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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

2017; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1093/annonc/mdx393.065

1569-8041

Javier Sastre, Virginia de la Orden, A. Martínez, Inmaculada Bando, Iñigo Santamarı́a, Beatríz Bellosillo, Sarai Palanca, Isabel Peligros, Beatriz Mediero, Patricia Llovet, Vı́ctor Moreno, José María Viéitez, Pilar García‐Alfonso, Silvia Gil, M Morales, M.A. Salud Salvia, Guillermo Quintero, F.A. Gesto, Enrique Aranda, E. Rubio,

Cancer Cells and Metastasis

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.Table539PParametersCTCs> 3 p valueRASmut p valueBRAFmut p valueECOG0.00690.002–Primary location––< 0.0001Metastatic sitesLiver< 0.00010.010.02*BRAF mutant less frequently associated to liver involvementLung0.020.005Bone0.00020.0020.002Peritoneum––0.004Lymph nodes––0.005N° organ involved0.0010.007–Stage at diagnosis0.0020.02–CEA levels< 0.00010.02–* BRAF mutant less frequently associated to liver involvement Open table in a new tab 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. 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.