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KRAS mutation confers resistance to antibody-dependent cellular cytotoxicity of cetuximab against human colorectal cancer cells
KRAS mutation confers resistance to antibody-dependent cellular cytotoxicity of cetuximab against human colorectal cancer cells INTERNATIONAL JOURNAL OF CANCER Conti, S. L., Thomas, I., Hagedorn, J. C., Chung, B. I., Chertow, G. M., Wagner, T. H., Brooks, J. D., Srinivas, S., Leppert, J. T. 2014; 134 (9): 2245-2252Abstract
We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of cytoreductive nephrectomy occurred. We fitted multivariable proportional hazard models in full and propensity score-matched cohorts. We performed a difference-in-difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing cytoreductive nephrectomy increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of cytoreductive nephrectomy. Cytoreductive nephrectomy was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34 to 0.43). Median survival among patients receiving cytoreductive nephrectomy increased in the targeted therapy era (19 versus 13 months), while median survival among patients not receiving cytoreductive nephrectomy increased only slightly (4 versus 3 months). Difference-in-difference analysis showed a significant decrease in hazard of death among patients who received cytoreductive nephrectomy in the targeted therapy era. Despite decreased utilization in the targeted therapy era, cytoreductive nephrectomy remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of cytoreductive nephrectomy among patients with metastatic RCC treated with novel targeted therapies. © 2013 Wiley Periodicals, Inc.
View details for DOI 10.1002/ijc.28550
View details for Web of Science ID 000331006600013