Abstract

Introduction

Standard of care for glioblastoma includes concurrent chemoradiation and maintenance temozolomide with tumor treatment fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our initial experience evaluating toxicity and tolerability of scalp-sparing radiation with concurrent TTFields.

Methods

This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed glioblastoma were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent temozolomide (75 mg/m² daily), and TTFields. Maintenance therapy included standard temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity for concurrent TTFields with chemoradiation in newly diagnosed glioblastoma.

Results

We report the first ten patients on the trial. Eight were male, and two were female, with median age 61 years (range 49 to 73 years). Median KPS was 90 (range 70–90). Median follow-up was 7.9 months (2.8 to 17.9 months). Nine (90%) patients with unmethylated MGMT promotor, and one with methylated. Median time from surgery to radiation was 33 days (28 to 49 days). All patients completed concurrent chemoradiation plus TTFields without radiation or TTFields treatment interruption or discontinuation. Scalp dose constraints were achieved for all patients, with mean dose having a median value of 7.7 Gy (range 4.9 to 13.2 Gy), D20cc median 22.6 Gy (17.7 to 36.8 Gy), and D30cc median 19.8 Gy (14.8 to 33.4 Gy). Average daily use during concurrent phase had median value of 83.5% and 77% for maintenance. There was no related ≥ Grade 3 toxicity. Skin toxicity (erythema, dermatitis, pruritus) was noted in 80% of patients, however, these were limited to Grade 1 or 2 events which resolved spontaneously or responded to topical medications. Eight patients (80%) had progression, with median PFS of 6.9 months (range 2.8 to 9.6 months).

Conclusions

Concurrent TTFields with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trial is warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.

Trial registration

Clinicaltrials.gov Identifier NCT03477110

中文翻译：

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新诊断成胶质细胞瘤患者的头皮保留放疗，同时使用替莫唑胺和肿瘤治疗领域（SPARE）的初步经验。

摘要

介绍

胶质母细胞瘤的护理标准包括同时放化疗和维持替莫唑胺以及肿瘤治疗领域（TTFields）。临床前研究表明，TTFields和放射治疗具有协同作用。我们报告了我们的初步经验，即同时使用TTFields评估头皮保留辐射的毒性和耐受性。

方法

这是一项单臂试验研究（clinicaltrials.gov标识符：NCT03477110）。新诊断的成胶质细胞瘤的KPS≥60的成年患者（年龄≥18岁）是合格的。所有患者均接受头皮同时放疗（30次60 Gy），标准并发替莫唑胺（每天75 mg / m ²）和TTFields。维持治疗包括标准替莫唑胺和TTFields的延续。放射治疗通过TTFields阵列进行。在新诊断的胶质母细胞瘤中，主要终点是同时进行化学放射治疗的TT场的安全性和毒性。

结果

我们报告了该试验的前十名患者。男性8位，女性2位，中位年龄61岁（49-73岁）。KPS中位数为90（范围70-90）。中位随访时间为7.9个月（2.8至17.9个月）。九名（90％）患者患有未甲基化的MGMT启动子，一名患有甲基化。从手术到放疗的中位时间为33天（28至49天）。所有患者均完成了同时放化疗并接受了TTFields，无放射或TTFields治疗中断或中断。所有患者均达到头皮剂量限制，平均剂量中位数为7.7 Gy（范围为4.9至13.2 Gy），D20cc中位数为22.6 Gy（17.7至36.8 Gy）和D30cc中位数为19.8 Gy（14.8至33.4 Gy）。并发阶段的平均每日使用量的中位数为83.5％，维护的中位数为77％。没有相关的≥3级毒性。在80％的患者中注意到皮肤毒性（红斑，皮炎，瘙痒），但是，这些毒性仅限于1级或2级事件，这些事件会自发缓​​解或对局部用药产生反应。8名患者（80％）进展，中位PFS为6.9个月（2.8至9.6个月）。

结论

同时进行头皮化学放疗的TTFields是一种安全可行的治疗方法，毒性有限。有必要进行未来的随机前瞻性试验，以定义同时进行化学放疗的TTFields的治疗优势。

试用注册

Clinicaltrials.gov标识符NCT03477110