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    18F-FDG PET/CT parameters for prediction of response to neoadjuvant therapy and prognosis in rectal cancer
    (Wolters Kluwer Health, 2023) Ebinç, Senar; Güzel, Yunus; Oruç, Zeynep; Kömek, Halil; Kalkan, Ziya; Can, Canan; Taşdemir, Bekir; Urakçı, Zuhat; Kaplan, Muhammet Ali; Küçüköner, Mehmet; Işıkdoğan, Abdurrahman
    Objective This study aims to investigate the role of F-18 fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) parameters in the prediction of treatment response and the prognosis in locally advanced rectal cancer. Methods We investigated the relationship of 18F-FDG PET/CT parameters [rectal metabolic tumor volume (MTV), rectal total lesion glycolysis (TLG), rectal standard uptake value (SUV) max, rectal highest peak SUV, lymph node MTV, lymph node TLG, lymph node highest peak SUV] with the pathological response and disease-free survival (DFS) in 60 patients who received neoadjuvant therapy for a diagnosis of locally advanced rectal cancer. Patients with a total score of 0 were assigned to the low-risk group, patients with a score of 1 were assigned to the intermediate-risk group and patients with a score of 2 were assigned to the high-risk group. Results The multivariate analysis revealed that, from baseline PET CT parameters, lymph node highest peak SUV strongly predicted the pathological response at a cutoff value of 2.23. DFS was predicted by the lymph node highest peak SUV at a cutoff value of 3.13 and by the MTV value at a cutoff value of 27 cm3. The risk scoring performed with regard to rectal MTV and lymph node highest peak SUV values determined a median DFS of 19 months in patients with a risk score of 2, whereas the median DFS was not reached in patients with risk scores of 0 and 1 (P < 0.001). Conclusion This study determined that rectal MTV and lymph node highest peak SUV predicted the response to neoadjuvant therapy and DFS.
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    Adjuvan aromataz inhibitörü kullanan erken evre meme kanserli hastalarda vücut yağ oranının prognostik önemi
    (2017) Kalkan, Ziya; Kaplan, M. Ali
    Giriş ve amaç: Obezite postmenopozal meme kanseri gelişimi için bir risk faktörü ve meme kanseri için bir kötü prognoz göstergesidir. Aromataz inhibitörleri genelde postmenapozal dönemde olmak üzere premenopoz hastalarda LHRH analoğu ile birlikte kullanılmaktadırlar. Birçok çalışmada etkinliğine dair veriler açıklanmıştır. Ancak son zamanlarda yapılan çalışmalar obez hastalarda aromataz inhibitörlerinin daha az etkili olabileceği ve bunun muhtemel periferik yağ dokusunda aromataz enzim aktivitesinde artış ile ilgili olduğu düşünülmektedir. Obez hastalarda aromataz inhibitörlerine karşı direnç ve daha düşük sağkalım olduğu gösterilmiştir. Bizim çalışmamızın hedefi, vücut yağ oranının; meme kanserli hastalarda aromataz inhibitörlerine karşı direnci göstermede ve düşük sağkalım üzerine VKİ (vücut kitle indeksi) gibi parametrelere göre daha etkili bir parametre olup olmadığını araştırmak. Materyal ve metod: Ocak 2001-Mart 2017 yılları arasında meme kanseri tanısı almış erken evre olan ve opere edilen adjuvan aromataz inhibitörü tedavisi almış 18 yaşından büyük, vücut yağ oranı (Tanita cihazı ile) ölçümleri yapılmış 222 hasta ile çalışma yapıldı. Postmenapoz hastalar (n=192) ayrıca analiz edildi. Hastaların demografik özellikleri, vücut yağ oranı, vücut yüzey alanı, vücut kitle indeksi hasta dosyalarından değerlendirildi. Hastalar vücut yağ oranı (FAT%), vücut kitle indeksine (VKİ) göre analiz edildi. Tanıdan nüks tarihine kadar geçen süre hastalıksız sağkalım (HSK) olarak değerlendirildi. Bulgular: Tüm hastalarda (n=222); ortalama boy 157 ±6,432 cm, ortalama kilo 78 ±14 kg, median vücut yüzey alanı 1,78 (1,32-2,16) m2 ve ortalama VKİ’si 30,9 ±5,89 olarak tespit edildi. Tanita cihazı ile tartılan hastaların vücut yağ oranı yüzdesi (FAT%); ortalama 39,9 ±6,94, hastaların vücut yağsız kitle yüzdesi; ortalama 60,1 ±6,89 tespit edildi. VKİ < 30 ve VKİ ? 