Dilsa Mizrak Kaya

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a near-universal presence of KRAS mutations and limited responsiveness to immunotherapy. Biologic heterogeneity among KRAS subtypes may shape tumor immunobiology and treatment resistance. Methods: We evaluated 109 patients with advanced PDAC treated in early-phase trials between August 2014 and August 2023. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method, and Cox proportional hazard models were used to assess the clinical and molecular predictors of survival. Results: Among the 109 patients, 64% harbored KRAS mutations, 18% were KRAS wild type, and 17% had an unknown KRAS status. The median age was 65 years, and 83% had liver metastases. Among the KRAS-mutant tumors, subtype distribution was G12D (46%), G12V (31%), G12R (13%), and other variants (10%). Immunomodulatory agents were administered to 39% of the patients, most commonly in the first-line setting (49%). The median OS and PFS for the entire cohort were 5.65 and 2.73 months, respectively. The restricted mean OS (7.54 vs. 8.65, p = 0.53) and PFS (3.82 vs. 4.24, p = 0.70) did not differ between patients with KRAS mutants and wild-type KRAS. Among patients with KRAS mutations, receipt of immunomodulatory therapy was associated with shorter OS compared with those who did not receive immunomodulatory therapy, with the strongest association observed in the KRAS G12D subgroup. This pattern was not observed in KRAS wild-type tumors. On univariate analysis, immunomodulatory therapy exposure, number of prior treatment lines, and presence of liver metastases were each associated with inferior OS. On multivariable analysis, immunotherapy exposure demonstrated a non-significant trend toward inferior OS (hazard ratio [HR] 1.61, 95% Cl 0.98–2.66; p = 0.06), while the other variables remained independently associated with worse OS, suggesting confounding in the unadjusted association between immunomodulatory therapy and survival. Conclusions: Among patients with KRAS-mutant PDAC—particularly those with G12D—receipt of immunomodulatory therapy in early-phase trials was associated with shorter OS in this exploratory analysis. These findings should be considered hypothesis-generating and require validation in prospective, KRAS-subtype-informed studies.

This study aims to evaluate the effectiveness and real-world applicability of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC), focusing on pathological complete response (pCR) and disease-free survival (DFS) across different chemotherapy regimens. In this multicenter retrospective study, patients treated between January 2019 and January 2023, 437 patients with locally advanced rectal cancer who underwent total neoadjuvant therapy followed by surgery were analyzed. Standard fluoropyrimidine-based chemotherapy regimens (CAPOX, FOLFOX, or FOLFIRINOX) were used according to institutional practice, and long-course chemoradiotherapy constituted the predominant radiotherapy approach. Patients were grouped based on chemotherapy sequencing as induction, consolidation, or sandwich regimens. Outcomes were evaluated using multivariable logistic regression for pathological complete response and Kaplan–Meier analysis with Cox proportional-hazards modeling for disease-free survival. The median follow-up duration was 66 months. The overall pCR rate was 26.3% (n = 115). pCR rates did not differ significantly between induction, sandwich, and consolidation chemotherapy regimens. A longer interval (> 8 weeks) between radiotherapy and surgery was associated with a higher likelihood of achieving pCR. In contrast, cT4 disease and baseline CEA levels > 3 ng/mL were associated with lower pCR rates.The estimated 3-year disease-free survival (DFS) rate was 83.8%. Recurrence rates within 3 years were numerically higher in patients receiving induction and sandwich regimens compared with consolidation chemotherapy, although these differences did not reach statistical significance. In multivariable analysis, poor tumor regression grade, ypT4 stage, ypN + disease, and post-TNT CEA ≥ 3 ng/mL were independently associated with an increased risk of recurrence. TNT is effective and feasible in real-world settings, achieving pCR and DFS outcomes comparable to clinical trials. No statistically significant differences were observed in pCR or recurrence rates between induction, consolidation, and sandwich chemotherapy regimens. Prospective phase III trials are needed to compare DFS and OS outcomes across these treatment strategies. The online version contains supplementary material available at 10.1007/s12672-026-04842-3.

