Kadriye Başkurt

Background: The renin-angiotensin system (RAS) is expressed in prostate tissue and modulates tumor proliferation, angiogenesis, and androgen receptor signaling. Whether concomitant ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) use affects survival outcomes in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC) receiving androgen receptor pathway inhibitor (ARPI)-based therapy remains unknown. Methods: This multicenter retrospective study included 211 patients with de novo mHSPC treated with ARPI therapy at three institutions between January 2021 and December 2025. Patients were classified as ACEI/ARB users ( n = 87) or non-users ( n = 124). The primary endpoint was progression-free survival (PFS); overall survival (OS) and PSA response rates were secondary endpoints. Multivariable Cox regression and stabilized inverse probability of treatment weighting (IPTW) were used for survival analyses, with propensity-score matching and a statin-adjusted model as sensitivity analyses. Exploratory subgroup analyses were corrected for multiple comparisons using the Benjamini–Hochberg false discovery rate procedure. Results: At a median follow-up of 20.9 months, progression occurred in 19.5% of ACEI/ARB users versus 50.8% of non-users, and death in 4.6% versus 20.2%. In multivariable analysis, ACEI/ARB use was associated with improved PFS (HR 0.35, 95% CI 0.20–0.65, p = 0.001) and OS (HR 0.28, 95% CI 0.09–0.88, p = 0.029; 29 deaths, 4 among ACEI/ARB users). The PFS association persisted after IPTW adjustment (HR 0.57, p = 0.032) and across propensity-score matching, statin-adjusted, and hypertensive-only sensitivity analyses. OS estimates were directionally consistent but imprecise because of the small number of deaths (IPTW HR 0.24, 95% CI 0.06–0.91). PSA50 and PSA90 response rates were significantly higher in ACEI/ARB users (95.4% vs. 82.3%, p = 0.004; 87.4% vs. 71.0%, p = 0.005). Conclusions: In this retrospective cohort, concomitant ACEI/ARB use was associated with improved PFS and deeper PSA responses in patients with de novo mHSPC receiving ARPI therapy. The OS findings were consistent in direction but underpowered because of the small number of deaths. Given the potential for residual and unmeasured confounding, these findings should be considered hypothesis-generating and require external validation and prospective evaluation.

Purpose: Regorafenib-induced hand-foot skin reaction (HFSR) is a common dose-limiting toxicity. We evaluated whether prophylaxis with oral zinc plus topical clobetasol is associated with lower clinically significant HFSR compared with either strategy alone. Methods: ZINCLO-HAND was a prospective, multicenter, pragmatic, nonrandomized comparative study across 13 oncology centers in Türkiye. Adults initiating regorafenib were managed at physician discretion with oral zinc, topical clobetasol propionate 0.05%, or the combination for 8 weeks. The primary end point was grade ≥2 HFSR within the prophylaxis period. Secondary end points included grade 3 HFSR, treatment modification, relative dose intensity, and patient-reported outcomes. Results: Of 179 enrolled patients, 156 were evaluable: zinc, n = 49; clobetasol, n = 52; combination, n = 55. Grade ≥2 HFSR occurred in 38.8%, 38.5%, and 16.4% of patients, respectively ( P = .016). In multivariable logistic regression adjusted for age, Eastern Cooperative Oncology Group performance status, tumor type, and initial regorafenib dose intensity, zinc monotherapy (adjusted odds ratio [OR], 3.37 [95% CI, 1.30 to 8.71]; P = .012) and clobetasol monotherapy (adjusted OR, 3.15 [95% CI, 1.26 to 7.88]; P = .014) were associated with higher odds of grade ≥2 HFSR versus combination prophylaxis. Median relative dose intensity was comparable across groups. HFSR-attributable treatment modification occurred in 30.6%, 28.8%, and 12.7% of patients, respectively. Conclusion: In this nonrandomized prospective cohort, zinc plus topical clobetasol was associated with lower clinically significant regorafenib-induced HFSR and fewer HFSR-attributable treatment modifications. These findings support consideration of combination prophylaxis in routine practice and warrant randomized confirmation.

Histologic Subtypes, Treatment Patterns, and Survival Outcomes in Cervical Cancer: A Population-based SEER Study - Acta Haematologica Oncologica Turcica

Background: Prognostic biomarkers for risk stratification remain limited in de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen receptor pathway inhibitors (ARPIs). We evaluated baseline serum 25-hydroxyvitamin D [25(OH)D] and developed and externally validated a progression-free survival (PFS) model. Methods: This multicenter retrospective study included 273 patients initiating ARPI-based therapy between January 2021 and April 2026. Etlik City Hospital formed the training cohort (n = 192; 85 PFS events), and Gazi University and Kütahya City Hospital formed the external validation cohort (n = 81; 27 PFS events). LASSO-penalized Cox regression retained age, ISUP grade group, CHAARTED disease volume, log-transformed PSA, and hemoglobin. Model B added continuous 25(OH)D. Internal validation used 1000 bootstrap resamples. Performance was assessed by the Harrell C-index, time-dependent AUC, and calibration at 1 and 2 years. PFS was the primary endpoint; overall survival analyses were exploratory. The study was not prospectively registered. Results: Higher baseline 25(OH)D was associated with longer PFS in Model B (HR per 10-ng/mL increase, 0.64; 95% CI, 0.49-0.83; P < .001). Adding 25(OH)D improved model fit (likelihood-ratio χ² = 12.71; P < .001) and increased apparent C-index from 0.712 to 0.740. In external validation, C-indices were 0.71 (95% CI, 0.64-0.78) and 0.76 (95% CI, 0.69-0.83), respectively (Δ = 0.05; 95% CI, 0.01-0.10). Conclusions: Baseline 25(OH)D added modest prognostic information beyond clinical factors, with supportive external validation. These findings do not establish treatment-predictive utility or benefit from vitamin D supplementation. Prospective validation is needed before clinical implementation.

