K-RAS and N-RAS mutations in testicular germ cell tumors

The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients’ demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAF^V600E (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAF^V600E and BRAF^non-V600E and their analysis according to specific tumor localizations showed that all four BRAF^non-V600E mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.

Objective: The Prognostic Nutritional Index (PNI), reflects the nutritional and immunological status of the patient and has been associated with outcomes in various cancers. In this study, the prognostic significance of PNI in metastatic hormone‐sensitive prostate cancer (mHSPC) and its potential role in guiding treatment decisions between abiraterone acetate and enzalutamide is investigated.Methods: Retrospective analysis was performed on 167 mHSPC patients treated between 2019 and 2024. PNI was calculated using the formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm³). Patients were stratified into high and low PNI groups according to a cutoff value of 49.98, determined via receiver operating characteristic (ROC) analysis. Survival outcomes, including overall survival (OS), radiographic progression‐free survival (rPFS), and PSA progression‐free survival (PSA‐PFS), were assessed. Treatment responses to abiraterone acetate and enzalutamide were compared within PNI strata.Results: Patients with PNI > 49.98 had significantly longer median OS than those with PNI ≤ 49.98 (36.6 months vs. 30.0 months, p < 0.01). Multivariate analysis identified high PNI, ECOG performance status 0–1, and absence of visceral metastasis as independent predictors of improved OS. Among patients with low PNI, those treated with enzalutamide had superior OS compared to those receiving abiraterone acetate (p = 0.004), while no significant OS difference was noted between treatments in the high PNI group (p = 0.55).Conclusion: PNI serves as a significant prognostic biomarker in mHSPC, correlating with overall survival and potentially influencing treatment efficacy between abiraterone acetate and enzalutamide. Integrating PNI into clinical practice may aid in tailoring individualized treatment options.

Introduction: This study aimed to assess the role of the adjusted PNI-IMDC risk scoring system in stratifying the intermediate group of metastatic RCC patients who received TKIS in the first-line setting. Methods: A total of 185 patients were included. The adjusted PNI and IMDC model was used to divide the intermediate group into two groups: intermediate PNI-high and intermediate PNI-low groups. The statistical data were analyzed using Kaplan–Meier and Cox regression analysis. Results: The results showed that the adjusted PNI-IMDC risk score, classic IMDC, and PNI had similar prognostic values. Adjusted PNI-IMDC risk score might be used for a more homogeneous differentiation of the classic intermediate group. On the other hand, multivariate analysis revealed that the presence of nephrectomy, adjusted favorable/intermediate (PNI-high) group, ECOG performance score, and presence of bone metastasis were independent predictors of OS. Conclusions: Pre-treatment PNI, as a valuable and potential add-on biomarker to the adjusted PNI-IMDC classification model, can be helpful for establishing an improved prognostic model for intermediate group mRCC patients treated with first-line TKISs. Further validation studies are needed to clarify these findings.

Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01).The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.