Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma

Beasley, Aaron B.; Isaacs, Timothy; Khattak, Muhammad A.; Freeman, James B.; Allcock, Richard; Chen, Fred K.; Pereira, Michelle R.; Yau, Kyle S.; Bentel, Jacqueline M.; Vermeulen, Tersia; Calapre, Leslie; Millward, Michael; Ziman, Melanie; Gray, Elin S.

doi:10.1200/po.17.00279

Cited by 36 publications

(65 citation statements)

References 30 publications

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“…CTCs were most frequently detected amongst the metastatic group compared to the early-stage disease group. Our study, along with others [10,11,12,13], confirms that CTCs are detectable in primary uveal melanoma. In early-stage disease, the presence of CTCs correlated with gene expression profiling.…”

Section: Discussionsupporting

confidence: 91%

“…Measurement of circulating tumor DNA (ctDNA) is another important tool in liquid biopsy to monitor disease status of uveal melanoma. A study by Beasley et al [12] showed that ctDNA was able to detect metastatic disease earlier than imaging while Bidard et al showed that in metastatic uveal melanoma ctDNA predicted poor outcomes [16]. Liquid biopsy remains an active area of interest in regards to uveal melanoma.…”

Section: Discussionmentioning

confidence: 99%

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Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma

Anand

Roszik

Gombos

et al. 2019

Cancers

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Nearly 50% of uveal melanoma (UM) patients develop metastatic disease, and there remains no current standard assay for detection of minimal residual disease. We conducted a pilot study to check the feasibility of circulating tumor cell (CTC) detection in UM. We enrolled 40 patients with early or metastatic UM of which 20 patients had early-stage disease, 19 had metastatic disease, and one was not evaluable. At initial blood draw, 36% of patients had detectable CTCs (30% in early-stage vs. 42% in metastatic), which increased to 54% at data cutoff (40% in early-stage vs. 68% in metastatic). Five early-stage patients developed distant metastases, 60% (3/5) had detectable CTCs before radiographic detection of the metastasis. Landmark overall survival (from study enrollment) at 24 months was statistically lower in CTC-positive vs. negative early-stage UM (p < 0.05). Within this small dataset, the presence of CTCs in early-stage UM predicted an increased risk of metastatic disease and was associated with worse outcomes.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma

Anand

Roszik

Gombos

et al. 2019

Cancers

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“…Tumor cells spread through blood vessels and can be captured using various techniques. Molecular analysis of these circulating tumor cells (CTCs) can provide useful molecular information regarding the parent tumors . Such information can enhance our understanding of response and resistance mechanisms to immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study

et al. 2019

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Background PD‐1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD‐L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD‐1 inhibitor pembrolizumab. Methods Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6–12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD‐L1. Results CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD‐L1+ CTCs (14/25, 64%) had significantly longer progression‐free survival (PFS) compared with patients with PD‐L1− CTCs (26.6 months vs. 5.5 months; p = .018). The 12‐month PFS rates were 76% versus 22% in the PD‐L1+ versus PD‐L1− CTCs groups (p = .012), respectively. A multivariate linear regression analysis confirmed that PD‐L1+ CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052–1.012; p = .026). Conclusion Our results reveal the potential of CTCs as a noninvasive real‐time biopsy to evaluate PD‐L1 expression in patients with melanoma. PD‐L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS. Implications for Practice The present data suggest that PD‐L1 expression on circulating tumor cells may predict response to pembrolizumab in advanced melanoma. This needs further validation in a larger trial and, if proven, might be a useful liquid biopsy tool that could be used to stratify patients into groups more likely to respond to immunotherapy, hence leading to health cost savings.

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“…For these reasons, we believe that treatment strategies for pelvic locoregional metastases should be multidisciplinary and could benefit greatly from the detailed characterisation of biomolecular characteristics and relative chemosensitivity of metastatic melanoma cells, a possibility that is offered by liquid biopsies, using purified circulating tumour cells (CTCs) obtained from individual patients. This method has been approved for prognosis by USA Food and Drug Administration [23] and despite a lack of methodological consensus, is under investigation as a potential method for identifying therapeutic strategies for cancers, including melanoma [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma

Cited by 36 publications

References 30 publications

Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma

Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma

PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study

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

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