Person: YUMUK, PERRAN FULDEN
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YUMUK
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PERRAN FULDEN
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Publication Open Access Role of baseline Ga-68-PSMA PET/CT-derived whole-body volumetric parameters in predicting survival outcomes of metastatic castration-resistant prostate cancer patients receiving first-line treatment(2022-08-01) AKIN TELLİ, TUĞBA; ÖZGÜVEN, SALİH; FİLİZOĞLU, NUH; ÖZTÜRK, MEHMET SAADEDDİN; ARIKAN, RUKİYE; DEMİRCAN, NAZIM CAN; BAŞOĞLU TÜYLÜ, TUĞBA; ALSAN ÇETİN, İLKNUR; ÖNEŞ, TUNÇ; DANE, FAYSAL; YUMUK, PERRAN FULDEN; AKIN TELLİ T., ÖZGÜVEN S., Alan O., Filizoglu N., ÖZTÜRK M. S. , Sariyar N., Isik S., Arikan R., DEMİRCAN N. C. , BAŞOĞLU TÜYLÜ T., et al.Objective We aimed to evaluate whether baseline Ga-68-PSMA PET/CT-derived whole-body volumetric parameters could be used as predictive biomarkers for survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line treatment. Materials and methods This retrospective study included 54 mCRPC patients, who underwent baseline Ga-68-PSMA PET/CT imaging within 1 month before starting first-line treatment. Pre-treatment prostate-specific antigen (PSA) levels and treatments were recorded. SUVmax, SUVmean, whole-body PSMA-derived tumor volume (wbPSMA-TV), and whole-body total lesion PSMA (wbTL-PSMA) were calculated for all patients. PSA response was defined as a decline of >= 50% from pre-treatment value at 12 weeks. Overall survival (OS) was measured from the start of the first-line treatment for mCRPC. Results Docetaxel and abiraterone/enzalutamide were administered to 32 and 22 patients in the first-line setting, respectively. wbPSMA-TV (rho = 0.582, p = 0.004) and wbTL-PSMA (rho = 0.564, p = 0.007) showed moderate positive correlations with PSA levels. Older age (p = 0.02), higher wbPSMA-TV (p = 0.007), higher PSA (p = 0.01), higher number of bone metastases (p = 0.02), and lack of PSA response (p = 0.03) were significantly associated with an increased risk of mortality. Multivariate analysis determined wbPSMA-TV (HR: 1.003, 95% CI 1.001-1.004, p = 0.001) and PSA response (HR: 2.241, 95% CI 1.189-4.222, p = 0.01) as independent predictors of OS. Conclusion The wbPSMA-TV may be a useful tool to reflect tumor burden and predict survival outcomes in patients with mCRPC.Publication Metadata only Prognostic Role of Immune Markers in Triple Negative Breast Carcinoma(SPRINGER, 2020) KAYA, HANDAN; Sahin Ozkan, Hulya; Ugurlu, Mustafa Umit; Yumuk, Perran Fulden; Kaya, HandanTumor immune microenvironment (TIME) is a significant prognostic parameter for triple negative breast carcinomas (TNBC) due to being a target for immunotherapeutic agents and its essential role during the cancer immunoediting process. In this study, CD8, FOXP3, CD163, PD-L1/SP142 and PD-L1/SP263 antibodies were examined in a sample of 51 TNBC cases. Patients who received neoadjuvant therapy were excluded. CD8, FOXP3 and CD163 antibodies were evaluated separately in intratumoral area (ITA) and tumor stroma (TS). PD-L1 status was also examined in tumor cells (TC) and immune cells (IC) using both SP142 and SP263 antibodies. In multivariate Cox regressions, the only antibody that was found to be significantly associated with survival was SP142. SP142-positivity in TC and IC was related to increased overall survival. Higher CD163 expression in ITA and SP263-positivity in IC were associated with younger age. Lymphatic/angioinvasion was more frequent in cases with negative/low CD8 and FOXP3 expressions. Moreover, metastatic axillary lymph node(s) was associated with negative/low FOXP3 expression in TS. CD8, FOXP3, CD163, SP142 and SP263 expressions were positively correlated with each other, except a mild discordance caused by CD163 in ITA. Although PD-L1 status with both SP142 and SP263 antibodies were concordant in the majority of cases, 33.3% and 13.7% of the cases showed SP142-negative/SP263-positive pattern in TC and IC respectively. In conclusion, we suggest that composition, density and localization of the immune cells and the check point molecules are important prognostic parameters in TNBC. Immunohistochemistry can be used as an accessible and less expensive tool to demonstrate TIME.Publication Metadata only Differences in PET/CT standardized uptake values involvement and survival compared to histologic subtypes of lung adenocarcinoma(SAGE PUBLICATIONS LTD, 