1. 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.
- Author
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Sastre J, Orden V, Martínez A, Bando I, Balbín M, Bellosillo B, Palanca S, Peligros Gomez MI, Mediero B, Llovet P, Moral VM, Viéitez JM, García-Alfonso P, Calle SG, Ortiz-Morales MJ, Salud A, Quintero G, Lopez C, Díaz-Rubio E, and Aranda E
- Subjects
- Adolescent, Adult, Aged, Bevacizumab therapeutic use, Biomarkers, Tumor blood, Bone Neoplasms genetics, Bone Neoplasms mortality, Bone Neoplasms secondary, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Cell Count, Colorectal Neoplasms genetics, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, DNA Mutational Analysis, Female, Fluorouracil therapeutic use, Humans, Irinotecan therapeutic use, Leucovorin therapeutic use, Liver Neoplasms genetics, Liver Neoplasms mortality, Liver Neoplasms secondary, Lung Neoplasms genetics, Lung Neoplasms mortality, Lung Neoplasms secondary, Male, Microsatellite Instability, Middle Aged, Mutation, Neoplasm Staging, Organoplatinum Compounds therapeutic use, Oxaliplatin therapeutic use, Prognosis, Progression-Free Survival, Prospective Studies, Proto-Oncogene Proteins B-raf genetics, Risk Assessment methods, Young Adult, ras Proteins genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor genetics, Bone Neoplasms drug therapy, Colorectal Neoplasms drug therapy, Liver Neoplasms drug therapy, Lung Neoplasms drug therapy, Neoplastic Cells, Circulating
- Abstract
Background: 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., Patients and Methods: 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., Results: 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., Conclusions: 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., Trial Registration Number: VISNU 1 ClinicalTrials.gov ID: NCT01640405/ VISNU 2 ClinicalTrials.gov ID: NCT01640444., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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