Esin Oktay

Background/Objectives: Oral mucositis (OM) is a serious toxicity that develops due to cancer treatment and impairs patients’ quality of life. Ankaferd Hemostat (AH), a phytotherapeutic agent, has anti-inflammatory and tissue-healing properties. This study evaluated the clinical outcomes and safety of topical AH in adult patients with solid tumors who developed grade 3 or 4 OM during systemic anticancer therapy. Methods: A single-center retrospective, single-arm study was conducted between 2020 and 2024 and included 43 patients with solid tumors. They developed OM while undergoing systemic cancer therapy and were treated with topic AH. Mucositis severity was graded using the World Health Organization (WHO) OM scale, and pain intensity was assessed using a Numeric Rating Scale (NRS) daily, from baseline until clinical resolution. Treatment response, recovery time and adverse events were analyzed. Results: Of the 43 patients included in the study, 81.4% had grade 3 OM and the others had grade 4 OM. Grade 0 was observed in 86% of patients after treatment. Among the 37 patients achieving Grade 0, median time to recovery was 4 days (IQR 4–5). The median NRS score was 5 points before treatment and 0 after treatment (p < 0.001). No Grade ≥ 2 adverse events were observed. Only one patient reported mild dry mouth. Conclusions: In this retrospective cohort, AH mouthwash was associated with rapid mucosal recovery and no severe adverse events were documented in patients with high-grade OM, supporting its potential to reduce oncological treatment toxicity; prospective controlled studies are warranted to confirm these findings.

Background: Neuroendocrine prostate cancer (NEPC) is a rare and aggressive malignancy with limited prognostic tools. The Lung Immune Prognostic Index (LIPI), derived from dNLR and lactate dehydrogenase, has demonstrated prognostic value in small-cell lung cancer but has not been evaluated in NEPC. This study assessed the prognostic role of LIPI in NEPC. Methods: This multicenter retrospective study included 34 patients with NEPC (21 secondary, 13 de novo) from four centers in Turkey. Laboratory data were collected at NEPC diagnosis (T3), initial prostate cancer diagnosis (T1), and castration-resistant prostate cancer diagnosis (T2). LIPI was scored using original fixed cut-offs. Survival analyses included Kaplan–Meier, Cox regression, and ROC methods. Results: At NEPC diagnosis, 18 patients (52.9%) had Good LIPI and 16 (47.1%) Intermediate + Poor LIPI. Intermediate + Poor LIPI was associated with significantly shorter overall survival (median 4 vs. 15 months; log-rank p = 0.001; HR 3.83, 95% CI 1.65–8.90). In multivariable analysis, albumin was an independent predictor (HR 0.37, p = 0.015), while LIPI showed a trend (HR 2.35, p = 0.091). LIPI demonstrated the highest discriminatory ability for 6-month overall survival (AUC 0.763, p = 0.009). LIPI at earlier disease stages did not predict time to transformation or castration resistance. Among secondary NEPC patients, worsening LIPI trajectory was associated with shorter survival (median 4 vs. 10 months; log-rank p = 0.031). Conclusions: LIPI at NEPC diagnosis was associated with overall survival and demonstrated the highest discriminatory ability among the inflammatory indices assessed. As a routine blood-based score, LIPI may support risk stratification at NEPC diagnosis. Prospective validation is warranted.

