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

Autor: Javier Sastre, Milagros Balbín, Guillermo Quintero, Virginia Moreno Moral, Virginia de la Orden, Antonio Martínez, Beatriz Mediero, Inmaculada Bando, Patricia Llovet, Enrique Aranda, Maria José Ortiz-Morales, Sarai Palanca, Pilar García-Alfonso, Jose María Vieitez, Antonieta Salud, Silvia Gil Calle, Beatriz Bellosillo, Carlos F. Lopez, Eduardo Díaz-Rubio, Maria Isabel Peligros Gomez
Rok vydání: 2020
Předmět:
Oncology
Male
Lung Neoplasms
Organoplatinum Compounds
FOLFIRINOX
Colorectal cancer
DNA Mutational Analysis
Leucovorin
Cell Count
Metastasis
0302 clinical medicine
Carcinoembryonic antigen
Circulating tumor cell
CEA
FOLFOX
Antineoplastic Combined Chemotherapy Protocols
Prospective Studies
biology
Liver Neoplasms
Gastroenterology
Mutational status
Middle Aged
Neoplastic Cells
Circulating
Prognosis
Progression-Free Survival
Bevacizumab
Oxaliplatin
030220 oncology & carcinogenesis
FOLFIRI
030211 gastroenterology & hepatology
Female
Microsatellite Instability
Fluorouracil
Colorectal Neoplasms
medicine.drug
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Adolescent
Bone Neoplasms
Irinotecan
Risk Assessment
BRAF
03 medical and health sciences
Young Adult
Internal medicine
medicine
Biomarkers
Tumor
Humans
neoplasms
Aged
Neoplasm Staging
Performance status
business.industry
medicine.disease
digestive system diseases
Gene expression profiles
Mutation
biology.protein
ras Proteins
Microsatellite instability
Camptothecin
business
Zdroj: CLINICAL COLORECTAL CANCER
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
instname
ISSN: 1533-0028
Popis: This is a post hoc analysis of biomarkers from a large cohort of patients with chemo-naive 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. 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-naive metastatic CRC population. Patients and Methods: A total of 1202 patients from the Spanish VISNU-1 (FOLFIRINOX/bevacizumab vs. FOLFOX/bevacizumab) and VISNU-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-naive metastatic CRC is not explained by associations with poor clinicopathologic prognostic factors, except right-sided primary tumors. (C) 2020 Elsevier Inc. All rights reserved.
Databáze: OpenAIRE
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