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92 result(s) for "Nahit Şendur, Mehmet"
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Evaluation of the Cellsway Microfluidic CTC Enrichment and Identification Platform for CTC Detection in Metastatic NSCLC
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Standard tissue biopsies are invasive and unsuitable for repeated monitoring. Liquid biopsy technologies, particularly circulating tumor cell (CTC) analysis, offer a minimally invasive alternative for real-time disease tracking. To address the need for efficient and reproducible CTC isolation, we developed the Cellsway microfluidic CTC enrichment and identification platform, which employs inertial hydrodynamics in a spiral-shaped microfluidic channel comprising hydrofoil-shaped pillars to enable high-throughput, label-free enrichment of CTCs while preserving cell integrity, followed by an optimized CTC identification assay. Analytical performance assessed through spiking experiments using NSCLC cell lines demonstrated recovery rates of 91.9% for H1975 cells and 78.3% for A549 cells. Clinical validation was performed on blood samples from 51 stage IV NSCLC patients. A 7.5 mL volume of peripheral blood was processed with the SwayBox platform, and enriched CTCs were identified through an optimized multiplex immunofluorescence protocol. CTCs were detected in 47% of NSCLC patients, with counts ranging from 0 to 72 cells per 7.5 mL of blood. At a cutoff of 1 CTC per 7.5 mL, the assay achieved a specificity of 95%. Patient-derived CTCs exhibited smaller mean diameters compared to cultured NSCLC cell lines, yet were effectively enriched through hydro-dynamic tuning. These findings demonstrate that the Cellsway platform enables efficient and re-producible CTC isolation with high specificity, supporting its potential utility for clinical monitoring and precision oncology in NSCLC.
Long-Term Outcomes of Patients Undergoing Conversion Surgery After Induction Chemotherapy: Turkish Oncology Group Study
Background and Objectives: Conversion surgery for liver metastatic colorectal cancer (mCRC) has been associated with prolonged survival. This study aimed to evaluate the efficacy and safety of integrating biological therapies with fluorouracil-based induction chemotherapy in patients with isolated liver mCRC who subsequently underwent curative resection of both the primary tumor and liver metastases. Materials and Methods: This multicenter, retrospective study, conducted by the Turkish Oncology Group (TOG), included 116 patients from 11 tertiary centers who underwent conversion surgery following induction chemotherapy between 2009 and 2024. Results: The median age was 57 years, with 62% male patients. The median follow-up period was 55.3 months. The median progression-free survival (PFS) and overall survival (OS) were 21.1 and 53.7 months, respectively. No significant differences in PFS or OS were observed based on biological therapy use or tumor localization. Among patients with RAS/RAF wild-type tumors, PFS and OS were comparable between those receiving Anti-EGFR and Anti-VEGF therapy. In RAS/RAF mutant tumors, the addition of Anti-VEGF therapy did not confer a survival benefit. Factors associated with shorter PFS included advanced tumor stage (ypT3-T4), lymph node metastasis, and multiple metastases, while shorter OS was linked to advanced tumor stage and lack of objective response. Conclusions: Surgical resection plays a pivotal role in improving survival outcomes in patients with potentially resectable liver mCRC. Optimizing induction chemotherapy regimens may enhance conversion rates and prolong long-term survival. Further studies are needed to refine treatment selection based on tumor localization, mutation status, and molecular biomarkers.