Background: Alternative immune checkpoints such as lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and V-domain Ig suppressor of T-cell activation (VISTA) have emerged as potential modulators of tumor immune escape. However, their expression patterns and prognostic significance in advanced laryngeal squamous cell carcinoma (LSCC) remain insufficiently characterized. This study aimed to evaluate LAG-3, TIM-3, and VISTA expression on tumor-infiltrating lymphocytes (TILs), examine their association with CD8+ TIL density and clinicopathological features, and determine their impact on survival outcomes. Methods: In this retrospective observational cohort study, 132 patients who underwent total or partial laryngectomy for stage III–IV LSCC were included. Tissue microarrays were constructed using three 2 mm cores per case. Immunohistochemical expression of LAG-3, TIM-3, VISTA, and CD8 was assessed exclusively on TILs. Survival outcomes were analyzed using Kaplan–Meier and Cox proportional hazards models. Results: LAG-3, TIM-3, and VISTA positivity rates were 26.5%, 51.5%, and 53.8%, respectively. High CD8+ TIL density was observed in 69.7% of cases. Significant positive correlations were identified among checkpoint markers (all p < 0.05); VISTA positivity did not significantly correlate with CD8 infiltration (r = 0.149, p = 0.088). LAG-3 positivity was associated with lower thyroid cartilage invasion (p = 0.006). Kaplan–Meier analysis demonstrated no significant differences in overall survival (OS) or disease-free survival (DFS) according to checkpoint expression or CD8 status. In multivariable analysis, extranodal extension (HR = 2.719, p = 0.005) and thyroid cartilage invasion (HR = 1.970, p = 0.043) were independent predictors of worse OS. CD8 negativity showed a trend toward adverse OS (HR = 1.825, p = 0.084). None of the immune markers independently predicted DFS. Conclusions: In advanced surgically treated LSCC, LAG-3, TIM-3, and VISTA expression correlate with CD8+ TIL density but do not independently predict survival outcomes. These findings suggest that alternative immune checkpoint expression reflects immune engagement rather than intrinsic tumor aggressiveness and may hold greater predictive than prognostic relevance in LSCC.

This retrospective study provides valuable insights into the impact of HER2 status on treatment outcomes in advanced gastric cancer patients receiving first-line chemotherapy plus trastuzumab. The research focused on comparing two groups of HER2-positive patients: those with IHC 2+/FISH positive status and those with IHC 3+ status. The study's cohort consisted of 144 patients, with 45 (31.3%) identified as HER2 positive. Among the HER2-positive patients, 12 (26.7%) were classified as IHC 2+/FISH positive, while 33 (73.3%) were classified as IHC 3+. The researchers assessed diverse clinical and pathological aspects, encompassing patient characteristics, neoplasm positioning, and histological variants. They also explored therapeutic outcomes and long-term survival data. The study's findings revealed no significant differences in treatment efficacy between the two HER2-positive groups. Objective response rates and disease control rates were comparable, with 50% vs. 75% vs. 51.5% and 75.8%, respectively (p=0.946). Progression-free survival was similar, with a median of 8.5 months in the IHC 2+/FISH positive group and 9.6 months in the IHC 3+ group (p=0.87). Overall survival also showed no statistically significant difference, with median durations of 13.2 months and 16.2 months for the IHC 2+/FISH positive and IHC 3+ groups, respectively (p=0.38). These results suggest that the efficacy of first-line chemotherapy plus trastuzumab in advanced gastric cancer is comparable across different HER2-positive statuses, indicating that this treatment approach may be equally effective for patients with either IHC 2+/FISH positive or IHC 3+ HER2 status. This information is crucial for clinicians in making informed decisions regarding treatment strategies for HER2-positive advanced gastric cancer patients.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors such as palbociclib have improved the treatment of hormone receptor-positive, luminal A breast cancer; however, therapeutic resistance remains a major challenge. Wild-type p53-induced phosphatase 1 (Wip1) is a negative regulator of the p53 pathway and is often over-expressed in luminal breast cancers. This study aimed to determine whether Wip1 inhibition enhances the anti-proliferative and pro-apoptotic effects of the CDK4/6 inhibitor palbociclib in luminal A breast cancer cells and to elucidate the underlying cell cycle-related mechanisms. MCF-7 cells were treated with palbociclib and Wip1 inhibitor GSK2830371, alone or in combination. Cell viability was assessed using the WST-1 assay, cell cycle distribution was analysed by flow cytometry, and apoptosis was evaluated using Annexin V/7-aminoactinomycin D staining. Expression of cell cycle regulators (CDK2, CDK4, CDK6, cyclin D1/D3, Rb, phospho-Rb) and p53-related proteins (p53, phospho-p53 Ser15, p21, p27) was determined by Western blot analysis. The combined treatment produced a concentration-dependent reduction in cell viability and a marked increase in both early and late apoptotic populations compared with monotherapies. While palbociclib alone induced G1 arrest, co-treatment with GSK2830371 shifted cells toward G2 accumulation. This was accompanied by enhanced phosphorylation of p53, up-regulation of p21 and p27, and dephosphorylation of Rb, indicating dual checkpoint engagement. These findings demonstrate that Wip1 inhibition augments palbociclib-mediated cell cycle arrest and apoptosis through modulation of the p53-Rb axis. The dual blockade of Wip1 and CDK4/6 may represent a promising therapeutic strategy for p53-proficient luminal A breast cancer.

