Framework for Statistical Parametric Mapping of the Interactions between Glioblastoma Location, Treatment, Prognostic Variables, and Survival Using a Phase III Trial.

experimental_design

A total of 592 prospectively enrolled patients with newly diagnosed glioblastoma from the phase III AVAglio trial, randomized to postsurgical chemoradiation with or without bevacizumab, were retrospectively analyzed.

共有592名新诊断为胶质母细胞瘤的患者，这些患者是来自III期AVAglio试验的前瞻性入组患者，被随机分配到术后放化疗组，有或没有贝伐单抗，进行了回顾性分析。

Statistical parametric mapping was conducted with multivariate Cox proportional hazards models at the voxel-wise level, incorporating dedicated interaction variables to evaluate the impact of baseline tumor volume and treatment arm on survival for different tumor locations from magnetic resonance imaging (MRI) scans, with subsequent cluster-based correction for multiple testing and mathematical estimation of regional survival curves.

在体素水平上，采用多变量Cox比例风险模型进行了统计参数映射，并结合专门的交互变量来评估基线肿瘤体积和治疗组对MRI扫描中不同肿瘤位置的生存影响，随后进行了基于簇的多重测试校正和区域生存曲线的数学估计。

Results

Tumor location in the right prefrontal cortex was an independent favorable prognostic factor [median hazard ratio(HR) = 0.57] for survival, whereas tumor involvement in left hemisphere eloquent areas with language and visual functions was unfavorable (median HR = 1.69).

右前额叶皮层的肿瘤位置是独立的有利预后因素（中位风险比HR=0.57）对生存，而左半球的语言和视觉功能区的肿瘤涉及是不利的（中位HR=1.69）。

Larger presurgical tumor volumes were associated with shorter survival independent of tumor location (HR = 1.005), but the effect was larger for tumor locations including eloquent structures (HR ranging 1.008-1.015), whereas nonsignificant for anterior frontal locations.

较大的术前肿瘤体积与较短的生存期独立于肿瘤位置相关（HR = 1.005），但对于包括重要结构的肿瘤位置，其影响更大（HR范围在1.008-1.015之间），而对于前额叶位置则无显著影响。

Bevacizumab seemed to grant a survival benefit when specific brain regions were involved or spared by the tumor, but this result was not confirmed after correction for multiple testing.

贝伐单抗似乎在特定脑区受肿瘤影响或未受肿瘤影响时能提供生存益处，但这一结果在进行多重测试校正后并未得到确认。

Conclusions

This workflow allows to map the survival effects of variables onto specific brain tumor locations, revealing location dependency of prognostic variables such as tumor volume, and potentially of treatment schemes, with relevant implications in risk stratification and clinical management.

该工作流程能够将变量的生存效应映射到特定的脑肿瘤位置，揭示了预后变量（如肿瘤体积）的位置依赖性，以及可能的治疗方案，这对于风险分层和临床管理具有重要意义。