RESUMEN
BACKGROUND: KRAS mutations occur in 40% of colorectal cancers (CRCs), affecting the efficacy of agents targeting the epidermal growth factor receptor. However, the effect of KRAS mutation status on the activity of non-epidermal growth factor receptor-targeting chemotherapy has not been fully elucidated. The aim of the present study is to evaluate the effect of KRAS status on the activity of different chemotherapeutic regimens. PATIENTS AND METHODS: A retrospective chart review of chemotherapy-treated patients with metastatic CRC with known KRAS status was undertaken. Chemotherapy effects were measured by progression-free survival, time to chemotherapy resistance, and overall survival. Analysis was performed for the different chemotherapy regimens, and according to the KRAS mutation status while adjusting for potential confounders. RESULTS: KRAS mutations were detected in 43% of 223 patients with metastatic CRC who were treated at the Ottawa Hospital. The baseline distribution of KRAS wild-type (WT) and mutant status was similar. The median follow-up was 27.2 months. Regimens received included single agents or combinations of 2 or 3 chemotherapies. Among those treated with capecitabine-based regimens, survival was longer for patients with KRAS WT status (hazard ratio, 0.47; 95% confidence interval, 0.23-0.95; P < .0001) when compared with those with mutant status. The median overall survival was 46.7 versus 32.6 months for patients with KRAS WT versus mutant status, respectively. The time to chemotherapy resistance was also significantly longer for patients with WT status (hazard ratio, 0.49; 95% confidence interval, 0.25-0.97; P = .0398). A trend for progression-free survival did not reach statistical significance. CONCLUSION: Patients with KRAS WT tumors may benefit more from capecitabine-based treatments than patients with mutant status. Further research is needed to explain this data.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVES: The purpose of this study was to analyze the patterns of recurrence following intraoperative radiofrequency ablation (RFA) combined with hepatic resection for patients with colorectal liver metastases (CLM). METHODS: Patients undergoing liver resection (with or without RFA) for CLM were examined. Rates and patterns of disease recurrence, as well as overall survival were assessed using Kaplan-Meier and Cox analyses. RESULTS: A total of 174 patients underwent liver resection for CLM (150 without and 24 with intraoperative RFA). RFA was used to treat 41 tumors (median 1.6 cm). The 3-year overall survival was 65.5% and 61.4% (adjusted HR 1.02, 95% CI 0.55-1.88). Median recurrence-free survival was 7.4 versus 12.7 months with RFA versus non-RFA, respectively (adjusted HR 1.51, 95% CI 0.94-4.42). On multivariate analysis, neither survival nor recurrence-free survival was significantly associated with RFA. In total, there were two RFA ablation zone local failures. An ablation site recurrence was the sole site in one patient (4.2%). CONCLUSION: RFA was used as an adjunct to resection in patients with greater disease burden. Despite this, RFA was not significantly associated with a higher risk of local failure and was not associated with worse survival, when compared with liver resection alone.