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Introduction: The molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs. Materials and methods: On July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores. Results: A total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05–1.1). Conclusions: Our review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.

Background and aims: Hepatic steatosis of nonalcoholic etiology (nonalcoholic fatty liver disease; NAFLD) is an emergent condition that may lead to hepatic cirrhosis and finally to liver cancer. We evaluate the risk of developing hepatocellular carcinoma (HCC) and quantify the prognosis in terms of recurrence (DFS) as well as HCC-specific and overall survival (CSS and OS) of patients with and without NAFLD. Methods: We searched published articles that evaluated the risk and outcomes of HCC in patients with steatosis/steatohepatitis from inception to July 2021 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Prospective cohort, case-control, or retrospective studies were selected that were published in English and provided incidence and survival rates of HCC patients with NAFLD. A random-effects model was created to estimate the pooled effect size. The primary outcome of interest was HCC incidence. The secondary endpoints were DFS, CSS, and OS. Results: In total, 948 217 patients with NAFLD were analyzed, from n = 103 observational studies. NAFLD significantly increased the risk of HCC (HR = 1.88 [95% CI, 1.46-2.42]; P < .01] but not risk of recurrence (HR = 0.99 [95% CI, 0.85-1.15]; P = .9) or overall mortality (HR = 1.04 [95% CI, 0.88-1.24]; P = 0.64). Conversely, NAFLD increased HCC-related mortality risk (HR = 2.16 [95% CI, 0.85-5.5]; P = .1). Risk of HCC was increased in Western countries but not in Asian countries. Conclusions: Patients with NAFLD have an increased risk of HCC as compared to patients without NAFLD. NAFLD also increases liver cancer (HCC) mortality. These results justify applying general measures to patients with proven NAFLD and monitoring patients with NASH and fibrosis.