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 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 Open Access Efficacy and safety of perioperative FLOT (5-FU, LV, oxaliplatin, docetaxel) chemotherapy in gastric and gastroesophageal junction adenocarcinoma: Real-life data from Turkish oncology group(ELSEVIER, 2021-09) YUMUK, PERRAN FULDEN; Erol, C.; Basoglu, T.; Sakin, A.; Ozden, E.; Cubuk, D.; Yumuk, P. F.; Dogan, M.; Oksuzoglu, B.; Yildirim, H. C.; Oner, I.; Eryilmaz, M. Karakurt; Dulgar, O.; Bekmez, E. Turkmen; Dogan, N.; Ozen, M.; Gurler, F.; Paksoy, N.; Aksoy, A.; Hizal, M.; Sendur, M. A. N.Publication Open Access Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group)(2022-01-01) YUMUK, PERRAN FULDEN; Erol C., Sakin A., Başoglu T., Özden E., ÇABUK D., Doğan M., Öksüzoğlu B., YILDIRIM H. Ç. , Öner İ., Karakurt Eryilmaz M., et al.© TÜBİTAK.Background/aim: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. Materials and methods: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. Results: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5–20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3–4 toxicity was seen in 23.6% patients. Conclusion: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.Publication Open Access Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: A Turkish oncology group study(2023-01-01) BAŞOĞLU TÜYLÜ, TUĞBA; YUMUK, PERRAN FULDEN; BAŞOĞLU TÜYLÜ T., Sakin A., Erol C., Ozden E., ÇABUK D., Cilbir E., Tataroglu ozyukseler D., Ayhan M., Sendur M. A., Dogan M., et al.Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice. Clinicians should tailor treatment regimens according to patients\" multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.Publication Open Access Practicality and potential restrictions of unresectable hepatocellular carcinoma prognostic index(2022-09-01) DEMİRTAŞ, COŞKUN ÖZER; ÖZDOĞAN, OSMAN CAVİT; BALTACIOĞLU, FEYYAZ; ÖNEŞ, TUNÇ; YUMUK, PERRAN FULDEN; DULUNDU, ENDER; GÜNDÜZ, FEYZA; DEMİRTAŞ C. Ö. , Ricco G., ÖZDOĞAN O. C. , BALTACIOĞLU F., ÖNEŞ T., YUMUK P. F. , DULUNDU E., Uzun S., Colombatto P., Oliveri F., et al.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 Open Access Proposal and Validation of a Novel Scoring System for Hepatocellular Carcinomas Beyond Curability Borders(JOHN WILEY & SONS LTD, 2022-03) DEMİRTAŞ, COŞKUN ÖZER; Demirtas, Coskun Ozer; Ricco, Gabrielle; Ozdogan, Osman Cavit; Baltacioglu, Feyyaz; Ones, Tune; Yumuk, Perran Fulden; Dulundu, Ender; Uzun, Sinan; Colombatto, Pierro; Oliveri, Filippo; Brunetto, Maurizia Rosanna; Gunduz, FeyzaOptimal scoring system for clinical prognostic factors in patients with unresectable hepatocellular carcinoma (HCC) is currently uncertain. We aimed to develop and externally validate an easy to use tool, particularly for this population, and named it the unresectable hepatocellular carcinoma prognostic index (UHPI). We evaluated the data of patients with treatment-naive unresectable HCC who were diagnosed in the training center from 2010 to 2019 (n = 209). A simple prognostic model was developed by assigning points for each covariate in proportion to the beta coefficients in the Cox multivariable model. Predictive performance and distinction ability of the UHPI were further evaluated in an independent European validation cohort (n = 147) and compared with 11 other available models. A simple scoring system was derived, assigning 0.5/1/2 scores for six independent covariates including, the Child-Pugh score, Eastern Cooperative Oncology Group performance status, maximum tumor size, vascular invasion or extrahepatic metastasis, lymph node involvement, and alpha-fetoprotein. The UHPI score, ranging from 0 to 6, showed superior performance in prognosis prediction and outperformed 11 other staging or prognostic models, giving the highest homogeneity (c-index, 6-month and 1-year area under the receiver operator characteristic curves), lowest Akaike information criterion, and -2 log-likelihood ratio values. The UHPI score allocated well the risk of patients with unresectable HCC for mortality within the first year, using two cut-off values (low-risk, <0.5; intermediate-risk, 0.5-2; high-risk, >2). Conclusion: The UHPI score can predict prognosis better than other systems in subjects with unresectable HCC and can be used in clinical practice or trials to estimate the 6-month and 1-year survival probabilities for this group.Publication Open Access An Open-Label, Multinational, Multicenter, Phase IIIb Study with Subcutaneous Administration of Trastuzumab in Patients with HER2-Positive Early Breast Cancer to Evaluate Patient Satisfaction(2022-12-30) YUMUK, PERRAN FULDEN; Cicin, İrfan; Oukkal, Mohammed; Mahfouf, Hassen; Mezlini, Amel; Larbaoui, Blaha; Ahmed, Slim Ben; Errihani, Hassan; Alsaleh, Khalid; Belbaraka, Rhizlane; Yumuk, Perran Fulden; Goktas, Burce; Özgüroğlu, Mustafa