30 olan hasta grupları analiz edildi (p=0.873). Her iki grup arasında istatistiksel olarak anlamlı fark yoktu. Tüm hastalarımızı fatmass oranı 45’den küçük ve büyük olarak kategorize edilerek hastalıksız sağkalım bilgileri değerlendirildi (p=0.015). Her iki grup arasında istatistiksel olarak anlamlı fark vardı. Multivariate analizde yaş, grade ve fatmass değişkenleri hastalıksız sağkalımı anlamlı etkileyen bağımsız prognostik faktörler olarak bulundu. Fatmass [<45 ve ?45, OR (odds ratio): 3,511 , %95 CI:1,568-7,865, p=0.002], grade [OR:2,124, %95 CI:1,140-3,955, p=0.018], yaş [ <50 ve >50, OR:0,942 , %95 CI=0,912-0,973, p<0.001]. Hastalarımızın 192’si (%86,5) postmenopozal olarak tespit edildi. Postmenapozal hastaların tanı anında ortalama yaş 59 (42-91) idi. Çalışmaya alınan postmenopozal hastalarda ortalama boy 157 ±6,710 cm, median kilo 78,6 ±13,6 kg, median vücut yüzey alanı 1,78 (1,32-2,16) m2 ve ortalama VKİ’si 30,9 ±5,66 olarak tespit edildi. Tanita cihazı ile tartılan hastaların vücut yağ oranı yüzdesi (FAT%); ortalama 40,1 ±6,65, hastaların vücut yağsız kitle yüzdesi; ortalama 59,9 ±6,59 tespit edildi. Postmenopozal hastalarımızı VKİ (Vücut Kitle İndeksi) <30 ve ?30 olarak ayırıp analiz ettik (p=0.936). Her iki grup arasında istatistiksel olarak anlamlı fark yoktu. Postmenopoz hastalarımız fatmass oranı 45’den küçük ve büyük olarak kategorize edilerek hastalıksız sağkalım bilgileri değerlendirildi (p=0.037). Her iki grup arasında istatistiksel olarak anlamlı fark vardı. Multivariate analizde fatmass değişkeni hastalıksız sağkalımı anlamlı etkileyen tek bağımsız prognostik faktör olarak bulundu. Fatmass [<45 ve ?45, OR (odds ratio): 3,157, %95 CI:1,234-8,078, p=0.016]. Tartışma ve sonuç: Literatürde meme kanseri olan hastalarda vücut yağ oranın hastalıksız sağkalım ve prognoz üzerine direk etkisini baz alarak yapılan çalışmaya rastlanılmamıştır. Literatürdeki tüm çalışmalar postmenopozal erken evre meme kanseri hastalarındaki aromataz inhibitörlerine karşı direnci vücut kitle indeksi (VKİ) ile açıklamışlardır, aromataz inhibitör direncini vücut yağ oranı (fatmass) ile açıklayan herhangi bir çalışma yoktur. Çalışmamız vücut yağ oranının (fatmass) aromataz inhibitörlerine karşı direnci öngörmede vücut kitle indeksinden (VKİ) daha başarılı olduğunu gösteren ilk çalışmadır. Anahtar Kelimeler: Meme kanseri, Aromataz inhibitörleri, Vücut yağ oranı
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    Assessing the clinical impact of Lutetium-177 DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) on metastatic neuroendocrine tumors: A multicenter real-world data from Türkiye
    (Kare Publishing, 2023) Ünal, Çağlar; Selçuk, Nalan Alan; Biricik, Fatih Selçuk; Alan, Özkan; Ordu, Çetin; Selvi, Oğuzhan; Kalkan, Ziya; Oruç, Zeynep
    Objectives: This study aimed to evaluate the clinical outcomes, including progression-free survival (PFS), overall survival (OS), Objective Response Rate (ORR), and Disease Control Rate (DCR), in patients received Lutetium-177 (Lu-177) DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) for metastatic neuroendocrine tumors. This study further stratified outcomes based on tumor grade, Ki-67 status, primary tumor localization, number of treatment cycles, and associated adverse effects. Methods: We conducted a multicenter retrospective study analyzing the data of 73 patients with metastatic NETs across 17 different hospitals in various regions of Türkiye. A total of 73 metastatic NET patients underwent Lu-177 DOT-ATATE PRRT between December 2013 and March 2023. Results: Over a median follow-up of 52.7 months, patients showed a median PFS of 13.7 months and OS of 51.2 months. The ORR was 29.6%, and the DCR was 66.2%. Grade 1 and 2 tumor patients had superior outcomes (PFS: 16.9 months, OS: 55.5 months) compared to grade 3 tumor patients (PFS: 8.5 months, OS: 29.5 months). Based on their Ki-67 status, those ≤ 20% had prolonged PFS (16.9 months) and OS (55.5 months) than those between 21 and 55% (PFS: 5.9 months, OS: 41.3 months). Regarding primary tumor localization, the PFS values were 13.1, 15.3, 13.7, and 8.6 months for pancreatic, GIS, lung, and unknown origin tumors, respectively. The OS across tumor types fluctuated between 41.1 and 54.1 months. Patients who received more than four cycles demonstrated significantly improved median PFS (22.4 months) and OS (90.3 months) compared to those who received ≤ 4 cycles (median PFS: 9.3 months; median OS: 41.8 months). Grade 3-4 adverse effects were observed in 21.9% of patients. Conclusion: Our findings affirm that PRRT is a potent and well-tolerated treatment for metastatic NETs. Notably, patients who received more than 4 cycles of PRRT experienced a markedly improved median PFS and OS compared to their counterparts who received ≤4 cycles.
