No abstract

Background: Venous thromboembolism (VTE) in malignancy is associated with poor outcomes. We conducted a retrospective review of VTE in patients with endometrial cancer to characterize the VTE incidence, identify factors that contribute to VTE risk, and compare survival outcomes in patients with and without VTE. Methods: A retrospective chart review identified 422 eligible patients who underwent surgery for endometrial cancer (1 January 2014 to 31 July 2016). The primary outcome was VTE. Binary logistic regression identified risk factors for VTE; significant risk factors were included in a multivariate analysis. Kaplan–Meier estimates are reported, and log rank tests were used to compare the Kaplan–Meier curves. Risk-adjusted estimates for overall survival based on VTE were determined using a multivariate Cox proportional hazards model. Results: The incidence of VTE was 6.16% overall and 0.7% within 60 days postoperatively. Non-endometrioid histology, stages 3 and 4 disease, laparotomy, and age (p < 0.1) were identified as factors associated with VTE and were included in a multivariate analysis. The overall death rate in patients with VTE was 42% (9% without VTE): hazard ratio, 5.63; 95% confidence interval, 2.86 to 11.08; p < 0.0001. Adjusting for age, stage of disease, and histology, risk of death remained significant for patients with a VTE: hazard ratio, 2.20; 95% confidence interval, 1.09 to 4.42; p = 0.0271. Conclusions: A method to identify patients with endometrial cancer who are at high risk for VTE is important, given the implications of VTE for patient outcomes and the frequency of endometrial cancer diagnoses. Factors identified in our study might assist in the recognition of such patients.

BackgroundThe CELESTIAL, RESORCE, and REACH‐2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0‐1) and liver function (Child‐Pugh‐A). This study characterizes subsequent treatments received by HCC patients after sorafenib, and determines the proportion of patients eligible for novel therapies if strict eligibility criteria (SEC) were utilized compared to more liberal modified eligibility criteria (MEC, including ECOG 2, Child‐Pugh‐B7).MethodsHCC patients who received sorafenib between 2008 and 2017 were included from the Canadian HCC CHORD Database. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, and REACH‐2 trial SEC or MEC. Median overall survival (mOS) was assessed using the Kaplan‐Meier method.ResultsA total of 730 patients were identified; and 172 (23.6%) received subsequent treatment. Patients who received subsequent treatment had longer mOS than those who did not (12.1 vs 3.3 months; P < .001). Using SEC, only 13.1% of patients would be eligible for cabozantinib, regorafenib, or ramucirumab. Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Higher ineligibility for regorafenib and ramucirumab was driven by trial‐specific criteria, including sorafenib intolerance (28%) for RESORCE and AFP <400 (58.9%) for REACH‐2.ConclusionsA small proportion of real‐world HCC patients would be eligible for cabozantinib, regorafenib, or ramucirumab if SEC in clinical trials were followed, while more than double would be eligible if MEC were applied. Patients who received subsequent treatment had improved mOS, regardless of whether they met SEC or MEC.

Several systems (tumor‐node‐metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC], Okuda, Cancer of the Liver Italian Program [CLIP], and albumin–bilirubin grade [ALBI]) were developed to estimate the prognosis of patients with hepatocellular carcinoma (HCC) mostly prior to the prevalent use of sorafenib. We aimed to compare the prognostic and discriminatory power of these models in predicting survival for HCC patients treated with sorafenib and to identify independent prognostic factors for survival in this population. Patients who received sorafenib for the treatment of HCC between 1 January 2008 and 30 June 2015 in the provinces of British Columbia and Alberta, and two large cancer centers in Toronto, Ontario, were included. Survival was assessed using the Kaplan–Meier method. Multivariate Cox regression was used to identify predictors of survival. The models were compared with respect to homogeneity, discriminatory ability, monotonicity of gradients, time‐dependent area under the curve, and Akaike information criterion. A total of 681 patients were included. 80% were males, 86% had Child–Pugh class A, and 37% of patients were East Asians. The most common etiology for liver disease was hepatitis B (34%) and C (31%). In all model comparisons, CLIP performed better while BCLC and TNM7 performed less favorably but the differences were small. The utility of each system in allocating patients into different prognostic groups varied, for example, TNM poorly differentiated patients in advanced stages (8.7 months (m) (95% CI 6.5–11.5) versus 8.4 m (95% CI 7.0–9.6) for stages III and IV, respectively) while ALBI had excellent discrimination of early grades (15.6 m [95% CI 13.0–18.4] versus 8.3 m [95% CI 7.0–9.2] for grades 1 and 2, respectively). On multivariate analysis, hepatitis C, alcoholism, and prior hepatic resection were independently prognostic of better survival (P < 0.01). In conclusion, none of the prognostic systems was optimal in predicting survival in sorafenib‐treated patients with HCC. Etiology of liver disease should be considered in future models and clinical trial designs.