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Publication Metadata only A novel and clinically useful weight-optimized dynamic conformal arc in stereotactic radiation therapy of non-small cell lung cancer: dosimetric comparison of treatment plans with volumetric-modulated arc therapy(Elsevier, 2023) N/A; N/A; N/A; Sağlam, Yücel; Selek, Uğur; Bölükbaşı, Yasemin; Other; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; N/A; 27211; 216814Purpose: This study constitutes a feasibility assessment of dynamic conformal arc (DCA) therapy as an alternative to volumetric-modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT) of lung cancer with the free-breathing technique using four-dimensional computed tomography. Methods: A total of 25 patients who received 50 Gy in four fractions treated using VMAT technique having two partial coplanar arcs with 6 MV beams for non-small cell lung cancer (NSCLC) were included. Plans were re-planned using a novel and clinically technique of weight optimized based on dynamic conformal Arcs with two coplanar partial dynamic conformal arcs (WO-DCA). For the two partial arcs, MLC aperture around the PTV was automatically generated at different margins for both arcs and maintained dynamically around the target during arc rotation. Weight of the two arcs using optimization method was adjusted between the arcs to maximize tumor coverage and protect organs at risk (OAR). The clinical VMAT and WO-DCA plans were compared via the RTOG-0915 protocol for conformity and dose to the organs at risk (OAR). Additionally, delivery efficiency, quality assurance pass rate, monitor unit and beam treatment time were recorded. Results: The mean value of quality assurance (QA) pass rate 98.16 ± 1.27 in WO-DCA and 92.87 ± 1.56 in VMAT. The rate was higher in WO-DCA (p < 0.001 and t = 8.75). The values of beam-on time (BOT) and monitor units (MU) in the VMAT technique were 4.20 (3.45–4.95) and 3155 (2279–4867) and they were 3.10 (2.85–3.35) and 2167 (1702–2948) in WO-DCA. These values were significantly improved with WO-DCA (p < 0.001 and p < 0.001) Conclusions: As there is, no beam modulation through the target, WO-DCA plans could potentially minimize small-field dosimetry error without MLC interplay effects via respiratory motion and provide similar doses to OAR and the tumor while providing faster treatment delivery by significantly reducing MU and BOT in lung cancer for tumors of appropriate localization. Additionally, providing WO-DCA eliminate patient-specific VMAT quality assurance; potentially offering cost-effective, same day SBRT treatments.Publication Metadata only Approachment to the postmenopausal adnexal masses(Günes Kitap Kırtasiye, 2016) Yılmaz, Ercan; Coşkun, Ebru İnci; Taşkıran, Çağatay; Faculty Member; School of Medicine; 134190The masses originated from the adnexia can be seen in almost every period of the female reproductive era, they can also be pathological or sometimes physiological lesions. Since these can be seen in postmenopausal period and can be prone to be malignant, these lesions have a big importance. It is critical to evaluate the malignancy potential of these masses especially before the surgery in postmenopausal women. Fort his purpose, a lot of tests or criteria like anamnesis, family history, imaging methods and laboratory tests are being used. Besides, it is also very important to decide to choose the kind of management; follow up or surgery for the cystic lesions which have malignant and benign characteristics. The variation of the surgical modalities, affect and change a lot of factors like survival time and operation time. In this review, it has been aimed to discuss the most suitable management and therapeutic options for the masses especially detected in the postmenopausal period. Additionally, it is attempted to highlight some wrong management pathways for suggestion.Publication Metadata only Association between high initial CEA, CA 19-9 levels and HER-2 status and their prognostic values on overall survival in metastatic gastric cancer(Zerbinis Publications, 2021) Tural, Deniz; Selçukbiricik, Fatih; Ertürk, Kayhan; Balık, Emre; Kuvvet, Fadime Buket