Purpose Current guidelines for tumor lysis syndrome management recommend rasburicase for high-risk patients. Adherence to guidelines has not been well studied, and the correlation between uric acid reduction and clinically relevant outcomes, such as acute kidney injury, remains unclear. Our study aims to describe rasburicase utilization patterns and outcomes in cancer patients with varying risks for tumor lysis syndrome. Methods In this retrospective cohort study, we included cancer inpatients who received rasburicase for tumor lysis syndrome management at two affiliated academic hospitals from 2009 to 2015. Patients were classified by tumor lysis syndrome risk categories prior to drug administration. Primary outcomes included acute kidney injury incidence and renal recovery. Secondary outcomes included uric acid nadir, mortality, and hospital length-of-stay. Results Among 164 patients, 42 (26%) had high-, 63 (38%) had intermediate-, and 59 (36%) had low-risk for tumor lysis syndrome. A total of 94 patients (57%) had existing renal dysfunction prior to rasburicase use. This occurred more frequently in low- (68%) compared to intermediate- (57%) and high- (43%) risk patients ( p = 0.044). A greater proportion of patients in the high-risk group (78%) had renal recovery when compared to the intermediate- (61%) or low- (45%) risk groups ( p = 0.056). Despite a similar length of stay, the high-risk group had a significantly lower 30-day mortality (10%) when compared to intermediate- (25%) or low- (32%) risk groups ( p = 0.029). Conclusions Our results suggest that rasburicase may be frequently prescribed to treat hyperuricemia unrelated to tumor lysis syndrome in cancer patients. Improved education and adherence to guidelines may improve clinical and economic outcomes associated with rasburicase administration.
6528 Background: The Surveillance, Epidemiology, and End Results (SEER) registries lack information on the Epidermal Growth Factor Receptor (EGFR) mutation and Anaplastic Lymphoma Kinase (ALK) gene rearrangement test results. With the goal of enabling population-based outcomes research in molecularly selected NSCLC subgroups, we conducted a validation study of NLP for ascertainment of EGFR and ALK testing from electronic pathology reports (e-paths) of patients included in the Seattle-Puget Sound (SPS) and Kentucky Cancer (KCR) SEER registries. Methods: We obtained 4,278 and 1,041 e-paths pertaining to 1,634 and 565 patients with stage IV non-squamous NSCLC diagnosed from 1/1/2011 to 12/31/2013 and included in the SPS and KCR registries, respectively. Two oncologists independently reviewed all reports to generate a gold-standard dataset. We used 855 of the SPS reports to train hybrid rule-based and machine learning algorithms for detection of test status (reported vs. not reported), and test result if reported (positive vs negative) for EGFR mutational analysis and ALK testing by FISH, IHC, or gene sequencing. In the remaining 3,423 SPS reports, we conducted a 5-fold cross-validation analysis to estimate the internal NLP sensitivity, specificity, positive predictive value, and negative predictive value for test status and results, respectively. We used a hierarchical rules system to assess the NLP accuracy at the patient level. For external validation, we repeated all analyses in the KCR dataset. Results: In the SPS internal validation report sample, the validity metrics ranged from 97% to 99% for EGFR and ALK test status, and from 95% to 100% for EGFR and ALK test results, respectively. In the KCR external validation report sample, the metrics ranged from 74% to 96% for EGFR and ALK test status, and 2% to 100% for test results, respectively. At the patient level, the NLP accuracy for EGFR and ALK was 95% and 96% (SPS cohort), and 70% and 72% (KCR cohort) respectively. Conclusions: NLP is a valid method for determining EGFR and ALK test status and results for patients included in SEER registries with access to e-path, but the algorithms likely need to be registry-specific.
Introduction: While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes in tumor lysis syndrome (TLS) is unknown. There are no studies demonstrating improvement of acute kidney injury (AKI) in patients with TLS and pre-existing renal dysfunction. In this study, we aim to address the comparative effectiveness of rasburicase versus allopurinol in cancer patients with hyperuricemia and AKI. Methods: In this retrospective cohort study, we included all hospitalized cancer patients with uric acid levels greater than 7.0 mg/dL and concurrent AKI who received either rasburicase or allopurinol from 2009 to 2015 at University of Washington affiliated hospitals. Inverse probability of treatment weighting (IPTW) using the propensity score was used to account for potential confounders and to estimate the causal effect associated with differential drug treatment. Balance after weighting was assessed by calculating standardized differences and variance ratios, where a standardized difference of less than 0.1 was considered adequate balance. Naïve linear and logistic regressions and weighted outcome regressions were performed after sampling weight assignment. The primary outcome of the study included renal function recovery defined by a final creatinine value return to less than 50% of baseline creatinine and not requiring dialysis at the time of discharge, death, or 30 days, whichever occurred first. Secondary outcomes included final creatinine, creatinine nadir and uric acid nadir within 7 days of drug administration. Results: Over the 6-year study period, a total of 150 patients met the inclusion criteria; 89 received rasburicase and 61 received allopurinol. After IPTW, 140 weighted patients were included in the final analysis with adequate balance of baseline characteristics (standardized difference <0.1 in age, sex, ICU admission, TLS risk, tumor type, chemotherapy type and timing, creatinine, LDH, potassium, phosphate, and calcium). In the weighted analysis, rasburicase was associated with a significantly lower mean uric acid nadir within 7 days compared to allopurinol (2.70 versus 5.82 mg/dL, p<0.01). However, the likelihood of renal function recovery (OR=0.90, p=0.79), the creatinine nadir within 7 days (1.80 versus 1.66 mg/dL, p=0.51), and the final creatinine value by 30 days (2.08 versus 2.07 mg/dL, p=0.98) were not significantly different for patients receiving rasburicase versus allopurinol (Table 1). The average time for final creatinine assessment was 12 days and overall survival did not significantly differ between the two cohorts. In subgroup analyses, the likelihood of renal recovery with rasburicase in patients at low-risk for TLS was associated with an odds ratio of 0.47 (p=0.12) compared to an odds ratio of 1.76 (p=0.34) for those at intermediate- and high-risk for TLS. Similarly, there was a trend towards benefit of rasburicase in improving renal function in patients with underlying high grade myeloid and very aggressive leukemia and lymphomas as opposed to those with more indolent malignancies, such as solid tumors and multiple myeloma (Figure 1). Conclusion: Among cancer patients with hyperuricemia and AKI, rasburicase administration was associated with a significant early reduction in uric acid but not associated with an improvement in the incidence of renal recovery or survival when compared to allopurinol. Though the benefit of rasburicase in higher grade malignancies remains inconclusive, this study emphasizes that uric acid correction alone may not be the most clinically effective strategy in treating AKI, particularly if renal dysfunction is unrelated to TLS. Disclosures No relevant conflicts of interest to declare.
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