2021) BOZKURTLAR, EMİNE; Ercelep, Ozlem; Alan, Ozkan; Telli, Tugba A.; Tuylu, Tugba B.; Arikan, Rukiye; Demircan, Nazim Can; Simsek, Eda T.; Babacan, Nalan A.; Kaya, Serap; Dane, Faysal; Bozkurtlar, Emine; Ones, Tunc; Lacin, Tunc; Yumuk, Perran FuldenPurpose: Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes. Methods: We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes. Results: The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p= 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p= 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p= 0.000). There was no significant difference in OS between histologic subtypes (p= 0.66), but PFS was significantly different between the groups (p= 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes. Conclusion: Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.Publication Metadata only QT interval prolongation related to afatinib treatment in a patient with metastatic non-small-cell lung cancer(MOSBY-ELSEVIER, 2020) KOCAKAYA, DERYA; Demircan, Nazim Can; Telli, Tugba Akin; Tuylu, Tugba Basoglu; Arikan, Rukiye; Kocakaya, Derya; Sahin, Ahmet Anil; Ercelep, Ozlem; Dane, Faysal; Yumuk, Perran FuldenAfatinib improves survival in metastatic non-small-cell lung cancer driven by activating epidermal growth factor receptor mutations. QT interval prolongation is a possible side effect of tar geted anticancer drugs, but this has not been reported before with afatinib. We report a case of metastatic pulmonary adenocarcinoma with epidermal growth factor receptor exon 19 deletion who was treated with first-line afatinib. The patient was started on afatinib with a total dose of 40 mg/day and experienced grade 3 (> 500 ms) QT interval prolongation in the seventh week. Dose was interrupted and then reduced to 30 mg/day after the event repeated. QT prolongation occurred only once with the reduced dose and radiologic oligoprogression was detected. Local therapy was performed and afatinib was continued as 30 mg/day. To the best of our knowledge, this case marks the first QT interval prolongation associated with afatinib. It is prudent to perform a baseline cardiologic evaluation and electrocardiogram monitoring in non-small cell lung cancer patients treated with this drug. (c) 2020 Elsevier Inc. All rights reserved.Publication Metadata only Multicenter real life clinical outcomes of pdl-1 tested patients with non small cell lung cancer (NSCLC) in Turkey(2022-09-01) YUMUK, PERRAN FULDEN; Yazici O., Gurler F., Acar R., Gurbuz M., Guven D. C. , Tuylu T. B. , Araz M., Kilickap S., Erturk I., Senler F. C. , et al.Publication Metadata only A rare case of gastric cancer with bilateral breast metastasis during pregnancy(SAGE PUBLICATIONS LTD, 2021) MEMİŞOĞLU, ASLI; Basoglu, Tugba; Telli, Tugba Akin; Demircan, Nazim Can; Arikan, Rukiye; Ercelep, Ozlem; Ozguven, Salih; Soysal, Sunullah; Memisoglu, Asli; Dane, Faysal; Yumuk, Perran FuldenBackground Gastric cancer is rare during pregnancy and often diagnosed at a later stage due to overlapping symptoms of pregnancy. Breast metastasis of gastric cancer is another uncommon entity. We present a rare case of breast metastasis of gastric cancer during pregnancy. Case report A 26-year-old female was diagnosed with gastric cancer at 14 weeks of gestation and underwent total gastrectomy. She rejected adjuvant chemotherapy and continued pregnancy without any follow-up. Cancer recurred in bilateral breasts at 34th week of gestation mimicking primary inflammatory breast cancer. Management and outcome It was difficult to diagnose breast metastasis during pregnancy because of overlapping pregnancy symptoms. Following an unresponsive period to antibiotherapy, a fine needle biopsy on breast was performed and signet cell adenocarcinoma metastasis was determined. We started chemotherapy after delivery. There was a near complete response after first line of chemotherapy. Unfortunately, cancer was relapsed within three months and we started second-line chemotherapy. Discussion To our knowledge, this is the fourth case reported in medical literature of gastric cancer presented with breast metastasis during pregnancy. We will try to draw attention to diagnosis, treatment and different presentation of gastric cancer during pregnancy with review of the literature.Publication Metadata only Response Assessment With Molecular Characterization of Circulating Tumor Cells and Plasma MicroRNA Profiling in Patients With Locally Advanced Breast