Evidence map›Paper›PMID 29175734›Full record

ArticleEuropean journal of cancer (Oxford, England : 1990)2018

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients.

S Valpione, G Gremel, P Mundra, P Middlehurst, E Galvani, M R Girotti, R J Lee, G Garner, N Dhomen, P C Lorigan and 1 more

Open access · hybridAbstract read
In one paragraph

Article in European journal of cancer (Oxford, England : 1990), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 4 pooled it
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 4 syntheses or guidelines pooled it, 168 citations in OpenAlex.

  1. Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  16. Immunoregulatory properties of cell free DNA.Cellular and molecular life sciences : CMLS · 2025
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

S ValpioneMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK; Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
G GremelMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
P MundraMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
P MiddlehurstMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
E GalvaniMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
M R GirottiMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
R J LeeMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
G GarnerMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
N DhomenMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK.
P C LoriganChristie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
R MaraisMolecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK. Electronic address: richard.marais@cruk.manchester.ac.uk.
University of Manchester · GBCancer Research UK Manchester Institute · GBThe Christie NHS Foundation Trust · GB

Funding

Cancer Research UK 22902Cancer Research UK C5759/A12328Wellcome Trust 100282/Z/12/Z
6 · The paper itself

Abstract

introductionTumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. MATERIALS AND

methodsA prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients.

resultsBaseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm

conclusionsWe have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.

Indexed as

AdolescentAdultAgedAged, 80 and overBiomarkers, TumorCell-Free Nucleic AcidsFemaleHumansKaplan-Meier EstimateMaleMelanomaMiddle AgedNeoplasm MetastasisPrognosisProspective StudiesTumor BurdenBiomarkers, TumorCell-Free Nucleic AcidsMelanomaPrognostic biomarkerTotal circulating cell-free DNATumour burden

Identifiers

PMID29175734
PMCPMC5769519
OpenAlexW2769575972

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.