Dasgupta Pushan, Lin Heather, Kumar Gayatri, Soomro Zaid, Ayala Max M, Parra Edwin R, Weathers Shiao-Pei, Lang Frederick F, Bhat Krishna P, de Groot John, Majd Nazanin K
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
J Neurooncol. 2025 Jun 25. doi: 10.1007/s11060-025-05131-9.
While checkpoint inhibitor therapy (CPI) has transformed treatment in multiple solid tumors, its efficacy in glioblastoma (GBM) remains limited. Understanding the molecular and clinical factors that influence glioblastoma's response to CPI is essential to improving outcomes.
We identified patients with recurrent GBM, who had been treated with CPI and determined the association between their molecular, clinical, and demographic characteristics and survival outcomes.
We identified 35 patients with recurrent GBM treated with CPI. PIK3CA mutation was associated with a statistically significant shorter OS duration, calculated from CPI initiation (p-value = 0.014). Tumor tissue without the mutation had less PD-1 expression in CD3+/CD8 + T cells. RB1 and TERT promoter mutations were associated with shorter PFS durations (p-value = 0.009, 0.053, respectively). Length of CPI therapy of more than 6 months was associated with increased PFS and OS (p-value = 0.069, 0.088, respectively), while steroid use at baseline was associated with a shorter OS (p-value = 0.0016). Multifocal disease was associated with shorter PFS and OS durations (p-value = 0.0011, 0.0015, respectively) among all patients.
In glioblastoma, PIK3CA, RB1, TERT promoter mutations, steroid use prior to start of CPI, and multifocal disease may be associated with a poor response to CPI while increased length of CPI may be associated with improved response. Our results may provide the rationale for clinical trials combining PI3K inhibitors with CPI in glioblastoma. The small sample size and retrospective nature of the study carries selection bias and/or confounding effects and larger studies need to be done to validate these results.
虽然检查点抑制剂疗法（CPI）已经改变了多种实体瘤的治疗方式，但其在胶质母细胞瘤（GBM）中的疗效仍然有限。了解影响胶质母细胞瘤对CPI反应的分子和临床因素对于改善治疗效果至关重要。
我们确定了接受过CPI治疗的复发性GBM患者，并确定了他们的分子、临床和人口统计学特征与生存结果之间的关联。
我们确定了35例接受CPI治疗的复发性GBM患者。PIK3CA突变与从CPI开始计算的总生存期（OS）显著缩短相关（p值=0.014）。无该突变的肿瘤组织在CD3+/CD8+T细胞中的PD-1表达较低。RB1和TERT启动子突变与较短的无进展生存期（PFS）相关（p值分别为0.009、0.053）。CPI治疗时间超过6个月与PFS和OS增加相关（p值分别为0.069、0.088），而基线时使用类固醇与较短的OS相关（p值=0.0016）。在所有患者中，多灶性疾病与较短的PFS和OS相关（p值分别为0.0011、0.0015）。
在胶质母细胞瘤中，PIK3CA、RB1、TERT启动子突变、CPI开始前使用类固醇以及多灶性疾病可能与对CPI反应不佳相关，而延长CPI治疗时间可能与反应改善相关。我们的结果可能为胶质母细胞瘤中PI3K抑制剂与CPI联合的临床试验提供理论依据。本研究的样本量小且具有回顾性，存在选择偏倚和/或混杂效应，需要进行更大规模的研究来验证这些结果。
