Guadagni Stefano, Fiorentini Giammaria, Papasotiriou Ioannis, Apostolou Panagiotis, Masedu Francesco, Sarti Donatella, Farina Antonietta Rossella, Mackay Andrew Reay, Clementi Marco
Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, 67100, L'Aquila, Italy.
Department of Oncology and Hematology, Ospedali Riuniti Marche Nord, 61121, Pesaro, Italy.
BMC Res Notes. 2020 Mar 24;13(1):176. doi: 10.1186/s13104-020-05021-5.
Circulating tumour cells (CTCs) from liquid biopsies provide an exceptional opportunity to obtain real-time tumour information and are under current investigation in several cancers, including cutaneous melanoma, but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic melanoma (MM) CTCs, from 7 patients with stage IIIC, BRAF wild-type metastatic melanomas, localized exclusively to the pelvic region, un-eligible for immunotherapy and treated with melphalan hypoxic pelvic perfusion (HPP), is both feasible and useful in predicting response to therapy. Viable MM CTCs (> 5 cells/ml for all 7 blood samples), enriched by transient culture, were characterised in flow cytometry-based Annexin V-PE assays for chemosensitivity to several drugs.
Using melphalan as a standard, chemosensitivity cut-off values of > 60% cell death, were predictive of patient RECIST 1.1 response to melphalan HPP therapy, associated with calculated 100% sensitivity, 66.67% specificity, 33.33% positive predictive, 100% negative predictive, and 71.43% accuracy values. We propose that the methodology in this study is both feasible and has potential value in predicting response to therapy, setting the stage for a larger study. Trial registration Clinical Trials.gov Identifier NCT01920516; date of trial registration: August 6, 2013.
液体活检中的循环肿瘤细胞（CTC）为获取实时肿瘤信息提供了绝佳机会，目前正在包括皮肤黑色素瘤在内的多种癌症中进行研究，但在方法标准化、活细胞数量少以及CTC识别准确性方面存在重大缺陷。在这项初步研究中，我们报告称，对7例IIIC期、BRAF野生型转移性黑色素瘤患者（肿瘤仅局限于盆腔区域，不适合免疫治疗且接受马法兰低氧盆腔灌注（HPP）治疗）的液体活检衍生的转移性黑色素瘤（MM）CTC进行化疗敏感性检测，在预测治疗反应方面既可行又有用。通过短暂培养富集的活MM CTC（所有7份血样中>5个细胞/ml），在基于流式细胞术的膜联蛋白V-PE检测中对几种药物的化疗敏感性进行了表征。
以马法兰为标准，细胞死亡>60%的化疗敏感性临界值可预测患者对马法兰HPP治疗的RECIST 1.1反应，计算得出的敏感性为100%，特异性为66.67%，阳性预测值为33.33%，阴性预测值为100%，准确性为71.43%。我们认为本研究中的方法在预测治疗反应方面既可行又具有潜在价值，为更大规模的研究奠定了基础。试验注册ClinicalTrials.gov标识符NCT01920516；试验注册日期：2013年8月6日。
