Researcher: Taşkıran, Çağatay
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Taşkıran, Çağatay
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Publication Metadata only The risk of recurrence in endometrial cancer patients with low-volume metastasis in the sentinel lymph nodes: a retrospective multi-institutional study(MDPI, 2023) Buda, Alessandro; Paniga, Cristiana; Taskin, Salih; Mueller, Michael; Zapardiel, Ignacio; Fanfani, Francesco; Puppo, Andrea; Casarin, Jvan; Papadia, Andrea; De Ponti, Elena; Grassi, Tommaso; Mauro, Jessica; Turan, Hasan; Gungor, Mete; Ortag, Firat; Imboden, Sara; Garcia-Pineda, Virginia; Mohr, Stefan; Siegenthaler, Franziska; Perotto, Stefania; Landoni, Fabio; Ghezzi, Fabio; Scambia, Giovanni; Fruscio, Robert; Vatansever, Doğan; Taşkıran, Çağatay; School of MedicineThe surgical management of apparent early-stage endometrial cancer is still unclear. Nodal involvement is prognostic, but the role of retroperitoneal staging is still debated. Sentinel node mapping has been introduced and accepted as a valid alternative to full lymphadenectomy. Furthermore, ultrastaging provides a more accurate analysis of the excised lymph nodes by detecting a higher rate of low-volume metastasis. The aim of this study was to evaluate the impact of low-volume metastasis on recurrence-free survival in women with apparent early-stage endometrial cancer in a large retrospective multi-institutional collaboration.The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.Publication Metadata only Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer(Academic Press Inc Elsevier Science, 2023) Pignata, Sandro; Bookman, Michael; Sehouli, Jalid; Miller, Austin; Penson, Richard T.; Anderson, Charles; Hietanen, Sakari; Myers, Tashanna; Madry, Radoslaw; Willmott, Lyndsay; Lortholary, Alain; Thomes-Pepin, Jessica; Aghajanian, Carol; Mccourt, Carolyn; Stuckey, Ashley; Wu, Xiaohua; Nishio, Shin; Copeland, Larry J.; He, Yvette; Molinero, Luciana; Patel, Sheetal; Lin, Yvonne G.; Khor, Victor K.; Moore, Kathleen N.; Taşkıran, Çağatay; School of MedicineObjective: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer. Methods: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically. Prespecified PRO analyses focused on disease-related abdominal pain and bloating symptoms (European Organisation for Research and Treatment of Cancer QLQ-OV28), functioning, and health-related quality of life (HRQoL) (QLQ-C30). Results. After 38 months' median follow-up, the OS hazard ratio in the PD-L1-positive population was 0.83 (95% CI, 0.66-1.06; p= 0.13); median OSwas not estimablewith atezolizumab versus 49.2monthswith placebo. The hazard ratio for OS in the ITT population was 0.92 (95% CI, 0.78-1.09; median 50.5 versus 46.6 months, respectively). At week 9, similar proportions of patients in both arms of the neoadjuvant cohort showed >= 10-point improvement from baseline in abdominal pain and bloating, functioning, and HRQoL. In the primary surgery cohort, similar proportions of patients in each arm had improved, stable, or worsened physical and role function and HRQoL from baseline over time. Neither cohort showed differences between arms in treatment-related symptoms or overall side-effect bother. Conclusions: Incorporation of atezolizumab into standard therapy for newly diagnosed ovarian cancer does not significantly improve efficacy or impose additional treatment burden for patients.Publication Metadata only Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study(BMJ Publishing Group, 2023) Cucinella, Giuseppe; Schivardi, Gabriella; Zhou, Xun Clare; Alhilli, Mariam; Wallace, Sumer; Wohlmuth, Christoph; Baiocchi, Glauco; Tokgozoglu, Nedim; Raspagliesi, Francesco; Buda, Alessandro; Zanagnolo, Vanna; Zapardiel, Ignacio; Jagasia, Nisha; Giuntoli, Robert; Glickman, Ariel; Peiretti, Michele; Lanner, Maximilian; Chacon, Enrique; Di Guilmi, Julian; Pereira, Augusto; Laas-Faron, Enora; Fishman, Ami; Nitschmann, Caroline C.; Kurnit, Katherine; Moriarty, Kristen; Joehlin-Price, Amy; Lees, Brittany; Covens, Allan; De Brot, Louise; Bogani, Giorgio; Landoni, Fabio; Grassi, Tommaso; Paniga, Cristiana; Multinu, Francesco; De Vitis, Luigi Antonio; Hernández, Alicia; Mastroyannis, Spyridon; Ghoniem, Khaled; Chiantera, Vito; Shahi, Maryam; Fought, Angela J.; McGree, Michaela; Mariani, Andrea; Glaser, Gretchen; Taşkıran, Çağatay; School of MedicineObjective: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. Methods: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. Results: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. Conclusions: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.Publication Open Access Influence of genomic landscape on cancer immunotherapy for newly diagnosed ovarian cancer: biomarker analyses from the IMagyn050 