Association Between Baseline Circulating Tumor Cells, Molecular Tumor Profiling, and Clinical Characteristics in a Large Cohort of Chemo-naïve Metastatic Colorectal Cancer Patients Prospectively Collected

• Published in: Clinical colorectal cancer Vol. 19; no. 3; pp. e110 - e116
• Main Authors: Sastre, Javier, Orden, Virginia de la, Martínez, Antonio, Bando, Inmaculada, Balbín, Milagros, Bellosillo, Beatriz, Palanca, Sarai, Peligros Gomez, Maria Isabel, Mediero, Beatriz, Llovet, Patricia, Moral, Virginia Moreno, Viéitez, José Maria, García-Alfonso, Pilar, Calle, Silvia Gil, Ortiz-Morales, Maria José, Salud, Antonieta, Quintero, Guillermo, Lopez, Carlos, Díaz-Rubio, Eduardo, Aranda, Enrique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2020
• Subjects: BRAF; CEA; Gene expression profiles; Microsatellite instability; Mutational status; Gene expression profiles; BRAF; Mutational status; Microsatellite instability; CEA
• ISSN: 1533-0028; 1938-0674
• DOI: 10.1016/j.clcc.2020.02.014

Clinicopathologic characteristics and prognostic and predictive factors offer valuable guidance when selecting optimal first-line treatment in patients with metastatic colorectal cancer (CRC). The association between baseline circulating tumor cell (bCTC) count, molecular tumor profile, and clinicopathologic features was analyzed in a chemo-naïve metastatic CRC population. A total of 1202 patients from the Spanish VISNÚ-1 (FOLFIRINOX/bevacizumab vs. FOLFOX/bevacizumab) and VISNÚ-2 (FOLFIRI/bevacizumab vs. FOLFIRI/cetuximab; RAS-wildtype) studies were analyzed for mutational status and bCTC count. The association between clinicopathologic characteristics and bCTC count, mutational status, and microsatellite instability (MSI) was analyzed in 589 eligible patients. Interestingly, 41% of the population studied presented ≥3 bCTC count. bCTC count ≥3 was associated with worse performance status (according Eastern Cooperative Oncology Group scale), stage IV at diagnosis, at least 3 metastatic sites, and elevated carcinoembryonic antigen (CEA) levels; but not with RAS or BRAF mutations or high MSI. BRAFmut (BRAF mutated) tumors were associated with right-sided primary tumors, peritoneum, distant lymph node metastasis, and less frequent liver involvement. RASmut (RAS mutated) was associated with worse performance status; stage IV at diagnosis; right-sided primary tumors; liver, lung, and bone metastases; at least 3 metastatic sites; and elevated CEA, whereas PIK3CAmut (PIK3CA mutated) tumors were associated with right-sided primary tumors, high CEA serum levels, and older age. High MSI was associated with right-sided primary tumors, distant lymph nodes metastasis, and lower CEA levels. In our study, elevated bCTCs and RASmut were associated with clinicopathologic features known to be associated with poor prognosis; whereas the poor prognosis of BRAFmut tumors in chemo-naïve metastatic CRC is not explained by associations with poor clinicopathologic prognostic factors, except right-sided primary tumors. VISNU 1 ClinicalTrials.gov ID: NCT01640405/ VISNU 2 ClinicalTrials.gov ID: NCT01640444 This is a post hoc analysis of biomarkers from a large cohort of patients with chemo-naïve metastatic colorectal cancer. Both high baseline circulating tumor cell count and RAS mutated were associated with clinical or pathologic features classically associated with poor prognosis. Selection of high- and low-risk populations may help to individualize approaches in the future.