Background and Objectives: Small-cell lung cancer (SCLC) is an exceedingly aggressive neoplasm distinguished by an unfavorable prognosis. Recent studies have confirmed chemo-immunotherapy as the conventional first treatment for extensive-stage small-cell lung cancer (ES-SCLC), but the impact of treatment duration remains unclear. The goal of this study was to find out how the length of treatment affected progression-free survival (PFS) and overall survival (OS) in patients with ES-SCLC who were receiving first-line atezolizumab plus chemotherapy. Materials and Methods: This retrospective multicenter study comprised 82 patients from six oncology centers in Turkey between 2017 and 2024. Patients were categorized into two categories according to the quantity of chemotherapy cycles they had undergone: standard treatment (≤4 cycles) and extended treatment (≥5 cycles). For the purpose of analyzing survival outcomes and related clinical determinants, as well as the demographic structures and features of the patients, both univariate and multivariate Cox regression models were utilized. Results: The median number of atezolizumab cycles was 8 (1–63). OS was 29.46 months after 15.8 months of follow-up, while PFS was 10.63 months. When comparing the two groups, we found no statistically significant differences in either PFS (p = 0.952) or OS (p = 0.374). Significant associations with OS were seen in the standard therapy group for both ECOG PS 1 (p = 0.028). Thoracic radiation considerably decreased progression risk (HR = 0.41, p = 0.031) in the extended group. Conclusions: While prolonging chemo-immunotherapy beyond four cycles did not significantly improve survival, the selected patient subgroups may benefit from personalized approaches. Thoracic radiotherapy emerged as a key modifier of outcome.

Objective: The aim of this study is to investigate the usability of microRNA16-5P and 221-3P levels as biomarkers in determining thyroid cancers. Material and Methods: Patients who underwent thyroid surgery due to suspicious thyroid nodules were included in the study. A total of 142 patients who agreed to participate in the study had 3-5 cc venous blood taken into EDTA tubes and biochemistry tubes before the operation. In the postoperative period, 68 patients with malignant pathology results and 74 patients with benign pathology results were grouped as the control group. miRNA16-5p and miRNA221-3p levels were measured in serum samples taken from the patients. The levels of miRNA levels in malignant and benign patient groups were analyzed. Results: The miRNA 16-5p and miRNA221-3p levels of malignant patients were statistically significantly lower than those of benign patients (p

Background One of the major dilemmas in the treatment of renal cell carcinoma (RCC) is the resistance to therapy that leads to a state of unresponsiveness, which is observed after a certain period. Among the potential causes of this, the impact of autophagy activation and the resulting endoplasmic reticulum (ER) stress due to the accumulation of misfolded or unfolded proteins has not been previously investigated. Methods Patients treated in medical oncology clinics of a total of 3 centers between January 2011 and May 2022 were included. In the pathology preparations of a total of 83 patients diagnosed with metastatic RCC, we examined the effects of autophagy activation induced by mTOR inhibition through the analysis of LC3 and Beclin1 molecules, the differentiation from classical apoptosis pathways with the Bcl-2 level, the hypoxic condition with the HIF-1α level, and ER stress with the eukaryotic initiation factor 2α (eIF2α) level. Results İn our study, found no significant effects of LC3 (p = 0.298), Beclin1 (p = 0.287), Bcl-2 (p = 0.435), and HIF-1α (p = 0.179) levels on either progression-free survival or overall survival. However, eIF2α (p = 0.017) was found to be a significantly decisive factor. Conclusion Based on these results, we suggest that eIF2α may serve as a novel biomarker to predict survival and treatment response in metastatic RCC patients.