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    Causes of liver test abnormalities in newly diagnosed cancer patients and the investigation of etiological factors
    (Taylor & Francis Ltd, 2024) Urakçı, Zuhat; Ebinç, Senar; Oruç, Zeynep; Kalkan, Ziya; Kaplan, Muhammet Ali; Küçükköner, Mehmet; Işıkdoğan, Abdurrahman
    Objectives: In this study, we aimed to investigate the causes of liver test abnormalities in newly diagnosed patients naive to anti-tumoral therapy. Method: This study included a total of 490 patients with ALT levels > 5X ULN on liver function tests at the initial presentation to our clinic. Data from 247 (50.4%) patients diagnosed with cancer (cohort A) and 243 (49.6%) patients without cancer (cohort B) were compared with regard to the etiology of liver test abnormalities and the risk factors. Results: The most common etiological factor in cohort A was presence of liver metastasis (31.2%, n = 77). In the comparison of the two groups with regard to etiological factors; the rates of liver metastasis [31.2% vs 0%, (p < 0.001)], drug-induced liver toxicity [30/4% vs 19.8%, (p = 0.007)], pancreaticobiliary pathology [21.5% vs 14%, (p = 0.03)] and chronic viral hepatitis [14.2% vs 7.4%, (p = 0.02)] were higher in the cohort A. The rate of NAFLD was higher in the cohort B [6.9% vs 42.2% (p < 0.001). Conclusion: In our study, the most common cause of liver test abnormalities was the presence of liver metastasis in cohort A and NAFLD in cohort B.
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    Comparison of Two Chemotherapy Regimens After First-Line Treatment for HER2-Negative Metastatic Gastric Cancer
    (Springernature, 2023) Urakci, Zuhat; Ebinc, Senar; Tunc, Sezai; Kalkan, Ziya; Oruc, Zeynep; Kucukoner, Mehmet; Kaplan, Muhammet Ali
    Aim: Metastatic stage gastric cancer is a disease with a poor prognosis and the likelihood of achieving a cure in these patients is low. Treatment response to subsequent-line treatments is poor. We aimed to investigate the effectiveness of the folinic acid, fluorouracil and irinotecan (FOLFIRI) and paclitaxel+carboplatin regimens, which are used in subsequent lines of therapy in advanced-stage gastric cancer.Materials and methods: This study included 40 patients who have metastatic stage gastric cancer and received FOLFIRI or paclitaxel+carboplatin therapy in subsequent lines of therapy between 2017 and 2022. The data of the patients were analyzed retrospectively.Results: At diagnosis median age was 51 (23-88) years. The tumor was localized in the gastroesophageal junction in eight (20%) patients and in other gastric locations in 32 (80%) patients. At diagnosis, 75% (n=30) of the patients presented with the disease in the metastatic stage, while 25% (n=10) presented with stage II -III disease. Regarding the treatments received in the second and further lines of therapy, 18 (45%) patients received paclitaxel+carboplatin and 22 (55%) patients received a FOLFIRI regimen. Of these treatments, 67.5% (n=27) were given as the second line and 32.5% (n=13) were given as third-line therapy. The objective response rate (ORR) was 45.5% in the FOLFIRI arm compared to 16.7% in the paclitaxel+carboplatin arm (p=0.05). Both treatment arms had a median progression-free survival (PFS) of three months (p=0.82). The median overall survival (OS) time was seven months in the FOLFIRI arm compared to eight months in the paclitaxel+carboplatin arm (p=0.71). Side effects were similar between both treatment arms.Conclusion: This study determined that FOLFIRI and paclitaxel+carboplatin treatments have similar OS, PFS, and side effect profiles in subsequent line treatment of gastric cancer. The FOLFIRI treatment regimen yielded a higher ORR.
