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 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 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 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 Real-world assessment of quality-of-life in patients with breast cancer treated with adjuvant endocrine therapy(2022-07-01) ARIKAN, RUKİYE; BAŞOĞLU TÜYLÜ, TUĞBA; DANE, FAYSAL; YUMUK, PERRAN FULDEN; KÖSTEK, OSMAN; AKIN TELLİ T., ÖZTÜRK M. S., Alan O., Hasanov R., KÖSTEK O., Arikan R., BAŞOĞLU TÜYLÜ T., Kaya S., Ercelep O., Babacan N. A., et al.Objective: The aim of this study was to investigate quality-of-life (QoL) in breast cancer (BC) patients treated with adjuvant endocrine therapy (AET). Methods: We designed a cross-sectional study of 233 BC patients treated with AET and used the Functional Assessment of Cancer Therapy - Breast questionnaire. Results: No significant difference was observed between endocrine agents. Duration of AET did not affect QoL. In the entire cohort, multivariate analysis determined age (p = 0.034) and switching treatment from tamoxifen to aromatase inhibitors (p = 0.049) as significant positive coefficients of QoL, while comorbidity (p = 0.072) tended to be associated with lower scores. Education level (p = 0.001) and chemotherapy (p = 0.04) were significant predictors of QoL in the tamoxifen group, while comorbidity (p = 0.04), surgery type (p = 0.02), radiotherapy (p = 0.006) and stage (p = 0.009) had a significant impact on QoL in aromatase inhibitors group. Conclusion: Evaluating the well-being of BC patients by QoL questionnaires is of great importance to identify particular subgroups that may require supportive care.Publication Open Access Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?(BMC, 2020-12) DANE, FAYSAL; Alan, Ozkan; Akin Telli, Tugba; Aktas, Bilge; Koca, Sinan; Okten, Ilker Nihat; Hasanov, Rahib; Basoglu, Tugba; Arikan, Rukiye; Demircan, Nazim Can; Ercelep, Ozlem; Kaya, Serap; Ugurlu, Mustafa Umit; Kaya, Handan; Akgul Babacan, Nalan; Dane, Faysal; Yumuk, Perran FuldenPurpose Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. Methods Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin x fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. Results Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2),p= 0.01]. Conclusion Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.Publication Metadata only Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience(SAGE PUBLICATIONS LTD, 2021) ATASOY, BESTE MELEK; Alan, Ozkan; Telli, Tugba Akin; Tuylu, Tugba Basoglu; Arikan, Rukiye; Demircan, Nazim Can; Ercelep, Ozlem; Kaya, Serap; Babacan, Nalan Akgul; Atasoy, Beste M.; Bozkurt, Suheyla; Bayri, Yasar; Gul, Dilek; Ekinci, Gazanfer; Ziyal, Ibrahim; Dane, Faysal; Yumuk, P. FuldenPurpose Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. Methods Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. Results At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). Conclusion Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.Publication Metadata only Modified Glasgow Prognostic Score, Prognostic Nutritional Index and ECOG Performance Score Predicts Survival Better than Sarcopenia, Cachexia and Some Inflammatory Indices in Metastatic Gastric Cancer(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2021) DANE, FAYSAL; Demirelli, Bulent; Babacan, Nalan Akgul; Ercelep, Ozlem; Ozturk, Mehmet Akif; Kaya, Serap; Tanrikulu, Eda; Khalil, Suleyman; Hasanov, Rahib; Alan, Ozkan; Telli, Tugba Akin; Koca, Sinan; Aribal, Mustafa Erkin; Kuzan, Beyza; Dane, Faysal; Yumuk, Perran FuldenBackground: Gastric carcinoma (GC) patients usually present with locally advanced or metastatic disease; therefore treatment aim is mainly palliation. In this study our purpose is to analyze the prognostic values of the sarcopenia index (SI), cachexia index (CIn) and other inflammatory indexes (advanced lung cancer inflammation index [ALI], modified Glasgow Prognostic Score [mGPS], prognostic index [PI], prognostic nutritional index [PNI] and neutrophil-to-lymphocyte ratio [NLR]) in metastatic GC patients. Methods: Data from the files of metastatic GC patients, who applied to Medical Oncology outpatient clinic in Marmara University Pendik Education and Research Hospital between January 2011 and June 2016, were retrospectively reviewed. Five hundred seventy patients with gastric cancer were detected. Exclusion criteria were the inability to reach the patient surveys for prognostic index calculations, the presence of additional comorbidities to affect the laboratory parameters, and the absence of metastatic disease. Finally, 87 of these patients were included in this study. For SI calculation L3 level muscle area was measured from patients' computed tomography (CT) by a radiologist. SI reference value was obtained from western-EGWSOP (The European Working Group on Sarcopenia in Older People) and eastern (Harada Y, et al.) sources separately, as Turkey doesn't have a reference value for SI. NLR cutoff value was accepted as the median value of patients' NLR measurements. Statistical analysis was conducted using SPSS. Kaplan-Meier and Cox regression models were used to assess independent prognostic factors. The area under the curve was used to compare the prognostic value of indexes. Results: The median length of follow-up of 87 patients was nine months (1-64 mo,/s), and 78 patients died during follow-up. Fifty-nine patients were male (63%), and the median age was 62 (range, 23-88). According to univariate analysis high mGPS and PI score, PNI level <45, NLR level >= 3.41, ALI level <18, CI level under 35, SI (Harada Y, et al) <= 44.5 for males and <= 36.5 for females, ECOG score >= 2, weight loss more than 10% during last 6 mo, BMI under 24 were poor prognostic factors. Age, gender, having multiple organ metastasis, history of gastric surgery, positivity C-erb-B2, SI (EGWSOP) <= 52.4 for males, and <= 38.4 for females did not have any impact on survival. According to multivariate analysis, high mGPS (score 2) (HR 2,494, 95% CI 1.25-4 .94, p = 0.02), PNI (score 1) (HR 4.2, 95% CI 1.73-10.1, p < 0.001) and ECOG score (>= 2) (HR 1.541, 95% CI 1,089-4,214, p = 0.004) have been found to be independent prognostic factors which are determining the survival. mGPS was found to be more valuable than other indexes for predicting mortality by measuring the AUC with ROC analysis. Conclusions: In our study, mGPS, PNI and ECOG score were independent indicators for shorter survival in metastatic gastric cancer patients. mGPS and PNI, which can be done by using only serum CRP, albumin level and complete blood count, might be inexpensive, practical and beneficial to use in routine clinical practice to determine survival.