ABSTRACT
BACKGROUND: The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints. PATIENTS AND METHODS: One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment. RESULTS: The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095). CONCLUSIONS: The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/blood , Colorectal Neoplasms/drug therapy , Neoplastic Cells, Circulating/pathology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Bevacizumab , Capecitabine , Colorectal Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE: Renal carcinoma develops as a consequence of the accumulation of several genetic aberrations. Alterations in the p16 gene have been described in many tumors. Methylation of its promoter in CpG islands is the most common mechanism of inactivation of this gene. The aim of this study was to establish whether p16 gene methylation leads to a loss of the encoded protein in 57 patients with renal carcinoma, and if this aberration has any value in predicting disease progression in these patients. METHODS: Gene promoter methylation was determined by deoxyribonucleic acid treated with sodium bisulfite to subsequently amplify methylated and unmethylated regions rich in CpG islands. The p16 protein product was detected for immunohistochemical examination. RESULTS: Hypermethylation of the p16 gene was detected in 22.9% of the patients, none of whom had the protein product. A lack of p16 protein was confirmed in 52.9% of the tumors, indicating another genetic alteration or posttranscriptional modifications preventing the codification of this protein. Through multivariate analysis of overall survival, gene methylation was found to have independent prognostic value: the absence of alteration confers an undefined risk of death. CONCLUSIONS: Of the molecular modifications described for renal carcinoma, aberrations in the p16 gene are frequent. In these patients, methylation of the p16 gene promoter seems to afford a protective effect against the risk of death.
Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , CpG Islands/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Methylation , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Survival RateABSTRACT
BACKGROUND: As the enzyme telomerase extends the life of the cell through its ability to lengthen telomeres, its activity in different types of tumor has been evaluated as a possible factor involved in tumorigenesis. The aim of this study was to assess the prognostic significance of telomerase activity in patients with colorectal carcinoma. PATIENTS AND METHODS: Telomerase activity was determined in 103 patients undergoing surgery for colorectal cancer between 2001 and 2003. Telomerase activity was determined by an enzyme-linked immunoassay based on the amplification of telomeric repeat sequences (TRAP assay). RESULTS: 90% of our study population showed telomerase activity. Telomerase activity was related to tumor stage and site: a lower proportion of patients with stage A tumors showed telomerase activity compared to more advanced stages; and more patients with colon than with rectal carcinomas were telomerase positive. Multivariate analysis revealed that by adjusting for tumor stage, telomerase activity could be used to predict the risk of death or recurrence (p < 0.001). CONCLUSIONS: Activation of telomerase seems to be a frequent event related to the stage of the tumor in colorectal tumorigenesis. Our findings suggest that telomerase activity can predict a greater risk of death or recurrence, irrespective of the more conventional prognostic factors.
