Abstract 13: Ethnic disparities in prognosis associated with persistence of the systemic inflammatory response in metastatic renal cell carcinoma.

Abstract Background: Significant racial disparities in survival have been reported for kidney cancer patients in studies from the Surveillance, Epidemiology, and End Results program. These disparities could not be attributed to age, gender, tumor stage or size, histologic subtype or surgical treatment. Comparable studies of medical therapy with targeted agents for metastatic renal cell carcinoma (mRCC) are needed with a focus on defining possible biological mechanisms for these disparities. Methods: A single institution retrospective study was conducted at the Winship Cancer Institute of Emory University. Inclusion criteria were as follows: (1) diagnosis of mRCC, (2) treatment with at least 1 targeted agent and (3) serum C-reactive protein and albumin monitored on at least 3 separate occasions that were at least 2 weeks apart. Risk stratification was performed on the basis of the Inflammation Intensity Index of the Systemic Inflammatory Response (SIR) Kinetics Model. Ethnicity was not a risk stratification factor. Statistical analysis was conducted using SAS V9.3 and R V2.15. The Kaplan-Meier method was used to generate overall survival (OS) curves. One- and 2-year OS estimates were calculated with significant differences determined by the log-rank test. Results: A cohort of 55 patients was identified from among 635 patients who were evaluated for kidney cancer during the screening period of January 1, 2005 to June 30, 2011. Twenty seven patients were alive as of the cut off date of July 1, 2012. One patient was alive when lost to follow up on Day 961. The SIR was assessed a total of 804 times with a median of 14 time points per patient (range 3 to 49). A total of 113 lines of systemic therapy were administered with a median of 2 per patient (range 1 to 5). The median OS for the entire cohort was 30.6 months with a median follow up of 27.1 months (95% CI = 22.0, 31.3). The projected 1-Yr and 2-Yr OS rates were 78% and 56%, respectively for the cohort as a whole. The median OS for non-Hispanic whites (n=39) was 38.4 months (95% CI 5.0, 25.6) vs. 8.6 months (95% CI 23.7, 49.4) for blacks (n=14) and Hispanics (n=2) with a log-rank p value of <0.0001. The median age was 65 (range 26-83) for non-Hispanic whites and 56 (41-73) for blacks and Hispanics. No significant differences were observed in terms of gender or lines of systemic therapy, however, the rates of nephrectomy were 97% for non-Hispanic whites (38/39), 100% for Hispanics (2/2) but only 43% for blacks (6/14). Conclusions: There is a robust inverse correlation between the intensity of the SIR of the host's innate immune system and OS in cancer patients. Nephrectomy has been associated with decreases in the intensity of the SIR in patients with mRCC. The survival advantage of Non-Hispanic whites may be related to the lack of nephrectomy among blacks as well as possible drug resistance associated with an unrelenting SIR in blacks and Hispanics in spite of targeted therapy. Citation Format: Wayne B. Harris, Jingjing Gao, Dana C. Nickleach, Yuan Liu, Omer Kucuk, Viraj Master. Ethnic disparities in prognosis associated with persistence of the systemic inflammatory response in metastatic renal cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 13. doi:10.1158/1538-7445.AM2013-13 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.