Background:Biomarkers guiding immunotherapy in non-small cell lung cancer (NSCLC) are limited. The glucose-to-lymphocyte ratio (GLR), integrating metabolic and immune status, has shown prognostic value in several cancers but has not been systematically evaluated in patients receiving PD-1 blockade. Methods:We retrospectively analyzed 837 patients with advanced or metastatic NSCLC treated with nivolumab across 21 oncology centers in Turkey (2015-2025). Baseline GLR was calculated from fasting glucose and absolute lymphocyte counts. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier and compared with log-rank tests. Multivariate Cox regression models identified independent predictors. Receiver operating characteristic (ROC) analysis determined the optimal GLR cut-off for OS, which was subsequently applied to PFS analyses for consistency. Results:The optimal GLR cut-off for mortality was ≥70.76 (AUC = 0.635, 95% CI: 0.597-0.674; p < 0.001). Patients with GLR <70.76 achieved significantly longer OS (median 24.1 vs 9.6 months; p < 0.001) and PFS (9.7 vs 5.8 months; p < 0.001) compared with those with GLR ≥70.76. In multivariate analysis, high GLR and poor ECOG performance status independently predicted worse OS. Prior thoracic radiotherapy was associated with improved outcomes. Conclusion:Baseline GLR is a practical, cost-effective biomarker that independently predicts OS in advanced NSCLC patients treated with nivolumab. Elevated GLR likely reflects metabolic dysfunction and impaired immune reserve, both unfavorable for PD-1 blockade efficacy. Prospective studies are warranted to validate GLR and define its role in clinical decision-making.

Aims: Pleural mesothelioma is an aggressive malignancy with poor prognosis and limited therapeutic options. Reliable prognostic models are essential for risk stratification and clinical decision-making. The recently developed PLACE score has shown promising results in Chinese populations; however, its generalizability remains uncertain. This study aimed to externally validate the PLACE prognostic score in a Turkish cohort of patients with metastatic epithelioid pleural mesothelioma. Methods: This retrospective cohort study included patients diagnosed with metastatic epithelioid pleural mesothelioma at a single tertiary center between January 2016 and September 2025. Clinical and laboratory data at diagnosis were collected, and the PLACE score was calculated for each patient. Overall survival (OS) was analyzed using the Kaplan–Meier method, and differences between risk groups were compared using the log-rank test. Cox proportional hazards regression analysis was performed to evaluate the association between prognostic variables and survival. The discriminative ability of the PLACE score was assessed using receiver operating characteristic (ROC) curve analysis. Results: A total of 48 patients were included, with a median age of 66 years. According to the PLACE score, 33.3% of patients were classified as low-risk and 66.7% as high-risk. The median overall survival was 21.06 months. Patients in the low-risk group had significantly longer survival compared to the high-risk group (37.98 vs. 15.6 months, p=0.033). The PLACE score demonstrated limited discriminative ability, with an area under the curve (AUC) of 0.617 (95% CI: 0.413–0.821). In Cox regression analysis, high-risk patients had a significantly increased risk of mortality (HR: 2.28, 95% CI: 1.04–4.95, p=0.037). In multivariable analysis, the PLACE risk group remained an independent predictor of overall survival. Conclusion: The PLACE score retains prognostic significance in Turkish patients with metastatic pleural mesothelioma but demonstrates reduced discriminative performance compared to the original study. These findings emphasize the need for external validation and potential population-specific recalibration of prognostic models.