Ejmi Eurasian Journal of Medical Investigation

Objective: Colorectal cancer (CRC) is one of the most common cancers worldwide and is one of the leading causes of cancer-related deaths. The causal link between inflammation and cancer has been proposed based on the observation that tumors often develop in a chronic inflammatory environment and that inflammatory cells are present in tumor biopsy specimens. Epidemiological studies have revealed that chronic inflammation provides a basis for different types of cancer. There is a great deal of evidence to suggest that chronic inflammation can support cancer development and that tumor-induced inflammation maintains tumor progression by creating a snowball effect. Endoglin is a transmembrane glycoprotein identified in vascular endothelial cells and has been shown to be associated with angiogenesis and inflammation in various diseases. This study aimed to investigate the relationship between endoglin and the inflammatory microenvironment in colorectal cancer patients. Material and Method: 50 patients diagnosed with colorectal cancer and 50 healthy volunteers were included in the study. In plasma samples, endoglin and commonly known inflammation markers such as sPLA2, cPLA2, NfκB, and TGFβ1 levels were measured by ELISA (enzyme-linked immunosorbent assay) method. In addition, endoglin and PLA2 mRNA expression were determined by Real-Time PCR. Result and Discussion: In colorectal cancer patients, plasma endoglin, NfκB, TGFβ1 levels were found to be significantly higher than in the control group, while no significant difference was found between the groups in cPLA2 and sPLA2 levels. A significant positive correlation was found between plasma endoglin levels and NFκB in the colorectal cancer group. Gene expression analyses showed that endoglin and PLA2 mRNA expression levels were significantly higher in the colorectal cancer group than in the control group. In conclusion, this study showed that the increase in endoglin in colorectal cancer may be associated with the development of inflammation and may play a role in poor prognosis associated with the inflammatory microenvironment.

Purpose: Testicular cancer is the most common solid tumor in young men between the ages of 20-35 and has excellent clinical outcomes with appropriate treatment. Neutrophil-to-lymphocyte-ratio (NLR) is related with prognosis and relapse in different solid tumors. We aimed to investigate the relation of presence and size of regional lymph node metastasis with NLR in testicular cancer. Materials and Methods: A total of 72 testicular cancer patients were included in the study. All medical records were retrospectively collected. NLR was calculated as the count of neutrophil divided by the count of lymphocyte. Chest and abdomen computed tomograpy (CT) scans of all patients were evaluated for metastases. Results: The mean age was 32.18 +/- 8.89 years. The pathologic classification was seminoma in 43% and nonseminoma in 57% of patients. Of 72 patients, 32 (44.4%) had lymph node positivity and 40 (55.6%) hadnot. The mean NLR value was 2.63 +/- 1.79 for all cohort. The mean NLR was significantly lower in patients with lymph node negative disease (for lymph node positive and negative disease 3.19 +/- 2.32 and 2.25 +/- 1.06, respectively.). In the ROC analysis, 2.5 was determined as the cut-off value for NLR to assess lymph node status. Conclusion NLR is a cheap and readily available index that can be used to determine lymph node metastases in testicular GCTs.

Immune checkpoint blockade therapy for esophageal squamous cell carcinoma

Background: Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b gastric adenocarcinoma (GAC). The natural history of patients with GAC who have baseline −PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC.Methods: We identified 238 GAC patients with baseline −PCyt who were followed for the development of peritoneal carcinomatosis (PC). Standard statistical methods were employed.Results: Of 238 patients, 192 had attempted surgery after preoperative therapy. Of these, 13 patients (6.8%) had GPC and one had liver metastases, thus surgery was aborted. We followed 164 patients who had an R0 resection. The median follow‐up duration was 3.4 (range, 0.6‐18) years. The rate of PC was 13.4%, (22/164 patients) and the median time to PC was 15.6 months. Female gender was associated with PC on multivariate analysis. The 5‐year OS rate for patients without subsequent PC was 75%.Conclusion Even with baseline −Cyt, ∼25% of patients develop PC following multimodality therapy. Patients who do not develop PC have an excellent OS rate. Further research is warranted to detect PC at baseline by the use of biomarkers.