Geady Caryn, Bannon James J, Reza Shagheyegh, Madanat-Harjuoja Laura, Reinke Denise, Schuetze Scott, Crompton Brian, Hope Andrew, Haibe-Kains Benjamin
Dept. of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Princess Margaret Cancer Research, University Health Network, Toronto, Ontario, Canada.
medRxiv. 2025 May 14:2025.04.11.25325700. doi: 10.1101/2025.04.11.25325700.
Radiomics offers a non-invasive approach to tumor characterization, yet its application in metastatic cancers is limited by intertumor heterogeneity-variability in radiomic phenotypes across lesions within the same patient. We introduce Measured Intrapatient Radiomic Variability (MIRV), a novel metric quantifying heterogeneity using standard-of-care imaging. Applied to 397 metastatic soft-tissue sarcoma (STS) patients from the SARC021 trial, MIRV was calculated from pretreatment CT scans using pairwise Euclidean distance and cosine dissimilarity between lesions. Euclidean distance captures absolute differences in radiomic features, while cosine dissimilarity assesses variation in feature patterns independent of magnitude. Higher MIRV correlated with greater variability in tumor-specific response classification (TSRC) and volumetric response, independent of baseline tumor volume. In a subset with liquid biopsy data, MIRV showed a moderate association with ctDNA positivity, suggesting links to molecular heterogeneity. While MIRV was not prognostic for overall survival (OS) in the full cohort, higher MIRV was significantly associated with worse survival in leiomyosarcoma patients (n=165, p=0.007). These findings establish MIRV as a biomarker for intertumor heterogeneity, with potential to predict mixed treatment responses and guide personalized therapy in metastatic STS. Future studies should assess its relevance across other tumor types and therapeutic settings.
放射组学提供了一种非侵入性的肿瘤特征描述方法,但其在转移性癌症中的应用受到肿瘤间异质性的限制,即同一患者体内不同病灶的放射组学表型存在变异性。我们引入了患者内测量放射组学变异性(MIRV),这是一种使用标准护理成像来量化异质性的新指标。将其应用于SARC021试验的397例转移性软组织肉瘤(STS)患者,通过使用病灶间的成对欧几里得距离和余弦差异,从治疗前的CT扫描中计算出MIRV。欧几里得距离捕捉放射组学特征的绝对差异,而余弦差异则评估特征模式的变化,与大小无关。较高的MIRV与肿瘤特异性反应分类(TSRC)和体积反应的更大变异性相关,与基线肿瘤体积无关。在有液体活检数据的子集中,MIRV与ctDNA阳性呈中度相关,提示与分子异质性有关。虽然在整个队列中MIRV对总生存期(OS)无预后价值,但在平滑肌肉瘤患者(n = 165,p = 0.007)中,较高的MIRV与较差的生存期显著相关。这些发现确立了MIRV作为肿瘤间异质性的生物标志物,具有预测混合治疗反应和指导转移性STS个性化治疗的潜力。未来的研究应评估其在其他肿瘤类型和治疗环境中的相关性。