517 Background: Pts with HER2+ EBC achieving pCR post neoadjuvant chemotherapy (NACT) with trastuzumab (H) and pertuzumab (P) show favorable outcomes. Yet, management varies widely within healthcare systems, including access to continuation of adjuvant (adj) P. We compared diagnostic and treatment practices across countries. Methods: PEARL-HER2 is an international retrospective real-world cohort including pts with HER2+ EBC achieving pCR (ypT0/isN0) after NACT-HP (Jan 2014 to Dec 2023). This descriptive preliminary analysis (data cut-off Jan-2026) summarizes diagnostic and treatment data stratified by country. Results: 1345 pts with pCR were included. Significant heterogeneity in pts and disease characteristics was observed (Table 1). Diagnostic methods also varied: use of breast MRI ranged from 11-97% across countries (>85% in Spain/Portugal; Peru, 11%), while FDG-PET/CT ranged from 0-72% (overall 20%; Turkey, 72%; p<0.001). Anthracycline-based NACT varied from <20% in Argentina and Brazil to >85% in Portugal and Turkey (p<0.001). Adj P was administered to 33% of pts overall (0-97%; p<0.001), with high use in countries with public reimbursement and minimal in those without. Among ER+ pts, ET use was uniformly high (98%; p=0.590), but regimen selection varied substantially (p<0.001): tamoxifen (42%) and aromatase inhibitor (58%). Events occurred in 6% of pts (invasive/non-invasive relapses and death); median FU was 40 months (IQR 24–62). Conclusions: This analysis indicates marked cross-country variability in management of HER2+ EBC. Use of adj P closely aligned with national reimbursement policies, highlighting access as a major determinant of care beyond clinical risk and guideline recommendations. Characteristics Argentina (N=155) Belgium (N=217) Brazil (N=107) Italy (N=52) Peru (N=18) Portugal (N=603) Spain (N=110) Turkey (N=83) Total (N=1345) P-value Age, median (IQR) 47 (41–56) 54 (45–63) 46 (40–52) 53 (45–61) 45 (41–56) 52 (45–62) 53 (44–59) 51 (45–61) 51 (43–61) <0.001 Pre-/perimenop., n (%) 96 (62) 91 (43) 72 (72) 26 (50) 13 (72) 286 (48) 52 (48) 38 (46) 674 (51) <0.001 NST histology, n (%) 145 (95) 197 (91) 89 (83) 48 (94) 18 (100) 558 (93) 103 (95) 83 (100) 1241 (93) <0.001 ER–, n (%) 77 (50) 95 (44) 61 (58) 16 (31) 5 (28) 277 (46) 57 (52) 44 (53) 632 (47) <0.001 cN0, n (%) 58 (37) 28 (13) 43 (40) 24 (46) 2 (11) 267 (44) 50 (46) 21 (25) 493 (37) <0.001 Breast MRI | PET-CT, n (%) 123 (80) | 14 (9) 126 (58) | 63 (29) 73 (71) | 27 (26) 13 (25) | 13 (25) 2 (11) | 0 (0) 521 (86) | 70 (12) 102 (97) | 21 (19) 35 (42) | 60 (72) 995 (75) | 268 (20) <0.001 | <0.001 Anthracycline-based NACT, n (%) 19 (12) 137 (63) 19 (18) 44 (85) 2 (11) 532 (88) 84 (76) 79 (95) 916 (68) <0.001 ET use in ER+, n (%) 79 (98) 112 (95) 46 (98) 35 (97) 13 (100) 339 (98) 58 (100) 43 (98) 725 (98) 0.590 Adj P, n (%) 89 (57) 210 (97) 63 (59) 20 (39) 0 (0) 49 (8) 9 (8) 0 (0) 440 (33) <0.001 Public adj P reimbursement Yes, high risk Yes, N+ only No Yes, since 2023 No No No No — — Percentages exclude missing data.

BACKGROUND/OBJECTIVES:Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by substantial biological heterogeneity and variable clinical outcomes. Reliable prognostic tools are needed to improve risk stratification following neoadjuvant chemotherapy (NACT). This study aimed to evaluate the association of the Clinical-Pathologic Stage, Estrogen/Grade (CPS-EG) score with pathological complete response (pCR) and survival outcomes in patients with locally advanced TNBC treated with NACT. METHODS:In this multicenter retrospective cohort study, 690 patients with locally advanced TNBC treated with NACT between 2010 and 2024 at 25 oncology centers were included. Patients were categorized according to CPS-EG score (≤3 vs. >3). Associations between CPS-EG score, clinicopathological characteristics, pCR, disease-free survival (DFS), and overall survival (OS) were analyzed. Survival outcomes were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS:Patients with a CPS-EG score > 3 had significantly lower pCR rates and higher recurrence rates compared with those with a CPS-EG score ≤ 3 (p < 0.001 for both). Five-year OS rates were 83.7% and 54.1% in the CPS-EG ≤ 3 and > 3 groups, respectively, while the corresponding five-year DFS rates were 76.4% and 51.9% (p < 0.001 for both). In the multivariable analysis, CPS-EG > 3 remained independently associated with worse OS (HR 1.46, 95% CI 1.08-1.98, p = 0.015) and DFS (HR 1.73, 95% CI 1.26-2.38, p < 0.001). CONCLUSIONS:A higher CPS-EG score is associated with a lower likelihood of achieving pCR and poorer long-term survival outcomes in patients with locally advanced TNBC treated with NACT. The CPS-EG score represents a simple and readily available tool that may support risk stratification and clinical decision-making in routine practice.

