From the Dr. Senckenberg Institute of Neurooncology (P.S.Z., M.V., J.P.S., M.W.R.), University Cancer Center (UCT) Frankfurt (P.S.Z., K.F., M.V., E.F., P.N.H., J.P.S., M.W.R.), Frankfurt Cancer Institute (FCI) (P.S.Z., K.F., M.V., E.F., P.N.H., J.P.S., M.W.R.), Institute of Neurology (Edinger-Institute) (K.F., P.N.H.), Institute of Biostatistics and Mathematical Modeling (N.F.), Department of Neurosurgery (M.-T.F.), and Department of Radiotherapy and Oncology (E.F.), University Hospital Frankfurt, Goethe University; German Cancer Consortium (DKTK) (P.S.Z., K.F., M.V., E.F., P.N.H., J.P.S., M.W.R.), Frankfurt am Main; and Division of Clinical Neurooncology, Department of Neurology and Centre of Integrated Oncology (U.H.), University Hospital Bonn, Germany.
Neurology. 2022 May 17;98(20):e2073-e2083. doi: 10.1212/WNL.0000000000200254. Epub 2022 Mar 29.
To investigate the association of radiochemotherapy-induced cytopenia with sex and its potential effect on survival in patients with glioma.
We retrospectively analyzed cytopenia during temozolomide-based concomitant radiochemotherapy in 492 patients with glioma. Histologic grading, molecular pathology, surgical procedures, adjuvant chemotherapy subsequent to the radiochemotherapy phase, and overall survival (OS) were recorded. The extent of cytopenia was correlated with sex and outcome.
Treatment-induced severe cytopenia (leukocytopenia, lymphocytopenia, neutropenia, and thrombocytopenia) was more frequent in women than men (44 vs 18%; = 0.0002). In women with -wt high-grade astrocytomas, there was a negative correlation of severe cytopenia in general and thrombocytopenia in particular during temozolomide radiochemotherapy with OS independent from other predictors (92 [77-111] vs 73 [21-127] weeks; < 0.05). In men, there was also a trend for this unfavorable effect. In addition, severe cytopenia in all blood cell lineages correlated with reduced temozolomide dose exposure during radiochemotherapy (all < 0.05 in the total cohort) and reduced dose exposure was independently associated with worse OS (hazard ratios for OS in complete vs reduced temozolomide dose in the total and female cohort 0.66 [0.47-0.92] and 0.4 [0.24-0.69], < 0.05).
Our analysis of treatment-induced cytopenia in a large cohort of patients with glioma confirms that women are at higher risk and demonstrates an association of cytopenia with shortened survival in women.
This study provides Class II evidence that women with glioma treated with temozolomide-based concomitant radiochemotherapy have more frequent treatment-induced severe cytopenia than men and that severe myelosuppression correlates with worse OS in women.
探讨替莫唑胺同步放化疗引起的血细胞减少与性别之间的关系及其对胶质瘤患者生存的潜在影响。
我们回顾性分析了 492 例接受替莫唑胺同步放化疗的胶质瘤患者的血细胞减少情况。记录了组织学分级、分子病理学、手术过程、放化疗后辅助化疗以及总生存期（OS）。分析血细胞减少的严重程度与性别和结果之间的相关性。
与男性相比，女性在接受替莫唑胺同步放化疗时更易发生治疗诱导的严重血细胞减少（白细胞减少、淋巴细胞减少、中性粒细胞减少和血小板减少）（44% vs 18%； = 0.0002）。在 -wt 高级别星形细胞瘤的女性患者中，替莫唑胺同步放化疗期间的严重血细胞减少（总体和血小板减少）与 OS 呈负相关，且独立于其他预测因素（92 [77-111] 周 vs 73 [21-127] 周； < 0.05）。在男性中，这种不利影响也存在趋势。此外，所有血细胞谱系的严重血细胞减少与同步放化疗期间替莫唑胺的剂量暴露减少相关（在整个队列中均 < 0.05），且剂量暴露减少与 OS 更差独立相关（总队列和女性队列中完全缓解与替莫唑胺剂量减少的 OS 风险比分别为 0.66 [0.47-0.92] 和 0.4 [0.24-0.69]； < 0.05）。
我们对大量胶质瘤患者接受替莫唑胺同步放化疗引起的治疗诱导性血细胞减少进行的分析证实，女性的风险更高，并表明血细胞减少与女性的生存时间缩短有关。
本研究提供了 II 级证据，表明接受替莫唑胺同步放化疗的胶质瘤女性患者比男性患者更易发生治疗诱导的严重血细胞减少，且严重骨髓抑制与女性患者的 OS 更差相关。
