神经母细胞瘤的放射基因组学：影像学表型、肿瘤基因组特征与生存之间的关系。
Radiogenomics of neuroblastomas: Relationships between imaging phenotypes, tumor genomic profile and survival.
作者信息
Brisse Hervé J, Blanc Thomas, Schleiermacher Gudrun, Mosseri Véronique, Philippe-Chomette Pascale, Janoueix-Lerosey Isabelle, Pierron Gaelle, Lapouble Eve, Peuchmaur Michel, Fréneaux Paul, Galmiche Louise, Algret Nathalie, Peycelon Matthieu, Michon Jean, Delattre Olivier, Sarnacki Sabine
机构信息
Imaging Department, Institut Curie, Paris, France.
Paris Sciences et Lettres Research University, Paris, France.
出版信息
PLoS One. 2017 Sep 25;12(9):e0185190. doi: 10.1371/journal.pone.0185190. eCollection 2017.
PURPOSE
This study investigated relationships between neuroblastomas (NBs) imaging phenotypes, tumor genomic profile and patient outcome.
PATIENTS AND METHODS
This IRB-approved retrospective observational study included 133 NB patients (73 M, 60 F; median age 15 months, range 0-151) treated in a single institution between 1998 and 2012. A consensus review of imaging (CT-scan, MRI) categorized tumors according to both the primarily involved compartment (i.e., neck, chest, abdomen or pelvis) and the sympathetic anatomical structure the tumors rose from (i.e., cervical, paravertebral or periarterial chains, or adrenal gland). Tumor shape, volume and image-defined surgical risk factors (IDRFs) at diagnosis were recorded. Genomic profiles were assessed using array-based comparative genomic hybridization and divided into three groups: "numerical-only chromosome alterations" (NCA), "segmental chromosome alterations" (SCA) and "MYCN amplification" (MNA). Statistical analyses included Kruskal-Wallis, Chi2 and Fisher's exact tests and the Kaplan-Meier method with log-rank tests and Cox model for univariate and multivariate survival analyses.
RESULTS
A significant association between the sympathetic structure origin of tumors and genomic profiles was demonstrated. NBs arising from cervical sympathetic chains were all NCA. Paravertebral NBs were NCA or SCA in 75% and 25%, respectively and none were MNA. Periarterial NBs were NCA, SCA or MNA in 33%, 56% and 11%, respectively. Adrenal NBs were NCA, SCA or MNA in 16%, 36% and 48%, respectively. Among MNA NBs, 92% originated from the adrenal gland. The sympathetic anatomical classification was significantly better correlated to overall survival than the compartmental classification (P < .0003). The tumor volume of MNA NBs was significantly higher than NCA or SCA NBs (P < .0001). Patients with initial volume less than 160 mL had significantly better overall survival (P < .009). A "single mass" pattern was significantly more frequent in NCA NBs (P = .0003). The number of IDRFs was significantly higher in MNA NBs (P < .0001).
CONCLUSION
Imaging phenotypes of neuroblastomas, including tumor origin along the sympathetic system, correlate with tumor genomic profile and patient outcome.
目的
本研究调查神经母细胞瘤（NBs）的影像学表型、肿瘤基因组特征与患者预后之间的关系。
患者与方法
这项经机构审查委员会批准的回顾性观察性研究纳入了1998年至2012年间在单一机构接受治疗的133例NB患者（73例男性，60例女性；中位年龄15个月，范围0 - 151个月）。通过对影像学检查（CT扫描、MRI）进行共识性评估，根据主要受累部位（即颈部、胸部、腹部或骨盆）以及肿瘤起源的交感神经解剖结构（即颈交感神经链、椎旁或动脉周围链或肾上腺）对肿瘤进行分类。记录诊断时肿瘤的形状、体积和图像定义的手术风险因素（IDRFs）。使用基于阵列的比较基因组杂交技术评估基因组特征，并将其分为三组：“仅染色体数目改变”（NCA）、“染色体节段改变”（SCA）和“MYCN扩增”（MNA）。统计分析包括Kruskal - Wallis检验、卡方检验和Fisher精确检验，以及用于单因素和多因素生存分析的Kaplan - Meier法和对数秩检验以及Cox模型。
结果
肿瘤的交感神经结构起源与基因组特征之间存在显著关联。起源于颈交感神经链的NBs均为NCA。椎旁NBs分别有75%为NCA和25%为SCA，无一例为MNA。动脉周围NBs分别有33%为NCA、56%为SCA和11%为MNA。肾上腺NBs分别有16%为NCA、36%为SCA和48%为MNA。在MNA NBs中，92%起源于肾上腺。交感神经解剖学分类与总生存期的相关性显著优于受累部位分类（P <.0003）。MNA NBs的肿瘤体积显著高于NCA或SCA NBs（P <.0001）。初始体积小于160 mL的患者总生存期显著更好（P <.009）。“单一肿块”模式在NCA NBs中显著更常见（P =.0003）。MNA NBs的IDRFs数量显著更高（P <.0001）。
结论
神经母细胞瘤的影像学表型，包括沿交感神经系统的肿瘤起源，与肿瘤基因组特征和患者预后相关。
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