e23009 Background: Screen failure and treatment dropout remain major barriers to successful conduct of oncology clinical trials, particularly in real-world, middle-income settings. Data evaluating both patient- and center-related factors influencing screen failure, dropout, and time to dropout are limited. Methods: This multicenter retrospective analysis included 1,229 oncology patients screened for clinical trials across 13 centers in Türkiye. Causes of screen failure and dropout were descriptively analyzed. Time to dropout was assessed using median values and compared across subgroups using the Mann–Whitney U and Kruskal–Wallis tests. Results: Overall, 1,155 patients experienced screen failure, and 74 patients dropped out after trial initiation. Patients with screen failure had a median age of 64 years, and 67.3% were male. The most frequent cancer types among screen failure patients were lung (57.0%), breast (13.7%), and prostate cancer (8.6%). The primary causes of screen failure in the overall cohort were non-fulfillment of inclusion criteria (69.4%), presence of exclusion criteria (21.4%), and patient non-compliance (4.1%). Among the 74 patients who dropped out, 63.5% were male, with a median age of 62 years; the most common diagnoses were lung (44.6%), gastric (27.0%), and breast cancer (23.0%). The leading causes of dropout were adverse events (33.8%), disease progression (28.4%), and patient dissatisfaction (14.9%). Median time (months) to dropout was significantly shorter in female patients (3 vs 7, p = 0.014), patients without comorbidities (7 vs 8, p = 0.036), those treated in neoadjuvant or adjuvant compared with metastatic settings (7.5 vs 6.5 vs 8, p < 0.001), patients receiving parenteral compared with oral or oral plus parenteral regimens (7 vs 9.5 vs 13, p = 0.035), and in centers with a clinical research unit or a clinical research center compared with centers without an administratively organized unit (7 vs 6.5 vs 10, p = 0.010). Finally, time to dropout decreased with increasing sub-investigator research experience, defined as the total number of clinical trials in which the sub-investigator had previously participated (0–5, 6–10 and > 10 trials, respectively; median 9.5 vs 7 vs 5 months; p = 0.022). Principal investigator experience and total trial volume per center were not associated with time to dropout. Conclusions: In this multicenter study, screen failure in clinical trials was predominantly driven by eligibility criteria, while treatment dropout was mainly related to toxicity and disease progression. Time to dropout varied according to patient characteristics, treatment setting, route of administration, and center-level factors, underscoring the influence of both clinical and operational elements on trial retention. These findings highlight the importance of pragmatic trial design and strengthened research infrastructure to improve feasibility and retention.

Background and Objectives: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard of care for eligible patients with locally advanced bladder cancer (LABC). However, adjuvant chemotherapy (AC) remains widely used in real-world practice. Host-related inflammatory and nutritional biomarkers may also influence survival outcomes. This study aimed to compare survival outcomes between NAC and AC and to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS), with particular emphasis on the Prognostic Nutritional Index (PNI). Methods: This multicenter retrospective study included 262 patients with locally advanced bladder cancer. The median age was 66 years, and 84% of patients were male. Patients were treated with neoadjuvant chemotherapy followed by radical cystectomy or adjuvant chemotherapy after surgery between August 2021 and March 2025. The Prognostic Nutritional Index (PNI) was calculated using pretreatment laboratory values. ROC analysis was used to determine the optimal PNI cut-off for predicting mortality, and the derived threshold (49.97) was applied for stratification in all survival analyses. Survival outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazards regression was used to identify independent prognostic factors. Results: Among 262 patients, 138 (52.7%) received NAC, and 124 (47.3%) received AC. Median follow-up was 33.6 months (95% CI: 29.4-37.8). No statistically significant differences in OS (p = 0.388) or PFS (p = 0.499) were observed between treatment groups. In univariate analyses, nodal stage, pathological complete response (pCR), and PNI were significantly associated with both OS and PFS. In multivariate analysis, low PNI (≤49.97) remained an independent predictor of mortality (HR 1.78, 95% CI 1.04-3.38; p = 0.044), while N3 nodal stage independently predicted disease progression (HR 5.92, 95% CI 1.06-32.84; p = 0.042). Conclusions: In this multicenter real-world cohort, nodal stage and systemic inflammatory-nutritional status were key determinants of prognosis in patients with locally advanced bladder cancer receiving perioperative chemotherapy. PNI emerged as an independent predictor of overall survival, suggesting that host-related biomarkers may improve prognostic stratification beyond traditional clinicopathological factors.

