Preprint Article Version 1 NOT YET PEER-REVIEWED

Comparison of Two EpCAM-Based Methods for CTC Detection and Molecular Characterization in Advanced Colorectal Cancer

  1. Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico Universitario San Carlos, Centre afilliated to Red de Centros CIBER, 28040 Madrid, Spain
  2. CTC Unit, Hospital Clínico Universitario San Carlos, 28040 Madrid, Spain
  3. UGC de Medicina Preventiva, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
  4. Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHIM, Universidad Autónoma de Madrid, 28049 Madrid, Spain
  5. Medical Oncology Department, IMIBIC, Hospital Universitario Reina Sofía, Córdoba, University of Córdoba, RETICC, 14002 Córdoba, Spain
Version 1 : Received: 20 November 2016 / Approved: 21 November 2016 / Online: 21 November 2016 (09:52:20 CET)

How to cite: Cabezas-Camarero, S.; De La Orden, V.; Veganzones-De-Castro, S.; Medievo-Valeros, B.; Fuentes-Ferrer, M.; Sánchez-Ruiz, A.; Provencio, M.; Aranda, E.; Sastre, J.; Díaz-Rubio, E. Comparison of Two EpCAM-Based Methods for CTC Detection and Molecular Characterization in Advanced Colorectal Cancer. Preprints 2016, 2016110105 (doi: 10.20944/preprints201611.0105.v1). Cabezas-Camarero, S.; De La Orden, V.; Veganzones-De-Castro, S.; Medievo-Valeros, B.; Fuentes-Ferrer, M.; Sánchez-Ruiz, A.; Provencio, M.; Aranda, E.; Sastre, J.; Díaz-Rubio, E. Comparison of Two EpCAM-Based Methods for CTC Detection and Molecular Characterization in Advanced Colorectal Cancer. Preprints 2016, 2016110105 (doi: 10.20944/preprints201611.0105.v1).

Abstract

Circulating tumor cells (CTC) have shown to be prognostic in advanced colorectal cancer (advCRC), but their value for predicting response to treatment or as a source of molecular data is debated. We compared CellSearch® (Janssen Diagnostics, LLC) and IsoFluxTM (Fluxion Biosciences Inc, South San Francisco, CA) systems for the enumeration of CTC in patients with newly diagnosed advCRC (group 1; n=34). Using castPCRTM we studied KRAS status in CTC isolated with IsoFluxTM and compared it with that of the primary tumor in patients from group 1 and in KRAS wild-type (KRASWT) patients with progressive disease (group 2; n=22). Median number of CTC detected with CellSearch® (groups 1 and 2) was 1 (range: 0-78) and with IsoFluxTM (group 1) was 8 (range: 0-419), showing a modest correlation (r=0.345, P=0.036), which improved if lung metastases (r=0.805, P=0.016) or if lung and liver metastases were present (r=0.812, P=0.05). A Bland-Altman plot showed that the higher the number of CTC detected the larger the difference between both methods in favor of IsoFluxTM. After a median follow-up since CTC collection of 16 months (range: 1-30) CellSearch® ≥ 3 CTC (HR 2.77, 95% CI 0.77-9.95) and IsoFluxTM ≥ 11 CTC (HR 4.14, 95% CI 1.05-16.19) were established as the best cutoff points for predicting survival. Using castPCRTM we found KRAS mutations in CTC in 4 out of 8 patients from group 1 and in 2 out of 3 patients from group 2. None of these mutations were found in the primary tumor using standard methods, possibly reflecting intratumor heterogeneity or treatment selection pressure. We conclude that IsoFluxTM is more efficient than CellSearch® in the isolation of CTC in patients with advCRC, achieving, in a majority of cases, the established minimum of CTC for castPCRTM-based genetic analyses.

Subject Areas

circulating tumor cells; CTC, liquid biopsy; KRAS; colorectal cancer; EpCAM; CellSearch; IsoFlux; castPCR; intratumor heterogeneity

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