Background: Glioblastoma is the most common malignant brain tumor in adults. Even after maximal safe resection and adjuvant chemoradiotherapy, patients normally relapse after a few years or even months. Standard treatment for recurrent glioblastoma is not yet defined, with re-resection, re-irradiation, and systemic therapy playing key roles. Usually, re-irradiation is combined with concurrent chemotherapy, harnessing the radiosensitizing effects of alkylating agents. Methods: A retrospective analysis of 101 patients with recurrent glioblastoma treated with re-irradiation was conducted, evaluating the survival impact of concurrent chemotherapy regimens, as well as prior resection. Patients were subcategorized according to concurrent chemotherapy (temozolomide vs. CCNU vs. combination of both vs. none) and details are given regarding treatment toxicity and patterns of relapse after first- and second-line treatment. Results: Patients were treated with normo-fractionated re-irradiation (with prescription dose of ~40 Gy to the PTV), resulting in a moderate cumulative EQD2 (~100 Gy). The mean overall survival was 11.3 months (33.5 months from initial diagnosis) and mean progression free survival was 9.5 months. Prior resection resulted in increased survival (p< 0.001), especially when gross total resection was achieved. Patients who received concurrent chemotherapy had significantly longer survival vs. no chemotherapy (p< 0.01), with the combination of CCNU and TMZ achieving the best results. Overall survival was significantly better in patients who received the CCNU + TMZ combination at any time during treatment (first or second line) vs. monotherapy only. The treatment of larger volumes (mean PTV size = 112.7 cm3) was safe and did not result in worse prognosis or increased demand for corticosteroids. Overall, the incidence of high-grade toxicity or sequential radionecrosis (5%) was reasonably low and treatment was tolerated well. While second-line chemotherapy did not seem to influence patterns of relapse, patients who received TMZ + CCNU as first-line treatment had a tendency towards better local control with more out-field recurrence. Conclusions: Normo-fractionated re-irradiation appears to be safe and is accompanied by good survival outcomes, even when applied to larger treatment volumes. Patients amenable to undergo re-resection and achieving concurrent systemic therapy with alkylating agents had better OS, especially when gross total resection was possible. Based on existing data and experiences reflected in this analysis, we advocate for a multimodal approach to recurrent glioblastoma with maximal safe re-resection and adjuvant second chemoradiation. The combination of TMZ and CCNU for patients with methylated MGMT promoter yielded the best results in the primary and recurrent situation (together with re-RT). Normo-fractionated RT enables the use of more generous margins and is tolerated well.
背景：胶质母细胞瘤是成人中最常见的恶性脑肿瘤。即使经过最大安全切除和辅助放化疗，患者通常仍会在数年甚至数月后复发。复发性胶质母细胞瘤的标准治疗方案尚未明确，再切除、再放疗和全身治疗在其中发挥关键作用。通常，再放疗会联合同步化疗，以利用烷化剂的放射增敏效应。 方法：本研究对101例接受再放疗的复发性胶质母细胞瘤患者进行回顾性分析，评估同步化疗方案及既往切除史对生存的影响。根据同步化疗方案（替莫唑胺 vs. 洛莫司汀 vs. 两者联合 vs. 无化疗）对患者进行亚组分类，并详细报告治疗毒性反应以及一线和二线治疗后的复发模式。 结果：患者接受常规分割再放疗（计划靶区处方剂量约40 Gy），累积EQD2剂量适中（约100 Gy）。平均总生存期为11.3个月（自初次诊断起33.5个月），平均无进展生存期为9.5个月。既往接受切除手术可提高生存率（p<0.001），尤其是在实现大体全切除的情况下。接受同步化疗的患者生存期显著长于未化疗者（p<0.01），其中洛莫司汀联合替莫唑胺方案疗效最佳。在治疗期间（一线或二线）任何时间接受洛莫司汀+替莫唑胺联合治疗的患者，其总生存期显著优于仅接受单药治疗者。较大靶区体积（平均PTV体积=112.7 cm³）的治疗安全性良好，未导致预后恶化或皮质类固醇需求增加。总体而言，高级别毒性反应或继发放射性坏死的发生率（5%）处于合理低位，治疗耐受性良好。虽然二线化疗似乎不影响复发模式，但一线接受替莫唑胺+洛莫司汀治疗的患者表现出更好的局部控制趋势，且更多出现野外复发。 结论：常规分割再放疗安全性良好且伴随较好的生存结局，即使应用于较大治疗靶区时亦然。适合接受再切除并同步接受烷化剂全身治疗的患者总生存期更优，特别是在可能实现大体全切除的情况下。基于现有数据及本分析反映的经验，我们主张对复发性胶质母细胞瘤采用多模式治疗策略，包括最大安全范围再切除和辅助二次放化疗。对于MGMT启动子甲基化患者，替莫唑胺联合洛莫司汀方案在初治和复发情况下（联合再放疗）均取得最佳疗效。常规分割放疗允许使用更宽松的边界设置，且耐受性良好。
肿瘤(癌症)患者之家