Cell-Free DNA in Metastatic Colorectal Cancer

A Systematic Review and Meta-Analysis

Karen-Lise G Spindler, Anders Kindberg Boysen, Niels Pallisgård, Julia S Johansen, Josep Tabernero, Morten M Sørensen, Benny V Jensen, Torben F Hansen, David Sefrioui, Rikke F Andersen, Ivan Brandslund, Anders Jakobsen

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

BACKGROUND: Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor-specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta-analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection.

MATERIALS AND METHODS: A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction and individual patients' data.

RESULTS: Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta-analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03-2.82, p < .0001).

CONCLUSION: The total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut-off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor-specific mutations was emphasized in a large individual patients' data meta-analysis.

OriginalsprogEngelsk
TidsskriftOncologist
Vol/bind22
Udgave nummer9
Sider (fra-til)1049-1055
ISSN1083-7159
DOI
StatusUdgivet - 2017

Fingeraftryk

Meta-Analysis
Colorectal Neoplasms
DNA
Magnetics
Mutation
Neoplasms
Polymerase Chain Reaction
Palliative Care
PubMed
Reference Values
Research Personnel
Guidelines
Confidence Intervals

Citer dette

Spindler, K-L. G., Boysen, A. K., Pallisgård, N., Johansen, J. S., Tabernero, J., Sørensen, M. M., ... Jakobsen, A. (2017). Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Oncologist, 22(9), 1049-1055. https://doi.org/10.1634/theoncologist.2016-0178
Spindler, Karen-Lise G ; Boysen, Anders Kindberg ; Pallisgård, Niels ; Johansen, Julia S ; Tabernero, Josep ; Sørensen, Morten M ; Jensen, Benny V ; Hansen, Torben F ; Sefrioui, David ; Andersen, Rikke F ; Brandslund, Ivan ; Jakobsen, Anders. / Cell-Free DNA in Metastatic Colorectal Cancer : A Systematic Review and Meta-Analysis. I: Oncologist. 2017 ; Bind 22, Nr. 9. s. 1049-1055.
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title = "Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis",
abstract = "BACKGROUND: Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor-specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta-analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection.MATERIALS AND METHODS: A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction and individual patients' data.RESULTS: Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta-analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95{\%} confidence interval 2.03-2.82, p < .0001).CONCLUSION: The total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut-off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor-specific mutations was emphasized in a large individual patients' data meta-analysis.",
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Spindler, K-LG, Boysen, AK, Pallisgård, N, Johansen, JS, Tabernero, J, Sørensen, MM, Jensen, BV, Hansen, TF, Sefrioui, D, Andersen, RF, Brandslund, I & Jakobsen, A 2017, 'Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis', Oncologist, bind 22, nr. 9, s. 1049-1055. https://doi.org/10.1634/theoncologist.2016-0178

Cell-Free DNA in Metastatic Colorectal Cancer : A Systematic Review and Meta-Analysis. / Spindler, Karen-Lise G; Boysen, Anders Kindberg; Pallisgård, Niels; Johansen, Julia S; Tabernero, Josep; Sørensen, Morten M; Jensen, Benny V; Hansen, Torben F; Sefrioui, David; Andersen, Rikke F; Brandslund, Ivan; Jakobsen, Anders.

I: Oncologist, Bind 22, Nr. 9, 2017, s. 1049-1055.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Cell-Free DNA in Metastatic Colorectal Cancer

T2 - A Systematic Review and Meta-Analysis

AU - Spindler, Karen-Lise G

AU - Boysen, Anders Kindberg

AU - Pallisgård, Niels

AU - Johansen, Julia S

AU - Tabernero, Josep

AU - Sørensen, Morten M

AU - Jensen, Benny V

AU - Hansen, Torben F

AU - Sefrioui, David

AU - Andersen, Rikke F

AU - Brandslund, Ivan

AU - Jakobsen, Anders

N1 - © AlphaMed Press 2017.

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor-specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta-analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection.MATERIALS AND METHODS: A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction and individual patients' data.RESULTS: Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta-analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03-2.82, p < .0001).CONCLUSION: The total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut-off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor-specific mutations was emphasized in a large individual patients' data meta-analysis.

AB - BACKGROUND: Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor-specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta-analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection.MATERIALS AND METHODS: A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction and individual patients' data.RESULTS: Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta-analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03-2.82, p < .0001).CONCLUSION: The total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut-off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor-specific mutations was emphasized in a large individual patients' data meta-analysis.

U2 - 10.1634/theoncologist.2016-0178

DO - 10.1634/theoncologist.2016-0178

M3 - Review

VL - 22

SP - 1049

EP - 1055

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 9

ER -

Spindler K-LG, Boysen AK, Pallisgård N, Johansen JS, Tabernero J, Sørensen MM et al. Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2017;22(9):1049-1055. https://doi.org/10.1634/theoncologist.2016-0178