Funingana Ionut-Gabriel, Piyatissa Pubudu, Reinius Marika, McCague Cathal, Basu Bristi, Sala Evis
Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.
Cancers (Basel). 2022 Oct 17;14(20):5076. doi: 10.3390/cancers14205076.
Clinical trials for oncology drug development have long relied on surrogate outcome biomarkers that assess changes in tumor burden to accelerate drug registration (i.e., Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria). Drug-induced reduction in tumor size represents an imperfect surrogate marker for drug activity and yet a radiologically determined objective response rate is a widely used endpoint for Phase 2 trials. With the addition of therapies targeting complex biological systems such as immune system and DNA damage repair pathways, incorporation of integrative response and outcome biomarkers may add more predictive value. We performed a review of the relevant literature in four representative tumor types (breast cancer, rectal cancer, lung cancer and glioblastoma) to assess the preparedness of volumetric and radiomics metrics as clinical trial endpoints. We identified three key areas-segmentation, validation and data sharing strategies-where concerted efforts are required to enable progress of volumetric- and radiomics-based clinical trial endpoints for wider clinical implementation.
长期以来，肿瘤学药物研发的临床试验一直依赖替代结局生物标志物来评估肿瘤负荷的变化，以加速药物注册（即实体瘤疗效评价标准第1.1版（RECIST v1.1）标准）。药物诱导的肿瘤大小缩小是药物活性的一个不完美替代标志物，但放射学确定的客观缓解率是2期试验广泛使用的终点。随着针对免疫系统和DNA损伤修复途径等复杂生物系统的疗法的增加，纳入综合反应和结局生物标志物可能会增加更多预测价值。我们对四种代表性肿瘤类型（乳腺癌、直肠癌、肺癌和胶质母细胞瘤）的相关文献进行了综述，以评估体积测量和放射组学指标作为临床试验终点的准备情况。我们确定了三个关键领域——分割、验证和数据共享策略，需要共同努力，以使基于体积测量和放射组学的临床试验终点取得进展，以便更广泛地在临床中实施。
