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.

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival.

Prognostic Significance of HALP Score in Second-Line Nivolumab Treatment of Advanced Non-Small Cell Lung Cancer - Namık Kemal Medical Journal

Background and Objectives: Medication adherence is a key determinant of treatment effectiveness in early-stage breast cancer, particularly during long-term systemic therapies. As breast cancer is increasingly diagnosed at younger ages, a growing number of women continue to carry active parenting responsibilities during treatment. However, the associations between parenting-related psychosocial factors and medication adherence remain insufficiently explored. This study aimed to examine the associations between parenting stress, spiritual well-being, and medication adherence in women with early-stage breast cancer who maintain active parenting roles. Materials and Methods: This multicenter, cross-sectional study included 432 women with early-stage (I–III) breast cancer receiving active systemic therapy across nine oncology centers. Parenting stress was assessed using the Parenting Stress Scale (PSS), spiritual well-being using the Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being Scale (FACIT-Sp-12), and medication adherence using the 6-item Modified Morisky Adherence Scale (MMAS-6). Spearman correlation analyses and multivariable linear regression models were used to evaluate associations between variables. Mediation analysis was performed using Hayes’ PROCESS macro (Model 4) with 5000 bootstrap samples to assess statistical mediation. Results: Parenting stress was positively associated with poorer medication adherence (ρ = 0.248, p < 0.01), whereas spiritual well-being was negatively associated with non-adherence (ρ = −0.225, p < 0.01). Parenting stress showed a strong inverse association with spiritual well-being (ρ = −0.597, p < 0.01). In multivariable regression analyses, both parenting stress and spiritual well-being were independently associated with medication adherence (β = 0.180, p = 0.002 and β = −0.199, p = 0.001, respectively). Mediation analysis demonstrated a significant indirect statistical association between parenting stress and medication adherence through spiritual well-being (indirect effect = 0.0155), consistent with partial statistical mediation. Conclusions: Medication adherence among women with early-stage breast cancer and active parenting responsibilities is associated with psychosocial context in addition to clinical factors. Parenting stress is associated with poorer adherence, whereas greater spiritual well-being is associated with better adherence within a statistical mediation framework. These findings generate hypotheses for future longitudinal and interventional studies.

Aims: Claudin 18.2 (CLDN18.2) has moved from tight-junction biology into the center of biomarker-driven oncology, particularly in gastric and gastroesophageal junction malignancies. With the clinical development of zolbetuximab and newer CLDN18.2-directed therapeutic platforms, the field has expanded rapidly and now requires quantitative mapping rather than narrative description alone.Methods: A bibliometric and scientometric analysis was performed using the Web of Science Core Collection database. Publications related to CLDN18.2 published between 2004 and 2026 were identified using predefined CLDN18.2- and zolbetuximab-related search terms. After document-type and language filtering, 490 English-language articles and reviews were included. Bibliometrix/Biblioshiny and VOSviewer were used to evaluate publication growth, collaboration patterns, citation structure, thematic evolution, and conceptual trends within the literature. Results: The final corpus comprised 490 publications, 3,265 authors, 246 sources, and 15,756 cited references. Annual growth was 23.17%, with a pronounced acceleration after 2018 and a sharp expansion after 2022. Exponential regression outperformed linear modeling, supporting a non-linear growth pattern. China, Japan, the United States, Germany, and South Korea were leading contributors. Productive authors and institutions clustered around translational gastric cancer research and CLDN18.2-targeted therapy development. Keyword and thematic analyses showed a transition from epithelial biology and tight-junction terminology toward gastric cancer, gastroesophageal junction adenocarcinoma, zolbetuximab, biomarker testing, immunotherapy, and targeted therapeutic strategies.Conclusion: CLDN18.2 research has rapidly evolved into a clinically relevant precision-oncology field shaped by biomarker guided gastric cancer therapeutics, international collaboration, and emerging targeted treatment platforms. The continued exponential growth of the literature suggests that CLDN18.2 will likely remain an expanding focus of translational and clinical oncology research.

Background/Objectives: The study aimed to compare the treatment effectiveness of patients with locally advanced rectal cancer undergoing standard neoadjuvant therapy or total neoadjuvant therapy. It also sought to identify prognostic factors for disease-free survival and overall survival and parameters predictive of pathological complete response. Materials and Methods: A retrospective analysis was conducted on 239 patients diagnosed with locally advanced rectal cancer between 2016 and 2022 at several medical centers in Turkey. Clinical data, including neoadjuvant chemoradiotherapy types, chemotherapy regimens, surgical outcomes, and survival metrics, were collected. Statistical analyses included chi-square tests, Kaplan–Meier survival analysis, and Cox proportional hazard models to evaluate prognostic factors for disease-free survival and overall survival and logistic regression to identify predictors of pathological complete response. Results: Among 239 patients, 46.9% received total neoadjuvant therapy, while 53.1% underwent standard neoadjuvant therapy. Total neoadjuvant therapy was associated with a significantly higher pathological complete response rate (45.5% vs. 14.9% in standard neoadjuvant therapy; p < 0.001) and longer disease-free survival (median 124.2 vs. 72.4 months). The 3-year overall survival rate for all patients was 90.7%, and disease-free survival was 76.8%. Multivariate analysis identified pathological complete response (HR: 2.34), total neoadjuvant therapy (HR: 5.12), and type of surgery (HR: 8.12) as independent prognostic factors for disease-free survival, and pathological complete response and absence of lymphovascular invasion as independent prognostic factors for overall survival. Logistic regression analysis showed that total neoadjuvant therapy (OR: 4.40) and initial neoadjuvant chemotherapy (OR: 2.02) were independent predictors of achieving pathological complete response. Conclusions: Total neoadjuvant therapy significantly improves pathological complete response rates, disease-free survival, and overall survival in patients with locally advanced rectal cancer compared to standard neoadjuvant therapy. Total neoadjuvant therapy and achieving pathological complete response are strong independent prognostic factors for both disease-free survival and overall survival, suggesting that a more intensive neoadjuvant approach may lead to better outcomes in locally advanced rectal cancer. The increased pathological complete responses rate with total neoadjuvant therapy has created an opportunity for the development of new treatment modalities and the advancement of non-surgical management strategies in the future.