Abstract

Purpose

There remains no standard of care for patients with recurrent and chemorefractory glioblastoma. Re-irradiation (reRT) provides an additional management option. However, published series predominantly focus on small reRT volumes utilizing stereotactic hypofractionated regimens. Concerns regarding toxicity have limited utilisation of reRT for larger recurrences, however this may be mitigated with use of bevacizumab (BEV).

Methods and materials

A prospective database of patients managed with the EORTC-NCIC (Stupp) protocol 60 Gy chemoradiotherapy protocol for glioblastoma between 2007 and 2021 was reviewed for those patients receiving reRT for chemorefractory relapse. Serial MRI and PET were used to establish true progression and exclude patients with pseudoprogression or radionecrosis from reRT. The primary endpoint was overall survival (OS) from date of reRT. Prognostic factors were also assessed.

Results

447 patients managed for glioblastoma under the Stupp protocol were identified, of which 372 had relapsed and were thus eligible for reRT. 71 patients underwent reRT. Median relapse-free survival from diagnosis for the reRT and overall cohorts were similar at 11.6 months (95%CI:9.4–14.2) and 11.8 months (95%CI:9.4–14.2) respectively. 60/71 (85%) reRT patients had received BEV prior to reRT and continued concurrent BEV during reRT. Of the 11 patients not managed with BEV during reRT, 10 required subsequent salvage BEV. ReRT patients were younger (median 53 vs. 59 years, p < 0.001), had better performance status (86% vs. 69% ECOG 0–1, p = 0.002) and more commonly had MGMT promoter-methylated tumours (54% vs. 40%, p = 0.083) compared to non-reRT patients. Median reRT PTV volume was 135cm³ (IQR: 69-207cm³). Median OS from reRT to death was 7.1 months (95%CI:6.3–7.9). Patients aged < 50, 50–70 and > 70 years had post-reRT median OS of 7.7, 6.4 and 6.0 months respectively (p = 0.021). Median post-reRT survival was longer for patients with ECOG performance status 0–1 compared to 2–3 (8.1 vs. 6.3 months, p = 0.039). PTV volume, site of relapse, MGMT promoter-methylation status and extent of initial surgical resection were not associated with post-reRT survival. ReRT was well-tolerated. Out of the 6 patients (8%) admitted to hospital after reRT, only one was for reRT toxicity. This was a CTCAE grade 3 radiation necrosis event in a patient managed without prior BEV.

Conclusion

Patients with recurrent glioblastoma who have been previously treated with 60 Gy radiotherapy have a meaningful survival benefit from large volume re-irradiation which is well tolerated. ReRT should not be ignored as a salvage treatment option in patients with chemorefractory progressive disease.

中文翻译：

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既往大剂量放疗后用贝伐珠单抗进行大分割再照射治疗复发化疗难治性胶质母细胞瘤：对于大体积复发患者的可行选择

摘要

目的

对于复发性和化学难治性胶质母细胞瘤患者仍然没有标准的护理。重新照射 (reRT) 提供了额外的管理选项。然而，已发表的系列主要关注利用立体定向大分割方案的小体积 reRT。关于毒性的担忧限制了 reRT 对于较大复发的使用，但是使用贝伐单抗 (BEV) 可以减轻这种情况。

方法和材料

对 2007 年至 2021 年间接受 EORTC-NCIC (Stupp) 方案 60 Gy 胶质母细胞瘤放化疗方案管理的患者的前瞻性数据库进行了审查，以了解因化学难治性复发而接受再放疗的患者。使用系列 MRI 和 PET 来确定真实进展，并将假性进展或放射性坏死的患者排除在再放疗之外。主要终点是自重新RT之日起的总生存期（OS）。还评估了预后因素。

结果

确定了 447 名根据 Stupp 方案接受胶质母细胞瘤治疗的患者，其中 372 名患者复发，因此有资格接受再放疗。 71 名患者接受了再放射治疗。 reRT 和整体队列的诊断后中位无复发生存期相似，分别为 11.6 个月 (95% CI:9.4–14.2) 和 11.8 个月 (95% CI:9.4–14.2)。 60/71 (85%) reRT 患者在 reRT 之前接受了 BEV，并在 reRT 期间继续同时进行 BEV。在 reRT 期间未接受 BEV 治疗的 11 名患者中，有 10 名需要随后抢救 BEV。 ReRT 患者更年轻（中位 53 岁 vs. 59 岁，p  < 0.001），具有更好的体能状态（86% vs. 69% ECOG 0-1，p  = 0.002），并且更常见有 MGMT 启动子甲基化肿瘤（54% vs. 69%） . 40%, p  = 0.083) 与非 reRT 患者相比。中位 reRT PTV 体积为 135cm ³（IQR：69-207cm ³）。从再 RT 到死亡的中位 OS 为 7.1 个月 (95% CI:6.3–7.9)。年龄 < 50 岁、50-70 岁和 > 70 岁的患者 reRT 后中位 OS 分别为 7.7、6.4 和 6.0 个月 ( p  = 0.021)。 ECOG 体力状态为 0-1 的患者的中位 reRT 生存期比 2-3 的患者更长（8.1 个月与 6.3 个月，p  = 0.039）。 PTV 体积、复发部位、MGMT 启动子甲基化状态和初始手术切除范围与 reRT 后生存无关。 ReRT 的耐受性良好。在 reRT 后入院的 6 名患者 (8%) 中，只有 1 名患者因 reRT 毒性而入院。这是一名 CTCAE 3 级放射性坏死事件，患者之前未接受过 BEV 治疗。

结论

先前接受过 60 Gy 放疗的复发性胶质母细胞瘤患者可以从耐受性良好的大剂量再照射中获得有意义的生存获益。 ReRT 作为化疗难治性进展性疾病患者的挽救治疗选择，不应被忽视。