Background and Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but their use is associated with a spectrum of immune-related adverse events (irAEs), including endocrine disorders. This study aims to investigate the incidence, timing, treatment modalities, and impact of ICI-related endocrine side effects in cancer patients. Materials and Methods: This retrospective study analyzed 139 cancer patients treated with ICIs between 2016 and 2022. Data regarding endocrine irAEs, including hypothyroidism, hyperthyroidism, hypophysitis, and diabetes mellitus, were collected. The study examined the timing of irAE onset, management approaches, and the association between irAEs and treatment outcomes. Results: The most common endocrine irAE was hypothyroidism (65.5%), followed by hyperthyroidism (2.3%), hypophysitis (8.6%), and diabetes mellitus (0.7%). These disorders typically emerged within the first six months of ICI therapy. Most cases were managed conservatively or with hormone replacement therapy. Patients who developed endocrine irAEs exhibited a higher objective response rate (ORR) and clinical benefit rate (CBR) compared to those without irAEs. Conclusions: Endocrine dysfunction is a significant toxicity of ICI therapy. Early recognition, prompt diagnosis, and appropriate management are crucial to minimize their impact on patient health and quality of life. This study highlights the potential association between irAEs and improved clinical outcomes. Further research is needed to elucidate the underlying mechanisms and identify predictive biomarkers for irAE development.

Background: Mast cells are integral components of the tumor microenvironment and have been implicated in the regulation of tumor progression in various malignancies. The association between inflammation and colorectal cancer (CRC) development has become increasingly recognized. Depending on the tumor microenvironment, mast cells may exert either pro-tumorigenic or antitumorigenic functions. Objective: This study aimed to evaluate the relationship between stromal mast cell density and prognostic factors in patients with CRC. Methods: In this retrospective cohort study, 81 patients who underwent curative surgical resection for CRC were analyzed. Immunohistochemical staining for mast cell tryptase (MCT) was performed on paraffin-embedded tumor specimens. Mast cells were quantified in regions of hot spots within the tumor stroma. Patients were categorized as high mast cell density (MCC-H, ≥22 cells/HPF) or low mast cell density (MCC-L, <22 cells/HPF). Associations with clinicopathological parameters were assessed using chi-square or Fisher’s exact tests. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier estimates and log-rank tests. Independent prognostic factors were identified using multivariate Cox proportional hazards regression, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. Results: ROC analysis identified an MCC cut-off of 22 cells/HPF (AUC = 0.61; sensitivity = 0.67, specificity = 0.52) for mortality prediction. Multivariate analysis revealed lymph node involvement (HR: 1.41, 95% CI: 1.03–1.94, p = 0.033) and macroscopic tumor perforation (HR: 0.15, 95% CI: 0.04–0.55, p = 0.004) as independent predictors of PFS. High MCC (≥22) independently predicted improved OS (HR: 0.07, 95% CI: 0.006–0.87, p = 0.039). A significant association was observed between OS, MCC, and lymph node stage. Conclusions: Stromal mast cell count is an independent prognostic factor for overall survival in patients with CRC. Our findings suggest that MCC may serve as a reliable prognostic biomarker following surgical resection and could aid in postoperative risk stratification.

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.