Background and Objectives: CDK4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone receptor-positive HER2 negative (HR(+)/HER2(-)) breast cancer. Despite their efficacy, interstitial lung disease (ILD) remains a rare but potentially fatal adverse effect. This study aims to evaluate the incidence and clinical characteristics of ILD associated with CDK4/6 inhibitors in breast cancer patients in Turkey. Materials and Methods: A retrospective multicenter analysis included 464 breast cancer patients treated with CDK4/6 inhibitors between January 2017 and April 2024. Patients receiving ribociclib or palbociclib were evaluated for the development of ILD. Radiological assessments were performed to confirm ILD and exclude other conditions. Clinical characteristics, treatment regimens, and outcomes were analyzed. Results: ILD was identified in 10 patients (2.1%). The average age of the affected patients was 62.5 ± 9.85 years. Hypersensitivity pneumonitis and nonspecific interstitial pneumonia (NSIP) were the most common radiological patterns. Palbociclib was implicated in six cases, while ribociclib was associated with four cases. Grade 3 pulmonary toxicity was observed in eight patients, and Grade 4 toxicity in two patients. One patient who was on palbociclib died due to ILD. No significant correlation was found between ILD and age, smoking status, lung metastases, or prior thoracic radiotherapy. Conclusions: The incidence of CDK4/6 inhibitor-associated ILD in Turkish breast cancer patients appears higher than previously reported in clinical trials. More robust, long-term studies are necessary to identify potential risk factors and mitigate ILD-related mortality.

Background and Objectives: KRAS genes are among the most prominent oncogenes that trigger tumor formation in colorectal cancer (CRC) and serve as predictive biomarkers for resistance to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. However, the prevalence and mutation spectrum of the KRAS gene family in mCRC patients in Turkey have not been sufficiently analyzed. This study investigates the frequency and distribution of mutations in the KRAS gene family across different regions of Turkey and examines gender-related variations. Materials and Methods: This multicenter observational study included 2458 histologically confirmed mCRC patients collected from 52 centers across Turkey. In a central laboratory, KRAS mutations in codons 12 and 13 were analyzed using polymerase chain reaction (PCR). Statistical analyses were performed using chi-square tests and Monte Carlo simulations, with a significance threshold set at p < 0.05. Results: Depending on the region, KRAS mutations were detected in 45% of patients, ranging from 39.6% to 47.5%. The mutation rate was significantly higher in female patients (48.8%) compared to male patients (42.6%) (p = 0.002). Codon 12 mutations were more frequent than codon 13 mutations. G12D, G12V, and G13D mutations accounted for 80% of all detected mutations. The G12V mutation was prevalent in female patients (p = 0.007). Based on region, mutation diversity was similar, and no statistically significant difference was found (p > 0.05). Conclusions: This large-scale, multicenter study provides the most comprehensive dataset of KRAS mutations in mCRC patients in Turkey. This study revealed regional trends, as well as gender differences. The findings highlight the importance of routine KRAS genotyping in guiding personalized treatment strategies, especially regarding candidate selection for anti-EGFR therapies. Further research is required to elucidate the prognostic and therapeutic implications of specific KRAS mutations.

Background Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have significantly improved clinical outcomes in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR + /HER2−) metastatic breast cancer. Hepatotoxicity is a known class-related adverse event that may interrupt or modify treatment. However, real-world evidence on its incidence, risk factors, and management strategies—particularly rechallenge approaches—remains limited. This study aimed to evaluate the frequency and clinical characteristics of CDK4/6 inhibitor-associated hepatotoxicity, to identify risk factors, and to assess the outcomes and safety of rechallenge following liver injury. Methods This retrospective multicenter study included 544 patients with HR+ /HER2− metastatic breast cancer who were treated with ribociclib or palbociclib between January 2017 and July 2024 in oncology centers across Turkey. Abemaciclib was not included due to reimbursement limitations during the study period. Patient characteristics, comorbidities, concomitant medications, and herbal or dietary supplement use were recorded. Liver function tests and viral hepatitis serologies were analyzed. Hepatotoxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0), and causality was assessed with the Roussel Uclaf Causality Assessment Method (RUCAM). Management strategies—including dose interruption, dose reduction, switching to another CDK4/6 inhibitor, and outcomes of rechallenge were evaluated. Results Hepatotoxicity occurred in 10.5% of patients, most commonly in a hepatocellular pattern. Ribociclib was the most frequently used agent. Younger age, herbal supplement use, and hepatitis B carrier status were significantly associated with increased risk of hepatotoxicity. All hepatotoxic events were managed conservatively. None of the patients developed acute liver failure or required invasive evaluation. Dose reduction or switching to the alternate agent was attempted in most patients after enzyme normalization and was successful in the majority, with no recurrence of severe hepatotoxicity. Conclusion CDK4/6 inhibitor-related hepatotoxicity is manageable with careful monitoring and individualized strategies. Timely dose interruption, switching agents, or cautious rechallenge allowed most patients to resume therapy safely. These findings support the continued use of CDK4/6 inhibitors in eligible patients, even after hepatotoxicity events.

Background and Objectives: Early-onset breast cancer (EOBC), particularly in patients under 40, presents with distinct biological characteristics and worse survival outcomes compared to late-onset cases. Despite intensive treatments, EOBC patients, especially those with hormone receptor-positive, HER2-negative (HR+/HER2-) subtypes, show poorer prognosis. CDK4/6 inhibitors, combined with endocrine therapy (ET) have become the standard for HR+/HER2- metastatic breast cancer, yet younger patients are underrepresented in clinical trials. This study aims to evaluate the efficacy of ribociclib and palbociclib with ET in HR+/HER2- metastatic breast cancer, addressing the critical gap in understanding treatment outcomes in younger patient populations. Materials and Methods: This multicenter, retrospective study evaluated the efficacy and safety of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors, ribociclib, and palbociclib, in combination with endocrine therapy in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer. Results: A total of 198 patients treated between 2019 and 2023 were analyzed for progression-free survival, overall survival, and prognostic factors. Very early-onset breast cancer, which is diagnosed before the age of 35, was identified as an independent prognostic factor for poor progression-free survival. Additional factors associated with poorer outcomes included liver metastasis, progesterone receptor negativity, high tumor grade, and the concurrent use of fulvestrant with CDK4/6 inhibitors. Both ribociclib and palbociclib demonstrated similar efficacy, and dose reductions due to treatment-related adverse events did not compromise therapeutic outcomes. Conclusions: This study is the first to focus specifically on the treatment of early-onset breast cancer with CDK4/6 inhibitors, providing critical insights into the unique challenges faced by this patient population. The findings underscore the urgent need for personalized treatment strategies, routine genetic testing, and dedicated clinical trials designed to address the specific needs of these high-risk subgroups. By advancing our understanding of the clinical and molecular landscape of early-onset breast cancer and very early-onset breast cancer, this study lays the groundwork for improving outcomes in these underserved patients through tailored therapeutic approaches.

Aims: It was aimed to evaluate the prevalence of anxiety and depression among cancer patients, and examine their association with quality of life (QoL). Methods: A cross-sectional study was conducted, including 750 adult cancer patients at a tertiary oncology outpatient clinic. Anxiety and depression status were measured using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI), respectively, while QoL was assessed with the EORTC QLQ-C30. Sociodemographic and clinical data were collected through structured forms. Comparative, correlation, and subgroup analyses were performed, with p

Background/Aims: The treatment of hepatocellular carcinoma (HCC), which accounts for 90% of all liver cancers, is highly varied. The use of second-line treatments following progression on first-line atezolizumab and bevacizumab (Atez/Bev) for advanced HCC remains controversial. The aim of this study was to analyze the real-world clinical results of second-line treatments in progression after Atez/Bev and to determine the factors affecting prognosis. Materials and Methods: Fifty-eight patients treated with second-line sorafenib, regorafenib, and cabozantinib for progression after first-line Atez/Bev for advanced/metastatic HCC from 20 centers in Türkiye between October 2020 and June 2024 were retrospectively analyzed. Responses were evaluated by Response criteria, specifically Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. Median overall survival (OS) and progression-free survival (PFS) were computed with the Kaplan–Meier method. The Cox regression model was utilized to analyze multivariate analyses. Results: About 82.8% of the patients were male and the median age of the whole group was 62 (range, 18-78) years. All patients progressed after first-line Atez/Bev and were given second-line treatment. The most commonly used second-line treatment option was sorafenib (70.7%), followed by regorafenib (12.1%) and cabozantinib (10.3%). Both median PFS (4.1 months) and median OS (7.8 months) were longer in patients treated with sorafenib compared to other treatments. In univariate analyses, Child–Pugh score B, alpha-fetoprotein (AFP) levels (>200 ng/mL), extrahepatic spread, and Prognostic Nutritional Index (PNI) < 47.6 substantially raised the risk of overall mortality. Multivariate analysis showed that extrahepatic spread (HR (Hazard ratio): 0.41, P = .012), PNI level (HR: 0.24, P =.005), and AFP level (HR:1.97, P = .049) were independent predictors of OS. Conclusion: Although second-line therapies after Atez/Bev show different degrees of efficacy, survival rates are consistent with the literature. Extrahepatic spread, AFP level, and PNI level are the main prognostic factors. In light of this information, personalized treatment strategies may improve outcomes for this challenging patient group. Cite this article as: Majidova N, Yaslıkaya S, Mıldanoglu MM, et al. Efficacy of second-line treatments after atezolizumab and bevacizumab in advanced hepatocellular carcinoma and related prognostic factors: A multicenter study by the turkish oncology group (TOG). Turk J Gastroenterol. 2025;36(5):293-301.