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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 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 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.Publication Metadata only Management of discrete pulmonary nodules(Springer, 2016) Bayrak, Yusuf; N/A; N/A; Dilege, Şükrü; Tanju, Serhan; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 122573; 214690In the case of a pulmonary nodule on preoperative examination or during postoperative follow-up of breast cancer patients, it can be difficult to distinguish between primary lung cancer, a metastatic pulmonary tumor, and a benign pulmonary lesion. The size, morphology, and number of nodules are helpful parameters for differential diagnoses in many cases, whereas more interventional methods are required to clarify the etiology of progression at follow-up. Benign lesions such as atypical pneumonia, tuberculosis, atypical mycobacteria, inflammatory granuloma, rheumatoid nodules, and atypical bronchoalveolar hyperplasia are also common in immunocompromised patients who underwent multiple cycles of chemotherapy.Publication Metadata only Role of emotion regulation and fear of compassion on depression and anxiety in patients with colorectal cancer(Kartal Eğitim ve Araştırma Hastanesi, 2022) Kılıç, Özge; Dikmen, Yasemin; N/A; Özata, İbrahim Halil; Yalçınay-İnan, Merve; Tüfekçi, Tutku; Ağcaoğlu, Orhan; Kuşçu, Kemal; Balık, Emre; Teaching Faculty; Doctor; Researcher; Faculty Member; Faculty Member; Faculty Member; School of Medicine; N/A; School of Medicine; School of Medicine; School of Medicine; N/A; Koç University Hospital; N/A; N/A; N/A; 177151; N/A; 327608; 175476; N/A; 18758INTRODUCTION: Maladaptive emotion regulation (ER) styles act as transdiagnostic mechanisms that underlie many psychiatric symptoms linked to cancer. ER and fear of compassion (FC) were studied in breast cancer, but their effects on psychiatric symptoms of colorectal cancer (CRC) patients are not studied. We aim to examine the role of ER and FC on depression and anxiety in Turkish CRC patients. METHODS: This observational, cross-sectional study recruited 38 patients with CRC who were being followed up by the general surgery department of a university hospital. Emotion Regulation Questionnaire, Fear of Compassion Scale, the Exercise of Self-care Agency Scale, Hospital Anxiety and Depression Scale, Distress Thermometer, Numeric Pain Intensity Scale, and Ostomy Adjustment Inventory were applied. Multiple regression analyses were performed to identify factors affecting depression and anxiety levels. RESULTS: Twenty-nine men and 9 women (median age=56.5, 28–69), most of whom were married and highly educated, were recruited. Expressive suppression (p=0.013) and pain (p=0.010) positively (Model, R2=0.42, p<0.001) and self-care agency (p=0.021) negatively influenced anxiety levels. Expressive suppression (p=0.017) and male gender (p=0.020) positively influenced depression levels (Model, R2=0.28, p=0.003). There was no association between cognitive reappraisal and levels of depression and anxiety. Among ostomates (n=17), 11 patients had low and 6 patients had medium adaptation to an active ostomy. No patient exhibited high adjustment to an ostomy. DISCUSSION AND CONCLUSION: Findings indicate that in CRC patients, expressive suppression affects levels of anxiety and depression while cognitive reappraisal does not. FC was not found to be related to anxiety and depression. Physicians should carefully observe the patients’ and the caregivers’ ER strategies and the dynamic and interactive psychological states to understand which patients need psychological and psychiatric interventions. We suggest future studies explore the interventions that target expressive suppression patterns to prevent anxiety and depression in CRC patients. / GİRİŞ ve AMAÇ: Uyumsal olmayan emosyon düzenleme biçimleri, kanserle ilişkili psikiyatrik belirtilerin altında yatan tanılar üstü