Meyerheim Marcel, Panagiotidou Foteini, Georgiadi Eleni, Soudris Dimitrios, Stamatakos Georgios, Graf Norbert
Pediatric Oncology and Hematology, Faculty of Medicine, Saarland University, Homburg, Germany.
In Silico Oncology and In Silico Medicine Group, Institute of Communication and Computer Systems, School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece.
Front Physiol. 2025 Apr 17;16:1465631. doi: 10.3389/fphys.2025.1465631. eCollection 2025.
Nephroblastoma or Wilms' tumor is the most prevalent type of renal tumor in pediatric oncology. Although the overall survival rate for this condition is excellent today (∼90%), there have been no significant improvements over the past two decades. In silico models aim to simulate tumor progression and treatment responses over time; they hold immense potential for enhancing the predictive accuracy and optimizing treatment protocols as they are inspired by the digital twin paradigm.
The present study uses T2-weighted magnetic resonance images, chemotherapy treatment plans, and post-surgical histological profiles from three patients enrolled in the SIOP 2001/GPOH clinical trial, where each patient represents a distinct clinically assessed risk group. We investigated the clinical adaptation of the Nephroblastoma Oncosimulator to the datasets from these patients with the goal of deriving appropriate value distributions of the model input parameters that enable accurate prediction of tumor volume reduction in response to preoperative chemotherapy.
Our primary focus was on the total cell kill ratio as a parameter reflecting treatment effectiveness. We derived the distribution of this parameter for one patient from each risk group: low ( = 0.875, [0.750, 0.875], = 178), intermediate ( = 0.875, [0.750, 0.875], = 175), and high ( = 0.485, [0.438, 0.532], = 103). Statistically significant differences were observed between the high-risk group and both the low- and intermediate-risk groups ( < 0.001).
The present work establishes a foundation for further studies using available retrospective datasets and additional patients per risk group. These efforts are expected to help validate the findings, advance model development, and extend this mechanistic multiscale discretized cancer model. However, clinical validation is ultimately required to assess the potential uses of the model in clinical decision-support systems.
肾母细胞瘤是小儿肿瘤学中最常见的肾脏肿瘤类型。尽管目前这种疾病的总体生存率很高(约90%),但在过去二十年中并没有显著提高。计算机模拟模型旨在模拟肿瘤随时间的进展和治疗反应;由于受到数字孪生范式的启发,它们在提高预测准确性和优化治疗方案方面具有巨大潜力。
本研究使用了参加SIOP 2001/GPOH临床试验的三名患者的T2加权磁共振图像、化疗治疗计划和术后组织学资料,每名患者代表一个不同的临床评估风险组。我们研究了肾母细胞瘤肿瘤模拟器对这些患者数据集的临床适应性,目的是得出模型输入参数的合适值分布,以便准确预测术前化疗后肿瘤体积的缩小情况。
我们主要关注作为反映治疗效果参数的总细胞杀伤率。我们得出了每个风险组中一名患者的该参数分布:低风险组(= 0.875,[0.750, 0.875],= 178)、中风险组(= 0.875,[0.750, 0.875],= 175)和高风险组(= 0.485,[0.438, 0.532],= 103)。高风险组与低风险组和中风险组之间均观察到统计学上的显著差异(< 0.001)。
本研究为利用现有回顾性数据集和每个风险组增加更多患者进行进一步研究奠定了基础。这些努力有望有助于验证研究结果、推进模型开发并扩展这种机械多尺度离散化癌症模型。然而,最终需要进行临床验证以评估该模型在临床决策支持系统中的潜在用途。