Bayram; Celayir, Özde Melisa; Babashov, Farid; Şentürk, Begüm Güler; Mandel, Nil Molinas; Faculty Member; Faculty Member; Faculty Member; Doctor; Doctor; Doctor; Researcher; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 202015; N/A; 18758; 176242; 329382; N/A; 327593; 194197Purpose: This study aimed to investigate the correlations between baseline levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) and immunohistochemical (IHC), Human epidermal growth factor receptor (HER-2) expressions; and question their prognostic values in patients with metastatic gastric cancer. Methods: Gastric cancer patients were retrospectively analyzed. Demographic information, clinical stages, immunohistochemical HER-2 expressions and serum CEA, serum CA 19-9 levels were evaluated at the time of diagnosis. The correlations between HER-2 IHC expressions and the initial marker levels were assessed, and survival analyses were performed. Results: A total of 411 patients were included in the study. Median age of patients was 58 years (range: 22-90); males: 297 (72.3%); females: 114 (27.7%). Median overall survival (OS) was 24 months (range: 19-29). Patient HER-2 IHC expression 0, 1, 2, 3 ratios were 43, 22, 16, and 19%, respectively. At the time of diagnosis, the median value of CEA was 4 (range: 3-5), and the median value of CA 19-9 was 18 (range: 14-22). The increase in CEA and CA 19-9 levels were correlated with the increase of IHC levels (p=0.0001). OS of patients with high initial CEA levels (>5 ng/mL) were significantly shorter than those with low initial CEA levels (<5 ng/mL). Conclusion: Significant positive correlations were shown between HER-2 IHC expressions and CEA, CA 19-9 levels. Baseline CEA, CA 19-9 levels predicted HER-2 positivity and this directly affected treatment and OS.Publication Metadata only Breast cancer screening services: trade-offs in quality, capacity, outreach, and centralization(Springer Nature, 2004) Chick, Stephen E.; Güneş, Evrim D.; Department of Business Administration; Karaesmen, Zeynep Akşin; Faculty Member; Department of Business Administration; College of Administrative Sciences and Economics; 4534This work combines and extends previous work on breast cancer screening models by explicitly incorporating, for the first time, aspects of the dynamics of health care states, program outreach, and the screening volume-quality relationship in a service system model to examine the effect of public health policy and service capacity decisions on public health outcomes. We consider the impact of increasing standards for minimum reading volume to improve quality, expanding outreach with or without decentralization of service facilities, and the potential of queueing due to stochastic effects and limited capacity. The results indicate a strong relation between screening quality and the cost of screening and treatment, and emphasize the importance of accounting for service dynamics when assessing the performance of health care interventions. For breast cancer screening, increasing outreach without improving quality and maintaining capacity results in less benefit than predicted by standard models.Publication Metadata only Collecting duct carcinoma: epidemiology, clinical characteristics and survival(Elsevier Inc., 2023) Panunzio, Andrea; Tappero, Stefano; Hohenhorst, Lukas; Cano Garcia, Cristina; Piccinelli, Mattia; Barletta, Francesco; Tian, Zhe; Tafuri, Alessandro; Briganti, Alberto; De Cobelli, Ottavio; Chun, Felix K.H.; Terrone, Carlo; Kapoor, Anil; Saad, Fred; Shariat, Shahrokh F.; Cerruto, Maria Angela; Antonelli, Alessandro; Karakiewicz, Pierre I.; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/AIntroduction: Collecting duct carcinoma (CDC) is a rare renal malignancy. We relied on a large population-based cohort to address epidemiology, clinical characteristics, and treatment of CDC patients. We also tested survival in the overall cohort, as well as in stage-specific fashion. Materials and methods: Within Surveillance, Epidemiology, and End Results (2004–2018) database, we identified 399 CDC patients. Based on Kaplan-Meier plots survival estimates, conditional survival rates were