BACKGROUND Glioblastoma (GBM) is an aggressive primary brain tumor with median overall survival (OS) of less than one year in unselected adult patients. There is no standard therapy at recurrence. We aimed to evaluate OS in a consecutive series of GBM patients from Norway’s two largest regional health authorities, compare the effect of physicians’ choice of antineoplastic treatment upon recurrence and identify prognostic and predictive factors. MATERIAL AND METHODS Clinicopathological data from n=467 patients with histologically confirmed GBM diagnosed and treated at Haukeland and Oslo university hospitals from January 2015 to December 2017 was retrospectively collected. Data included tumor location, methylation status of the methylguanine-DNA methyltransferase (MGMT) promoter and mutation of the isocitrate dehydrogenase (IDH) genes, patient age and sex, extent of tumor resection at primary diagnosis, and treatment at first, second and third tumor recurrences. Cox-proportional hazards regression with pairwise analyses adjusted for multiple testing with Scheffé’s post-hoc test were used to adjust effect of multiple risk factors on mortality. RESULTS Median OS was 12.1 months and 21.4 % and 6.8 % of patients were alive at 2 and 5 years, respectively. Treatment at recurrence varied between institutions but did not impact OS (p=0.201). Median time to progression was 8.2 months. Age, MGMT promoter methylation, tumor location and extent of tumor resection were all independent prognostic factors for OS. Patients receiving radiotherapy to 60 Gray with concomitant and adjuvant temozolomide at primary diagnosis had best outcome with median OS of 16.1 months and 9.3% were alive at 5 years. At first recurrence patients eligible for gammaknife/stereotactic radiosurgery (GK/SRS) or surgery, alone or combined with chemotherapy, had superior survival compared to chemotherapy alone (p<0.0001 and p=0.014, respectively). On Scheffé’s post-hoc analyses only GK/SRS was superior to chemotherapy (p=0.01). At second and third recurrence none of the antineoplastic strategies came across as superior or inferior to each other using Cox. On Scheffé’s post-hoc analyses chemotherapy alone and combined with bevacizumab were superior at second recurrence (p=0.008 and p=0.042, respectively) and chemotherapy combined with bevacizumab was superior at third recurrence (p=0.043), compared to no antineoplastic treatment. Our retrospective study is limited by small sample sizes and heterogeneous treatment groups, especially at second and third recurrences, as well as patient selection. CONCLUSION Recurrence treatment differed between the two institutions but there was no difference in OS. Our findings underline the lack of standard therapy upon GBM recurrence and the urgent need for novel therapeutic strategies.

中文翻译：

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P14.65 467 名胶质母细胞瘤患者的连续系列生存：预后因素的影响和两个独立机构的复发治疗

背景 胶质母细胞瘤 (GBM) 是一种侵袭性原发性脑肿瘤，在未经选择的成年患者中，中位总生存期 (OS) 不到一年。复发时没有标准疗法。我们旨在评估来自挪威两个最大区域卫生当局的连续系列 GBM 患者的 OS，比较医生选择抗肿瘤治疗对复发的影响，并确定预后和预测因素。材料和方法 回顾性收集了 2015 年 1 月至 2017 年 12 月在 Haukeland 和奥斯陆大学医院诊断和治疗的组织学证实的 GBM 患者 n=467 的临床病理学数据。数据包括肿瘤位置、甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子的甲基化状态和异柠檬酸脱氢酶（IDH）基因的突变，患者的年龄和性别，初次诊断时的肿瘤切除范围，以及第一次、第二次和第三次肿瘤复发时的治疗。使用 Scheffé 事后检验调整多重检验的成对分析的 Cox 比例风险回归来调整多种风险因素对死亡率的影响。结果 中位 OS 为 12.1 个月，2 年和 5 年时分别有 21.4% 和 6.8% 的患者存活。复发时的治疗因机构而异，但不影响 OS (p=0.201)。中位进展时间为 8.2 个月。年龄、MGMT 启动子甲基化、肿瘤位置和肿瘤切除范围都是 OS 的独立预后因素。在初步诊断时接受 60 Gray 放疗并伴随和辅助替莫唑胺的患者具有最佳结果，中位 OS 为 16.1 个月和 9 个月。3% 的人在 5 年时还活着。与单独的化学疗法相比，适合接受伽马刀/立体定向放射外科 (GK/SRS) 或手术的首次复发患者的生存率优于单独的化学疗法（分别为 p < 0.0001 和 p = 0.014）。在 Scheffé 的事后分析中，只有 GK/SRS 优于化疗（p=0.01）。在第二次和第三次复发时，使用 Cox 时，没有一种抗肿瘤策略优于或低于对方。在 Scheffé 的事后分析中，与未进行抗肿瘤治疗相比，单独化疗和联合贝伐单抗在第二次复发时表现优异（分别为 p = 0.008 和 p = 0.042），而化疗联合贝伐单抗在第三次复发时表现优异（p = 0.043）。我们的回顾性研究受到样本量小和治疗组异质性的限制，特别是在第二次和第三次复发以及患者选择时。结论 两个机构的复发治疗存在差异，但 OS 无差异。我们的研究结果强调了 GBM 复发缺乏标准治疗以及迫切需要新的治疗策略。