Deniz Can Guven

Background and Objectives: Treatment-emergent neuroendocrine prostate cancer (t-NEPC) is an aggressive resistance phenotype arising during metastatic castration-resistant prostate cancer (mCRPC). Because metastatic biopsy is not routinely feasible in advanced disease, real-world data on clinically defined t-NEPC/aggressive-variant prostate cancer (AVPC)-like disease remain limited. We aimed to characterize the clinical features, treatment patterns, survival outcomes, and prognostic factors of this clinically defined phenotype. Materials and Methods: We retrospectively reviewed 354 patients with prostate cancer treated at our institution between 2010 and 2020. Seventy-four patients with mCRPC who were clinically identified as having a t-NEPC/AVPC-like phenotype and had a treatment plan for platinum- and/or etoposide-based neuroendocrine-directed systemic therapy were included. Overall survival (OS) and radiographic progression-free survival (rPFS) were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: At clinical identification of the phenotype, the median age was 66.4 years, and visceral metastases were present in 67.6% of patients, most commonly in the liver (55.4%). Median intervals from prostate cancer diagnosis and CRPC onset to clinical identification of the phenotype were 47.5 and 22.7 months, respectively. Neuroendocrine-directed therapy was initiated in 72 patients; platinum–etoposide was the most common first-line regimen (n = 41, 55.4%). Median OS was 4.4 months (95% confidence interval [CI], 2.9–5.8), and median rPFS was 3.5 months (95% CI, 2.7–4.2). In an exploratory, unadjusted analysis, median OS did not differ significantly between doublet chemotherapy and monotherapy (7.0 vs. 3.5 months; p = 0.167). Gleason score ≥9, hemoglobin Conclusions: The clinically defined t-NEPC/AVPC-like phenotype was associated with an aggressive clinical course and poor survival. Earlier recognition, improved biomarker-based diagnostic strategies, and more effective therapeutic approaches are needed.

Objective: The hemoglobin–albumin–lymphocyte–platelet (HALP) score is an inflammation and nutrition -based biomarker in various solid tumors; however, its prognostic value in patients with metastatic breast cancer treated with antibody–drug conjugates (ADCs) remain unclear. We aimed to evaluate the association between HALP score and overall survival (OS) in this patient population.Materials and Methods: This retrospective cohort study included female patients with metastatic breast cancer treated with ADCs between December 2017 and October 2024. The HALP score was calculated from baseline hemoglobin, albumin, lymphocyte, and platelet values. Patients were categorized into low and high HALP groups according to the median HALP value. Survival was evaluated using the Kaplan–Meier method, with associations assessed through univariate and multivariate Cox regression models. Results: A total of 111 female patients with metastatic breast cancer treated with ADCs were included in the analysis (median age, 51 years). The median HALP score was 30.1, and patients were stratified into low- and high-HALP groups. Overall survival was significantly shorter in the low-HALP group compared with the high-HALP group (median OS, 31.0 vs 76.0 months; p < 0.001). In multivariate analysis, a low HALP score remained independently associated with shorter OS (HR 3.03, 95% CI 1.67–5.47; p < 0.001).Conclusion: The HALP score is an independent prognostic marker for overall survival in women with metastatic breast cancer treated with ADCs and may serve as a simple tool for risk stratification in this setting.

