Person: YUMUK, PERRAN FULDEN
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YUMUK
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PERRAN FULDEN
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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 Effect of PET/CT standardized uptake values on complete response to treatment before definitive chemoradiotherapy in stage III non-small cell lung cancer(SPRINGER INTERNATIONAL PUBLISHING AG, 2019) DANE, FAYSAL; Ercelep, O.; Alan, O.; Sahin, D.; Telli, T. A.; Salva, H.; Tuylu, T. B.; Babacan, N. A.; Kaya, S.; Dane, F.; Ones, T.; Alkis, H.; Adli, M.; Yumuk, F.PurposeThe standard treatment for patients with stage III non-small cell lung cancer (NSCLC), unsuitable for resection and with good performance, is definitive radiotherapy with cisplatin-based chemotherapy. Our aim is to evaluate the effect of the maximum value of standardized uptake values (SUVmax) of the primary tumor in positron emission tomography-computed tomography (PET/CT) before treatment on complete response (CR) and overall survival.MethodsThe data of 73 stage III NSCLC patients treated with concurrent definitive chemoradiotherapy (CRT) between 2008 and 2017 and had PET/CT staging in the pretreatment period were evaluated. ROC curve analysis was performed to determine the ideal cut-off value of pretreatment SUVmax to predict CR.ResultsMedian age was 58years (range 27-83years) and 66 patients were male (90.4%). Median follow-up time was 18months (range 3-98months); median survival was 23months. 1-year overall survival (OS) rate and 5-year OS rate were 72 and 19%, respectively. Median progression-free survival (PFS) was 9months; 1-year PFS rate and 5-year PFS rate were 38 and 19%, respectively. The ideal cut-off value of pretreatment SUVmax that predicted the complete response of CRT was 12 in the ROC analysis [AUC 0.699 (0.550-0.833)/P<0.01] with a sensitivity of 83%, and specificity of 55%. In patients with SUVmax<12, CR rate was 60%, while, in patients with SUV12, it was only 19% (P=0.002). Median OS was 26months in patients with pretreatment SUVmax<12, and 21months in patients with SUVmax12 (HR=2.93; 95% CI 17.24-28.75; P=0.087). CR rate of the whole patient population was 26%, and it was the only factor that showed a significant benefit on survival in both univariate and multivariate analyses.ConclusionPretreatment SUVmax of the primary tumor in PET/CT may predict CR in stage III NSCLC patients who were treated with definitive CRT. Having clinical CR is the only positive predictive factor for prolonged survival.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 Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey(HUMANA PRESS INC, 2011) DANE, FAYSAL; Basaran, Gul; Turhal, Nazim Serdar; Cabuk, Devrim; Yurt, Nevin; Yurtseven, Gul; Gumus, Mahmut; Teomete, Mehmet; Dane, Faysal; Yumuk, Perran FuldenWeight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases had statistically significant impact on weight gain following adjuvant therapy in breast cancer patients (P = 0.000, P = 0.008, P = 0.015 and P = 0.017 respectively). This study shows that Turkish women with early breast cancer gain weight after adjuvant systemic therapy, in line with European and American counterparts. This increase in weight is maintained at least one year after adjuvant therapy. Given the adverse consequences of weight gain in terms of both breast cancer prognosis and general health, it is necessary to inform patients about this change and to develop strategies for weight maintenance during and after systemic therapy.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 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 Metadata only Efficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma(SPRINGER, 2011) ATASOY, BESTE MELEK; Abacioglu, Ufuk; Caglar, Hale B.; Yumuk, Perran F.; Akgun, Zuleyha; Atasoy, Beste M.; Sengoz, MericThe current standard therapy for newly diagnosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m(2) for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1-14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8-4.2) and the median OS was 7 months (95% CI 5.1-8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7-32.2) and the 1-year OS rate was 12% (95% CI -1-25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3-4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high-grade glioma previously treated with temozolomide.