Triple-positive breast cancer (TPBC), characterized by concurrent ER, PR, and HER2 positivity, poses unique therapeutic challenges due to ER–HER2 crosstalk. The optimal adjuvant endocrine therapy in TPBC patients receiving anti-HER2 regimens remains poorly defined. This multicenter retrospective cohort study included 1044 early-stage TPBC patients (stage II–III) treated with neoadjuvant chemotherapy and HER2-targeted therapy between 2007 and 2024. Disease-free survival (DFS) was analyzed using Kaplan–Meier estimates and Cox regression models, with separate multivariate analyses for premenopausal (n = 474) and postmenopausal (n = 570) patients. At a median follow-up of 52 months, the 5-year DFS was 88.2

Background Germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2−) metastatic breast cancer (MBC) represents a biologically distinct subset in which the efficacy of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors remains incompletely characterized. Given the interplay between DNA damage repair deficiency and cell-cycle regulation, BRCA-associated tumors may demonstrate differential therapeutic sensitivity. We evaluated real-world outcomes, safety, and prognostic factors in a multicenter cohort. Methods This multicenter retrospective cohort study included patients with pathogenic germline BRCA1 and/or BRCA2 mutations treated with a CDK4/6 inhibitor plus endocrine therapy for HR+/HER2 − MBC (June 2020–September 2025) at participating centers in Turkey. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared by log-rank testing. Cox proportional hazards models were used for univariable and multivariable analyses. Results Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) BRCA2, and 3 (2.5%) dual BRCA1 + BRCA2 mutations; 66.9% received CDK4/6 inhibitors as first-line therapy. Ribociclib was used in 69.4% and palbociclib in 29.8%. Objective response rate was 69.4% and clinical benefit rate 82.6%. Median PFS was 17.0 months and median OS was 47.0 months. PFS differed significantly by BRCA subtype (25.0 months for BRCA1, 14.0 months for BRCA2, and 6.0 months for BRCA1 + 2; log-rank p = 0.013). Median OS also differed (57.0, 49.0, and 11.0 months, respectively; log-rank p = 0.016). PFS did not differ between ribociclib and palbociclib (p = 0.192); OS favored ribociclib at a borderline level (p = 0.050), not confirmed in Cox regression. In multivariable analysis, ECOG ≥ 1 (HR 1.846; p = 0.010) and fulvestrant-based therapy (HR 1.735; p = 0.041) predicted shorter PFS; fulvestrant predicted worse OS (HR 2.389; p = 0.008). Dose reductions occurred in 16.5% and discontinuation in 2.5%. Conclusions CDK4/6 inhibitor–based therapy demonstrates clinically meaningful activity in gBRCAm HR+/HER2 − MBC; however, survival outcomes differ by BRCA subtype, suggesting underlying biological heterogeneity. These findings support further investigation of BRCA subtype–specific tumor biology and its implications for therapeutic sequencing in this molecularly defined population.

Second-line chemotherapy is widely used in metastatic urothelial carcinoma after progression on first-line platinum-based therapy, but its independent contribution to survival, as opposed to selection of healthier patients, remains unclear. In this multicenter retrospective cohort of 142 patients treated with first-line platinum-based chemotherapy across seven Turkish centers, overall survival (OS) from first-line progression was compared between patients who received second-line chemotherapy (n = 80) and those who did not (n = 62), using multivariable Cox regression, inverse probability of treatment weighting (IPTW), propensity-score matching, landmark analysis, and a time-dependent Cox model. Median OS was 7.4 versus 4.7 months (log-rank p = 0.064). Second-line chemotherapy was independently associated with improved OS on multivariable analysis (adjusted hazard ratio [aHR] 0.620; 95% confidence interval [CI] 0.423–0.907; p = 0.014); Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (aHR 3.881; p = 0.001) and lower albumin (aHR 0.671; p = 0.018) were also independent predictors. The association remained significant after IPTW (HR 0.648; p = 0.025) and after a time-dependent Cox model (HR 0.632; p = 0.019), and was unchanged in ECOG-restricted and Bellmunt-adjusted analyses (p = 0.008, p = 0.029); it narrowly missed significance after propensity-score matching (HR 0.645; p = 0.051) and did not reach significance in the 3-month landmark analysis (HR 0.743; p = 0.180). Power was limited (~49%). In a time-dependent Cox model—the analysis least susceptible to immortal-time bias, as it retains the full cohort and classifies pre-treatment person-time as unexposed—second-line chemotherapy remained independently associated with improved OS (HR 0.632; p = 0.019), closely consistent with the primary multivariable estimate. The conventional Cox, IPTW, and propensity-score-matched analyses, which treat second-line receipt as a baseline exposure, were directionally concordant but share a common time-related bias and are therefore not independent confirmations. ECOG performance status was a consistent predictor throughout.

Purpose:As survivorship improves, second primary malignancies (SPMs) have become a clinically relevant late effect of localised breast cancer treatment. Evidence from the Middle East and Balkans is scarce, and contemporary data from Türkiye are lacking. Materials and methods:We conducted a rigorous retrospective, multicentre cohort study within the Turkish Oncology Group across 14 tertiary centres. The medical records of 6, 552 women with early-stage breast cancer (2008-2022) were meticulously reviewed. SPMs were defined according to IARC/SEER multiple-primary rules, and only the first SPM per patient was included. We calculated standardised incidence ratios (SIRs) with exact Poisson 95% confidence intervals (CIs) using age- and period-specific national female incidence rates averaged over the 2010-2020 period. Person-years were stratified by attained age and calendar period to ensure the accuracy and reliability of our results. Results:During a median follow-up of 5.4 years (interquartile range, 1.1-9.4), 174 women developed pathologically confirmed SPMs. Breast cancer survivors had a significantly higher SPM risk compared to the general population (SIR, 1.66; 95% CI, 1.42-1.93). Excluding breast primaries, the excess remained (SIR 1.78; 95% CI, 1.51-2.09). The most significant increases were observed for thyroid cancer (SIR 7.09; 95% CI, 4.45-10.70) and sarcomas (SIR 7.14; 95% CI, 3.43-13.10), followed by ovarian (SIR 4.35; 95% CI, 2.58-6.89) and pancreatic cancers (SIR 4.08; 95% CI, 1.11-10.50). Risks for colorectal, brain, bladder, kidney, gastric, and contralateral breast cancers did not differ from expectations (all p>0.05). Conclusion:Turkish breast cancer survivors face a markedly increased SPM risk, especially for thyroid, sarcoma, and ovarian cancers. These findings should be interpreted cautiously in the context of treatment selection, surveillance intensity, hereditary predisposition, and regional background cancer risks. Prospective population-based studies incorporating detailed treatment exposures, germline testing, and standardized follow-up data are needed to clarify the mechanisms underlying these associations.

Nivolumab is currently widely used in the treatment of lung cancer. Studies have been conducted using flat doses of 240 mg and 3 mg/kg. In fact, studies involving a small number of patients have begun to explore low-dose immunotherapies. The literature on the optimal dose of immunotherapy, the use of weight based, or fixed doses is very recent and has become a one of the subject of ongoing research. This multicenter study included 716 patients with NSCLC. Patients receiving standard doses of 3 mg/kg and 240 mg of nivolumab were divided into subgroups based on their weight. Patients weighing 80 kg have already received a flat dose. However, patients weighing < 80 kg who received a flat dose were considered to be receiving high-dose therapy. Conversely, patients weighing more than 80 kg who received a flat dose were maintained on a low dose. Therefore, overall survival, progression-free survival, and toxicity were examined according to weight-based usage. The median progression free survival (PFS) for those receiving a 3 mg/kg dose was 6 months, whereas it was 9.8 months for those receiving a flat dose (p < 0.001). The median (metastatic overall survival) OS for those receiving a 3 mg/kg dose was 12 months, whereas it was 14 months for those receiving a 240 mg dose (p = 0.03). This study was based on real-world data. Therefore, our results may be instructive regarding the nivolumab dose, which is a commonly used treatment for NSCLC patients. Our results suggest that a flat dose may be preferred in all groups and as a subgroup, especially in patients weighing < 80 kg.

Background and Objectives: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care for resectable gastric and gastroesophageal junction adenocarcinoma; however, up to 50% of patients develop metastatic recurrence. These patients have prior exposure to platinum and taxane agents, and optimal first-line treatment in the metastatic setting remains undefined. This study aimed to characterize real-world treatment patterns and outcomes in patients progressing after perioperative FLOT, focusing on relapse timing and HER2 status. Materials and Methods: This retrospective, multicenter cohort study included 296 patients from 31 centers across Türkiye, stratified into early relapse (≤6 months, n = 114) and late relapse (>6 months, n = 182) groups. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS for the entire cohort were 6 and 9 months, respectively. Early relapsers had significantly shorter median PFS (4 vs. 6 months, p = 0.029) and OS (8 vs. 12 months, p = 0.047); however, early relapse timing did not retain independent prognostic significance on multivariable analysis. No significant difference in PFS or OS was observed between cytotoxic chemotherapy regimens in either relapse group. HER2 positivity was the only independent predictor of improved PFS on multivariable Cox analysis (HR 0.48, 95% CI 0.29-0.81; p = 0.006). In the late relapse group, trastuzumab-based chemotherapy achieved a median PFS of 14 months and OS of 18 months, significantly superior to all cytotoxic regimens (PFS p = 0.007; OS p = 0.029). Conclusions: In patients progressing after perioperative FLOT, cytotoxic chemotherapy regimen selection did not demonstrate a statistically significant survival difference in this retrospective cohort, regardless of relapse timing. HER2 positivity is the dominant predictive biomarker, and trastuzumab-based therapy suggests a potential survival benefit that warrants prospective validation. Comprehensive biomarker profiling at metastatic diagnosis and prospective trials designed for this post-FLOT population are needed to establish evidence-based treatment standards.

