Unlike other tumors, the anatomical extent of brain tumors is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumor progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumor entities, to assess the association of anatomical tumor features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma. Anatomical phenotyping was performed on a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumor. Tumor probability in different topographic, phylogenetic and ontogenetic parcellation units was assessed on preoperative MRI through normalization of the relative tumor prevalence to the relative volume of the respective structure. We analyzed the spatiotemporal tumor dynamics by cross-referencing preoperative against preceding and subsequent MRIs of the respective patient. The association between anatomical phenotype and outcome defined prognostically critical anatomical tumor features at diagnosis. Based on a hypothesized sequence of anatomical tumor progression, we developed a three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma. This staging system was validated internally in the original cohort and externally in an independent cohort of 300 consecutive patients. While primary central nervous system lymphoma showed highest probability along white matter tracts, metastases enriched along terminal arterial flow areas. Neuroepithelial tumors mapped along all sectors of the ventriculocortical axis, while adjacent units were spared, consistent with a transpallial behavior within phylo-ontogenetic radial units. Their topographic pattern correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. While a ventriculofugal growth dominated in neuroepithelial tumors, a gradual deviation from this neuroepithelial spatiotemporal behavior was found with progressive histopathological dedifferentiation. The proposed three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma correlated with the degree of histological dedifferentiation and proved accurate in terms of survival upon both internal and external validation. In conclusion, this study identified specific spatiotemporal phenotypes in brain tumors through topographic probability and growth pattern assessment. The association of anatomical tumor features with survival defined critical steps in the anatomical sequence of neuroepithelial tumor progression, based on which a staging system for WHO grade 2 and 3 gliomas and glioblastoma was developed and validated.

中文翻译：

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脑肿瘤的解剖表型和分期

与其他肿瘤不同，脑肿瘤的解剖范围没有通过分期进行客观化和量化。分期系统基于了解肿瘤进展的解剖顺序及其与组织病理学去分化和存活的关系。本研究的目的是描述最常见脑肿瘤实体的时空表型，评估解剖肿瘤特征与生存概率的关联，并为 WHO 2 级和 3 级胶质瘤和胶质母细胞瘤开发分期系统。对首次诊断为原发性或继发性脑肿瘤的 1000 名患者的连续队列进行解剖表型分析。不同地形的肿瘤概率，通过将相对肿瘤患病率标准化为相应结构的相对体积，在术前 MRI 上评估系统发育和个体发育分割单元。我们通过交叉参考术前和相应患者的先前和随后的 MRI 来分析时空肿瘤动态。解剖表型和结果之间的关联定义了诊断时的预后关键解剖肿瘤特征。基于假设的解剖肿瘤进展序列，我们为 WHO 2 级和 3 级胶质瘤和胶质母细胞瘤开发了一个三级分期系统。该分期系统在原始队列内部得到验证，并在由 300 名连续患者组成的独立队列外部得到验证。虽然原发性中枢神经系统淋巴瘤沿白质束的概率最高，沿终末动脉血流区域富集的转移灶。神经上皮肿瘤沿着脑室皮质轴的所有部分绘制，而相邻的单位则幸免于难，这与系统个体发育径向单位内的跨苍白球行为一致。它们的地形模式与系统发育和个体发生过程中径向单位的收敛和发散的形态发生过程相关。虽然脑室生长在神经上皮肿瘤中占主导地位，但随着进行性组织病理学去分化，发现这种神经上皮时空行为逐渐偏离。针对 WHO 2 级和 3 级胶质瘤和胶质母细胞瘤提出的三级分期系统与组织学去分化程度相关，并在内部和外部验证后证明在生存方面是准确的。综上所述，该研究通过地形概率和生长模式评估确定了脑肿瘤的特定时空表型。解剖肿瘤特征与生存的关联定义了神经上皮肿瘤进展的解剖序列中的关键步骤，在此基础上开发并验证了 WHO 2 级和 3 级胶质瘤和胶质母细胞瘤的分期系统。