Delgado-Ortet Maria, Bura Vlad, Funingana Ionut-Gabriel, Hulse David, Rundo Leonardo, Brenton James D, Sala Evis, Escudero Sanchez Lorena
Department of Radiology, University of Cambridge, Cambridge, United Kingdom.
Cancer Research UK Cambridge Centre, CRUK and University of Cambridge, Cambridge, United Kingdom.
Front Oncol. 2025 Jun 5;15:1546324. doi: 10.3389/fonc.2025.1546324. eCollection 2025.
High-grade serous carcinoma is a highly metastatic disease with a limited longterm disease control from systemic anti-cancer treatment, for which the radiological treatment response assessment metrics are imprecise. In this work, we developed noninvasive imagingbased measurements of spatial and longitudinal heterogeneity in a retrospective analysis of a phase 2 non-randomized study of germline BRCA1/BRCA2 mutated (gBRCAm) ovarian cancer patients treated with combination of PARP inhibitors (PARPi) and immune checkpoint inhibitors (ICIs).
Lesions identified in CT images at baseline, week 4 (after PARPi only) and week 12 (after 8 weeks of PARPi + ICIs) were manually segmented. Anatomical networks of the metastatic sites were constructed to represent patterns of disease distribution. Volume and first-order radiomic features were computed and compared to different assessments of treatment response.
The average number of edges per patient in the anatomical networks and total volumetric burden decreased with treatment were measured, differentiating between responders and nonresponders. Changes in volume at week 4 provided better indication of long-term response than the default RECIST assessment at the same time-point. Significant differences were also found between responders and non-responders in the first-order radiomic feature Energy.
In this feasibility study, we have demonstrated that noninvasive image-based analysis can identify quantitative imaging features associated with the response to the combination of PARPi and ICIs. These can be used to identify markers of response to ICIs from negative trials of a disease with limited response to ICIs.
高级别浆液性癌是一种具有高度转移性的疾病,全身抗癌治疗对其长期疾病控制有限,且其放射治疗反应评估指标并不精确。在本研究中,我们在一项针对携带种系BRCA1/BRCA2突变(gBRCAm)的卵巢癌患者的2期非随机研究的回顾性分析中,开发了基于非侵入性成像的空间和纵向异质性测量方法,这些患者接受了聚ADP核糖聚合酶抑制剂(PARPi)和免疫检查点抑制剂(ICIs)联合治疗。
对基线、第4周(仅使用PARPi后)和第12周(PARPi + ICIs治疗8周后)CT图像中识别出的病变进行手动分割。构建转移部位的解剖网络以表示疾病分布模式。计算体积和一阶放射组学特征,并与不同的治疗反应评估进行比较。
测量了每位患者解剖网络中平均边数以及随治疗而减少的总体积负担,以此区分反应者和无反应者。第4周时的体积变化比同一时间点的默认RECIST评估更能预示长期反应。在一阶放射组学特征能量方面,反应者和无反应者之间也发现了显著差异。
在这项可行性研究中,我们证明了基于非侵入性图像的分析可以识别与PARPi和ICIs联合治疗反应相关的定量成像特征。这些特征可用于从对ICIs反应有限的疾病的阴性试验中识别对ICIs反应的标志物。