Immune checkpoint inhibitors such as nivolumab have brought meaningful benefits to patients with advanced non-small cell lung cancer (NSCLC), yet many patients still experience limited responses. Vitamin D is a key modulator of immune function, and deficiency is common in individuals with cancer. Given its potential role in shaping immunotherapy response, we retrospectively assessed whether baseline vitamin D levels were associated with clinical outcomes in advanced NSCLC patients treated with nivolumab. We retrospectively analyzed patients with stage IV NSCLC treated with nivolumab across multiple centers, predominantly as second-line therapy. Prior to nivolumab initiation, all patients were confirmed to be negative for common driver mutations, including EGFR, ALK, ROS1, and other actionable genomic alterations. Baseline serum 25-hydroxyvitamin D levels were measured prior to nivolumab initiation, and patients were categorized as having severe deficiency (< 10 ng/mL), deficiency (10–20 ng/mL), or sufficient levels (≥ 20 ng/mL). The presence of liver metastases was recorded at baseline. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards models adjusted for age, sex, ECOG performance status, liver metastasis, and other metastatic sites were used to evaluate the independent prognostic value of vitamin D status. Objective response rates (ORR) were assessed in patients with available radiologic data. A total of 890 patients were screened, and after excluding those with missing baseline vitamin D data, 305 patients were included in the analysis. The median age was 64 years (range 34–85), and 68% of patients were male. Vitamin D levels were < 10 ng/mL in 30%, 10–20 ng/mL in 44%, and ≥ 20 ng/mL in 26% of patients. Patients with severe vitamin D deficiency were numerically older (median age 65 vs. 63 years) and had higher rates of ECOG PS ≥ 2 (15.1% vs. 7.5%) and squamous histology (37.6% vs. 27.5%), though these differences were not statistically significant (p > 0.05 for all). Liver metastases were present in 54 patients (17.7%), and the distribution was similar across vitamin D groups (p = 0.92). Median PFS was shortest in patients with severe vitamin D deficiency (3.4 months), intermediate in the 10–20 ng/mL group (5.2 months), and longest in patients with sufficient levels (8.1 months). Median OS ranged from 8.6 months in the < 10 ng/mL group to 15.8 months in the ≥ 20 ng/mL group. Patients with liver metastases had significantly shorter OS compared to those without (median OS 9.8 vs. 13.6 months, HR 1.48, p = 0.006). Vitamin D deficiency was associated with significantly worse PFS and OS on univariate analysis. In multivariable analysis, vitamin D levels < 20 ng/mL remained independently associated with poorer OS. ORR was numerically higher in patients with sufficient vitamin D levels (30% vs. 14%). Lower baseline vitamin D levels were associated with inferior clinical outcomes in advanced NSCLC patients treated with nivolumab. Patients with vitamin D levels ≥ 20 ng/mL demonstrated longer PFS and OS and a trend toward higher response rates. These findings support a prognostic role for vitamin D status in immunotherapy-treated NSCLC; however, prospective studies are required to determine whether vitamin D optimization can causally enhance immunotherapy efficacy.

Background: Trastuzumab deruxtecan (T-DXd) has transformed the treatment landscape of human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC), with significant improvements in survival reported in clinical trials. However, limited data exist regarding its performance in real-world settings, particularly in lower-middle-income countries (LMICs). Objectives: To evaluate the real-world effectiveness and safety of T-DXd in patients with HER2+ mBC in Türkiye. Design: A multicenter retrospective cohort study. Methods: This multicenter, retrospective cohort study, conducted by the Turkish Oncology Group, evaluated the real-world outcomes and tolerability of T-DXd in patients with HER2+ mBC across 27 oncology centers in Türkiye. The primary endpoints were real-world progression-free survival (rwPFS) and overall survival (rwOS). Secondary endpoints included response rate, safety (with adverse events (AEs) graded according to CTCAE v5.0), and evaluation of the first post-T-DXd treatments. Results: A total of 269 patients were included. The median age was 49 years (interquartile range: 42–59), and the median follow-up was 12.9 months. The median rwPFS was 17.9 months (95% confidence interval: 13.3–22.5), and the median rwOS was 35.7 months (95% confidence interval: 27.8–43.6). The objective response rate was 71.4%, and the disease control rate was 95.2%. Patients receiving T-DXd in the second line experienced significantly longer rwPFS compared with those treated in later lines ( p < 0.001). Treatment-related AEs of any grade occurred in 68.4% of patients. Interstitial lung disease was reported in 21 patients (7.8%), with 4 cases being grade ⩾3. Conclusion: In this large national real-world cohort from an LMIC, T-DXd demonstrated robust antitumor activity and a manageable safety profile in patients with HER2+ mBC. These findings are consistent with prior clinical trial data and support the applicability of T-DXd in broader clinical settings.