randomized clinical trial(American Association for Cancer Research Inc., 2023) Landen, Charles N.; Molinero, Luciana; Hamidi, Habib; Sehouli, Jalid; Miller, Austin; Moore, Kathleen N.; Bookman, Michael; Lindemann, Kristina; Anderson, Charles; Berger, Regina; Myers, Tashanna; Beiner, Mario; Reid, Thomas; Van Nieuwenhuysen, Els; Green, Andrew; Okamoto, Aikou; Aghajanian, Carol; Thaker, Premal H.; Blank, Stephanie V.; Khor, Victor K.; Chang, Ching-Wei; Lin, Yvonne G.; Pignata, Sandro; Taşkıran, Çağatay; School of MedicinePurpose: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial. Patients and Methods: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed deathligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay.HRDwas defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates. Results: Among biomarker-evaluable samples, 22% (234/1,050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1,024) had TMB ≥10 mut/Mb, and 0.3% (3/1,022) were MSIhigh. PFS was better in BRCA2-mutated versus BRCA2-nonmutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on ICs) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab inBRCA1-mutated tumors. Conclusions: Mostovariantumorshave lowTMBdespiteBRCA1/ 2mutations orHRD. NeitherBRCA1/2mutation norHRDpredicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors.Publication Open Access Patients with gynecological malignancies are similar to other IVF patients without cancer for clinical and molecular reproductive parameters and DNA damage response pattern(Nature Portfolio, 2024) Turan, Volkan; Esmaeilian, Yashar; Yusufoğlu, Sevgi; İltümür, Ece; Uğurlu Çimen, Deniz; Vatansever, Doğan; Taşkıran, Çağatay; Yakın, Kayhan; İncir, Said; Urman, Cumhur Bülent; Öktem, Özgür; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; Koç University HospitalThis study intended to investigate if gynecological cancers compromise ovarian function and reduce the success of assisted reproduction techniques (ART). No clinical and molecular data together is available on this issue for gynecological or other organ cancers. Steroidogenic pathways and DNA damage response characteristics of the granulosa cells retrieved from the 39 gynecological cancer patients were analyzed together with their clinical ART characteristics in comparison to 31 control ART patients. Patients with gynecological malignancies were similar to the control IVF patients for the number of mature oocytes retrieved, fertilization rates and embryo development competency. Molecular analyses of the granulosa cells retrieved from these cancer patients did not detect any perturbations in gonadotropin receptor expression and response, sex steroid production, cholesterol utilization/storage and, DNA damage response pattern in comparison to control IVF patients without cancer. This study provides the first reassuring clinical and molecular combined data set that the presence of gynecological malignancy does not appear to have any detrimental effect on clinical IVF cycle characteristics and ovarian functioning at molecular level.Publication Metadata only Correspondence on 'cardiophrenic and costophrenic lymphadenectomy in advanced ovarian cancer by prediaphragmatic subxiphoid approach: PS technique' by Stanciu(BMJ Publishing Group, 2024) Taşkıran, Çağatay; Bilir, Esra; Giray, Burak; Vatansever, Doğan; School of MedicinePublication Metadata only Identification of germline variants in 546 breast/ ovarian cancer families: complementary testing with multigene NGS and MLPA panels(Springernature, 2024) Celik, Levent; Karanlik, Hasan; Atalay, Can; Kaban, Kerim; Igci, Abdullah; Saraçoğlu, Hilal Pırıl; Börklü Yücel, Esra; Altunoğlu, Umut; Selçukbiricik, Fatih; Ertürk, Kayhan; Vatansever, Doğan; Laçin, Şahin; Tunalı, Didem; Avcı, Şahin; Ağcaoğlu, Orhan; Dilege, Ece; Taşkıran, Çağatay; Mandel, Nil Molinas; Kayserili, Hülya; Eraslan, Serpil; Graduate School of Health Sciences; School of Medicine; Koç University HospitalPublication Metadata only ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease(Elsevier, 2024) Ledermann, J. A.; Matias-Guiu, X.; Amant, F.; Concin, N.; Davidson, B.; Fotopoulou, C.; Gonzalez-Martin, A.; Gourley, C.; Leary, A.; Lorusso, D.; Banerjee, S.; Chiva, L.; Cibula, D.; Colombo, N.; Croce, S.; Eriksson, A. G.; Falandry, C.; Fischerova, D.; Harter, P.; Joly, F.; Lazaro, C.; Lok, C.; Mahner, S.; Marme, F.; Marth, C.; McCluggage, W. G.; Mcneish, I. A.; Morice, P.; Nicum, S.; Oaknin, A.; Perez-Fidalgo, J. A.; Pignata, S.; Ramirez, P. T.; Ray-Coquard, I.; Romero, I.; Scambia, G.; Sehouli, J.; Shapira-Frommer, R.; Sundar, S.; Tan, D. S. P.; van Driel, W. J.; Vergote, I.; Planchamp, F.; Sessa, C.; Fagotti, A.; Taşkıran, Çağatay; School of MedicineThe European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early -stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.Publication Metadata only The clinical utility of a pulsed bipolar system and its electrosurgical device during total laparoscopic hysterectomy(Mary Ann Liebert, Inc., 2017) N/A; N/A; Mısırlıoğlu, Selim; Türkgeldi, Engin; Boza, Ayşen; Öktem, Özgür; Ata, Mustafa Barış; Urman, Cumhur Bülent; Taşkıran, Çağatay; Doctor; Faculty Member; Doctor; Faculty Member; Faculty Member; Faculty Member; Faculty Member; N/A; School of Medicine; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; N/A; Koç University Hospital; N/A; N/A; N/A; N/A; N/A; 329649; N/A; 102627; 232576; 12147; 134190Objective: The aim of this research was to evaluate the efficacy and safety of the PlasmaKinetic (PK) PKS OMNI (R) (Gyrus ACMI, Maple Grove, MN) sealing device in laparoscopic hysterectomy. Materials and Methods: For this retrospective observational study, 60 patients who underwent multiport total laparoscopic hysterectomy between January 2014 and January 2015 in a tertiary-care university-based teaching hospital and an academically affiliated hospital were included in this study. The PKS OMNI is a bipolar electrosurgical device that takes energy from a PK generator workstation G400. This pulsed wave system has two different modes; cutting (High Cut 1,2,3) and coagulation (Vaporization 1,2,3). Results: Records of 60 patients were analyzed. The median age was 50 (range: ages 40-84), median body mass index was 26kg/m(2) (range: 22-32kg/m(2)), and median parity was 2 (range: 1-8). The median total operation time was 100 minutes (range: 70-240 minutes), estimated blood loss was 80mL (range: 30-250mL), and uterine weight was 207g (range: 50-900g). Degree of Surgical Difficulty and postoperative pain scores at rest were evaluated with a visual analogue scale system, from 0 to 10, and the medians of these scores were 5 (range: 3-7) and 4 (range: 2-6), respectively. The median recovery time of bowel movement was 16 hours (range: 8-26 hours), median spontaneous urination time was 7 hours (range: 4-29 hours), and median postoperative mobilization time was 8 hours (range: 6-10 hours). Conversion to laparotomy was needed in 1 patient due to severe pelvic adhesions. The median duration of hospital stay was 2 days (range: 2-4 days). Vaginal cuff dehiscence was detected in 1 (1.7%) patient who engaged in sexual intercourse on the 122nd day after surgery. Cuff cellulitis in 1 (1.7%) patient and unexplained fever in 1 (1.7%) patient were the other recorded complications. The median follow-up time was 12 months (range: 6-17 months). Conclusions: The PKS OMNI is a novel, underused energy modality that promotes quick recovery and acceptable operation time with minimal blood loss.Publication Metadata only Intraoperative endoscopic ultrasound guidance for laparoscopic excision of invisible symptomatic deep intramural myomas(Taylor & Francis Inc, 2018) Boza, Ayşen; Aksu, Sertan; Arslan, Tonguç; Urman, Cumhur Bülent; Ata, Mustafa Barış; Taşkıran, Çağatay; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; 12147; 182910; 134190The aim of this study was to evaluate the feasibility of intraoperative endoscopic ultrasound guidance for excision of symptomatic deep intramural myomas that are not otherwise visible at laparoscopy. Seventeen patients with symptomatic deep intramural myomas who underwent laparoscopic myomectomy with intraoperative endoscopic ultrasound guidance were followed up and reported. All myomas were removed successfully. The endometrium was breached in one patient. All patients were relieved of their symptoms and three patients presenting with infertility conceived. There were no short- or long-term complications associated with the procedure. One patient who had multiple myomas necessitated intravenous iron treatment prior to discharge. Laparoscopic removal of small symptomatic deep intramural myomas is facilitated by the use of intraoperative endoscopic ultrasound that enables exact localisation and correct placement of the serosal incision. IMPACT STATEMENT What is already known on this subject: When the myoma is symptomatic, compressing the endometrium, does not show serosal protrusion and is not amenable to hysteroscopic resection, laparoscopic surgery may become challenging. What do the results of this study add: The use of intraoperative endoscopic ultrasound under these circumstances may facilitate the procedure by accurate identification of the myoma and correct placement of the serosal incision. What are the implications of these findings for clinical practice and/or further research: Intraoperative ultrasound should be more oftenly used to accurately locate deep intramural myomas to the end of making laparoscopy feasible and possibly decreasing recurrence by facilitating removal of otherwise unidentifiable disease.