复发性胶质母细胞瘤再次手术后基因型变异对生存的影响。
Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma.
机构信息
Vivian L. Smith Department of Neurosurgery, McGovern Medical School at UT Health, Houston, TX, USA.
Department of Pathology and Laboratory Medicine, McGovern Medical School at UT Health, Houston, TX, USA.
出版信息
J Neurooncol. 2022 Jan;156(2):353-363. doi: 10.1007/s11060-021-03917-1. Epub 2022 Jan 8.
INTRODUCTION
Recurrent glioblastoma (rGBM) prognosis is dismal. In the absence of effective adjuvant treatments for rGBM, re-resections remain prominent in our arsenal. This study evaluates the impact of reoperation on post-progression survival (PPS) considering rGBM genetic makeup.
METHODS
To assess the genetic heterogeneity and treatment-related changes (TRC) roles in re-operated or medically managed rGBMs, we compiled demographic, clinical, histopathological, and next-generation genetic sequencing (NGS) characteristics of these tumors from 01/2005 to 10/2019. Survival data and reoperation were analyzed using conventional and random survival forest analysis (RSF).
RESULTS
Patients harboring CDKN2A/B loss (p = 0.017) and KDR mutations (p = 0.031) had notably shorter survival. Reoperation or bevacizumab were associated with longer PPS (11.2 vs. 7.4-months, p = 0.006; 13.1 vs 6.2, p < 0.001). Reoperated patients were younger, had better performance status and greater initial resection. In 136/273 (49%) rGBMs undergoing re-operation, CDKN2A/B loss (p = 0.03) and KDR mutations (p = 0.02) were associated with shorter survival. In IDH-WT rGBMs with NGS data (n = 166), reoperation resulted in 7.0-month longer survival (p = 0.004) than those managed medically. This reoperation benefit was independently identified by RSF analysis. Stratification analysis revealed that EGFR-mutant, CDKN2A/B-mutant, NF1-WT, and TP53-WT rGBM IDH-WT subgroups benefit most from reoperation (p = 0.03). Lastly, whether or not TRC was prominent at re-operation does not have any significant impact on PPS (10.5 vs. 11.5-months, p = 0.77).
CONCLUSIONS
Maximal safe re-resection significantly lengthens PPS regardless of genetic makeup, but reoperations are especially beneficial for IDH-WT rGBMs with EGFR and CDKN2A/B mutations with TP53-WT, and NF1-WT. Histopathology at recurrence may be an imperfect gauge of disease severity at progression and the imaging progression may be more reflective of the prognosis.
简介
复发性胶质母细胞瘤（rGBM）的预后较差。在缺乏有效辅助治疗 rGBM 的情况下，再次切除仍然是我们治疗策略中的重要手段。本研究评估了在考虑 rGBM 遗传构成的情况下，再次手术对进展后生存（PPS）的影响。
方法
为了评估复发性或经药物治疗的 rGBM 中的遗传异质性和治疗相关变化（TRC）的作用，我们从 2005 年 1 月至 2019 年 10 月收集了这些肿瘤的人口统计学、临床、组织病理学和下一代基因测序（NGS）特征。使用传统和随机生存森林分析（RSF）分析生存数据和再次手术。
结果
CDKN2A/B 缺失（p=0.017）和 KDR 突变（p=0.031）的患者的生存时间明显更短。再次手术或贝伐珠单抗治疗与更长的 PPS 相关（11.2 与 7.4 个月，p=0.006；13.1 与 6.2，p<0.001）。再次手术的患者年龄较小，表现状态较好，初始切除范围较大。在 273 例再次手术的 rGBM 中，有 136 例（49%）CDKN2A/B 缺失（p=0.03）和 KDR 突变（p=0.02）与较短的生存时间相关。在有 NGS 数据的 IDH-WT rGBM 中（n=166），再次手术导致生存时间延长 7.0 个月（p=0.004），明显优于单纯药物治疗。这一手术获益在 RSF 分析中得到了独立确认。分层分析显示，EGFR 突变、CDKN2A/B 突变、NF1-WT 和 TP53-WT rGBM IDH-WT 亚组从再次手术中获益最大（p=0.03）。最后，再次手术时是否存在 TRC 并不显著影响 PPS（10.5 与 11.5 个月，p=0.77）。
结论
最大限度的安全再次切除显著延长了 PPS，无论遗传构成如何，但再次手术对 EGFR 和 CDKN2A/B 突变且 TP53-WT 和 NF1-WT 的 IDH-WT rGBM 特别有益。复发时的组织病理学可能不是疾病严重程度的完美指标，影像学进展可能更能反映预后。
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