Metz Marie-Christin, Ezhov Ivan, Peeken Jan C, Buchner Josef A, Lipkova Jana, Kofler Florian, Waldmannstetter Diana, Delbridge Claire, Diehl Christian, Bernhardt Denise, Schmidt-Graf Friederike, Gempt Jens, Combs Stephanie E, Zimmer Claus, Menze Bjoern, Wiestler Benedikt
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, Munich, Germany.
Department of Informatics, Technical University of Munich, Munich, Germany.
Neurooncol Adv. 2023 Dec 27;6(1):vdad171. doi: 10.1093/noajnl/vdad171. eCollection 2024 Jan-Dec.
The diffuse growth pattern of glioblastoma is one of the main challenges for accurate treatment. Computational tumor growth modeling has emerged as a promising tool to guide personalized therapy. Here, we performed clinical and biological validation of a novel growth model, aiming to close the gap between the experimental state and clinical implementation.
One hundred and twenty-four patients from The Cancer Genome Archive (TCGA) and 397 patients from the UCSF Glioma Dataset were assessed for significant correlations between clinical data, genetic pathway activation maps (generated with PARADIGM; TCGA only), and infiltration () as well as proliferation (ρ) parameters stemming from a Fisher-Kolmogorov growth model. To further evaluate clinical potential, we performed the same growth modeling on preoperative magnetic resonance imaging data from 30 patients of our institution and compared model-derived tumor volume and recurrence coverage with standard radiotherapy plans.
The parameter ratio /ρ ( < .05 in TCGA) as well as the simulated tumor volume ( < .05 in TCGA/UCSF) were significantly inversely correlated with overall survival. Interestingly, we found a significant correlation between 11 proliferation pathways and the estimated proliferation parameter. Depending on the cutoff value for tumor cell density, we observed a significant improvement in recurrence coverage without significantly increased radiation volume utilizing model-derived target volumes instead of standard radiation plans.
Identifying a significant correlation between computed growth parameters and clinical and biological data, we highlight the potential of tumor growth modeling for individualized therapy of glioblastoma. This might improve the accuracy of radiation planning in the near future.
胶质母细胞瘤的弥漫性生长模式是精准治疗的主要挑战之一。计算肿瘤生长建模已成为指导个性化治疗的一种很有前景的工具。在此,我们对一种新型生长模型进行了临床和生物学验证,旨在弥合实验状态与临床应用之间的差距。
对来自癌症基因组图谱(TCGA)的124例患者和来自加州大学旧金山分校胶质瘤数据集的397例患者进行评估,以确定临床数据、遗传通路激活图谱(仅针对TCGA,由PARADIGM生成)与源自Fisher-Kolmogorov生长模型的浸润()以及增殖(ρ)参数之间的显著相关性。为了进一步评估临床潜力,我们对本机构30例患者的术前磁共振成像数据进行了相同的生长建模,并将模型得出的肿瘤体积和复发覆盖范围与标准放疗计划进行了比较。
参数比/ρ(在TCGA中P<0.05)以及模拟肿瘤体积(在TCGA/加州大学旧金山分校中P<0.05)与总生存期显著负相关。有趣的是,我们发现11条增殖通路与估计的增殖参数之间存在显著相关性。根据肿瘤细胞密度的临界值,我们观察到使用模型得出的靶体积而非标准放疗计划时,复发覆盖范围有显著改善,而放射体积没有显著增加。
通过确定计算得出的生长参数与临床和生物学数据之间的显著相关性,我们强调了肿瘤生长建模在胶质母细胞瘤个体化治疗中的潜力。这可能在不久的将来提高放射治疗计划的准确性。