Emir Çerme

Background: The Royal Marsden Hospital (RMH) score is a simple prognostic score based on serum albumin, lactate dehydrogenase, and the number of metastatic organ sites. Although its prognostic value has been demonstrated across several advanced cancer populations, evidence specifically in patients with de novo metastatic colorectal cancer (mCRC) initiating first-line treatment remains limited. Methods: This single-center retrospective cohort study included 189 patients with de novo mCRC who initiated first-line systemic treatment between January 2015 and January 2026. Patients were classified as low risk (RMH score 0–1) or high risk (RMH score 2–3). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and factors independently associated with survival outcomes were evaluated using multivariable Cox regression. Results: Of the 189 patients, 142 (75.1%) were classified as low risk and 47 (24.9%) as high risk. Median PFS and OS for the entire cohort were 11.3 and 27.4 months, respectively. Median PFS was 11.8 months in the low-risk group and 7.6 months in the high-risk group (p < 0.001). Median OS was 33.8 and 13.7 months, respectively (p < 0.001). After adjustment for relevant clinicopathological factors, high-risk RMH status remained independently associated with shorter PFS (HR, 2.16; 95% CI, 1.51–3.09; p < 0.001) and OS (HR, 2.95; 95% CI, 2.03–4.29; p < 0.001). Conclusions: The RMH score was independently associated with both PFS and OS in patients with de novo mCRC initiating first-line systemic treatment. Based on simple and routinely available baseline parameters, the RMH score may serve as a complementary prognostic marker alongside established clinical and molecular factors.

Objective: Cetuximab-induced skin toxicity has been proposed as a predictive biomarker of treatment efficacy in cetuximab-based regimens. However, its prognostic significance in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with the EXTREME regimen remains limited. This study investigated the impact of cetuximab-related skin toxicity on progression-free survival (PFS) and overall survival (OS) in R/M HNSCC. Methods: This single-center, retrospective cohort study included 79 patients with histopathologically confirmed unresectable locally advanced or metastatic HNSCC who received first-line platinum-based chemotherapy with 5-fluorouracil (5-FU) and cetuximab (EXTREME regimen) between June 2014 and July 2024. Patients were stratified by the presence or absence of cetuximab-related skin toxicity. Toxicities were graded per National Cancer Institute Common Terminology Criteria for Adverse Events NCI-CTCAE v5.0. Survival analyses were performed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Median age was 63 years (range 34-87), and 75.9% were male. Cetuximab-related skin toxicity was observed in 27 patients (34.2%), and was the most frequent toxicity type, followed by diarrhea (17.0%) and hypomagnesemia (13.2%). Patients with skin toxicity had significantly longer OS (14.1 vs. 10.1 months; HR: 0.545; 95% CI: 0.325-0.916; P = .022). No significant difference was observed in PFS (6.3 vs. 5.2 months; HR: 0.91; 95% CI: 0.57-1.47; P = .715). On multivariate analysis, skin toxicity was independently associated with improved OS (HR: 0.545; 95% CI: 0.325-0.916; P = .022). Eastern Cooperative Oncology Group (ECOG) ≥2 was an independent adverse prognostic factor for both PFS (HR: 3.084; 95% CI: 1.578-6.028; P < .001) and OS (HR: 6.419; 95% CI: 3.140-13.121; P < .001). Conclusion: Cetuximab-induced skin toxicity was independently associated with improved OS in R/M HNSCC patients treated with the EXTREME regimen, suggesting its potential role as a pharmacodynamic biomarker of cetuximab efficacy. Prospective studies incorporating molecular biomarkers are warranted. Cite this article as: Fidan MC, Safarov S, Abbasov H, et al. Cetuximab-related skin toxicity as a prognostic marker in recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis of the EXTREME regimen. Cerrahpaşa Med J. 2026, 50, 0093, doi: 10.5152/cjm.2026.26093.

Objective: In this research, the influence of the initial endothelial activation and stress index (EASIX) on the prognosis of patients with metastatic renal cell carcinoma (mRCC) undergoing first-line treatment with tyrosine kinase inhibitors (TKIs) was examined. Methods: This study, conducted retrospectively at a single center, included patients with mRCC who received first-line TKI therapy. The EASIX score was determined from serum lactate dehydrogenase, creatinine, and platelet count measurements taken within 15 days before starting treatment. Patients were divided into low and high EASIX groups according to the cohort’s median score. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated using the Kaplan–Meier method, and prognostic factors were identified through Cox regression analyses. Results: A total of 99 patients were included in the study. The median PFS was 11.5 months, while the median OS was 34.3 months. Those with elevated EASIX scores had notably reduced PFS and OS, with PFS at 8.6 months compared to 19.1 months (P < .001) and OS at 24.8 months versus 61.9 months (P = .003). In multivariate analyses, high EASIX remained an independent predictor of shorter PFS (hazard ratio [HR] = 2.77, 95% CI: 1.60-4.79; P < .001) and OS (HR = 2.53, 95% CI: 1.32-4.84; P = .005). Conclusion: Baseline EASIX was independently associated with survival outcomes in patients with mRCC undergoing first-line TKI treatment. As a simple and readily accessible biomarker, EASIX may provide additional prognostic information beyond conventional risk models. Prospective validation is warranted, particularly in the context of contemporary treatment strategies. Cite this article as: Günaltılı M, .i.ek E, Guliyev M, et al. Prognostic value of baseline endothelial activation and stress index in metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. Cerrahpaşa Med J. 2026, 50, 0053, doi: 10.5152/cjm.2026.26053.

Background and Objectives: Transfusion-related immunomodulation (TRIM) is a recognized immunosuppressive phenomenon whose interaction with immune checkpoint blockade remains poorly defined. We evaluated the impact of erythrocyte suspension transfusion on survival and immune-related toxicity in patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Materials and Methods: This retrospective, multicenter study included 253 patients with metastatic NSCLC treated with nivolumab across five centers between April 2018 and March 2025. Patients who received a transfusion within three months before or during nivolumab therapy were compared with non-transfused patients. Survival was assessed using Kaplan–Meier and Cox regression analyses. Results: Forty-two patients (16.6%) received transfusion. Transfused patients had significantly shorter progression-free survival (PFS) (median 3.6 vs. 9.3 months; HR = 2.28, 95% CI 1.47–3.56, p < 0.001) and overall survival (OS) (median 5.8 vs. 16.3 months; HR = 2.76, 95% CI 1.86–4.11, p < 0.001). In multivariable analysis, transfusion was an independent predictor of both shorter PFS (HR = 2.288, 95% CI 1.470–3.561, p < 0.001) and shorter OS (HR = 2.351, 95% CI 1.565–3.533, p < 0.001), independent of transfusion volume. No statistically significant association was detected between transfusion status and the incidence of nivolumab-related toxicity (p = 0.585), although this analysis was likely underpowered, whereas nivolumab-related toxicity was an independent favorable prognostic factor. Conclusions: Erythrocyte transfusion independently predicted poorer survival but not immune-related toxicity in nivolumab-treated metastatic NSCLC, supporting more judicious transfusion practices during immunotherapy.

Background/Objectives: Outcomes after perioperative FLOT for gastric and gastroesophageal junction adenocarcinoma remain variable, even among patients treated with curative intent. Although postoperative pathological findings are central to risk assessment, they do not fully capture patient-related factors that may influence recovery, treatment completion, and survival. This multicenter study evaluated routinely available clinical, laboratory, and pathological variables and assessed whether integrating these variables could improve postoperative prognostic stratification. Methods: We retrospectively analyzed 173 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT across seven oncology centers in Türkiye. Overall survival (OS) was the primary endpoint. Baseline inflammatory/nutritional status, pretreatment carcinoembryonic antigen (CEA), postoperative nodal status, and comorbidity burden were assessed. An exploratory modified FLOT Prognostic Score (mFPS) was constructed by assigning one point each for high inflammatory/nutritional risk, elevated CEA, ypN-positive disease, and age-adjusted Charlson Comorbidity Index ≥ 5. Results: At a median follow-up of 39.7 months, median OS was 41.4 months, with estimated 2-year and 5-year OS rates of 69% and 44%, respectively. Surgery was performed in 164 patients, and 83 patients completed planned adjuvant chemotherapy. In multivariable analysis, ypN-positive disease, higher comorbidity burden, and high inflammatory/nutritional risk were independently associated with shorter OS. Among the 126 patients with complete data available for all score components, the mFPS stratified patients into groups with significantly different outcomes: median overall survival was not reached in the low-risk group, compared with 56.1 months in the intermediate-risk group and 18.7 months in the high-risk group. Conclusions: Survival after perioperative FLOT was not determined by residual disease burden alone. Integrating postoperative nodal status with baseline host-related factors may help identify patients at increased risk of adverse outcomes following curative-intent treatment. The proposed score should be considered exploratory and requires external validation before clinical application.

Background: The C-reactive protein/albumin ratio (CAR) has emerged as a prognostic biomarker across several malignancies, but its role in de novo metastatic colorectal cancer (mCRC) has not been evaluated using a propensity score-matched design. Methods: This retrospective study included 212 patients with mCRC who received first-line fluoropyrimidine-based chemotherapy plus a biological agent. The optimal CAR cutoff (2.69) was determined by ROC analysis (AUC = 0.714). Propensity score matching (PSM), incorporating 16 clinical, pathological, and molecular covariates, was performed to balance low-CAR and high-CAR groups. Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan–Meier and multivariate Cox regression analyses. Results: PSM yielded 65 matched pairs (130 patients), eliminating all baseline imbalances present in the unmatched cohort. In the matched cohort, high CAR remained associated with shorter PFS (median 8.4 vs. 12.9 months; HR = 1.58, 95% CI 1.10–2.30, p = 0.014) and OS (median 22.7 vs. 31.1 months; HR = 1.70, 95% CI 1.15–2.50, p = 0.006). On multivariate analysis, CAR retained independent significance for OS (HR = 1.792, 95% CI 1.157–2.775, p = 0.009) alongside CEA level (HR = 3.331, p < 0.001) and BRAF mutation status (HR = 4.543, p = 0.040), but not for PFS, where mucinous component (HR = 2.335, p = 0.015) and CEA level (HR = 2.231, p = 0.045) were the dominant independent predictors. Conclusions: Baseline CAR is an independent prognostic factor for OS in mCRC, even after adjusting for established clinicopathological and molecular risk factors through propensity score matching. As an inexpensive and readily available biomarker, CAR may help identify patients with more aggressive disease biology who warrant closer monitoring, although prospective validation is needed before clinical implementation.

Objective: This study aimed to evaluate the prognostic significance of positron emission tomography/computed tomography (PET/CT)-derived sarcopenia in patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This retrospective single-center study included 77 patients treated between January 2018 and March 2025. Sarcopenia was assessed using skeletal muscle index (SMI) at the L3 level on fluorodeoxyglucose (FDG) PET/CT. Patients were classified as sarcopenic or non-sarcopenic. Clinical, nutritional parameters including body mass index (BMI) and prognostic nutritional index (PNI), and inflammatory parameters including pan-immune inflammation value (PIV) were analyzed. The primary endpoint was progression-free survival (PFS). Results: Sarcopenia was present in 35.1% of patients. After a median follow-up of 38 months, sarcopenic patients had significantly shorter PFS compared with non-sarcopenic patients (18 vs. 38 months; HR: 2.37, 95% CI 1.12–4.99, p = 0.02, multivariable analysis). In multivariable analysis, sarcopenia, recurrent disease, brain metastasis, and liver metastasis were independent predictors of PFS. No significant association was observed between sarcopenia and overall survival. BMI, PNI, and PIV were not associated with survival outcomes. Toxicity profiles were comparable between groups. Conclusions: PET/CT-derived sarcopenia may be a prognostic factor for PFS in patients receiving CDK4/6 inhibitors, whereas conventional nutritional and inflammatory markers are not. These findings support the clinical utility of imaging-based body composition assessment. Prospective studies incorporating functional measures of sarcopenia are warranted.

Purpose: This study aimed to characterize FAERS reports of immune-mediated upper gastrointestinal (GI) toxicities associated with immune checkpoint inhibitors and to explore disproportional reporting patterns across ICI classes and treatment regimens. Methods: Input data were downloaded from the public release of the FDA database including time period between January 1 2016, and December 31, 2024. 132 patients with upper-GI toxicity were included. Categorical variables were compared using either the chi-square test or Fisher's exact test. To evaluate the potential association between ICIs and specific upper-GI toxicity events of interest, a disproportionality analysis was conducted using the Reporting Odds Ratio (ROR) method. A signal was considered statistically significant when the lower bound of the 95% confidence interval for the ROR exceeded 1.0. Results: Anti-PD-1 agents showed higher disproportional reporting of upper-GI toxicities compared to anti-PD-L1 (p = 0.001, ROR = 3.83 95% CI: 1.53–15.23). A higher proportion of hospitalization among reported cases were observed in patients treated with concurrent chemotherapy, compared to those did not receive chemotherapy (ROR = 2.5; 95% CI: 1.05–5.921; p = 0.045). Conclusion: Anti-PD-1 therapy showed a stronger reporting signal for upper-GI toxicity than anti-PD-L1 therapy in FAERS, although the number of anti-PD-L1 cases was small. Concurrent chemotherapy was associated with a higher proportion of hospitalization among reported cases. These findings are exploratory and hypothesis-generating.

Background/Objectives: Immune checkpoint inhibitors (ICIs) improve outcomes in metastatic non-squamous non-small cell lung cancer (NSCLC), yet predictive biomarkers remain limited. This study investigated whether CD34-stained microvessel density (MVD) is associated with ICI efficacy. Methods: Patients with metastatic non-squamous NSCLC and tumor specimen suitable for anti-CD34 immunohistochemistry were included. In the derivation cohort, ROC analysis for objective response rate (ORR; CR + PR) identified a Youden-optimized threshold of 14.5 vessels/HPF (×400) (sensitivity 67%, specificity 93%; AUC 0.744, 95% CI 0.53–0.95; p = 0.021), which was applied without re-optimization to an internal validation cohort and a chemotherapy-only comparator. Results: In the derivation cohort, (n = 25), ORR was higher with MVD ≥ 14.5 than p = 0.004) and OS/TFST were longer (OS: 53.0 vs. 17.1 months, p = 0.037; TFST: 50.0 vs. 6.0 months, p = 0.014). In the validation cohort (n = 13), MVD ≥ 14.5 was associated with longer TFST (9.0 vs. 4.0 months; p = 0.035) and numerically longer OS (12.0 vs. 7.0 months; p = 0.059). As a cut-off-independent sensitivity analysis, continuous MVD (per five vessels/HPF) was associated with longer TFST (HR 0.663, 95% CI 0.454–0.969; p = 0.034). No association was observed in the chemotherapy-only cohort. Conclusions: Higher CD34-MVD may be a feasible vascular metric associated with ICI outcomes that warrants prospective validation.

Background/Objectives: We evaluated the clinical outcomes of two commonly used approaches for managing oligoprogression arising during first-line therapy for metastatic hormone-sensitive prostate cancer (mHSPC): metastasis-directed radiotherapy (RT) with continuation of the ongoing systemic regimen and immediate transition to another systemic treatment. Methods: A total of 81 patients with mHSPC who experienced radiologically confirmed oligoprogression during first-line systemic therapy were retrospectively evaluated. Oligoprogression was defined as progression involving three or fewer metastatic sites. Patients were categorized into an RT group (metastasis-directed RT with continuation of the same regimen) or a treatment-change group (immediate switch in systemic therapy without RT). Post-oligoprogression radiologic progression-free survival (rPFS) and overall survival (OS) were evaluated using Kaplan–Meier estimates and Cox proportional hazards models. Results: Thirty-one patients received metastasis-directed RT, whereas fifty underwent a change in systemic therapy. The median post-oligoprogression rPFS was 25.8 months (95% CI, 16.3–35.2) in the entire cohort and did not differ significantly between the treatment-change (26.8 months) and RT groups (22.7 months; p = 0.828). The median OS was 42.6 months overall, with comparable outcomes between the treatment-change (42.6 months) and RT groups (52.4 months; p = 0.452). Conclusions: In patients with mHSPC who developed oligoprogression during first-line systemic therapy, metastasis-directed RT with continuation of the same regimen and immediate change in systemic treatment were associated with comparable post-oligoprogression outcomes in our cohort. These findings suggest that both strategies may be feasible in selected patients. Prospective studies may help clarify which patients are more likely to benefit from each strategy.