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Abstract：
BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management.
METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications.
RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups.
CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.
METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications.
RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups.
CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.
摘要：
背景：肿瘤内出血，虽然不太常见，可能是神经胶质瘤的第一个临床表现，可以通过MRI检测到；然而，其对患者结局的确切影响仍不清楚且存在争议.2021年WHOCNS5分类强调了遗传和分子特征，开始建立出血和分子改变之间的相关性的必要性。这项研究旨在确定胶质瘤亚型中瘤内出血的患病率，并确定相关的分子和临床特征，以改善患者管理。
方法：回顾性分析2011年1月至2022年1月北京协和医院神经外科手术病理证实为脑胶质瘤患者的综合临床资料和影像学检查。根据术前磁共振成像将患者分为出血组和非出血组。对两组患者进行比较和生存分析。在亚组分析方面，我们把病人分为星形细胞瘤,IDH突变体;少突胶质细胞瘤,IDH-突变体,1p/19q-删除；胶质母细胞瘤，IDH-野生型;小儿型神经胶质瘤;或使用整合的组织学和分子特征的局限性神经胶质瘤,根据WHOCNS5分类。
结果：457名患者被纳入分析，包括67例（14.7%）瘤内出血患者。出血组明显年龄较大，术前Karnofsky表现评分较差。出血组有较高的神经功能缺损发生率和较高的Ki-67指数。分子分析表明CDKN2B,KMT5B,出血组发生PIK3CA改变更多(CDKN2B，84.4%vs.62.2%,p=0.029;KMT5B,25.0%与8.9%,p=0.029;和PIK3CA,81.3%vs.58.5%,p=0.029)。生存分析显示，出血组的预后明显较差（出血18.4个月vs.非出血39.1个月，p=0.01)。在亚组分析中，多因素分析显示，肿瘤内出血仅是胶质母细胞瘤的独立危险因素，IDH-野生型（总共457例中的162例，HR=1.72，p=0.026），但在其他类型的神经胶质瘤中没有。CDK6的分子改变（出血组p=0.004，非出血组p<0.001），EGFR（出血组p=0.003，非出血组p=0.001），FGFR2（出血组p=0.007，非出血组p=0.001）与出血组和非出血组的总生存期较短相关。
结论：术前瘤内出血的胶质瘤患者与未出血的患者相比预后不良。CDKN2B,KMT5B,PIK3CA改变与肿瘤内出血发生率增加有关，这可能是未来进一步研究肿瘤内出血的目标。
方法：回顾性分析2011年1月至2022年1月北京协和医院神经外科手术病理证实为脑胶质瘤患者的综合临床资料和影像学检查。根据术前磁共振成像将患者分为出血组和非出血组。对两组患者进行比较和生存分析。在亚组分析方面，我们把病人分为星形细胞瘤,IDH突变体;少突胶质细胞瘤,IDH-突变体,1p/19q-删除；胶质母细胞瘤，IDH-野生型;小儿型神经胶质瘤;或使用整合的组织学和分子特征的局限性神经胶质瘤,根据WHOCNS5分类。
结果：457名患者被纳入分析，包括67例（14.7%）瘤内出血患者。出血组明显年龄较大，术前Karnofsky表现评分较差。出血组有较高的神经功能缺损发生率和较高的Ki-67指数。分子分析表明CDKN2B,KMT5B,出血组发生PIK3CA改变更多(CDKN2B，84.4%vs.62.2%,p=0.029;KMT5B,25.0%与8.9%,p=0.029;和PIK3CA,81.3%vs.58.5%,p=0.029)。生存分析显示，出血组的预后明显较差（出血18.4个月vs.非出血39.1个月，p=0.01)。在亚组分析中，多因素分析显示，肿瘤内出血仅是胶质母细胞瘤的独立危险因素，IDH-野生型（总共457例中的162例，HR=1.72，p=0.026），但在其他类型的神经胶质瘤中没有。CDK6的分子改变（出血组p=0.004，非出血组p<0.001），EGFR（出血组p=0.003，非出血组p=0.001），FGFR2（出血组p=0.007，非出血组p=0.001）与出血组和非出血组的总生存期较短相关。
结论：术前瘤内出血的胶质瘤患者与未出血的患者相比预后不良。CDKN2B,KMT5B,PIK3CA改变与肿瘤内出血发生率增加有关，这可能是未来进一步研究肿瘤内出血的目标。