Navigating second-line therapy in metastatic renal cell carcinoma: a comparative analysis of immune checkpoint inhibitors and tyrosine kinase inhibitors: a study of Turkish Oncology Group Kidney Cancer Consortium
Background: Despite progress in treatment, many metastatic renal cell carcinoma (mRCC) patients still experience progression after first-line tyrosine kinase inhibitor (TKI), necessitating effective second-line options. While guidelines endorse combination therapies, accessibility limitations often restrict therapy to TKI monotherapy. Objectives: Existing decision-making relies on limited evidence, lacking direct comparisons between the leading second-line options (cabozantinib and nivolumab) which surpass everolimus in advanced mRCC. To address this gap, this study compares the efficacy of TKI versus nivolumab in second line while investigating factors influencing outcomes. Design: This was a retrospective cohort study. Methods: Turkish Oncology Group Kidney Cancer Consortium includes more than 1000 mRCC patients from 13 centers in Türkiye. It has the largest national data. We extracted 214 patients treated with a TKI in the first line and nivolumab or TKI in the second line. Results: The median overall survival (OS) and time to treatment failure (TTF) were similar in the TKI-TKI and TKI-immune checkpoint inhibitor (ICI; 41.1 and 44.8 months, p = 0.446 for OS; 27.4 and 29.8 months, p = 0.857 for TTF). The presence of previous nephrectomy for TTF made a significant difference in univariable and multivariable analysis. Bone metastases negatively affected TTF in both univariable and multivariable analyses. In the neutrophil-to-lymphocyte ratio (NLR)-high group, OS and TTF were longer in patients treated with TKI-ICI than in the TKI-TKI. In multivariable analysis, NLR was an independent prognostic factor for OS and TTF to select ICI in the second-line. Conclusion: Our analysis revealed no significant difference in OS between patients receiving ICIs or TKIs as second-line therapy. In the subgroup of patients with elevated NLR, ICI therapy was found to cause no improvement in OS. This finding suggests the potential utility of NLR as a biomarker to guide targeted selection of ICI therapy among patients progressing after first-line TKIs. Furthermore, our study identified other noteworthy prognostic factors influencing outcomes, including the presence of bone or liver metastases, Eastern Cooperative Oncology Group performance status, and International Metastatic Renal Cell Carcinoma Database Consortium risk score.
The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study
Purpose We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). Methods Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. Results Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS ( p = 0.079, and p = 0.147, respectively). Among grade 1–2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1–2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3–4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups ( p = 0.063, and p = 0.210, respectively). Conclusion In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.
The relationship between adjuvant chemotherapy and thiol-disulfide compounds
Aim: Thiols are the organic compounds of the antioxidant system. There is limited data in the literature concerning chemotherapy (CT) in cancer and thiol balance. In this study, we aimed to evaluate the possible changes of thiol/disulfide levels with the recurrent CT cycles and type of cancer. Materials and Methods: The 40 healthy individuals and 40 patients who had been newly diagnosed with early-stage breast, ovary and endometrium cancer receiving adjuvant CT. Blood samples were taken from all patients three times as basal and after the first and second CT sessions. Results: We compared preadjuvant treatment levels of thiol and disulfide parameters in the patients group with the control group. The median of native thiol and total thiol was found to be higher in the control group than in the study group (P < 0.001). In addition, disulfide/native thiol and disulfide/total thiol rates were found to be higher in the patient group (P = 0.001). When we look at the comparison before and after CT in the patient group, disulfide/native thiol and disulfide/total thiol rates, which represent increased oxidative stress (OS) levels were found to be higher after CT than before CT measurement (P < 0.016). Discussion: This is the first study, which has researched the relationship between cancer type and thiol compounds and changes of thiol compounds during CT therapy, by using the method designed by Erel and Neşelioğlu. In this study, we found that pre-CT thiol disulfide balance in cancer patients shifted toward disulfide direction and OS levels may increase after repetitive CT sessions.
An unusual infection with long-term bevacizumab treatment for advanced nonsmall-cell lung cancer: Actinomycosis
Bevacizumab is an angiogenesis inhibitor with Food and Drug Administration approval for multiple tumor types (including colon, nonsquamous nonsmall-cell lung cancer, kidney and glioblastoma multiforme, cervix, and ovarian cancer). Here, we present a patient with actinomycosis who was on treatment with bevacizumab maintenance therapy following chemotherapy combined with bevacizumab. A 60-year-old male patient with lung adenocarcinoma was treated four cycles of carboplatin, paclitaxel with bevacizumab. And then, bevacizumab maintenance therapy was continued. After 38 months of bevacizumab maintenance, computed tomography showed a newly developed cavitary lesion in the upper lobe of the right lung. Bronchoscopy was performed and the pathology report of the biopsy was reported as actinomycosis. Bevacizumab treatment was discontinued and the patient was treated with amoxicillin-clavulanate. To our knowledge, our case is the first case of actinomycosis infection due to the possible bevacizumab treatment.