mekanizmalar olarak rol oynar. Emosyon düzenleme ve şefkat korkusu meme kanseri hastalarında incelenmiştir ancak kolorektal kanser hastalarında psikiyatrik belirtiler üzerine etkileri araştırılmamıştır. Emosyon düzenleme ve şefkat korkusunun depresyon ve anksiyete üzerindeki rolünü Türk kolorektal kanser hastalarında incelemeyi amaçladık. YÖNTEM ve GEREÇLER: Bu gözlemsel, kesitsel çalışmaya, bir üniversite hastanesinin genel cerrahi bölümü tarafından takip edilen 38 kolorektal kanser hastası alındı. Emosyon Düzenleme Ölçeği, Şefkat Korkusu Ölçeği, Özbakım Gücü Ölçeği, Hastane Anksiyete ve Depresyon Ölçeği, Distres Termometresi, Sayısal Ağrı Derecelendirme Ölçeği, ve Stomaya Uyum Envanteri uygulandı. Depresyon ve anksiyeteyi etkileyen faktörleri belirlemek için çoklu regresyon analizleri yapıldı. BULGULAR: Çalışmaya çoğu evli ve yüksek eğitimli (medyan yaş= 56.5, 28–69) olan 29 erkek, 9 kadın alındı. Anksiyete düzeyleri üzerine dışavurumu bastırma (p=0.013) ve ağrının (p=0.010) etkisi pozitif, özbakım gücünün (p=0.02) etkisi negatifti (Model, R2=0.42, p<0.001). Depresyon düzeyleri üzerineyse dışavurumu bastırma (p=0.017) ve erkek cinsiyet (p=0.020) pozitif yönde etki etmekteydi. (Model, R2=0.28, p=0.003). Bilişsel yeniden değerlendirme ile depresyon ve ve anksiyete arasında ilişki saptanmadı. Stomaya uyum aktif stomalı hastaların (n=17) 11’inde düşük, altısında ortaydı. Stomaya yüksek uyum gözlenmedi. TARTIŞMA ve SONUÇ: Sonuçlar, kolorektal kanser hastalarında dışavurumu bastırmanın anksiyete ve depresyon düzeylerini etkilediğini, bilişsel yeniden değerlendirmenin ise bu düzeyleri etkilemediğini göstermiştir. Şefkat korkusu anksiyete ve depresyonla ilişkili bulunmamıştır. Hekimler, hangi hastaların psikolojik veya psikiyatrik müdahaleye ihtiyaç duyduğunu anlamak için hasta ve bakımverenin emosyon düzenleme biçimlerini ve dinamik ve etkileşimli psikolojik durumlarını dikkatle gözlemelidir. Gelecek çalışmaların kolorektal kanser hastalarında anksiyete ve depresyonu önlemek için dışavurumu bastırma paternini hedef alan müdahaleleri araştırmasını öneririz.Publication Metadata only Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics(Nature Research, 2021) Muus, Christoph; Luecken, Malte D.; Eraslan, Gökcen; Sikkema, Lisa; Waghray, Avinash; Heimberg, Graham; Kobayashi, Yoshihiko; Vaishnav, Eeshit Dhaval; Subramanian, Ayshwarya; Smillie, Christopher; Jagadeesh, Karthik A.; Duong, Elizabeth Thu; Fiskin, Evgenij; Triglia, Elena Torlai; Ansari, Meshal; Cai, Peiwen; Lin, Brian; Buchanan, Justin; Chen, Sijia; Shu, Jian; Haber, Adam L.; Chung, Hattie; Montoro, Daniel T.; Adams, Taylor; Aliee, Hananeh; Allon, Samuel J.; Andrusivova, Zaneta; Angelidis, Ilias; Ashenberg, Orr; Bassler, Kevin; Bécavin, Christophe; Benhar, Inbal; Bergenstråhle, Joseph; Bergenstråhle, Ludvig; Bolt, Liam; Braun, Emelie; Bui, Linh T.; Callori, Steven; Chaffin, Mark; Chichelnitskiy, Evgeny; Chiou, Joshua; Conlon, Thomas M.; Cuoco, Michael S.; Cuomo, Anna S. E; Deprez, Marie; Duclos, Grant; Fine, Denise; Fischer, David S.; Ghazanfar, Shila; Madissoon, Elo; Nyquist, Sarah K.; Penland, Lolita; Shi, Xingyi; Sountoulidis, Alex; Travaglini, Kyle J.; Huyck, Heidie L.; N/A; Yıldırım, Ali Önder; Other; School of Medicine; N/AAngiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial–macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.Publication Metadata only Studying the physical and psychological symptoms of patients with cancer(Gülhane Military Medical Academy, 2013) Sever, Neşe; DInçer, Şefika; N/A; N/A; Seven, Memnun; Akyüz, Aygül; Faculty Member; Faculty Member; School of Nursing; School of Nursing; 32470; 42416Aim: Aim of the descriptive study was to evaluate the frequency and severity of physical and psychological symptoms so as to determine palliative care needs of cancer patients. Method: Total 142 patients who were treated in oncology clinic at an university hospital were enrolled in the cross sectional research. "Descriptive Information Questionnaire" was