derived according to disease stage. Cox regression models tested for predictors of cancer specific mortality (CSM). Results: Overall, 273 (68.4%) patients were male, 236 (59.2%) had T3-4 stages, 148 (37.1%) had lymph node invasion, and 156 (39.1%) had distant metastases at initial diagnosis. Nephrectomy alone was commonest in stage I-II (n = 91/99, 92%) and III (n = 94/116, 81%). Combination of both nephrectomy and systemic therapy was commonest in stage IV (n = 62/172, 36%). In the overall cohort, median cancer specific survival was 18 months. Provided a disease-free interval of 24 months, five-year Kaplan-Meier estimated survival at diagnosis increased from 74.2 to 91.0% in stage I–II, from 31.1 to 65.3% in stage III, and from 6.3 to 34.1% in stage IV. In multivariable Cox regression models addressing CSM, systemic therapy (Hazard Ratio [HR]: 0.47, P = 0.020), nephrectomy (HR: 0.37, P < 0.001) and combination of both (HR: 0.28, P < 0.001) exhibited a strong protective effect. Conclusion: Despite its highly aggressive phenotype and dismal survival, CDC is sensitive to nephrectomy and/or systemic therapy. Moreover, even for advanced stage, a more favorable prognosis can be achieved in patients, who benefit of disease-free interval after diagnosis and initial treatment.Publication Metadata only Crizotinib and PARP inhibitors act synergistically by triggering apoptosis in high-grade serous ovarian cancer(2019) Jönsson, Jenny-Maria; Hedenfalk, Ingrid; N/A; Şahin, İrem Durmaz; Faculty Member; School of Medicine; 303825High-grade serous ovarian cancer (HGSOC) is the predominant and most lethal histological type of epithelial ovarian cancer. During the last few years, several new treatment options with PARP inhibitors have emerged. The FDA has approved the PARP inhibitor olaparib (Lynparza™) as maintenance treatment after first-line platinum-containing chemotherapy and olaparib, niraparib (Zejula™) and rucaparib (Rubraca™) are approved as maintenance therapies in the recurrent, platinum-sensitive setting; nevertheless, development of resistance limits their efficacy. In this study, new combinatorial treatment strategies targeting key signaling pathways were explored to enhance the activity of PARP inhibitors in HGSOC. Carboplatin, olaparib, niraparib, the PI3K inhibitor LY294002 and the c-Met inhibitor crizotinib were used for this investigation. PARP inhibitors and carboplatin alone and in combination caused accumulation of DNA double-strand breaks and G2/M cell cycle arrest. In contrast, crizotinib alone or in combination with PARP inhibitors induced accumulation of cells in sub-G1. Crizotinib together with either of the PARP inhibitors was more strongly synergistic than combinations with a PARP inhibitor and carboplatin or the PI3K inhibitor. Sequential combination of crizotinib and a PARP inhibitor resulted in activation of ATM/CHK2 and inhibition of c-Met pathways, contributing to a decrease in RAD51 levels and induction of caspase-3 dependent apoptotic cell death and suggesting that the combination of crizotinib with a PARP inhibitor may be considered and further explored as a new therapeutic strategy in HGSOC.Publication Metadata only Design considerations for clinical trials of radiotherapy combined with immunotherapy(İstanbul Tıp Fakültesi, 2023) Welsh, James; Sezen, Duygu; Faculty Member; School of Medicine; 170535The discovery of synergistic effects between radiation and immunotherapy in pre-clinical studies has encouraged researchers to conduct clinical trials testing the effects of combined therapy in patients. The first step in conducting any clinical trial is to define the hypothesis and core objectives. The challenge while developing trials analyzing combinations of immunotherapy and radiation therapy (RT) is to select an appropriate hypothesis that can be tested in the future research, as well as raising new questions for investigation. Here, we review some of the concerns and challenges for designing clinical trials of RT combined with immunotherapy.Publication Metadata only Development of novel androgen receptor inhibitors to overcome castrate-resistant prostate cancer(Elsevier, 