Cancer During Neoadjuvant Chemotherapy(CIG MEDIA GROUP, LP, 2020) ERZİK, CAN; Akkiprik, Mustafa; Koca, Sinan; Ugurlu, M. Umit; Ekren, Ruchan; Eyuboglu, Irem Peker; Alan, Ozkan; Erzik, Can; Amuran, Gokce Gullu; Telli, Tugba Akin; Gulluoglu, M. Bahadir; Sezerman, Ugur; Yumuk, Perran FuldenPeripheral blood samples from 36 patients with locally advanced breast cancer who had undergone neoadjuvant chemotherapy were collected for circulating tumor cell (CTC) and plasma microRNA (miR) analysis. Pretreatment CTC and ALDH1 positivity (P = .0245) correlated, with miR-146b-5p and miR-199a-5p accompanied by CTC positivity. CTC and miR profiling of serial samples during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course. Background: Cells detaching from the primary tumor site are metastasis initiator cells, and the detection of CTC, known as liquid biopsy, is an important test of biomarkers of cancer progression. We investigated the molecular characterization of circulating tumor cells (CTCs), profiled the plasma microRNA (miR) content, and analyzed the relationship with the clinical outcomes by sampling the peripheral blood from patients with locally advanced breast cancer before and after neoadjuvant chemotherapy. Patients and Methods: Markers of breast cancer, epithelial-mesenchymal transition (EMT), drug resistance, and stem cells were used for CTC isolation and characterization. Plasma miR profiles were obtained from selected patients with CTC positivity determined using next-generation sequencing. Resutts: The proportion of CTC, EMT, and stem cell marker positivity was 16.7%, 8.3%, and 25% before and 18.2%, 15.2%, and 9.1% after treatment, respectively. A significant correlation was found between the pretreatment CTCs and ALDH1 positivity (P= .0245). These CTCs with stemness properties were observed in most hormone receptor-positive, human epidermal growth factor receptor 2 -negative cases and were also present with a high incidence in cases of early metastasis. miR-146b-5p and miR-199a-5p, which are involved in metastasis, invasion, and EMT, were accompanied by CTC positivity, and miR-4646-3p was associated with the development of early metastasis. Conclusions: Molecular characterization of CTCs and miR profiling of serial samples from patients with locally advanced breast cancer during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course and might be a key to developing new targeted therapies. (C) 2020 Elsevier Inc. All rights reserved.Publication Open Access Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma(2021) ÖZTÜRK, FATİH EMİN; Başoğlu, Tuğba; Akar, Kadriye Ebru; Bağcı, Pelin; Akgül Babacan, Nalan; Öztürk, Mehmet Akif; Öztürk, Fatih Emin; Demircan, Nazım Can; Arikan, Rukiye; Akın Telli, Tuğba; Ercelep, Özlem; Dane, Faysal; Yumuk, Perran FuldenBACKGROUND: Pancreatic ductal adenocarcinoma differs from other solid tumors with its unique immunosuppressive microenvironment and non-immunogenic feature. There are not many studies in the literature investigating the effect of these features on prognosis. AIM: To investigate the prognostic value of tissue-resident memory cells, tumor microenvironment features, and tumor-associated immune cells in resected pancreatic ductal adenocarcinomas. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Of 138 patients diagnosed with pancreatic ductal adenocarcinoma between 2011 and 2018, 81 were included in the study. Specimens from operated patients were reassessed separately as peritumoral and intratumoral areas for tissue resident memory and tumor microenvironmental elements (tumor infiltrating lymphocytes, tumor stroma, CD204+ macrophages, PDL1+ immune cells). Disease-free survival and overall survival were defined from the date of operation to the date of recurrence and the date of first diagnosis to the date of death, respectively. If the patient was alive, the last visit date was taken into account. RESULTS: The median age at diagnosis was 63 (range: 40-78). The median follow-up period was 18.9 months (range 1.4-80.4 months). Median overall survival was 23.7 months (1.4-80.4 months) and median disease-free survival was 10.8 months (1.4-74.4 months). Patients with higher intra-tumoral tissue-resident memory cell counts had a longer survival trend than those having lower values (25.6 months vs. 18 months, respectively, P = .84). According to microenvironmental evaluations, lower stromal score (defined as stroma having less desmoplasia and