BackgroundPercutaneous nephrostomy (PCN) is frequently employed to relieve malignant ureteral obstruction in patients with muscle-invasive bladder cancer (MIBC), yet its prognostic and infectious implications in non-metastatic disease remain poorly characterized. This study aimed to evaluate the association between PCN at diagnosis and clinical outcomes in patients with non-metastatic MIBC.MethodsWe retrospectively analyzed 199 patients with non-metastatic MIBC treated between January 2019 and March 2025 at two centers in Türkiye. Patients were grouped by PCN status at diagnosis. The primary endpoint was overall survival (OS); secondary endpoints were metastasis-free survival (MFS) and infection-related outcomes. Survival was analyzed using Kaplan–Meier and multivariable Cox regression, including ECOG performance status and treatment modality as covariates. Logistic regression was used to assess infectious outcomes. Collinearity was evaluated using variance inflation factor analysis.ResultsPCN was present in 27.1% of patients. Median OS was shorter in the PCN group compared with those without PCN (24 vs. 41 months; p = 0.004); however, PCN did not retain independent prognostic significance in the multivariable model after adjustment for ECOG performance status, CRP, N stage, and treatment modality (HR 0.433; 95% CI 0.175–1.068; p = 0.069). ECOG performance status (HR 1.819; p = 0.039), CRP (HR 1.005; p = 0.01), and N stage (HR 1.724; p = 0.023) were independent predictors of OS. A subgroup analysis within the hydronephrosis-positive population showed no significant difference in OS between PCN and non-PCN patients (26 vs. 29 months; p = 0.785). Treatment modality was the sole independent predictor of MFS (HR 0.594; p = 0.008). PCN was a strong and independent predictor of positive urine cultures (OR 2.685; 95% CI 1.055–6.837; p = 0.038) and infection-related hospitalizations (OR 13.995; 95% CI 4.923–39.785; p < 0.001).ConclusionsIn patients with non-metastatic MIBC, PCN was not an independent predictor of OS after comprehensive adjustment, suggesting that the survival disadvantage observed in unadjusted analysis reflects baseline clinical vulnerability rather than a direct effect of the procedure. PCN was, however, independently and strongly associated with infectious morbidity. These findings position PCN as a marker of clinical frailty that warrants careful multidisciplinary evaluation before placement and proactive management of infectious complications thereafter.

Background and Objectives: Metastatic pancreatic ductal adenocarcinoma carries a dismal prognosis and there is an unmet need for simple, widely available prognostic biomarkers to guide risk stratification and treatment planning. This study aimed to evaluate whether baseline EASIX score, calculated from routine laboratory parameters (LDH, creatinine, platelet count), predicts overall survival (OS) in patients with de novo metastatic pancreatic cancer. Materials and Methods: We performed a retrospective cohort study at a single tertiary center (Medical Oncology Department, Kocaeli University Faculty of Medicine) including 332 patients diagnosed with de novo metastatic pancreatic ductal adenocarcinoma between January 2019 and October 2025. Baseline EASIX was calculated using LDH, creatinine, and platelet count. Statistical analyses included ROC analysis with Youden index to determine exploratory cut-off, Kaplan-Meier survival estimation with log-rank test, and univariate and multivariate Cox proportional hazards regression to identify independent prognostic factors. The primary endpoint was OS, defined as time from initiation of first-line therapy to death from any cause. Results: A total of 332 patients were included. Median OS was 8.0 months overall. Patients with high EASIX (>2.505) had significantly shorter median OS compared with low EASIX patients (8.4 vs. 27.6 months, p < 0.001). ROC analysis was considered exploratory for overall survival; therefore, an additional fixed-time (12-month mortality) ROC analysis was performed to provide a discrimination estimate accounting for censoring. The AUC for EASIX was 0.887 (95% CI: 0.816-0.958), and the exploratory cut-off determined was 2.505 (sensitivity 96.95%, specificity 72.97%). In multivariate Cox regression, high EASIX remained an independent predictor of worse OS (HR 4.124; 95% CI: 2.011-8.457; p < 0.001) after adjustment for relevant covariates. Conclusions: Baseline EASIX score is an independent prognostic marker for overall survival in de novo metastatic pancreatic cancer, based on routine laboratory tests, and may facilitate exploratory risk stratification. Prospective validation in independent cohorts is warranted before clinical implementation.

