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 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 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 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 Open Access 5-Flourouracil-Induced Encephalopathy in Parkinson's Disease(AKAD DOKTORLAR YAYINEVI, 2012-03-31) DANE, FAYSAL; Korkmaz, Taner; Seber, Selcuk; Basaran, Gul; Yumuk, P. Fulden; Dane, Faysal; Kocar, Muharrem; Telli, Ferhat; Turhal, N. SerdarA 59 year-old male with Parkinson's disease developed encephalopathy during adjuvant treatment of rectal cancer. Acute neurotoxicity related to high dose 5-Flourouracil infusion is well described, but encephalopathy with low dose bolus 5-Flourouracil is rare. The advanced Parkinson's disease patients may be more prone to hyperammonemia associated encephalopathy caused by 5-Flourouracil. The prompt recognition of the symptoms is key to diagnosis and treatment.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.Publication Metadata only Clinical outcome of breast cancer patients with N3a (>= 10 positive lymph nodes) disease: has it changed over years?(HUMANA PRESS INC, 2011) DANE, FAYSAL; Basaran, Gul; Devrim, Cabuk; Caglar, Hale B.; Gulluoglu, Bahadir; Kaya, Handan; Seber, Selcuk; Korkmaz, Taner; Telli, Ferhat; Kocak, Muharrem; Dane, Faysal; Yumuk, Fulden P.; Turhal, Serdar N.It has been shown that breast cancer patients with N3a (10 positive lymph nodes) had a poor prognosis. We planned to investigate the clinical outcome BC patients who presented with N3a disease and had no evidence of systemic metastasis at the time of diagnosis. We made a retrospective chart review of breast cancer patients who had a parts per thousand yen10 positive lymph nodes and received adjuvant systemic therapy in Marmara University Hospital between 1998 and 2008. We recorded clinical, pathologic and treatment characteristics of the patients and analyzed the survival outcome. We identified 73 patients with N3a disease who were treated in Marmara University Hospital between 1998 and 2008. The median age was 52. Most (75%) of the patients had invasive ductal histology, 75% had T2/T3 tumors, 36% had grade 3 tumors. The median number of metastatic lymph nodes was 15. Estrogen and progesterone receptors were both positive in 61% and both negative in 16+ tumors. Her-2/neu status was assessed in 68% of the tumors; 18% of patients had 3+ and 50% had negative scores. Six patients had triple negative tumors. All patients except one received adjuvant chemotherapy and radiotherapy. Seventy-four percent of patients received anthracycline/taxane-based chemotherapy. Fifty-nine patients received adjuvant endocrine therapy, 42% them received aromatase inhibitors. Five of the 13 Her-2 positive patients received adjuvant trastuzumab. With a median follow-up of 47 months, 5-year disease and overall survival rates were 66 and 81%, respectively. Twenty-four patients had relapsed and 14 patients died. Her-2 status and the number of lymph nodes (< 20 vs. a parts per thousand yen20) had significant impact on disease-free survival in the univariate analysis (P = 0.03 and 0.05, respectively) and Her-2 retained its significant impact on disease-free survival in the multivariate analysis (P = 0.05). The prognosis of BC patients with N3a disease has changed favorably in the past decade with the current standards of care.