Real-World Survival Outcomes Following Metastasectomy in RAS Wild-Type mCRC: Insights from a Multicentre National Cohort Study
Background: Metastasectomy is a cornerstone of multimodal management in metastatic colorectal cancer (mCRC), yet contemporary real-world data focusing specifically on RAS wild-type (RAS-WT) disease remain limited. We aimed to evaluate survival outcomes and prognostic factors associated with metastasectomy in patients with RAS-WT mCRC using a large national multicentre registry. Methods: This retrospective cohort study utilized data from the ONKO-KOLON Türkiye registry. A total of 1079 patients with pathologically confirmed KRAS/NRAS wild-type mCRC were identified and categorized according to receipt of metastasectomy. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and compared with log-rank tests across multiple clinically relevant time origins, including metastatic diagnosis, initial colorectal cancer diagnosis, and time of metastasectomy. Prognostic factors within the metastasectomy cohort were assessed using univariate Cox proportional hazards models. Serum CEA and CA19-9 were analyzed after log10 transformation. Results: Among 1079 patients, 185 (17.1%) underwent metastasectomy. Patients receiving metastasectomy demonstrated significantly longer OS compared with those managed non-surgically when survival was calculated from the time of metastatic diagnosis (hazard ratio [HR] for death 0.36, 95% CI 0.27–0.47; p < 0.001), as well as improved PFS (HR for progression or death 0.39, 95% CI 0.30–0.52; p < 0.001). The survival advantage remained consistent when OS was measured from the time of initial colorectal cancer diagnosis (HR 0.37, 95% CI 0.25–0.50; p < 0.001). Median OS following metastasectomy was 43 months (95% CI 31.4–45.6). In univariate analyses within the metastasectomy cohort, higher baseline CA19-9 levels were significantly associated with inferior OS when analyzed both as a continuous variable (per log10 increase; HR 1.81, 95% CI 1.20–2.75; p = 0.005) and as a categorical variable (above vs. below threshold; HR 0.37, 95% CI 0.16–0.86; p = 0.021). Other clinicopathologic factors, including age, CEA, tumor sidedness, grade, MSI status, and metastatic burden, were not significantly associated with survival. Conclusions: In this large, real-world national cohort of RAS-WT mCRC, metastasectomy was strongly associated with prolonged survival across multiple clinically relevant time frames. Within surgically treated patients, baseline CA19-9 emerged as the most informative prognostic marker, while traditional clinicopathologic variables showed limited discriminatory value. These findings highlight the importance of careful patient selection and support further prospective studies integrating molecular and biomarker-based strategies to refine prognostication and optimize surgical decision-making in RAS-WT mCRC.
Predicting hepatocellular carcinoma survival with artificial intelligence
Despite the extensive research on hepatocellular carcinoma (HCC) exploring various treatment strategies, the survival outcomes have remained unsatisfactory. The aim of this research was to evaluate the ability of machine learning (ML) methods in predicting the survival probability of HCC patients. The study retrospectively analyzed cases of patients with stage 1–4 HCC. Demographic, clinical, pathological, and laboratory data served as input variables. The researchers employed various feature selection techniques to identify the key predictors of patient mortality. Additionally, the study utilized a range of machine learning methods to model patient survival rates. The study included 393 individuals with HCC. For early-stage patients (stages 1–2), the models reached recall values ​​of up to 91% for 6-month survival prediction. For advanced-stage patients (stage 4), the models achieved accuracy values ​​of up to 92% for 3-year overall survival prediction. To predict whether patients are ex or not, the accuracy was 87.5% when using all 28 features without feature selection with the best performance coming from the implementation of weighted KNN. Further improvements in accuracy, reaching 87.8%, were achieved by applying feature selection methods and using a medium Gaussian SVM. This study demonstrates that machine learning techniques can reliably predict survival probabilities for HCC patients across all disease stages. The research also shows that AI models can accurately identify a high proportion of surviving individuals when assessing various clinical and pathological factors.
Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group
Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial.