Mahmut Emre Yildirim

Background: Right-sided metastatic colon cancer represents a clinically distinct subgroup with inferior outcomes and uncertain optimal biologic treatment selection, even among patients with RAS wild-type disease. Real-world data focusing specifically on right-sided RAS wild-type metastatic colon cancer remain limited. This study aimed to describe clinicopathologic characteristics, metastatic patterns, treatment approaches, and survival outcomes in this population using a national multicenter registry. Methods: This retrospective multicenter cohort study was conducted using data from the ONKO-KOLON Türkiye registry. Patients with pathologically confirmed KRAS/NRAS wild-type metastatic colorectal cancer and available primary tumor localization were evaluated. The main analytic cohort included patients with right-sided metastatic colon cancer, defined as right colon or transverse colon tumors. Left-sided colon cancer patients were used as a contextual comparator, while rectal cancer patients were excluded from sidedness-based colon comparisons. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: Among 1079 patients in the source cohort, primary tumor localization was available in 1065 patients. Of these, 213 had right-sided colon cancer, 464 had left-sided colon cancer, and 388 had rectal cancer. In the right-sided cohort, median age was 61.5 years, 64.3% were male, and 66.7% had synchronous/de novo metastatic disease. Liver metastasis was the most common metastatic site (63.4%), followed by lymph node (31.0%), lung (21.1%), and peritoneal metastases (15.5%). First-line anti-VEGF-based treatment was used in 46.0% of patients, while anti-EGFR-based treatment was used in 40.8%. Among evaluable patients, the objective response rate was 46.8% and the disease control rate was 79.2%. Median progression-free survival was 10.0 months, and median overall survival was 24.0 months. In unadjusted exploratory analysis, median OS was 27.0 months with anti-EGFR-based treatment and 17.0 months with anti-VEGF-based treatment (log-rank p = 0.022), whereas median PFS was 10.0 months in both groups. In an extended covariate-adjusted multiple-imputation sensitivity model, the anti-EGFR OS estimate did not meet statistical significance (adjusted HR 0.66, 95% CI 0.43–1.00; p = 0.051). In a secondary contextual comparison, median overall survival was shorter in the right-sided than in the left-sided colon cancer group (24.0 vs. 28.0 months; HR 1.47, 95% CI 1.19–1.82; p < 0.001), whereas progression-free survival did not differ significantly. Conclusions: This study provides a descriptive account of metastatic patterns, treatment approaches, and outcomes in a dedicated right-sided RAS wild-type metastatic colon cancer cohort. The unadjusted OS difference between biological treatment groups was not confirmed after measured covariate adjustment and should not be interpreted as evidence of comparative treatment effectiveness. Because molecular profiling was incomplete, this study cannot identify biomarker-defined treatment subgroups. Prospective studies with complete, predefined molecular characterization are needed before molecularly informed treatment selection hypotheses can be evaluated in this population.

Aim: Efficacy of antiepidermal growth factor receptor (anti-EGFR) agents has been demonstrated in metastatic colorectal cancer (mCRC). Real-world evidence is especially important to detect patient findings outside of clinical trials. Therefore; we aimed to investigate the real-world data in patients with RAS wild-type mCRC. Methods: Medical records from 28 centers were collected for patients diagnosed with mCRC between January 2016 and April 2019. Patients were compared according to the first-line biological treatments as anti-EGFR group (Group A (panitumumab) and B (cetuximab)) and anti-VEGF group (Group C). Results: A total of 1064 patients with documented RAS wild-type mCRC were evaluated. Of these; 33%; 37% and 30% were treated with regimens including panitumumab; cetuximab; and anti-VEGF in the first-line; respectively. Overall response rate was 46.4%; 41.9% and 41.5% in A; B; and C groups; respectively (p = 0;170). The median OS was 26; 27; and 23 months in A; B and C group respectively (p = 0.044). The median PFS of the patients that treated with panitumumab; cetuximab and bevacizumab was 11;6; 11;0 and 9;6 months respectively (p = 0.012). ECOG performance status (PS) 0-1 and Braf wild-type status were found as independent prognostic factors in multivariate analysis for OS and only BRAF wild-type status for PFS (p

Background: Metastasectomy is a cornerstone of multimodal management in metastatic colorectal cancer (mCRC), yet contemporary real-world data focusing specifically on RAS wild-type (RAS-WT) disease remain limited. We aimed to evaluate survival outcomes and prognostic factors associated with metastasectomy in patients with RAS-WT mCRC using a large national multicentre registry. Methods: This retrospective cohort study utilized data from the ONKO-KOLON Türkiye registry. A total of 1079 patients with pathologically confirmed KRAS/NRAS wild-type mCRC were identified and categorized according to receipt of metastasectomy. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and compared with log-rank tests across multiple clinically relevant time origins, including metastatic diagnosis, initial colorectal cancer diagnosis, and time of metastasectomy. Prognostic factors within the metastasectomy cohort were assessed using univariate Cox proportional hazards models. Serum CEA and CA19-9 were analyzed after log₁₀ transformation. Results: Among 1079 patients, 185 (17.1%) underwent metastasectomy. Patients receiving metastasectomy demonstrated significantly longer OS compared with those managed non-surgically when survival was calculated from the time of metastatic diagnosis (hazard ratio [HR] for death 0.36, 95% CI 0.27–0.47; p < 0.001), as well as improved PFS (HR for progression or death 0.39, 95% CI 0.30–0.52; p < 0.001). The survival advantage remained consistent when OS was measured from the time of initial colorectal cancer diagnosis (HR 0.37, 95% CI 0.25–0.50; p < 0.001). Median OS following metastasectomy was 43 months (95% CI 31.4–45.6). In univariate analyses within the metastasectomy cohort, higher baseline CA19-9 levels were significantly associated with inferior OS when analyzed both as a continuous variable (per log₁₀ increase; HR 1.81, 95% CI 1.20–2.75; p = 0.005) and as a categorical variable (above vs. below threshold; HR 0.37, 95% CI 0.16–0.86; p = 0.021). Other clinicopathologic factors, including age, CEA, tumor sidedness, grade, MSI status, and metastatic burden, were not significantly associated with survival. Conclusions: In this large, real-world national cohort of RAS-WT mCRC, metastasectomy was strongly associated with prolonged survival across multiple clinically relevant time frames. Within surgically treated patients, baseline CA19-9 emerged as the most informative prognostic marker, while traditional clinicopathologic variables showed limited discriminatory value. These findings highlight the importance of careful patient selection and support further prospective studies integrating molecular and biomarker-based strategies to refine prognostication and optimize surgical decision-making in RAS-WT mCRC.

Triple-negative breast cancer (TNBC) has a poor prognosis, and neoadjuvant chemotherapy (NACT) is the standard treatment for locally advanced TNBC. In this study, we aimed to evaluate the efficacy of adding carboplatin to NACT regarding pathological complete response (pCR) and survival in the HER2-low and HER2-zero subgroups of TNBC patients. The study included 269 patients from five medical oncology clinics. Patients were divided into two groups: HER2-low (n = 152, 56.5%) and HER2-zero (n = 117, 43.5%). Among HER2-zero patients, 30 (25.6%) received carboplatin, while 38 (25.0%) HER2-low patients received carboplatin. The benefit of adding carboplatin to NACT regarding pCR and survival was assessed in both HER2-zero and HER2-low groups. When patients were evaluated according to HER2 status, the pCR rates were significantly higher in the HER2-zero group compared to the HER2-low group (45.2% versus 23.7%, p < 0.001). In the HER2-zero group, patients who received carboplatin had significantly higher pCR rates (63.3% versus 39.0%, p = 0.021). Similarly, in the HER2-low group, adding carboplatin significantly increased the pCR rates (36.8% versus 19.3%, p = 0.028). While carboplatin improved pCR rates in both HER2 subgroups, this benefit was not observed in patients with Grade 1 tumors, HER2 score 2-FISH negative tumors, or based on BRCA mutation status. Patients with pCR exhibited significantly prolonged DFS and OS (p = 0.002, p < 0.001, respectively). Our research demonstrates that the addition of carboplatin increases pCR rates in both HER2-zero and HER2-low patient cohorts. We suggest that carboplatin should be considered as an addition to standard neoadjuvant chemotherapy for eligible TNBC patients, regardless of HER2-zero or HER2-low status, when appropriate based on individual patient factors and toxicity considerations.

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.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, predominantly affecting older individuals. Despite the increasing use of immune checkpoint inhibitors (ICIs) like nivolumab in non-small cell lung cancer (NSCLC), the efficacy and safety in elderly patients, particularly those aged 65 and above, remain underexplored due to their underrepresentation in clinical trials. Methods: This retrospective study analyzed data from 60 elderly patients (≥65 years) with metastatic NSCLC who received nivolumab as second-line or later therapy between January 2020 and May 2023. Results: The median age was 67 years, with a predominance of males (78%). Nivolumab was administered for a median of 8 cycles, with 33.3% of patients receiving 15 or more cycles. The median OS was 23 months, and the 1-, 3-, and 5-year survival rates were 93.3, 54.1, and 18.6%, respectively. Multivariate analysis identified adenocarcinoma histology, fewer than 15 cycles of nivolumab, and non-response to prior therapies as independent predictors of poor OS. Nivolumab treatment was generally well-tolerated, with 45% of patients experiencing at least grade 1 toxicity. Conclusions: Nivolumab is effective and well-tolerated in elderly patients with metastatic NSCLC, providing survival benefits comparable to those observed in younger populations. The number of treatment cycles and initial response to therapy are key determinants of survival, underscoring the importance of continued treatment in this age group.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, predo-minantly affecting older individuals. Despite the increasing use of immune checkpoint inhibitors (ICIs) like nivolumab in non-small cell lung cancer (NSCLC), the efficacy and safety in elderly pa-tients, particularly those aged 65 and above, remain underexplored due to their underrepresenta-tion in clinical trials. Methods: This retrospective study analyzed data from 60 elderly patients (≥65 years) with metastatic NSCLC who received nivolumab as second-line or later therapy between January 2020 and May 2023. Results: The median age was 67 years, with a predominance of males (78%). Nivolumab was administered for a median of 8 cycles, with 33.3% of patients recei-ving 15 or more cycles. The median OS was 23 months, and the 1-, 3-, and 5-year survival rates were 93.3%, 54.1%, and 18.6%, respectively. Multivariate analysis identified adenocarcinoma histology, fewer than 15 cycles of nivolumab, and non-response to prior therapies as independent predictors of poor OS. Nivolumab treatment was generally well-tolerated, with 45% of patients experiencing at least grade 1 toxicity. Conclusion: Nivolumab is effective and well-tolerated in elderly patients with metastatic NSCLC, providing survival benefits comparable to those observed in younger populations. The number of treatment cycles and initial response to therapy are key determinants of survival, underscoring the importance of continued treatment in this age group.

Introduction The development of immune checkpoint inhibitors (ICIs) represents one of the most significant advancements in cancer treatment over the past decade. Nivolumab, a widely used ICI, has been incorporated into the therapeutic regimens for various cancers. As with any drug, this drug also has side effects, including class-specific immune-related adverse effects (irAEs). Although irAEs are not rare, their diagnosis can be challenging. This study examines the emergency department (ED) visits of patients undergoing nivolumab therapy, focusing on diagnostic challenges, evaluating the management, and outcomes of irAEs in the ED setting. Material and methods A retrospective cohort study was conducted on adult patients who received nivolumab therapy for any cancer between April 1, 2018, and March 31, 2023, at a large, urban tertiary care center. In this study, we evaluated the ED visits of patients receiving nivolumab. In addition to previous studies, we evaluated irAEs in detail (percentage, recognizability, risk factors, reasons for late recognition, and outcome). Patient data were collected from electronic medical records and patient’s medical files. The anamnesis, laboratory, and imaging results, ED management, and consultation notes were examined separately for each ED visit. Logistic regression models were employed to identify significant univariable predictors of ED visits and irAEs. Results A total of 199 patients were included in the study, all of whom had metastatic cancer. Of these, 154 patients (77.4%) received nivolumab therapy for non-small cell lung cancer. Most patients (71.9%, n = 143) had at least one additional comorbidity. One hundred and eleven patients (55.8%) presented to the ED. Hypertension (OR: 2.425, 95% CI: 1.226–4.795, p = 0.011) and chronic obstructive pulmonary disease (OR: 2.489, 95% CI: 1.133–5.468, p = 0.023) were identified as risk factors for ED visits. A total of 21 irAEs were diagnosed (14 in ED, 6 in the oncology clinic, and 1 in the inpatient ward). Univariate analysis found no significant association between irAE diagnosis and any specific factors. Conclusion A significant proportion of the patients treated with nivolumab for advanced cancer present to ED for ICI-related adverse events, although most cases were not attributable to irAEs. Due to the vague symptomatology of irAEs, their recognition and diagnosis in the ED can be challenging. Close collaboration between ED physicians and oncologists is paramount to the management of patients with cancer in the ED.

