NovoTTF-200A devices,and calculated as a percentage of daily TTFields usage.Results The median duration of TTFields was 4.2 months(ranged from 1.0 to 10.7 months),with a median compliance rate of 91.5%(67.0%-97.0%).TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients.From follow-up to April 2021,14 patients had stable symptoms and 10 had disease progression(8 died).The median PFS and OS of recurrent patients were 5.9 months(95%CI:3.3-8.6 months)and 8.5 months(95%CI:3.2-13.8 months),respectively;and the median PFS and OS of newly diagnosed patients were both 10.7 months(without 95%CI).The common adverse events included grading 1 dAE(58.3%)and grading 2 dAE(12.5%),without grading 3 or 4 dAE,manifested as contact or allergic dermatitis,erosion,folliculitis and ulcers.And 87.5%patients had stable HRQoL.Conclusions The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature;and the newly diagnosed patients need further survival follow-up.The patients'treatment compliance and safety are good.The dAE incidence(grading 1-2)is higher than that reported in the literature,and the toxicity was acceptable.