Flies Christina Maria, Friedrich Michel, Lohmann Philipp, van Garderen Karin Alida, Smits Marion, Tonn Joerg-Christian, Weller Michael, Galldiks Norbert, Snijders Tom Jan
Department of Neurology & Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Institute of Neuroscience and Medicine (INM-3, INM-4), Research Center Juelich, Juelich, Germany.
Neuro Oncol. 2024 May 3;26(5):902-910. doi: 10.1093/neuonc/noad247.
Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017.
Patients with ≥ 3 follow-up MRIs were included. Preliminary PD was defined as a ≥ 25% increase of the sum of products of perpendicular diameters (SPD) of a new or increasing lesion compared to baseline. PD required a second ≥25% increase of the SPD. Treatment-associated changes require stable or regressing disease after preliminary PD.
Of the 424 evaluable patients, 221 patients (52%) were randomized into the cilengitide and 203 patients (48%) into the control arm. After chemoradiation with or without cilengitide, preliminary PD occurred in 274 patients (65%) during available follow-up, and 88 of these patients (32%) had treatment-associated changes, whereas 67 patients (25%) had PD. The remaining 119 patients (43%) had no further follow-up after preliminary PD. Treatment-associated changes were more common in the cilengitide arm than in the standard-of-care arm (24% vs. 17%; relative risk, 1.3; 95% CI, 1.004-1.795; P = .047). Treatment-associated changes occurred mainly during the first 6 months after RT (54% after 3 months vs. 13% after 6 months).
With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.
影像学进展可能源于疾病进展（PD）或假性进展/治疗相关改变。我们根据2017年神经肿瘤学改良反应评估（RANO）标准，评估了接受标准放化疗联合或不联合整合素抑制剂西仑吉肽治疗的O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化胶质母细胞瘤的影像学进展情况。
纳入有≥3次随访MRI的患者。初步PD定义为新出现或增大的病灶垂直直径乘积之和（SPD）较基线增加≥25%。PD需要SPD再次增加≥25%。治疗相关改变要求在初步PD后疾病稳定或缩小。
在424例可评估患者中，221例患者（52%）被随机分配至西仑吉肽组，203例患者（48%）被分配至对照组。在接受含或不含西仑吉肽的放化疗后，274例患者（65%）在可获得的随访期间出现初步PD，其中88例患者（32%）有治疗相关改变，而67例患者（25%）有PD。其余119例患者（43%）在初步PD后未进一步随访。治疗相关改变在西仑吉肽组比在标准治疗组更常见（24%对17%；相对风险，1.3；95%CI，1.004 - 1.795；P = 0.047）。治疗相关改变主要发生在放疗后的前6个月（3个月后为54%，6个月后为13%）。
采用改良RANO标准，与之前关于MGMT启动子甲基化胶质母细胞瘤的研究相比，治疗相关改变的发生率较低。与标准治疗相比，西仑吉肽治疗后该发生率更高。改良RANO标准中推荐的确认性扫描并非总能获得，反映了当前的临床实践情况。
