Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Dual hepatitis B and C-associated hepatocellular carcinoma: clinical characteristics, outcome, and prognostic role of albumin-bilirubin grade.

BACKGROUND: Albumin-bilirubin (ALBI) grade is used to evaluate the outcome of patients with hepatocellular carcinoma (HCC) which is often associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study aimed to investigate the clinical characteristics, outcome, and prognostic role of ALBI grade in dual HBV/HCV-related HCC. METHODS: A total 3341 HCC patients with viral etiology were prospectively enrolled and retrospectively analyzed. Multivariate Cox proportional hazards model was used to identify independent prognostic predictors. RESULTS: Of all patients, 2083 (62%), 1068 (32%), and 190 (6%) patients had HBV, HCV, and dual HBV/HCV infection, respectively. The mean age of HBV, HCV, and dual virus group was 60, 68, and 64 years (p < 0.001), respectively. There was no significant survival difference between HBV, HCV, and dual HBV/HCV-related HCC group (p = 0.712). Multivariate Cox analysis in dual HBV/HCV-related HCC showed that multiple tumors [hazard ratio (HR): 1.537, p = 0.044], tumor size >3 cm (HR 2.014, p = 0.044), total tumor volume (TTV) >50 cm3 (HR 3.050, p < 0.001), vascular invasion (HR 3.258, p < 0.001), performance status 2-4 (HR 2.232, p < 0.001), ALBI grade 2-3 (HR 2.177, p < 0.001), and BCLC stage B-D (HR 2.479, p < 0.001) were independent predictors of poor survival. CONCLUSIONS: Dual viral infection does not accelerate the development of HCC in HBV carriers. Patient survival is similar between dual HBV/HCV-related HCC and single HBV- or HCV-related HCC group. The ALBI grade is a robust prognostic model in dual virus-related HCC to discriminate patient long-term survival.

Evaluation of alternative serum biomarkers to monitor the progression of chronic HBV and HCV infection.

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most serious health conditions affecting about 600 million people worldwide leading to a number of severe liver diseases. Due to the lack of warning signs or mild symptoms during the early stage of the infection, a molecular signature associated with disease progression would be useful. Based on our recent paper where candidate biomarkers were determined through topological and modularity analysis of protein interaction networks (PINs), this study was focused on the evaluation of MIF, TNFRSF1A, FAS and TMSB4X as diagnostic biomarkers in chronic HBV and HCV infections. The aim was to establish a molecular profile, by combining those markers, that would discriminate the different stages during the progression of chronic hepatitis. One hundred and fifteen patients infected with HBV or HCV categorized into three groups: non-cirrhotic, cirrhotic and with HCC, and 20 healthy subjects were enrolled in this study. Serum levels of the aforementioned factors were measured by ELISA. TNFRSF1A serum levels appeared statistically significantly increased in all patient groups compared to control group with a p-value of <0.05. Furthermore, the combination of TNFRSF1A and TMSB4X serum levels successfully classified 63, 47% of patients indicating an association with HBV and HCV infections. Thus, variations of serum levels of TNFRSF1A and TMSB4X could be associated with the different stages of the disease and may be utilized for further research. On the other hand, we found no contribution of MIF and FAS serum levels for successful classification of patients.

IL-6 significantly correlates with p-STAT3 expression and presents high variceal bleeding with mortality in cirrhotic patients: A cross-sectional study.

BACKGROUND/PURPOSE: Effective mediators activate downstream transducers regulating inflammation and angiogenesis. Correlation among mediators IL-6, IL-27, TNF-α, and VEGF with STAT proteins at diverse clinical-pathologic stages of cirrhotic patients remains limited. METHODS: Plasma mediators were assayed from 158 naïve liver cirrhosis (LC-total group) and 144 non-LC individuals. The LC-total group included 69 hepatitis B virus-infected (LC-HBV) patients, 40 hepatitis C virus-infected (LC-HCV) patients, and 49 patients without HBV-/HCV- infection (LC-NBNC). Another 144 non-LC individuals comprised 54 healthy persons (HG) and 90 chronic hepatitis patients (CH-total) as the control group. To correlate with plasma mediators, 52 paired liver tissues (CH: 41 and LC: 11 cases) served for p-STAT1 and p-STAT3 immunostaining. RESULTS: Although IL-6, IL-27, TNF-α, and VEGF were expressed significantly in CH-total versus HG (p = 0.011, p < 0.001, p = 0.007, p = 0.004, respectively) and overall viral hepatitis patients versus HG (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively), only IL-6 presented the strongest correlation in cirrhotic patients than noncirrhotic patients (LC-HBV vs. HG, p < 0.001, vs. CH-HBV, p = 0.001; LC-HCV vs. HG, p = 0.001, vs. CH-HCV, p = 0.031; LC-NBNC vs. HG, p < 0.001). Over-expressed IL-6 linked with poorer liver function (albumin: r = -0.346, p < 0.001; bilirubin: r = 0.271, p = 0.001; INR: r = 0.308, p < 0.001; Child-Turcotte-Pugh Classification C vs. A or B, p = 0.001, p = 0.007, respectively), variceal severity (p = 0.045), and bleeding (p = 0.047), as well as patients' mortality (p = 0.005). Furthermore, plasma IL-6 significantly correlated with tissues p-STAT3 expression (r = 0.737, p = 0.010) (IL-27: r = 0.078, p = 0.820; TNF-α: r = -0.145, p = 0.670; VEGF: r = 0.142, p = 0.678) in cirrhotic patients than noncirrhotic patients. CONCLUSION: Over-expression of IL-6 reflects hepatic dysfunction and varices bleeding with mortality, as well as correlates p-STAT3 expression in cirrhotic patients.