Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
German Cancer Consortium (DKTK), partner site, Munich, Germany.
Radiat Oncol. 2021 Aug 28;16(1):165. doi: 10.1186/s13014-021-01886-3.
Multifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological differences to unifocal glioma are not fully understood. The optimal treatment of patients suffering from multifocal high-grade glioma is not defined in the current guidelines, therefore individual case series may be helpful as guidance for clinical decision-making.
Patients with multifocal high-grade glioma treated with conventionally fractionated radiation therapy (RT) in our institution with or without concomitant chemotherapy between April 2011 and April 2019 were retrospectively analysed. Multifocality was neuroradiologically assessed and defined as at least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence. IDH mutational status and MGMT methylation status were assessed from histopathology records. GTV, PTV as well as the V30Gy, V45Gy and D2% volumes of the brain were analysed. Overall and progression-free survival were calculated from the diagnosis until death and from start of radiation therapy until diagnosis of progression of disease in MRI for all patients.
20 multifocal glioma cases (18 IDH wild-type glioblastoma cases, one diffuse astrocytic glioma, IDH wild-type case with molecular features of glioblastoma and one anaplastic astrocytoma, IDH wild-type case) were included into the analysis. Resection was performed in two cases and stereotactic biopsy only in 18 cases before the start of radiation therapy. At the start of radiation therapy patients were 61 years old in median (range 42-84 years). Histopathological examination showed IDH wild-type in all cases and MGMT promotor methylation in 11 cases (55%). Prescription schedules were 60 Gy (2 Gy × 30), 59.4 Gy (1.8 Gy × 33), 55 Gy (2.2 Gy × 25) and 50 Gy (2.5 Gy × 20) in 15, three, one and one cases, respectively. Concomitant temozolomide chemotherapy was applied in 16 cases, combined temozolomide/lomustine chemotherapy was applied in one case and concomitant bevacizumab therapy in one case. Median number of GTVs was three. Median volume of the sum of the GTVs was 26 cm. Median volume of the PTV was 425.7 cm and median PTV to brain ratio 32.8 percent. Median D2% of the brain was 61.5 Gy (range 51.2-62.7) and median V30Gy and V45 of the brain were 59.9 percent (range 33-79.7) and 40.7 percent (range 14.9-64.1), respectively. Median survival was eight months (95% KI 3.6-12.4 months) and median progression free survival after initiation of RT five months (95% CI 2.8-7.2 months). Grade 2 toxicities were detected in eight cases and grade 3 toxicities in four cases consisting of increasing edema in three cases and one new-onset seizure. One grade 4 toxicity was detected, which was febrile neutropenia related to concomitant chemotherapy.
Conventionally fractionated RT with concomitant chemotherapy could safely be applied in multifocal high-grade glioma in this case series despite large irradiation treatment fields.
多灶性高级别胶质瘤是一种罕见疾病，预后非常差。多灶性胶质瘤的发病机制和与单灶性胶质瘤的病理生理差异尚未完全阐明。目前的指南并未明确规定多灶性高级别脑胶质瘤患者的最佳治疗方法，因此，病例系列研究可能有助于为临床决策提供指导。
回顾性分析了 2011 年 4 月至 2019 年 4 月期间在我院接受常规分割放射治疗（RT）联合或不联合同期化疗的多灶性高级别脑胶质瘤患者。多灶性通过 MRI T1 对比增强序列进行神经影像学评估和定义，至少有两个独立的对比增强病灶。IDH 突变状态和 MGMT 甲基化状态从组织病理学记录中评估。分析了 GTV、PTV 以及脑的 V30Gy、V45Gy 和 D2%体积。所有患者从诊断到死亡以及从放射治疗开始到 MRI 诊断疾病进展的时间计算总生存期和无进展生存期。
20 例多灶性脑胶质瘤病例（18 例 IDH 野生型胶质母细胞瘤病例，1 例弥漫性星形细胞瘤，IDH 野生型病例，具有胶质母细胞瘤的分子特征和 1 例间变性星形细胞瘤，IDH 野生型病例）被纳入分析。在开始放射治疗前，2 例患者进行了手术切除，18 例患者仅进行了立体定向活检。在开始放射治疗时，患者的中位年龄为 61 岁（范围 42-84 岁）。组织病理学检查显示所有病例均为 IDH 野生型，11 例（55%）MGMT 启动子甲基化。处方方案分别为 15 例 60Gy（2Gy×30）、3 例 59.4Gy（1.8Gy×33）、1 例 55Gy（2.2Gy×25）和 1 例 50Gy（2.5Gy×20），同时接受替莫唑胺化疗的有 16 例，替莫唑胺/洛莫司汀联合化疗的有 1 例，贝伐珠单抗联合化疗的有 1 例。中位 GTV 数为 3 个。中位 GTV 总和体积为 26cm。中位 PTV 体积为 425.7cm，中位 PTV 与脑比值为 32.8%。中位脑 D2%为 61.5Gy（范围 51.2-62.7），中位脑 V30Gy 和 V45 分别为 59.9%（范围 33-79.7）和 40.7%（范围 14.9-64.1）。中位总生存期为 8 个月（95%可信区间 3.6-12.4 个月），中位放射治疗后无进展生存期为 5 个月（95%可信区间 2.8-7.2 个月）。8 例患者出现 2 级毒性，4 例患者出现 3 级毒性，包括 3 例水肿加重和 1 例新发癫痫。检测到 1 例 4 级毒性，为与同期化疗相关的发热性中性粒细胞减少症。
尽管照射治疗野较大，本病例系列研究中常规分割 RT 联合同期化疗可安全应用于多灶性高级别脑胶质瘤。
