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CtDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab.

ABSTRACT: Bevacizumab is included in an increasing number of clinical trials. To find biomarkers to predict and monitor treatment response, cancer and angiogenesis relevant mutations in tumour and circulating tumour DNA (ctDNA) were investigated in 26 metastatic melanoma patients treated with bevacizumab. Patients with >1% BRAF/NRAS ctDNA at treatment start had significantly decreased progression free survival (PFS) and overall survival (OS) (PFS: p?=?0.019, median 54 vs 774 days, OS: p?=?0.026, median 209 vs 1064 days). Patients with >1% BRAF/NRAS ctDNA during treatment showed similar results (PFS: p?=?0.002, OS: p?=?0.003). ?1% BRAF/NRAS ctDNA and normal lactate dehydrogenase (LDH) levels both significantly predicted increased response to treatment, but BRAF/NRAS ctDNA was better at predicting response compared to LDH at treatment start (OR 16.94, p?=?0.032 vs OR 4.57, p?=?0.190), and at predicting PFS (HR 6.76, p?=?0.002) and OS (HR 6.78, p?=?0.002) during therapy. ctDNA BRAF p.V600D/E/K and NRAS p.G12V/p.Q61K/L/R were better biomarkers for response prediction than TERT promoter mutations (OR 1.50, p?=?0.657). Next generation sequencing showed that all patients with ?2 mutations in angiogenesis-relevant genes had progressive disease, but did not reveal other biomarkers identifying responders. To conclude, ctDNA and LDH are useful biomarkers for both monitoring and predicting response to bevacizumab.

SUBMITTER: Forthun RB

PROVIDER: S-EPMC6877652 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab.

Forthun Rakel Brendsdal RB Hovland Randi R Schuster Cornelia C Puntervoll Hanne H Brodal Hans Petter HP Namløs Heidi Maria HM Aasheim Lars Birger LB Meza-Zepeda Leonardo A LA Gjertsen Bjørn Tore BT Knappskog Stian S Straume Oddbjørn O

Scientific reports 20191125 1

Bevacizumab is included in an increasing number of clinical trials. To find biomarkers to predict and monitor treatment response, cancer and angiogenesis relevant mutations in tumour and circulating tumour DNA (ctDNA) were investigated in 26 metastatic melanoma patients treated with bevacizumab. Patients with >1% BRAF/NRAS ctDNA at treatment start had significantly decreased progression free survival (PFS) and overall survival (OS) (PFS: p = 0.019, median 54 vs 774 days, OS: p = 0.026, median 20 ...[more]

PMID: 31767937

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Project description:PurposeTo predict survival in patients with metastatic melanoma by evaluating a combination of serum lactate dehydrogenase (LDH) level and initial computed tomographic (CT) findings of tumor devascularization after antiangiogenic therapy.Materials and methodsConsent was waived for this institutional review board-approved, retrospective, secondary analysis. Forty-four patients with metastatic melanoma received bevacizumab therapy in a randomized prospective phase II trial. Target lesions on the initial posttherapy CT images were evaluated by using Response Evaluation Criteria in Solid Tumors, the Choi criteria, and Morphology, Attenuation, Size, and Structure (MASS) criteria. Cox proportional hazards models were used to assess the association of baseline clinical variables including serum LDH and imaging findings with progression-free and overall survival. The receiver operating characteristic curve with area under the curve (AUC) was used to evaluate accuracy.ResultsIn multivariate analysis, a high baseline serum LDH level was associated with decreased progression-free survival (hazard ratio = 1.29 for each increase of 100 IU/L; P = .002) and overall survival (hazard ratio = 1.44 for each increase of 100 IU/L; P = .001). Evaluation with MASS criteria of the first CT examination after therapy strongly predicted progression-free (P < .001) and overall (P < .001) survival. Baseline serum LDH level was moderately accurate for predicting progression-free survival at 9 months (AUC = 0.793) and overall survival at 18 months (AUC = 0.689). The combination of baseline serum LDH levels and evaluation with MASS criteria at the first CT examination after therapy had significantly higher accuracy for predicting progression-free survival at 9 months (AUC = 0.969) and overall survival at 18 months (AUC = 0.813) than did baseline serum LDH levels alone for prediction of progression-free survival (P = .020).ConclusionA combination of baseline serum LDH levels and evaluation with MASS criteria at the first CT examination after bevacizumab therapy had the highest accuracy for predicting survival in patients with metastatic melanoma.

Dataset Information

CtDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab.

Publications

ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab.

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