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis. Effective prognostic tools are essential to guide risk-adapted strategies following neoadjuvant chemotherapy (NACT). In this multicenter retrospective study, we evaluated 690 patients with locally advanced TNBC treated between 2010 and 2023 across 25 oncology centers. Patients were stratified into CPS-EG risk groups: low (0–1), intermediate (2–3), and high (≥4). The CPS-EG score was strongly associated with pathological complete response (pCR), recurrence, disease-free survival (DFS), and overall survival (OS). Five-year DFS rates were 80.6%, 53.2%, and 31.5% in the low-, intermediate-, and high-risk groups, respectively, while OS rates were 76.7%, 53.2%, and 48.8% (p<0.001). Multivariate analysis confirmed CPS-EG as an independent predictor of both DFS and OS after adjusting for clinicopathological factors. These findings highlight the CPS-EG score as a simple, cost-effective, and widely applicable prognostic tool that may improve post-NACT risk stratification and support treatment decisions, especially in resource-limited oncology settings.

Background/Objectives: Non-small-cell lung cancer (NSCLC) is a common disease with a high mortality rate and is often treated with immunotherapies; however, prognostic markers are required to identify patients who are most likely to benefit from these treatments. Therefore, we designed this study to assess the prognostic significance of the C-PLAN index, which includes performance status (PS) and C-reactive protein (CRP). Methods: A total of 560 patients were included in this multicenter study. Patients had been diagnosed with NSCLC and had received nivolumab therapy. The C-PLAN index, defined in 2022, is a score derived from the combination of PS, CRP, lactate dehydrogenase (LDH), albumin, and neutrophil-lymphocyte ratio (NLR). Patients were classified into good-, moderate-, and poor-prognosis groups according to the C-PLAN score. Results: The median metastatic overall survival was 25 months in the group with a C-PLAN score < 2 and 6 months in the group with a C-PLAN score ≥ 2 (p < 0.001). The median metastatic progression-free survival was 11 months in the group with a C-PLAN score < 2 and 3 months in the group with a C-PLAN score ≥ 2. Conclusion: This is the first comprehensive study demonstrating that the C-PLAN index can be used for prognostic purposes in immunotherapy. This score, which can be easily, economically, and practically calculated in outpatient clinics, can predict patient prognosis and determine who should receive longer durations of immunotherapy.

BACKGROUND:The objective of this study is to evaluate the correlation between survival outcomes and renin angiotensin system inhibitors (RASI) use in patients treated nivolmab with metastatic non-small cell lung cancer (mNSCLC). METHODS:This retrospective cohort multicentre study was conducted on patients with mNSCLC patients treated Nivolumab monotherapy as second line therapy. Factors affecting the survival of patients receiving concurrent RASI therapy with nivolumab were analyzed. RESULTS:614 patients were included. A total of 288 patients (46.9%) were using concurrent RASI. Patients using RASIs had a median progression free survival (PFS) of 10 months compared to 7 months in non-users. In the multivariate analysis, RASI use (HR: 0.747, 95% CI: 0.594-0.941; p: 0.013) was associated with improved PFS. RASI use was also significantly associated with overall survival (OS), median OS of 20 months in users and 12 months in non-users. In the multivariate analysis, RASI use (HR: 0.600, 95% CI: 0.458-0.787; p < 0.001) was associated with improved OS. CONCLUSIONS:In this multicenter real-world study of patients with mNSCLC receiving second-line nivolumab, concomitant use of RASIs was associated with PFS and OS. The integration of RAS blockade into immunotherapy regimens could represent a promising strategy to enhance treatment efficacy.

Background/Objectives: Gastric cancer remains a leading cause of cancer-related mortality worldwide, with a significant number of patients diagnosed at locally advanced stages. While perioperative chemotherapy and surgical resection are the standard treatments, patient outcomes remain heterogeneous. This study aimed to investigate the prognostic and predictive effects of Body Mass Index (BMI) on pathological response, progression-free survival (PFS), and overall survival (OS) in patients receiving neoadjuvant chemotherapy. Methods: This retrospective, observational cohort study included 192 patients with locally advanced gastric cancer who underwent curative gastrectomy and neoadjuvant chemotherapy between 2018 and 2023. Patients were categorized based on an optimal BMI cutoff value of 24.9 kg/m2. Results: Patients with a BMI ≥ 24.9 kg/m2 demonstrated a 41% lower 5-year mortality risk compared to those with a lower BMI (HR = 0.59; 95% CI: 0.35-0.99; p = 0.044). The high BMI group had a significantly longer average PFS (54.1 months) compared to the low BMI group (41.4 months). High BMI was associated with a significantly reduced risk of progression (HR: 0.61; 95%CI: 0.38-0.97; p = 0.038. Log-linear regression confirmed that the complete response rate was 73.7% lower in patients with low BMI. Conclusions: BMI threshold of ≥24.9 kg/m2 is associated with improved pathological response and long-term survival in patients with locally advanced gastric cancer receiving neoadjuvant chemotherapy. These findings suggest that BMI potentially reflects the impact of nutritional status on treatment tolerability and oncological outcomes.