Hideki Zimermann Kamitani

Impact of TP53 somatic mutations on prognosis in endometrial cancer: a systematic review and meta-analysis

Endometrial cancer (EC) is the sixth most common female cancer and may rank fourth in cancer mortality by 2040. TP53 mutations and aberrant p53 expression are associated to aggressive tumor subtypes and poor prognosis, reducing overall survival (OS), disease-free survival, recurrence rates (RcR) and Mortality Risk (MR). The prognostic impact of TP53 mutations in EC remains unclear. A systematic search was conducted in PubMed, Embase, and the Cochrane Library. Hazard ratios (HR) and Risk Ratios (RR) with 95% confidence intervals (CI) were combined using random-effects models. Analyses were conducted in RStudio (v4.4.1), and heterogeneity was evaluated using the I Twenty-four studies comprising 5462 EC patients were included. TP53 mutations and aberrant p53 expression were associated with poorer outcomes. For OS, TP53 mutations had an HR of 2.27 (95% CI 1.47-3.49) and aberrant p53 had an HR of 5.01 (95% CI 2.44-10.30). For DFS, TP53 mutations had an HR of 4.20 (95% CI 1.79-9.86), while aberrant p53 had an HR of 2.17 (95% CI 1.27-3.72). TP53 mutations also increased RcR (RR: 2.88; 95% CI 2.18-3.80) and MR (RR: 2.33; 95% CI 1.11-4.88). Aberrant p53 showed a non-significant trend for recurrence (RR: 3.54; 95% CI 0.95-13.10). TP53 mutations and abnormal p53 expression in EC patients predict a poorer prognosis, characterized by increased RcR and MR, as well as lower DFS and OS.

PD-1/PD-L1 inhibitors in endometrial cancer with high microsatellite instability: a Kaplan-Meier-derived patient data meta-analysis

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors. This meta-analysis of randomized controlled trials aimed to assess the survival benefit of anti-PD-1/PD-L1 therapies in women with advanced or recurrent endometrial cancer (EC) and mismatch repair deficiency (dMMR). A systematic search was conducted in PubMed, Scopus, Cochrane, and Web of Science databases to compare PD-1/PD-L1 inhibitors versus standard therapy in patients with advanced/recurrent EC. Studies were screened based on predefined inclusion/exclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias Tool. We used DerSimonian and Laird random-effects models to estimate hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs). Five studies including 2,739 patients were analyzed, with 627 (22.90%) having dMMR tumors. ICIs significantly improved progression-free survival (HR 0.35; 95% CI 0.28-0.44) and overall survival (HR 0.40; 95% CI 0.28-0.57) in dMMR patients. No significant difference was found in objective response rate (RR 1.72; 95% CI 0.88-3.36). The addition of immunotherapy for treating patients with advanced or recurrent endometrial cancer with dMMR and high microsatellite instability significantly improved PFS and OS outcomes. PROSPERO (CRD22057890200).