Supplementary Material for: Gliomatosis Cerebri Growth Pattern: Association of Differential First-Line Treatment with Overall Survival in WHO Grade II and III Gliomas

Introduction: Gliomatosis cerebri (GC) is defined by diffuse, widespread glial tumor growth affecting three or more cerebral lobes. Previous studies in gliomas found no distinct histological or molecular GC subtype, yet the presence of GC is associated with worse median overall survival (OS). Here, we explored whether differing therapeutic strategies in first-line treatment could account for this. Methods: From our University Cancer Center database, 47 patients with histological diagnosis of WHO grade II or III glioma and GC imaging pattern were identified. GC criteria were confirmed by independent review. Patients with WHO grade II or III glioma with non-GC pattern served as control cohort (n = 343). Results: Within the GC patient cohort, lower WHO grade, mutated isocitrate dehydrogenase 1 (IDH1) status, and absence of contrast enhancement were associated with better OS. Compared to the control cohort, patients with GC had significantly shorter OS independent of histological diagnosis or IDH1 mutation status. Patients with GC preferentially received chemotherapy alone (62 vs. 18%), and less frequently radiochemotherapy (21 vs. 27%). OS was significantly shorter in the GC cohort compared to the non-GC cohort both for chemotherapy (3.9 vs. 7.6 years, p = 0.0085) and for combined radiochemotherapy (1.1 vs. 8.4 years, p < 0.0001). However, when only patients who received biopsy plus chemotherapy were analyzed, the differences lost statistical significance (3.5 vs. 6.6 years, p = 0.196). Conclusion: We found major differences in the selection of first-line therapies of GC versus non-GC patients. Our results suggest that these differences may partly account for the worse prognosis of GC patients.

引言：脑胶质瘤病（Gliomatosis cerebri, GC）被定义为累及至少三个脑叶的弥漫性、广泛性神经胶质肿瘤增生。既往针对胶质瘤的研究未发现具备独特组织学或分子特征的GC亚型，但GC的存在与更差的中位总生存期（overall survival, OS）相关。本研究旨在探讨一线治疗中不同的治疗策略是否可解释这一预后差异。

方法：本研究从本院癌症中心数据库中筛选出47例经组织学确诊为WHO Ⅱ级或Ⅲ级胶质瘤且具有GC影像学特征的患者。GC的诊断标准经独立评审确认。以具有非GC影像学特征的WHO Ⅱ级或Ⅲ级胶质瘤患者作为对照队列（n=343）。

结果：在GC患者队列中，较低的WHO分级、异柠檬酸脱氢酶1（isocitrate dehydrogenase 1, IDH1）突变状态以及无对比增强表现与更佳的总生存期相关。与对照队列相比，GC患者的总生存期显著更短，且该差异不受组织学诊断或IDH1突变状态的影响。GC患者更倾向于仅接受化疗（62% vs. 18%），而较少接受放化疗联合治疗（21% vs. 27%）。无论是仅接受化疗（3.9年 vs. 7.6年，p=0.0085）还是放化疗联合治疗（1.1年 vs. 8.4年，p<0.0001），GC队列的总生存期均显著短于非GC队列。但当仅分析接受活检联合化疗的患者时，该差异不再具有统计学意义（3.5年 vs. 6.6年，p=0.196）。

结论：本研究发现GC患者与非GC患者在一线治疗方案的选择上存在显著差异。研究结果提示，这些治疗策略的差异可能部分解释了GC患者较差的预后。