BackgroundElevated baseline neutrophil lymphocyte ratios (NLR) are now well established as a poor predictor of survival in renal cell carcinoma (RCC) and other cancers. Platelet Lymphocyte Ratios (PLR) have also recently shown similar effects. Despite these findings, the practical use of these ratios is still somewhat limited. We have previously shown that higher NLRs may be associated with increased concentrations of myeloid derived suppressor cells (MDSC). We hypothesized that increases in NLR or PLR (NLR/PLR failure) at 2 months while on immunotherapy could be a predictor of eventual treatment failure and overall survival.MethodsWe analyzed patients who received nivolumab therapy for RCC at our institution from 3/2016 to 6/2019. Patients with complete data on NLR and PLR at time = 0 and +2 months and those who had accurate response and overall survival information available were selected (n = 37). Information on comorbidities, previous therapy, demographics were collected for adjusted analysis. NLR failure was defined as an increase of 3 or more compared to baseline NLR. Cox proportional hazard models were used to analyze the risk of progression and death with NLR/PLR failure at 2 months (± 2 weeks). Kaplan Meier graphs were constructed to trace survival functions for PFS and OS by NLRResultsNLR failure was associated with a statistically significant increase in the risk of progression on nivolumab therapy (HR 4.26, 95% CI [1.47–12.3], p = 0.007), in an adjusted cox regression model that included baseline NLR. In this adjusted model, the value of baseline NLR to predict treatment failure was non-significant (HR 1.01, p – 0.69). Similarly, NLR failure increased the risk of death (HR 3.83 95% CI [1.23–11.9], p = 0.02), with a similar non-significant contribution of baseline NLR (HR 1.06, p = 0.06). NLR failure predicted PFS less than 6 months with 90% positive predictive value (9/10) and a 48% (12/25) negative predictive value, and survival less than 1 year with a 56% negative predictive value and 100% positive predictive value (10/10). PLR changes failed to show any association with PFS (HR 0.99, p = 0.93) or OS (HR 1.00, p = 0.93).ConclusionsAn increase in NLR of 3 or more at 2 months of therapy with nivolumab appears to predict for impending treatment failure and increasing risk of death with a high positive predictive value. NLR failure if validated in larger studies could be useful in treatment managementEthics ApprovalThe study was approved by UAB Comprehensive Cancer Centers Ethics Board
43 Background: Recent studies have recognized the high prevalence of germline mutations in genes affecting DNA repair in patients with prostate cancer. In recognition of their growing clinical significance, the NCCN guidelines recommend genetic counselling in prostate cancer pts with certain risk factors. The application of these guidelines in clinical practice were evaluated. Methods: All new clinic visits of prostate cancer pts at UAB from January 2019 – June 2019 were identified and analyzed. We constructed a flow diagram of the UAB two-step referral model, and performed a chart review and analyzed the new clinic visits. We then sent a 10-item questionnaire to providers at UAB to collect information on germline genetic testing patterns, general approach to testing, and the barriers of GC, and actions to overcome barriers. Results: From January to June 2019, 57 new prostate cancer patients were seen, of which 23 had metastatic disease, 20 had high or intermediate risk localized disease and remaining had biochemical recurrence. In total, 38 had an indication for GC. The most common indication was metastatic disease in 23 pts (40%) and localized high risk in 15 pts (26%). Significantly 33% of 24 patients with early onset prostate cancer < 60 yrs did not meet NCCN defined criteria for testing. Only 39% of the 38 eligible patients were referred, with testing completed in 11% of those with indications. The response rate to the survey was 91%. 30% of respondents reported that they would be comfortable completing genetic counseling themselves, and the most commonly reported barrier to providing the testing themselves was time, and lack of expertise/experience. 70% percent of providers cited that lack of genetics workforce was a barrier to genetic testing, and 60% cited lack of knowledge of genetic testing and genetics and the inadequate coordination of referrals were barriers. Conclusions: While a majority of prostate cancer patients seen in the oncology clinic meet criteria for GC, referrals are inconsistent, and only a handful of eligible patients complete testing. From the survey results, the areas that need to be improved from the provider’s side are education and comfort with genetic testing. From a systems perspective, the need for more genetics workforce, and better process workflows are required to improve the uptake of Genetic Testing Referral and Testing. The interventions of practice transformation and education need to be implemented, and tested at UAB to improve adherence to the NCCN guidelines for genetic testing of prostate cancer.
344 Background: IROC is an expanding multi-institution collaborative database which includes socioeconomic, genomic, pathologic, clinical and laboratory data in metastatic RCC patients (pts), primarily in the modern setting. Elevated baseline NLR is now an established poor prognostic factor in renal cell carcinoma (RCC) but currently has limited practical use. We hypothesized that an increase in NLR of 3 or more (NLR Failure) at 2 months on therapy could be a predictor of eventual treatment failure and shorter overall survival and thus augment the utility of this marker. Methods: Patients with complete data on NLR at time = 0 and +2 months of therapy were analyzed. Information on comorbidities, previous therapy, demographics were collected for adjusted analysis. NLR failure was defined as an increase of 3 or more compared to baseline NLR. Cox proportional hazard models were used to analyze the risk of progression and death with NLR failure at 2 months (+/- 2 weeks). Kaplan Meier graphs were constructed to trace survival functions for PFS and OS by NLR. Results: Among 165 pts; 121 were eligible (Table). NLR failure at 2 months was associated with a highly statistically significant increase in the risk of death in < 1 year (HR 6.82, 95% CI [3.16-14.70], p<0.001). In a model adjusted for NLR change, the value of baseline NLR to predict OS <1 year was non-significant (HR 1.02, p = 0.65). Similarly, NLR failure increased the risk of treatment failure in less than 6 months (HR 4.83 95% CI [ 2.29-10 .19], p<0.001), while baseline NLR did not predict it (HR 1.03, p = 0.34). These findings were unaffected by immunotherapy vs TKI therapy. NLR failure at 2 months had a 78% (11/14) positive predictive value for survival <1 year and 86% (12/14) [p=.0001] for treatment failure in 6 months. Conclusions: In this multi-institutional cohort of RCC pts; an increase in NLR of 3 or more at 2 months following therapy start predicts for an increasing risk of death and impending treatment failure with a high PPV. The prognostic value of baseline NLR is non-significant when adjusting for NLR change. NLR failure should be validated in prospective studies and could have clinical utility in management of RCC pts. [Table: see text]
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