Aim: This study aimed of our study is to investigate the factors affecting the level of arterial stiffness in cancer patients receiving immunotherapy. Materials and Methods: The height, weight, BMI, age, gender, type of cancer, previous cancer treatment, agents used in the treatment, current immunotherapy agents, comorbid conditions, smoking history of 42 patients diagnosed with renal cell carcinoma (RCC), lung cancer, malignant melanoma and receiving immunotherapy treatment were recorded at the time of their first application and their arterial stiffness levels were measured. Following the first measurement, the patients were seen again in the third and sixth therapy cycles and their measurements were repeated and recorded. Factors affecting the arterial stiffness level of the patients were evaluated. Results: It was observed that pulse wave velocity (NWV) increased with increasing age (p

Amaç: Küçük hücreli akciğer kanserinde (KHAK) yaklaşık 50 yıldır standart birinci basamak tedavi platin bazlı kemoterapi ile kombine etoposid rejimidir. Atezolizumabın yaygın evre KHAK birinci basamak tedavisinde kemoterapi ile kombine kullanımı yakın zamandan sağkalımı iyileştirdiği randomize bir çalışmada gösterilmiştir. Immunoterapi tedavisi uygulanmayan KHAK’li hastalara standart 6 kür platin bazlı kemoterapi uygulanarak en etkili sağkalım sonuçlarına ulaşılırken, atezolizumabın randomize çalışmasında standart 4 kür kemoterapi uygulanmıştır. Bu retrospektif çalışma, yaygın evre KHAK birinci basamak tedavisinde 6 kür kemoterapi ile kombine atezolizumabın gerçek yaşam verilerini sunmayı amaçlamaktadır. Gereçler ve Yöntemler: Çalışmaya kliniğimizdeki yaygın evre KHAK tanılı ve birinci basamak indüksiyon fazında karboplatin-etoposid artı atezolizumab ile kombine minimum 6 siklus tedavi alan hastalar dahil edildi. İndüksiyon fazı tamamlanan hastalara idame fazında atezolizumab 1200 mg 3 haftada bir uygulandı. İndüksiyon fazında 6 siklus atezolizumab ile kombine kemoterapiden az tedavi alan hastalar ile laboratuvar verileri eksik olan hastalar çalışma dışı bırakıldı. Hastaların özellikleri, uygulanan tedaviler ve tedaviye yanıt oranları ile sağ kalım verileri incelendi. Sağkalımı verilerini belirlemek için Kaplan-Meier testi kullanıldı ve metastaz bölgelerinin etkileri log-rank testi kullanılarak analiz edildi. Bulgular: Kriterleri karşılayan 24 hasta dahil edildi. Ortanca yaş 64 idi ve üçte ikisinde komorbid hastalık vardı. Medyan kemoterapi döngüsü sayısı 6 (6-12) ve atezolizumab döngüsü 8 (6-54) idi. Medyan 9,4 aylık takipten sonra medyan progresyonsuz sağkalım (PFS) ve genel sağkalım (OS) sırasıyla 9.5 ay (%95 GA 0.0-25.8) ve 30,1 aydı (%95 GA 3.26-57.004). Genel yanıt oranı %87.5 idi. Metastatik bölge sayısı (p = 0.77) ile OS arasında anlamlı bir fark bulunamadı. Hastaların yarısından fazlasında derece 3 yan etki gözlendi. En sık yan etkiler hematolojikdi ve toksisiteler yönetilebilirdi. Sonuç: Bu gerçek yaşam verileri, yaygın evre KHAK birinci basamak tedavisinde indüksiyon fazında en az altı siklus kemoterapi ile kombine atezolizumab etkiliğini ve güvenliliğini doğrulamaktadır.