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Diagnostic Delays Are Common Among Patients With Hepatocellular Carcinoma

Nishant Patel, Adam C. Yopp, and Amit G. Singal

Background: Most patients with hepatocellular carcinoma (HCC) present at advanced stages. The prevalence and clinical impact of delays during diagnostic evaluation among patients with HCC is unclear. Purpose: To identify and characterize factors associated with diagnostic delays among patients with HCC. Methods: Records were reviewed for consecutive patients with cirrhosis and HCC at a large urban hospital between January 2005 and July 2012. Time from presentation to diagnosis was determined using Kaplan-Meier analysis. Diagnostic delay was defined as time to diagnosis exceeding 3 months, and multivariate logistic regression was used to identify correlates of diagnostic delays. Results: Among 457 patients with HCC, 226 (49.5%) were diagnosed as outpatients. Among these, median time-to-diagnosis was 2.2 months, with 87 patients (38.5%) experiencing a diagnostic delay. Diagnostic delays were positively associated with the presence of hepatic encephalopathy (odds ratio [OR], 2.29; 95% CI, 1.03–5.07) and negatively associated with presentation after implementation of the electronic medical records (EMR) (OR, 0.28; 95% CI, 0.15–0.52) and presentation with an abnormal ultrasound (OR, 0.36; 95% CI, 0.19–0.67) on multivariate analysis. Higher rates of diagnostic delays were observed among those with hepatic encephalopathy (56% vs 35%), whereas lower rates were seen in those who presented after EMR implementation (26% vs 60%) and those who presented with an abnormal ultrasound with or without an elevated alpha fetoprotein level (27% vs 50%). Among 49 patients with mass-forming HCC and diagnostic delay, 18% had interval tumor growth of 2 cm or greater. Conclusions: Nearly 20% of patients with HCC wait more than 3 months from presentation to diagnosis, which can contribute to interval tumor growth.

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Therapeutic Delays Lead to Worse Survival Among Patients With Hepatocellular Carcinoma

Amit G. Singal, Akbar K. Waljee, Nishant Patel, Emerson Y. Chen, Jasmin A. Tiro, Jorge A. Marrero, and Adam C. Yopp

Although prior studies have shown underuse of appropriate therapy in patients with hepatocellular carcinoma (HCC), no studies to date have assessed the prevalence and clinical impact of therapeutic delays among patients with HCC. The goal of this study was to characterize and identify factors associated with underuse and delays in treatment of these patients. A retrospective cohort study was conducted of patients with cirrhosis diagnosed with HCC at a large urban safety net hospital between January 2005 and June 2012. Dates for HCC diagnosis and any treatments were recorded. Univariate and multivariate analysis was used to determine factors associated with treatment underuse and delayed treatment, which was defined as time from diagnosis to treatment exceeding 3 months. The authors identified 267 treatment-eligible patients with HCC, of whom only 62% received HCC therapy. On multivariate analysis, tumor stage (odds ratio [OR], 0.48; 95% CI, 0.36-0.65), Child-Pugh class (OR, 0.49; 95% CI, 0.28-0.84), and black race (OR, 0.55; 95% CI, 0.31-0.99) were associated with lower rates of treatment use. The median time to treatment was 1.7 months, with 31% of patients experiencing delayed treatment. Delayed treatment was associated with the presence of ascites (hazard ratio [HR], 2.8; 95% CI, 1.3-6.1) and current treatment with transarterial chemoembolization (HR, 4.8; 95% CI, 1.8-12.5). After adjusting for tumor stage and Child-Pugh class, treatment underuse (HR, 0.33; 95% CI, 0.24-0.46) and delayed treatment (HR, 0.50; 95% CI, 0.30-0.84) were both associated with significantly worse survival. Results showed that, in addition to one-third of patients not receiving HCC-directed therapy, another 30% experienced significant therapeutic delays, leading to worse survival.