rich in cells) and presence of peritumoral Crohn's-like inflammatory response were associated with higher survival (29.2 months vs. 19.7 months for low vs. high stromal scores, respectively, P = .16 and 30.2 months vs. 18.1 months for the presence of Crohn's-like inflammatory response P = .13). Decreased survival was observed in tumors with increased CD204+ tumor-associated macrophages which were immunosuppressive elements of the microenvironment (12 months vs. 26.3 months for intra-tumoral assessment, P = .29). CONCLUSION: Tissue-resident memory cells and other microenvironmental features may be prognostic in resectable pancreatic ductal adenocarcinomas. Further studies with larger cohorts are needed for validation.Publication Metadata only Enzalutamide versus Abiraterone Acetate as first-line treatment of castration resistant metastatic prostate cancer in geriatric (>= 75) patients(IMR PRESS, 2021) YUMUK, PERRAN FULDEN; Alkan, Ali; Guc, Zeynep Gulsum; Gurbuz, Mustafa; ozgun, Guliz; Degirmencioglu, Serkan; Dogan, Mutlu; Telli, Tugba Akin; Keskin, Ozge; Arslan, Cagatay; Bilgin, Burak; Goksu, Sema Sezgin; Demir, Hacer; Koksoy, Elif Berna; Kostek, Osman; Erturk, Ismail; Sakalar, Teoman; Yasar, Arzu; Turkkan, Gorkem; Kasim, Bu ra; Karaoglu, Aziz; oksuzoglu, Berna cakmak; Yumuk, Fulden; Sendur, Mehmet Ali; Coskun, Hasan Senol; cicin, Irfan; Karadurmu, Nuri; Tanriverdi, Ozgur; Akbulut, Hakan; Urun, YukselIntroduction: The efficacy and tolerability of Enzalutamide and Abiraterone Acetate have been reported in elderly patients with metastatic castration resistant prostate cancer (mCRPC). However, there is no randomized study directly comparing antitumor effects between these 2 agents in geriatric patients. We aimed to evaluate the efficacy of Enzalutamide (ENZA) and Abiraterone Acetate (AA) as a first-line treatment of mCRPC in elderly patients. Materials and methods: The geriatric patients (>= 75 years of age) with a diagnosis of mCRPC and treated with first-line ENZA or AA were included. The impacts of clinical parameters and treatment modalities on overall survival (mOS) were analyzed retrospectively and Cox regression analysis was performed. Results: One hundred thirty-four mCRPC patients (77 in AA, 57 in ENZA), with a median age of 81 (75-93) were analyzed. The patient and disease characteristics were similar between arms. While there were more grade 1-2 toxicities in AA arm (45.5% vs 17.5%, P = 0.001), the discontinuation due to toxicity was similar between groups (8.5% vs 5.9%, P = 0.81). The mOS was 18.0 months (95% CI, 15.2-20.7) in AA, and 20.0 months (95% CI, 4.4-35.5) in ENZA arm (P = 0.47). In multivariate analysis, high Gleason score (>= 8) (HR: 2.0 (95% CI, 1.1-3.4), P = 0.009) and high initial PSA values (>= 100 ng/mL) (HR: 2.6 (95% CI, 1.5-4.8), P = 0.001) were poor prognostic factors. The choice of AA vs ENZA was insignificant as a predictor of OS (HR: 0.87 (95% CI, 0.48-1.56), P = 0.65). Conclusion: In the first-line treatment of mCRPC in elderly (>= 75) patients, AA and ENZA showed similar results in terms of mPFS and mOS. The clinical impacts of second-generation androgen receptor pathway inhibitors in the elderly population should be tested in prospective randomized studies.Publication Open Access Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: the single-arm, open-label REGARD study(BMJ PUBLISHING GROUP, 2020-03) DANE, FAYSAL; Dane, Faysal; Ozgurdal, Kirhan; Yalcin, Suayib; Benekli, Mustafa; Aykan, Nuri Faruk; Yucel, Idris; Ozkan, Metin; Evrensel, Turkkan; Sevinc, Alper; Coskun, Hasan Senol; Sanli, Ulus Ali; Kara, Ismail Oguz; Yumuk, Perran FuldenObjectives Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC. Design Open-label, single-arm, phase IIIb study conducted between July 2013 and April 2015. Setting 11 tertiary centres in Turkey. Participants Eligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status <= 1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male. Interventions Patients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity. Primary and secondary outcome measures The primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints. Results The median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77% had a grade >= 3 TEAE. The most common grade >= 3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand-foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8). Conclusion The regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC.