Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas.
Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas.
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DOI：
10.3174/ajnr.a4631
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Rubin DL
中科院分区：
文献类型：
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作者：
Liu TT;Achrol AS;Mitchell LA;Du WA;Loya JJ;Rodriguez SA;Feroze A;Westbroek EM;Yeom KW;Stuart JM;Chang SD;Harsh GR 4th;Rubin DL
肿瘤位置已被证明是胶质母细胞瘤（GBM）患者的一个重要预后因素。本研究的目的是通过识别与肿瘤分子谱、患者特征和临床结局相关的基于MRI体素的肿瘤位置特征来表征GBM病变。从两个独立的队列中获得了384例GBM患者的术前T1解剖MR图像（N=253例来自我们当地（为保持匿名而保留姓名）医疗中心进行培训，N=131例来自癌症基因组图谱（TCGA）进行验证）。开发了自动计算图像分析管道，以确定每个患者中肿瘤的解剖位置。使用训练队列中确定的良好（总生存期（OS）> 17个月）和不良（OS < 11个月）生存组之间基于体素的肿瘤位置差异将TCGA队列中的患者分为两个脑位置组，比较其临床特征，mRNA表达和拷贝数变化，以阐明肿瘤位于不同脑区域的生物学基础。右侧枕颞侧脑室周围白色物质中的肿瘤与训练和测试队列中的不良生存率显著相关（均为对数秩P < 0.05），并且与其他位置的肿瘤相比具有更大的肿瘤体积。右心房周围位置的肿瘤与缺氧途径富集和PDGFRA扩增相关，使其成为亚组特异性治疗的潜在靶点。GBM中基于体素的位置与患者结果相关，并且可能具有指导个性化治疗的潜在作用。
Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma (GBM). The purpose of this study is to characterize GBM lesions by identifying MRI voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics and clinical outcomes. Preoperative T1 anatomic MR images of 384 GBM patients were obtained from two independent cohorts (N=253 from our local (name withheld to preserve anonymity) Medical Center for training and N=131 from the Cancer Genome Atlas (TCGA) for validation). An automated computational image analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival (OS) > 17 months) and poor (OS < 11 months) survival groups identified in the training cohort were used to classify patients in the TCGA cohort into two brain location groups, for which clinical features, mRNA expression, and copy number changes were compared to elucidate the biological basis of tumors located in different brain regions. Tumors in the right occipito-temporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both log-rank P < 0.05) and had larger tumor volume compared to tumors in other locations. Tumors in the right peri-atrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies. Voxel-based location in GBM is associated with patient outcome and may have a potential role for guiding personalized treatment.