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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2596 - Droplet digital PCR of circulating tumour DNA for the detection of RAS/BRAF mutation in metastatic colorectal cancer


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Targeted Therapy;  Pathology/Molecular Biology

Tumour Site

Colon and Rectal Cancer


Eric van Cutsem


Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281


E. van Cutsem1, K. Lesniewski-Kmak2, M.P. Saunders3, H. Wasan4, G. Argiles5, C. Borg6, G.M. Creemers7, M. Fedyanin8, R. Glynne-Jones9, P. Pfeiffer10, C.J.A. Punt11, D. Stroyakovskiy12, A.J. Ten Tije13, A. van de Wouw14, V. Cattan15, G. Desachy16, N. Amellal15, V.M. Moiseyenko17

Author affiliations

  • 1 Digestive Oncology, University Hospitals Leuven, 3000 - Leuven/BE
  • 2 Oncology, Szpital Morski, 81001 - Gdynia/PL
  • 3 Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 4 Oncology, Imperial College London - Hammersmith Hospital, W12 0HS - London/GB
  • 5 Gastrointestinal And Endocrine Tumors Group, Vall d'Hebron Institute of Oncology, VHIO, Barcelona/ES
  • 6 Medical Oncology, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 7 Oncology, Catharina Hospital Eindhoven, 5602 ZA - Eindhoven/NL
  • 8 Clinicla Pharmacology And Chemotherapy, N. N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU
  • 9 Radiotherapy, Mount Vernon Cancer Centre, HA6 2RN - Northwood/GB
  • 10 Experimental Research In Medical Cancer Therapy, Odense University Hospital, 5000 - Odense C/DK
  • 11 Oncology, Academic Medical Center, University of Amsterdam, 1100 DD - Amsterdam/NL
  • 12 Oncology, Moscow City Oncology Hospital No. 62, 143423 - Moscow/RU
  • 13 Oncology, Amphia Ziekenhuis-location Molengracht, 4818 CK - Breda/NL
  • 14 Oncology, VieCuri MC, 5912 BL - Venlo/NL
  • 15 Oncology, Servier, 92284 - Suresnes/FR
  • 16 Methodology And Data Valorisation, Instut de recherches internationales Servier, 92284 - Suresnes/FR
  • 17 Saint-petersburg Scientific Practical Center For Specialized Medical Care (oncological), Petrov Research Institute of Oncology, 197758 - Saint Petersburg/RU


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Abstract 2596


Circulating tumour DNA (ctDNA) provides a non-invasive approach for gene mutation detection. The aim of this study is to evaluate the concordance of RAS/BRAF mutational status in tumour tissue and plasma in metastatic colorectal cancer (mCRC) patients.


Plasma samples were collected prospectively from previously untreated mCRC patients (TASCO1 NCT02743221) and analysed centrally by droplet digital PCR (ddPCR) with sensitivity down to 0.2% for KRAS exon 2, 0.5% for NRAS exon 2 and BRAF. Tumour RAS/BRAF status was determined locally from primary or metastatic tumours according to routine practice.


Out of the 153 patients included, 121 had tissue and plasma mutation status available for KRAS exon 2, 129 patients for NRAS exon 2 and 70 patients for BRAF V600E. In these subgroups, the prevalence of KRAS exon 2, NRAS exon 2 and BRAF mutations detected in plasma was 30.6%, 0.8% and 11.4%, respectively vs. 47.1%, 1.6% and 12.9%, respectively in tumours. For KRAS, the concordance was 81.8% with a Kappa coefficient of 0.63. KRAS mutation was detected in tumour tissue and not in plasma for 21 patients (17.4%), potentially explained by low tumour burden or low tumour DNA shedding. KRAS mutation was detected in plasma but not in tumour tissue for just one patient. For NRAS, a concordance of 99.2% (kappa = 0.66) was observed between plasma and tumour tissue. One discordant case (0.8%) was observed for which NRAS was detected only in tissue. This case also presented KRAS mutation both in plasma and tumour tissue excluding an explanation related to tumour DNA shedding. For BRAF, a concordance of 95.7% (kappa = 0.80) was observed between plasma and tumour tissue: BRAF mutation was detected only in plasma in one case (1.4%) and only in tumour tissue in 2 cases (2.9%). One of the two cases displaying BRAF V600E in tumour but not in plasma also had an NRAS mutation in plasma and unknown NRAS status in tumours.


This study showed that RAS/BRAF mutations can be detected in plasma samples from mCRC patients by ddPCR. However, in the context of the study, analysis of the ctDNA did not allow detection of RAS/BRAF mutations in all patients where these mutations were present in the tumour.

Clinical trial identification

TASCO1 NCT02743221.

Legal entity responsible for the study

Servier Oncology.



Editorial Acknowledgement


E. Van Cutsem: Research funding: Amgen, Bayer, Boehringer, Celgene, Ipsen, Lilly, Merck, Merck KgA, Novartis, Roche, Sanofi, Servier. M.P. Saunders: Honoraria: Roche, Merck, Amgen, Servier, Eisai. G. Argiles: Advisor: Hoffman la Roche, BMS, Bayer. C. Borg: Advisory boards: Roche, Servier, Sanofi; Research grant: Roche. P. Pfeiffer: Research funding: Amgen, Celgene, Lilly, Merck KgA, Roche, Taiho, Servier. V. Cattan, G. Desachy, N. Amellal: Employee: Servier. All other authors have declared no conflicts of interest.

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