Background: Immune checkpoint inhibitors (ICIs) combined with first-line platinum–etoposide have changed the standard treatment of extensive-stage small-cell lung cancer (ES-SCLC), yet the role of consolidative thoracic radiotherapy (cTRT) in the chemo-immunotherapy era remains unclear. Objectives: To evaluate the association of cTRT after first-line chemo-immunotherapy with survival outcomes and treatment-related toxicity in ES-SCLC. Design: Systematic review and meta-analysis. Data Sources and Methods: We systematically identified studies evaluating cTRT following first-line chemo-immunotherapy in ES-SCLC. Overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs), and safety outcomes were pooled using risk differences (RDs), each with 95% confidence intervals (CIs). Results: Seventeen studies (all non-randomized) involving 2,263 patients were included. cTRT was associated with improved OS (HR 0.63, 95% CI 0.56–0.71; p2 =0%) and PFS (HR 0.56, 95% CI 0.46–0.68; p<0.00001). Sensitivity analyses restricted to propensity score–adjusted studies and anti–PD-L1-based regimens showed consistent results. cTRT increased any-grade pneumonitis (RD 0.12, 95% CI 0.03–0.21) and esophagitis (RD 0.22, 95% CI 0.04–0.40), without a significant increase in overall grade ≥3 adverse events (RD 0.02, 95% CI −0.05 to 0.09). Conclusion: In ES-SCLC treated with first-line chemo-immunotherapy, cTRT was associated with improved survival and increased localized thoracic toxicity, particularly any-grade pneumonitis and esophagitis, without a significant increase in overall grade ≥3 adverse events. Pending prospective randomized validation, these results could support the use of cTRT after the disease control with first-line chemo-immunotherapy.

This multicenter retrospective study evaluated the impact of type 2 diabetes mellitus (DM) on clinical outcomes and immune‐related adverse events (irAEs) in 450 patients with metastatic non‐small cell lung cancer (NSCLC) treated with second‐line nivolumab at 17 centers between 2016 and 2024. Among these patients, 118 (26.2%) had DM. Baseline demographic and clinical characteristics, including age, sex, smoking status, ECOG performance status, histology, and PD‐L1 expression, were similar between patients with and without DM. Nivolumab demonstrated similar antitumor activity in both groups, with no significant differences in median progression‐free survival (PFS), overall survival (OS), or objective response rates. However, the incidence of Grade 3–4 irAEs was significantly higher in patients with DM. HbA1c levels were not associated with survival outcomes in univariate analyses, and metformin or insulin use did not affect PFS or OS among patients with DM. These findings indicate that DM does not compromise immunotherapy efficacy but is associated with a higher risk of severe toxicity. Clinicians should consider metabolic status and closely monitor patients with DM receiving immunotherapy. Further prospective studies are needed to clarify underlying mechanisms and optimize treatment strategies for this population.

Background and Objectives: Neoadjuvant dual HER2 blockade combined with chemotherapy is the standard treatment approach for patients with high-risk early-stage or locally advanced HER2-positive breast cancer. However, the optimal chemotherapy backbone and the predictive value of systemic inflammatory biomarkers remain subjects of ongoing investigation. This study aimed to compare pathologic complete response (pCR) rates between neoadjuvant dose-dense doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab and pertuzumab (ddAC+THP) and docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and to evaluate the predictive performance of pretreatment inflammatory biomarkers. Materials and Methods: In this multicenter retrospective study, patients with HER2-positive breast cancer treated with neoadjuvant ddAC+THP or TCHP between 2019 and 2025 at three tertiary centers were evaluated. Pretreatment inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, were calculated from baseline laboratory parameters. Receiver operating characteristic analyses were performed to determine optimal cutoff values, and logistic regression analyses were used to identify predictors of pCR. Results: A total of 197 patients were included, of whom 138 received ddAC+THP and 59 received TCHP. Overall, 125 patients (63.5%) achieved pCR. The pCR rate was numerically higher in the ddAC+THP group than in the TCHP group (65.2% vs. 59.3%), although the difference was not statistically significant (p = 0.431). Among the evaluated biomarkers, SIRI demonstrated the highest discriminatory performance for predicting pCR (AUC: 0.725, 95% CI: 0.652–0.797), followed by NLR (AUC: 0.673, 95% CI: 0.595–0.750). In multivariable analysis, hormone receptor positivity (OR: 0.291, 95% CI: 0.131–0.645; p = 0.002) and elevated SIRI (>0.845) (OR: 0.088, 95% CI: 0.036–0.216; p < 0.001) were independently associated with lower odds of achieving pCR. No significant difference in pCR was observed between treatment regimens across predefined subgroup analyses. Conclusions: Neoadjuvant ddAC+THP and TCHP achieved comparable pCR outcomes in patients with HER2-positive breast cancer. SIRI was independently associated with a lower likelihood of achieving pCR and showed acceptable discriminatory performance. These findings suggest that SIRI may represent an exploratory, readily available inflammatory biomarker for pCR risk stratification; however, prospective validation is required before clinical application.