Background: Chronological age may influence immune function, but individuals of the same age may differ in biological aging. We evaluated the association between biological age and clinical outcomes in patients with solid tumors treated with immune checkpoint inhibitor monotherapy. Methods: This retrospective two-center study included 302 patients with advanced solid tumors receiving ICI monotherapy. Biological age was estimated using the Levine PhenoAge model. Age-adjusted biological aging (PhenoAgeAccel) was defined as the residual from regression of PhenoAge on chronological age. Survival outcomes were compared according to PhenoAgeAccel status. Results: The median age was 67 years; most patients had non–small cell lung cancer (78.5%) or renal cell carcinoma (18.5%). Median progression-free survival was 3.8 months (95% CI, 3.1–4.5) in patients with PhenoAgeAccel > 0, versus 7.7 months (95% CI, 5.6–9.7) in those with PhenoAgeAccel ≤ 0 ( p < 0.001). Median overall survival was 7.1 months (95% CI, 5.5–8.8) in patients with PhenoAgeAccel > 0, versus 20.4 months (95% CI, 15.1–25.8) in those with PhenoAgeAccel ≤ 0 ( p < 0.001). In multivariate analyses, PhenoAgeAccel remained an independent predictor of overall survival (HR = 2.19, 95% CI: 1.65–2.91; p < 0.001) and progression-free survival (HR = 1.93, 95% CI: 1.47–2.54; p < 0.001). Conclusion: Biological age was strongly associated with survival outcomes in patients receiving immune checkpoint inhibitor monotherapy. These findings require validation in prospective cohorts and may support the integration of biological age as a prognostic biomarker in future immunotherapy trials.

PURPOSE: Capecitabine-induced hand-foot syndrome (HFS) is a frequent toxicity that impairs quality of life and may require chemotherapy dose modification. Although prophylactic topical diclofenac showed benefit in a randomized trial, its effectiveness in routine clinical practice remains uncertain. We evaluated the real-world effectiveness of topical diclofenac for prevention of clinically significant capecitabine-induced HFS. METHODS: DICLO-HFS was a prospective, two-center observational study conducted in Türkiye between July 2023 and February 2024. Adults with colorectal or gastric cancer receiving capecitabine-based therapy were managed with either prophylactic 1% topical diclofenac twice daily or active monitoring according to routine practice. HFS was assessed weekly using Common Terminology Criteria for Adverse Events v5.0 by physicians not involved in treatment allocation. The primary end point was incidence of grade ≥2 HFS. Secondary end points included time to onset of grade ≥2 HFS and capecitabine dose reductions attributable to HFS. RESULTS: A total of 151 patients were included (71 diclofenac; 80 active monitoring). During a median follow-up of 19.1 weeks, grade ≥2 HFS occurred in 12 (16.9%) of 71 patients receiving diclofenac and 11 (13.8%) of 80 patients under active monitoring (odds ratio [OR], 1.28 [95% CI, 0.52 to 3.10]; P = .591). Time to onset did not differ between groups (log-rank P = .392). HFS-related dose reductions occurred in 24 (33.8%) of 71 and 20 (25.0%) of 80 patients, respectively (OR, 1.53 [95% CI, 0.76 to 3.10]; P = .235). In multivariable analysis, female sex and capecitabine monotherapy were independently associated with grade ≥2 HFS. CONCLUSION: In this prospective real-world study, prophylactic topical diclofenac did not reduce clinically significant capecitabine-induced HFS or delay its onset compared with active monitoring. These findings do not support routine diclofenac prophylaxis in everyday practice.

Chemotherapy‐induced peripheral neuropathy (CIPN) is a dose‐limiting toxicity of taxane‐based chemotherapy with limited preventive options. We evaluated whether dual‐site mechanical compression during paclitaxel infusion reduces CIPN in women with gynecologic cancers. In this prospective, intraindividual, self‐controlled study, patients receiving carboplatin–paclitaxel underwent compression of the nondominant hand (two surgical gloves) and ipsilateral lower limb (Class II stocking), while contralateral limbs served as controls. CIPN was assessed using CTCAE v5.0 and EORTC QLQ‐CIPN20 at baseline, Cycle 3, end of treatment (EOT), and 3‐ and 6‐month follow‐up. Among 76 patients (median age, 61 years), moderate‐to‐severe CIPN was observed less frequently in compression limbs than in control limbs at Cycle 3 (35.5% vs. 53.9%; p = 0.001), EOT (59.2% vs. 69.7%; p = 0.021), 3 months (28.9% vs. 52.6%; p = 0.015), and 6 months (20.3% vs. 33.8%; p = 0.002). Repeated‐measures analyzes showed significant time‐by‐limb interactions for sensory ( p = 0.003), lower‐extremity sensory ( p = 0.018), and motor domains ( p = 0.041). Sensory CIPN20 scores were lower in compression limbs in the upper extremities from EOT onward (7.5 vs. 10.2; p < 0.001) and in the lower extremities at 3‐month (8.7 vs. 10.7; p < 0.001) and 6‐month follow‐up (7.0 vs. 10.0; p < 0.001). EORTC QLQ‐CIPN20 sensory scores identified grade ≥ 2 neuropathy with AUC values > 0.92 at all time points. Dual‐site mechanical compression was associated with reduced incidence and persistence of CIPN. As a low‐cost and scalable intervention, this strategy may improve treatment tolerability and survivorship outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT07105553