Circulating tumour cell liquid biopsy in selecting therapy for recurrent cutaneous melanoma with locoregional pelvic metastases: a pilot study

Abstract

Objectives: Circulating tumour cells (CTCs) from liquid biopsies provide an exceptional opportunity to obtain realtime 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. Results: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.

Circulating tumour cell gene expression and chemosensitivity analyses: predictive accuracy for response to multidisciplinary treatment of patients with unresectable refractory recurrent rectal cancer or unresectable refractory colorectal cancer liver metastases

“…Although current clinical use of liquid biopsies remains limited, CTCs have been isolated from patients with a variety of tumour types [37,38], including CRC [17,18]. CTC research has evolved from prognostic studies based upon CTC enumeration, to predictive clinical response studies based upon the in vitro chemosensitivity and tumor gene expression profiles of cultured CTCs.…”

A Prospective Study of Intraarterial Infusion Chemotherapy in Advanced Wild-Type BRAF Melanoma Patients

“…[36][37][38][39][40] Moreover, the use of fresh tissues biopsies, liquid biopsies and purified circulating tumour cells in chemosensitivity and tumour gene expression assays can be used to develop more personalized locoregional or systemic treatment strategies, as recently reported. 41 With respect to locoregional chemotherapy and other therapy combinations, the use of ablative techniques, ECT, topical and intralesional therapy is under current investigation 7 , 11-14 and novel immunotherapies are increasing due to a broadening of eligibility criteria, with several clinical trials now including patients previously considered ineligible. 22 Furthermore, it has been reported that ILI with melphalan followed by systemic administration of ipilimumab provided an 85% ORR associated to increased T-cell infiltration in locoregional metastases of 26 melanoma patients, suggesting that locoregional chemotherapy administered as immune stimulant therapy could potentiate immune-responses.…”

Molecular Aspects of the Isolated Limb Infusion Procedure

“…These studies show the relation between melphalan and tumour immunogenicity and suggest that in the future there may be a place for concurrent or sequential administration of systemic targeted therapies or immunotherapies with ILI. Finally, precision oncotherapy is under investigation, and drug regimens may be selected by chemosensitivity tests on purified circulating tumour cells (CTCs) obtained from liquid biopsies in individual patients [49].…”