Introduction In the treatment of metastatic non-small cell lung cancer (mNSCLC), targeted therapies are utilized in the presence of driver mutations. Tyrosine kinase inhibitors (TKIs) have contributed positively to survival outcomes in this patient group. In driver mutant mNSCLC patients, caution is warranted for the development of small cell lung cancer (SCLC) differentiation following progression under TKI therapy. SCLC is associated with an aggressive course and shorter survival. The cornerstone of SCLC treatment is conventional chemotherapy. In this study, we aimed to present the development of SCLC differentiation in driver mutant mNSCLC patients who received at least one line of TKI therapy as a single-center experience. Patients and methods Between April 2013 and January 2024, the medical records of 144 patients diagnosed with mNSCLC and found to harbor driver mutations were retrospectively reviewed at Necmettin Erbakan University Faculty of Medicine Hospital, Oncology Clinic. All patients had received at least one line of TKI. The analysis included evaluation of driver mutations, treatments administered, and the rate of SCLC differentiation in this patient population. Results A total of 144 patients were included in the study. Among them, 122 patients (84.9%) had an EGFR mutation, 21 patients (15.1%) had an ALK mutation, and 1 patient had a ROS1 mutation. TKI therapy was administered as first-line treatment in 50% of the patients, as second-line in 40.3%, and as third-line in 6.3%. Biopsies were performed in 22 out of 144 patients after disease progression. Of these, 21 biopsies were from patients with EGFR mutations, and 1 was from a patient with an ALK mutation. Biopsies were conducted after first-line therapy in 8 cases, after second-line therapy in 11 cases, and after third-line therapy in 3 cases. SCLC differentiation was observed in 3 out of 22 patients (13.6%), all of whom had EGFR mutations. Additionally, 2 of these 3 patients developed SCLC differentiation following first-line TKI therapy, while 1 developed it after second-line TKI therapy. Discussion The rate of SCLC differentiation in NSCLC is generally low and is considered rare. It is estimated that the rate of SCLC differentiation in NSCLC ranges between 1% and 3%. In our clinic, when evaluating driver mutant mNSCLC patients who received at least one line of TKI therapy, SCLC differentiation was observed in 3 patients (13.6%). The limitations of our study include its retrospective nature and the small sample size. However, the findings suggest that SCLC differentiation is a potential occurrence in driver mutant mNSCLC patients treated with TKIs. Therefore, careful monitoring and the detection of possible differentiation are essential in the follow-up of these patients.

Background: Diabetes mellitus and cancer often coexist, increasing the risk of liver injury. Doxorubicin (DOXO) is a widely used antineoplastic drug with known hepatotoxic effects. Dapagliflozin (DAPA) and trimetazidine (TMZ) have been reported to exert hepatoprotective actions, but their combined effects remain unclear. Methods: Forty-eight male Sprague Dawley rats were allocated into six groups: control, streptozotocin (STZ), STZ + DOXO, STZ + DOXO + DAPA, STZ + DOXO + TMZ, and STZ + DOXO + DAPA + TMZ. Liver injury was assessed by histopathology, oxidative stress markers (MDA, GSH), and immunohistochemistry (Tumor Necrosis Factor-alpha (TNF-α), 8-Hydroxy-2′-deoxyguanosine (8-OHdG), Caspase-3, Transforming Growth Factor-beta 1 (TGF-β1), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Nuclear Factor kappa-B/p65 (NF-κB/p65)). Results: STZ and STZ + doxorubicin groups developed marked hepatic injury. Unexpectedly, the STZ + doxorubicin group showed lower alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, along with reduced Malondialdehyde (MDA) and elevated glutathione (GSH), suggesting compensatory antioxidant and apoptotic responses. Dapagliflozin more effectively normalized transaminases and reduced oxidative DNA damage, whereas trimetazidine exerted stronger effects on MDA, GSH, and inflammatory markers. The combination provided additive but not consistently superior benefits. Immunohistochemical analyses confirmed these findings, showing attenuated expression of TNF-α, 8-OHdG, caspase-3, and TGF-β1 and reduced TUNEL-positive hepatocytes and NF-κB/p65 immunoreactivity following treatment, indicating coordinated anti-apoptotic and anti-inflammatory effects. Conclusions: Dapagliflozin and trimetazidine each attenuated diabetes- and doxorubicin-related hepatic injury through partly distinct mechanisms, with the combination providing additive but not consistently superior effects. These findings suggest a potential hepatoprotective role for both agents; however, the clinical implications remain uncertain and require confirmation in further mechanistic and translational studies.