Background and Objectives: Lung cancer is the leading cause of cancer-related deaths. Spread through air spaces (STAS) is an adverse prognostic factor that has become increasingly known in recent years. This study aims to investigate the impact of STAS presence on overall survival (OS) and disease-free survival (DFS) in patients with surgically resected stage IA-IIIA lung cancer and to identify clinicopathological features associated with STAS. Materials and Methods: This research involved 311 lung cancer surgery patients. The relationship between the presence of STAS in the patients’ surgical pathology and OS and DFS values was examined. Clinicopathological features associated with the presence of STAS were determined. Results: There were 103 (33%) STAS-positive patients. Adenocarcinoma histological subtype, perineural invasion (PNI), and lymphovascular invasion (LVI) were significantly correlated with being STAS positive. STAS significantly predicted DFS and OS. One-year and five-year DFS rates were significantly lower in the STAS-positive group compared to the STAS-negative group (65% vs. 88%, 29% vs. 62%, respectively, p ≤ 0.001). Similarly, one-year and five-year OS rates were significantly lower in the STAS-positive group compared to the STAS-negative group (92% vs. 94%, 54% vs. 88%, respectively, p ≤ 0.001). In multivariate analysis, STAS was found to be an independent prognostic factor for both DFS and OS (HR: 3.2 (95%CI: 2.1–4.8) and 3.1 (95%CI: 1.7–5.5), p < 0.001 and Conclusions: In our study, STAS was found to be an independent prognostic biomarker in operated stage IA-IIIA lung cancer patients. It may be a beneficial pathological biomarker in predicting the survival of patients and managing their treatments.

Background and Objectives: Colorectal cancer (CRC) poses a major global health challenge, with high incidence rates and ongoing treatment debates. Adjuvant chemotherapy benefits for high-risk subgroups, particularly stage II disease, remain controversial. This study seeks to clarify this issue by specifically examining the impact of adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS) in patients diagnosed with T4 colon cancer. Materials and Methods: This retrospective study analyzed patients undergoing radical surgery for T4 colon cancer between 2002 and 2023. Results: Our study of 184 pT4 pN0 colon cancer patients revealed that 79.3% received adjuvant chemotherapy. Multivariate analysis demonstrated significant DFS improvement: a 60% reduction in risk for those who received adjuvant therapy (0.40 95% CI: 0.25–0.62, p < 0.001). Lymphovascular invasion (LVI) and adjuvant treatment were also significantly associated with OS. Adjuvant treatment reduced mortality by 60% (HR: 0.40, 95% CI: 0.23–0.68, p = 0.001). Patients with LVI had a 1.9-fold increase in mortality (HR: 1.94, 95% CI: 1.17–3.20, p = 0.011). These findings underscore the potential value of adjuvant chemotherapy and highlight the importance of treatment completion in managing T4 colon cancer. Conclusions: Our study identifies LVI and adjuvant chemotherapy as key prognostic factors in T4 colon cancer patients. These results support the consideration of adjuvant chemotherapy in this patient population.