Objective: Artificial intelligence (AI) is transforming healthcare, and large language models (LLMs) like ChatGPT and Google Bard have shown promise in providing medical information and decision support. The LLMs performed similarly or better than human participants in several board exams. However, their proficiency in complex clinical scenarios, like in oncology board exams, remains unclear. We aimed to assess the performance of three LLMs (ChatGPT 3.5, ChatGPT 4 and Google Bard) on the oncology board examination. Materials and Methods: We utilized a question bank from the Turkish Society of Medical Oncology Board Exam encompassing 290 multiple-choice questions from 2021-2023. ChatGPT 3.5, ChatGPT 4, and Google Bard were asked to answer each question in both Turkish and English, providing explanations and confidence levels with their answers. Results: The overall accuracy of LLMs was 59.3%, 42.8%, 36.2% for ChatGPT4, ChatGPT3.5, and Google Bard, respectively. The accuracy of ChatGPT 4 was significantly higher than that of ChatGPT 3.5 (p<0.001) and Google Bard (p<0.001), while the accuracy of ChatGPT3.5 was higher than that of Google Bard (p<0.001). Only the ChatGPT 4 was proficient in all three examination years (2021-2023). All LLMs performed better on translated questions than original Turkish ones. The LLMs were more accurate in general knowledge than case questions and were more confident in their answers for translated questions. Conclusion: LLMs had moderate success in a medical oncology board exam, with only ChatGPT 4 demonstrating proficiency. The efficacy of LLMs in clinical decision-making requires further development, especially in native languages and complex case interpretations.

Germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC) is a biologically distinct subset in which the efficacy of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors remains incompletely characterized. We evaluated real-world outcomes and prognostic factors in a multicenter retrospective Turkish cohort treated with a CDK4/6 inhibitor plus endocrine therapy (June 2020–September 2025). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier and Cox methods. Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) had BRCA2, and three (2.5%) had dual mutations; 66.9% received first-line therapy, with ribociclib in 69.4% and palbociclib in 29.8%. Objective response rate was 69.4% and the clinical benefit rate was 82.6%. Median PFS was 17.0 months and OS 47.0 months. PFS was numerically longer in BRCA1 than in BRCA2 carriers (25.0 vs. 14.0 months), although the difference was not statistically significant in the pairwise comparison (HR 1.50, 95% CI 0.88–2.56; log-rank p = 0.135); the dual BRCA1/2 subgroup (n = 3) had the poorest outcomes and was assessed descriptively. OS did not differ significantly between BRCA1 and BRCA2 carriers (57.0 vs. 49.0 months; log-rank p = 0.520). PFS did not differ between ribociclib and palbociclib (p = 0.192); OS favored ribociclib at borderline significance (p = 0.050), but this was not confirmed in Cox regression. In multivariable analysis, ECOG ≥ 1 (HR 1.85; p = 0.010) and fulvestrant-based therapy (HR 1.74; p = 0.041) predicted shorter PFS; fulvestrant also predicted worse OS (HR 2.39; p = 0.008). CDK4/6 inhibitor-based therapy shows meaningful activity in gBRCAm HR+/HER2- MBC; the numerically poorer outcomes observed in BRCA2 carriers are hypothesis-generating and warrant validation in larger cohorts.

Trastuzumab deruxtecan (T-DXd) has demonstrated significant efficacy in metastatic breast cancer (mBC) with varying HER2 expression. Statins have been show

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.