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Poster display session

2952 - Circulating tumor cells (CTCs), molecular alterations and their correlation with characteristics of patients (pts) with metastatic colorectal cancer (mCRC) treated in the Spanish TTD VISNÚ Program

Date

09 Sep 2017

Session

Poster display session

Topics

Translational Research;  Colon and Rectal Cancer

Presenters

Javier Sastre

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

J. Sastre1, V. de la Orden2, A. Martínez3, I. Bando4, I. Santamaría5, B. Bellosillo Paricio6, S. Palanca7, I. Peligros8, B. Mediero9, P. Llovet4, V. Moreno3, J.M. Viéitez10, P. Garcia-Alfonso11, S. Gil12, M.J. Ortiz Morales13, M.A. Salud Salvia14, G. Quintero15, F.A. Gesto16, E. Aranda Aguilar13, E. Diaz Rubio1

Author affiliations

  • 1 Medical Oncology, Hospital Clinico Universitario San Carlos. CIBERONC Instituto de Salud Carlos III, 28040 - Madrid/ES
  • 2 Ctc Unit. Molecular Oncology Laboratory, Hospital Universitario Clínico San Carlos, Madrid. CIBERONC Instituto de Salud Carlos III. Instituto de Investigación Sanitaria San Carlos, Madrid, Spain, 28040 - Madrid/ES
  • 3 Laboratory, Hospital Universitario Reina Sofía, Cordoba/ES
  • 4 Laboratory, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 5 Laboratory, Hospital Universitario Central de Asturias, 33011 - Oviedo/ES
  • 6 6- molecular Biology Laboratory, University Hospital del Mar, 8003 - Barcelona/ES
  • 7 Molecular Biology Unit, Hospital Universitario y Politécnico La Fe, Valencia/ES
  • 8 Pathology, Hospital General Universitario Gregorio Marañón, Madrid/ES
  • 9 Ctc Unit. Molecular Oncology Laboratory, Hospital Universitario Clínico San Carlos, Madrid. Instituto de Salud Carlos III. Instituto de Investigación Sanitaria San Carlos, Madrid, Spain, 28040 - Madrid/ES
  • 10 Medical Oncology, Hospital Universitario Central de Asturias, 33011 - Oviedo/ES
  • 11 Medical Oncology, Hospital Universitario Gregorio Marañón, Madrid/ES
  • 12 Medical Oncology, Hospital Universitario Regional y Virgen de la Victoria, 29010 - Malaga/ES
  • 13 Medical Oncology, IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC Instituto de Salud Carlos III. Spain, Cordoba/ES
  • 14 Medical Oncology, Hospital de Lleida Arnau de Vilanova, Lérida/ES
  • 15 Medical Oncology, Hospital Lucus Augusti, Lugo/ES
  • 16 Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander/ES
More

Resources

Abstract 2952

Background

CTCs, RAS and BRAF mutations are prognostic factor in mCRC pts. The VISNÚ program was designed to explore the impact of FOLFOXIRI + bevacizumab in a high-risk mCRC group according to CTCs ≥3 (VISNÚ-1) and to compare the efficacy of bevacizumab or cetuximab associated to FOLFIRI in a low-risk group according to CTCs < 3 and RAS wild-type (VISNÚ-2).

Methods

Blood samples for CTCs enumeration by Cell Search® method (Menarini – Silicon Biosystems, Inc) were collected at baseline, and samples of tumor tissue were used to determine KRAS-NRAS-BRAF-PIK3CA mutations. This preliminary analysis shows the correlation among CTCs, molecular mutations and clinical characteristics by chi-square analysis.

Results

1208 pts were screened for CTCs and RAS mutation and 590 of them were eligible for the VISNÚ program. In the screening population, CTCs ≥ 3 was found in 40.8%, RAS, BRAF and PI3K mutations were present in 51.4%, 7.5% and 11.3% of pts respectively. No correlation was found among CTCs and RAS, BRAF and PIK3CA mutations (p 0.29, 0.10 and 0.12 respectively). CTCs ≥ 3 was associated with worse ECOG, stage IV, liver, lung and bone metastases, > 2 metastatic sites and CEA levels > 5 ng/ml. RAS mutation correlated with worse ECOG, stage IV, liver, lung and bone metastases, > 2 metastatic sites and CEA levels > 5 ng/ml. BRAF mutation correlated with primary right colon location, and metastases in peritoneum, lymph nodes, bone and liver and high tendency for female (p = 0.058) (Table). PIK3CA mutation was only associated with right primary location and age > 65 years.

Conclusions

CTCs and RAS mutation are significantly associated with other clinical poor prognostic factors. The poor prognosis of BRAF-mutated tumors reported in the literature cannot be explained by its correlation with poor prognostic clinical characteristics.Table:

539P

ParametersCTCs> 3 p valueRASmut p valueBRAFmut p value
ECOG0.00690.002
Primary location< 0.0001
Metastatic sites
Liver< 0.00010.010.02*
Lung0.020.005
Bone0.00020.0020.002
Peritoneum0.004
Lymph nodes0.005
N° organ involved0.0010.007
Stage at diagnosis0.0020.02
CEA levels< 0.00010.02
*

BRAF mutant less frequently associated to liver involvement

Clinical trial identification

VISNÚ 1: NCT01640405 VISNÚ 2: NCT01640444

Legal entity responsible for the study

Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD)

Funding

Roche Farma SA

Disclosure

J.M. Viéitez: Consultant or advisory relationship and research funding: Roche. E. Aranda Aguilar: Honoraria for advisory role from Amgen, Bayer, Celgene, Mecrk, Roche, Sanofi. All other authors have declared no conflicts of interest.

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