developed by the authors and the adapted "Beck Depression Inventory (BAI)" and "Beck Anxiety Inventory (BDI)", "Edmonton Symptom Assessment System (ESAS)" to evaluate psychological and physical symptoms were used to collect data. Results: The mean age was 49.35±36.61 years and 54.9% of them were out-patients. %16.2 of the patients were diagnosed with colon and 13.4% breast cancer. The mean BDI score was 8.59±6.36 and 88.7% the patients have depressive symptoms. The mean BAI score was 11.39±7.53. The three most frequent problems were fatigue (87.3%), breathlessness (76.1%), and insomnia (67.6%). The mean of the highest-ranking problems were anorexia (6.02±2.77), fatigue (5.33±2.09) and insomnia (0.04±2.42). Conclusion: The study shows that some symptoms might be experienced by majority of the cancer patients as well as some symptoms might be felt more severe by fewer patients. Therefore, It should be assessed that both the frequency and severity of symptoms that patients experienced associated with cancer and its' treatment individually and focusing on primary care.Publication Metadata only Surgical management of bronchial carcinoid tumors: 11-year experience(Turkish Society of Cardiovacular Surgery, 2014) Dadaş, Erdoğan; Tanju, Serhan; Özkan, Berker; Bayrak, Yusuf; Kaba, Erkan; Toker, Alper; N/A; Dilege, Şükrü; Faculty Member; School of Medicine; 122573Background: This study aims to present surgical treatment, postoperative complications, and long-term outcomes in patients with a bronchial carcinoid tumor. Methods: Between January 2000 and December 2010, 57 patients (34 females, 23 males; mean age 43 years; range 13 to 83 years) underwent pulmonary resection for pre- and postoperatively pathologically confirmed bronchial carcinoid tumors. Type of surgery, histopathological types of carcinoid tumor, postoperative complications, and long-term results were evaluated. Results: Pathological examination revealed 44 (77%) typical and 13 (23%) atypical carcinoid tumors. Bronchial sleeve resection, pneumonectomy, lobectomy and sublobar resection were performed on 23 (40.3%), three (5.2%), 27 (47.3%) and four patients (7%), respectively. Eight patients (14%) had postoperative complications. There was no perioperative mortality. During the follow-up period, no mortality or local recurrence occurred. Conclusion: During long-term follow-up period, parenchyma-sparing resections (sleeve lobectomy and bronchial sleeve resection) can achieve good prognosis in patients with typical carcinoid tumor if tumor free surgical margins can be obtained. /Öz: Amaç: Bu çalışmada, bronşiyal karsinoid tümörlü hastalarda cerrahi tedavi, ameliyat sonrası komplikasyonlar ve uzun dönem sonuçlar sunuldu. Çalışma planı: Ocak 2000 - Aralık 2010 tarihleri arasında ameliyat öncesi ve sonrası patolojik olarak bronşiyal karsinoid tümör olduğu doğrulanmış 57 hastaya (34 kadın, 23 erkek; ort. yaş 43 yıl; dağılım 13-83 yıl) akciğer rezeksiyonu uygulandı. Cerrahi tipi, karsinoid tümörün histopatolojik tipi, ameliyat sonrası komplikasyonlar ve uzun dönem sonuçlar değerlendirildi. Bulgular: Patolojik muayenede 44 (%77) tipik, 13 (%23) atipik karsinoid tümör saptandı. Hastaların 23’üne (%40.3) bronşiyal sleeve reseksiyon, üçüne (%5.2) pnömonektomi, 27’sine (%47.3) lobektomi, dördüne (%7) sublobar rezeksiyon uygulandı. Sekiz hastada (%14) ameliyat sonrası komplikasyon gözlendi. Ameliyat sırası mortalite gözlenmedi. Takip döneminde hiçbir hastada ölüm ve lokal nüks olmadı. Sonuç: Parenkim koruyucu rezeksiyonlar (sleev lobektomi ve sleev bronşiyal rezeksiyon), tipik karsinoid tümörlü hastalarda, negatif cerrahi sınır elde etmek koşulu ile uzun dönem takip sürecinde iyi prognoz sağlayabilir.Publication Metadata only Surgical staging and advanced surgical techniques in early stage non-small cell lung cancers(Springer, 2016) Bayrak, Yusuf; N/A; N/A; N/A; Dilege, Şükrü; Tanju, Serhan; Erus, Suat; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; 122573; 214690; 175565N/A