Background and Objectives: Metastatic renal cell carcinoma (mRCC) remains a lethal disease despite advances with immune checkpoint inhibitors such as nivolumab. However, a substantial proportion of patients exhibit primary resistance or early progression, highlighting the need for reliable and easily accessible prognostic biomarkers. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel immunonutritional biomarker integrating systemic inflammation, nutritional status, and immune competence. Materials and Methods: In this retrospective single-center study, 91 patients with mRCC treated with nivolumab were analyzed. Patients were stratified into low and high CALLY index groups based on a receiver operating characteristic-derived cut-off (0.322). Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. Results: Patients with a low CALLY index demonstrated significantly shorter progression-free survival (4.5 vs. 13.5 months, p < 0.001) and overall survival (9.1 vs. 25.5 months, p = 0.003). Multivariate analysis confirmed the CALLY index as an independent prognostic factor for both progression-free survival (HR: 2.63, p = 0.002) and overall survival (HR: 1.88, p = 0.035). Conclusions: The CALLY index is a simple, cost-effective, and reproducible biomarker that independently predicts survival in nivolumab-treated mRCC. It may serve as a practical tool for risk stratification and personalized treatment planning in the immunotherapy era.

Background and Objectives: Erlotinib, a tyrosine kinase inhibitor (TKI), is an established therapy for patients with metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Preclinical and clinical evidence suggests that chronic stress, mediated through β-adrenergic signaling, promotes tumor progression, angiogenesis, and therapy resistance. Furthermore, interactions between β-adrenergic signaling and EGFR pathways have been hypothesized to negatively influence treatment responses. Based on this rationale, we investigated whether concomitant beta-blocker use may improve survival outcomes in EGFR-mutant NSCLC patients treated with erlotinib. Materials and Methods: This retrospective analysis included 103 patients with metastatic EGFR-mutant NSCLC who received erlotinib. Patients were classified according to concurrent beta-blocker use, defined as continuous therapy for at least six months prior to erlotinib initiation, prescribed for cardiovascular indications. Progression-free survival (PFS) and overall survival (OS) were compared between beta-blocker users and non-users. Results: Patients receiving erlotinib with concomitant beta-blocker therapy achieved a median PFS (mPFS) of 21.4 months (95% CI, 13.1–29.7), compared with 9.7 months (95% CI, 6.7–12.7) in non-users (p = 0.003). Median OS (mOS) was 32.4 months (95% CI, 14.8–50.0) in the beta-blocker group versus 19.9 months (95% CI, 14.8–25.0) in the non-beta-blocker group (p = 0.010). Multivariate Cox regression confirmed beta-blocker use as an independent prognostic factor for both PFS (p = 0.004) and OS (p = 0.014). Conclusions: Concomitant beta-blocker use was associated with significantly prolonged survival in patients with EGFR-mutant metastatic NSCLC receiving erlotinib. These findings support the hypothesis that β-adrenergic inhibition enhances the efficacy of EGFR-targeted therapy. Prospective studies are warranted to validate these results and to further elucidate the underlying biological mechanisms.

Introduction: The current study aimed to examine the relationship between 25 hydroxyvitamin D [25(OH)D] levels and demographic, clinical and laboratory parameters and response to treatment in patients living in a Central Anatolian city of Turkey and diagnosed with osteomalacia.Methods: A total of 533 patients who live in the continental climate, older than 18 years old, and have 25(OH)D levels lower than 30 ng/ml were enrolled prospectively. Patients' age, body mass index (BMI), type of clothing, season in which they were diagnosed, type of treatment and duration were recorded. At the time of diagnosis, the patients were evaluated with clinical and laboratory parameters at 1st, 2nd, and 4th months.Results: Mean serum 25(OH)D level was 7.59±4.41 ng/mL at the time of diagnosis. 25(OH)D level was 24.42±14.77 ng/ml after treatment, with severe deficiency (<10 ng/mL) in 74% of patients, deficiency ( 0.05). However, as BMI increased, the response given to the treatment decreased.Conclusions: The current study showed that vitamin D deficiency is common in study population. The current findings demonstrate that treatment and follow-up should be continued until achieving normal serum 25(OH)D levels, taking into account geographic and ethnical structures to bring vitamin D levels to adequate levels.Keywords: 25-hydroxytamin D; Osteomalacia; vitamin D deficiency

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.