Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy
| Autor: | Elin H. Kure, Halfdan Sorbye, Kjell Magne Tveit, Niels Pallisgaard, Olav Dajani, K. L.G. Spindler, Ole Christian Lingjærde, Julian Hamfjord, Tormod Kyrre Guren, Per Pfeiffer, Bengt Glimelius, Julia S. Johansen |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Male Colorectal cancer medicine.medical_treatment 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Medicine Digital polymerase chain reaction Prospective Studies prognostic biomarker Hazard ratio Liver Neoplasms Hematology Prognosis Chemotherapy regimen Oxaliplatin Survival Rate Cell-free fetal DNA 030220 oncology & carcinogenesis Lymphatic Metastasis Female Fluorouracil Colorectal Neoplasms Cell-Free Nucleic Acids medicine.drug medicine.medical_specialty interleukin 6 colorectal cancer BRAF 03 medical and health sciences Folic Acid Internal medicine Biomarkers Tumor Humans Retrospective Studies Chemotherapy Cancer och onkologi business.industry medicine.disease circulating cell-free DNA Circulating Cell-Free DNA 030104 developmental biology Clinical Trials Phase III as Topic Cancer and Oncology business Follow-Up Studies RAS |
| Zdroj: | Hamfjord, J, Guren, T K, Dajani, O, Johansen, J S, Glimelius, B, Sorbye, H, Pfeiffer, P, Lingjærde, O C, Tveit, K M, Kure, E H, Pallisgaard, N & Spindler, K-L G 2019, ' Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy ', Annals of Oncology, vol. 30, no. 7, pp. 1088-1095 . https://doi.org/10.1093/annonc/mdz139 Annals of Oncology Hamfjord, J, Guren, T K, Dajani, O, Johansen, J S, Glimelius, B, Sorbye, H, Pfeiffer, P, Lingjærde, O C, Tveit, K M, Kure, E H, Pallisgaard, N & Spindler, K L G 2019, ' Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy ', Annals of Oncology, vol. 30, no. 7, mdz139, pp. 1088-1095 . https://doi.org/10.1093/annonc/mdz139 |
| DOI: | 10.1093/annonc/mdz139 |
| Popis: | BACKGROUND: Metastatic colorectal cancer (mCRC) is a heterogeneous disease where prognosis is dependent both on tumor biology and host factors. Total circulating cell-free DNA (cfDNA) has shown to harbor prognostic information in mCRC, although less is known about the biological correlates of cfDNA levels in this patient group. The primary objective was to evaluate the prognostic value of pretreatment cfDNA in patients receiving the first-line oxaliplatin-based chemotherapy for mCRC, by using a predefined upper limit of normal (ULN) from a cohort of presumed healthy individuals. The secondary objective was to model cfDNA levels as a function of predefined tumor and host factors.PATIENTS AND METHODS: This was a retrospective post hoc study based on a prospective multicenter phase III trial, the NORDIC-VII study. DNA was purified from 547 plasma samples and cfDNA quantified by a droplet digital PCR assay (B2M, PPIA) with controls for lymphocyte contamination. Main clinical end point was overall survival (OS).RESULTS: cfDNA was quantified in 493 patients, 54 were excluded mainly due to lymphocyte contamination. Median cfDNA level was 7673 alleles/ml (1050-1 645 000) for B2M and 5959 alleles/ml (555-854 167) for PPIA. High cfDNA levels were associated with impaired outcome; median OS of 16.6 months for levels above ULN and 25.9 months for levels below ULN (hazard ratio = 1.83, 95% confidence interval 1.51-2.21, P CONCLUSION: cfDNA holds promise as a minimally invasive and clinically relevant prognostic biomarker in mCRC before initiating first-line oxaliplatin-based chemotherapy and may be a complex entity associated with tumor burden, liver metastases and systemic inflammatory response.TRIAL REGISTRATION: ClinicalTrials.gov, NCT00145314. |
| Databáze: | OpenAIRE |
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