2020) Saraç, Hilal; Cherkasov, Artem; Lack, Nathan Alan; Faculty Member; School of Medicine; 120842Inhibiting the androgen receptor (AR) is the standard of care to treat metastatic or recurrent prostate cancer. While treatment is initially effective, the cancer almost always develops resistance and progresses into a lethal castrate-resistant prostate cancer (CRPC). Notably, extensive clinical evidence has shown that the AR remains the main driver of growth and proliferation in CRPC patients. Yet, we increasingly find that conventional antiandrogens cannot effectively inhibit these resistant tumors. There is therefore a pressing need for new therapeutics that work through a novel mechanism of action to overcome drug resistance. This chapter describes our understanding of CRPC progression, highlights the underlying mechanisms of resistance, and provides an overview of the current preclinical and clinical small molecule AR inhibitors.Publication Metadata only Differences in overall survival between clear cell metastatic renal cell carcinoma patients versus population-based controls according to race/ethnicity in the United States(Elsevier Inc., 2023) Cano Garcia, Cristina; Nimer, Nancy; Piccinelli, Mattia Luca; Tappero, Stefano; Panunzio, Andrea; Barletta, Francesco; Incesu, Reha-Baris; Tian, Zhe; Saad, Fred; Kapoor, Anil; Briganti, Alberto; Terrone, Carlo; Shariat, Shahrokh F.; Antonelli, Alessandro; De Cobelli, Ottavio; Kluth, Luis A.; Becker, Andreas; Chun, Felix K.H.; Karakiewicz, Pierre I.; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/APurpose: To quantify differences in five-year overall survival (OS) between clear cell metastatic renal cell carcinoma (ccmRCC) patients and age- and sex-matched population-based controls, especially when race/ethnicity is considered. Methods: We relied on the Surveillance, Epidemiology and End Results database (2006–2016) to identify newly diagnosed (2006- 2011) ccmRCC patients of either Caucasian, Hispanic, African American, or Asian/Pacific Islander race/ethnicity. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with five-year follow-up. We compared OS between ccmRCC patients and controls. Multivariable Cox regression models tested for race/ethnicity effect on OS. Results: Of 3067 ccmRCC patients, 2167 (71%) were Caucasians vs. 488 (16%) Hispanics vs. 216 (7%) African Americans and 196 (6%) Asians/Pacific Islanders. At five years, OS difference between ccmRCC patients vs. population-based controls was greatest in African Americans (11 vs. 94%, Δ = 84%), followed by Hispanics (16 vs. 94%, Δ = 77%), Caucasians (16 vs. 89%, Δ = 73%) and Asians/Pacific Islanders (19 vs. 88%, Δ = 70%). In multivariable Cox regression models, African Americans exhibited highest Hazard Ratio for death (HR 1.3, p= 0.003). Conclusion: Relative to Life Tables’ derived age- and sex-matched controls, ccmRCC patients exhibit drastically worse OS, especially African Americans.Publication Metadata only Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy(BioMed Central Ltd, 2023) Karacin C.; Oksuzoglu B.; Demirci A.; Keskinkılıç M.; Baytemür N.K.; Yılmaz F.; Selvi O.; Erdem D.; Avşar E.; Paksoy N.; Demir N.; Göksu S.S.; Türker S.; Bayram E.; Çelebi A.; Yılmaz H.; Kuzu Ö.F.; Kahraman S.; Gökmen İ.; Sakin A.; Alkan A.; Nayır E.; Uğraklı M.; Acar Ö.; Ertürk İ.; Demir H.; Aslan F.; Sönmez Ö.; Korkmaz T.; Celayir Ö.M.; Karadağ İ.; Kayıkçıoğlu E.; Şakalar T.; Öktem İ.N.; Eren T.; Urul E.; Mocan E.E.; Kalkan Z.; Yıldırım N.; Ergün Y.; Akagündüz B.; Karakaya S.; Kut E.; Teker F.; Demirel B.Ç.; Karaboyun K.; Almuradova E.; Ünal O.Ü.; Oyman A.; Işık D.; Okutur K.; Öztosun B.; Gülbağcı B.B.; Kalender M.E.; Şahin E.; Seyyar M.; Özdemir Ö.; Selçukbiricik F.; Kanıtez M.; Dede İ.; Gümüş M.; Gökmen E.; Yaren A.; Menekşe S.; Ebinç S.; Aksoy S.; İmamoğlu G.İ.; Altınbaş M.; Çetin B.; Uluç B.O.; Er Ö.; Karadurmuş N.; Erdoğan A.P.; Artaç M.; Tanrıverdi Ö.; Çiçin İ.; Şendur M.A.N.; Oktay E.; Bayoğlu İ.V.; Paydaş S.; Aydıner A.; Salim D.K.; Geredeli Ç.; Yavuzşen T.; Doğan M.; Hacıbekiroğlu İ.; N/A; Selçukbiricik, Fatih; Faculty Member; School of Medicine; 202015Background: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.