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    COVİD-19 ve kanser yönetimi
    (Dicle Üniversitesi Tıp Fakültesi, 2021) Urakçı, Zuhat; Kalkan, Ziya; Ebinç, Senar
    Coronavirüs hastalığı 2019 (COVID-19) şiddetli akut solunum sendromu coronavirüs 2'nin (SARS-CoV-2) neden olduğu bulaşıcı bir hastalıktır. Dünya Sağlık Örgütü (DSÖ) Mart 2020’de COVID-19 salgınını küresel bir salgın olarak ilan etmiştir. Kanser hastalığının kendisi ve kanser tedavisinde kullanılan yöntem ve tedavilerin immünsupresyona neden olabilmelerinden dolayı bu hastalarda COVİD-19 hastalığına yakalanma riski artmaktadır. Ayrıca kanser hastalarında normal popülasyona göre COVİD-19’a bağlı mortalite oranları daha yüksektir. COVİD-19 pandemisi sürecinde birçok ülkenin sağlık sisteminde problemler baş göstermiş ve bu problemlerden dolayı çoğu alanda değişiklikler yapılma yoluna gidilmiştir. Bu bağlamda günlük onkolojik pratikte de değişik modifikasyonlar yapılmış, mevcut koşullara adaptasyon sağlanmaya çalışılmıştır. Rutin kanser taramaları geçici olarak durdurulmuş, rutin takiplerde bazı koşullarda takip aralıkları uzatılmıştır. Sağlık sistemlerindeki yüklenmelerden dolayı tanı aşamasında bazı farklılıklar yaşanmıştır. COVİD-19 pandemi sürecinde immünoterapi, hedefe yönelik ilaçlar ve hormonal ilaçlar COVİD-19 bulaş ve mortalite riskini arttırmadığından bu ilaçların kullanımı ile ilgili standart yaklaşımda belirgin bir farklılık görülmemektedir. Bununla birlikte hastane vizitlerini azaltma amacıyla immünoterapi kür aralıklarının uzatılabileceği önerilmiştir. Kemoterapi alan hastalarda immünsupresyon oluşturma ve enfeksiyon riski nedeni ile uluslararası kılavuzlar çerçevesinde bazı değişikliklere gidilmiştir. Küratif yaklaşımlarda ve kemoterapiye iyi yanıt alınabilecek tümörlerin tedavisinde standart yaklaşım önerilirken, metastatik evre palyatif tedavi alan ve kemoterapi etkinliği belirgin olmayan hastalarda hastayla birlikte tedaviye karar verilmesi önerilmiştir. Sağlık otoriteleri aşılama programlarında kanser tanılı hastalara öncelik tanımış, aşının kanser hastalarında COVİD-19 bulaşını önleme ve COVİD-19’a bağlı mortaliteyi azaltmada etkili olduğu gözlenmiştir.
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    Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study
    (Future Medicine LTD., 2022) Yasin, Ayşe İrem; Aydın, Sabin Göktaş; Sümbül, Bilge; Koral, Lokman; Şimşek, Melih; Geredeli, Çağlayan; Kalkan, Ziya
    Aim: To compare the seropositivity rate of cancer patients with non-cancer controls after inactive SARS-CoV-2 vaccination (CoronaVac) and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 non-cancer volunteers. An IgG level >= 50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: ClinicalTrials.gov) Plain language summary Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of CoronaVac, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.
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    Efficacy of capecitabine and temozolomide regimen in neuroendocrine tumors: Data from the Turkish Oncology Group
    (NLM (Medline), 2023) Ünal, Çağlar; Azizy, Abdulmunir; Karabulut, Senem; Taştekin, Didem; Akyıldız, Arif; Yaşar, Serkan; Kalkan, Ziya; Oruç, Zeynep
    INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.
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    Efficacy of pemetrexed plus a platinum rechallenge in the treatment of pleural mesothelioma
    (Via Medica, 2023) Urakçı, Zuhat; Ebinç, Senar; Oruç, Zeynep; Kalkan, Ziya; Kaplan, Muhammet Ali; Küçüköner, Mehmet; Işıkdoğan, Abdurrahman
    Introduction. Pemetrexed-based rechallenge therapies can be used as an option in the treatment of pleural mesothelioma. We aimed to investigate the efficacy of pemetrexed-based rechallenge in mesothelioma. Material and methods. A total of 132 patients who received chemotherapy for unresectable or metastatic pleural mesothelioma in the Medical Oncology Clinic of Dicle University Medical Faculty between 2005 and 2020 were included in our study. Pemetrexed plus platinum rechallenge treatments were compared with other chemotherapy regimens in terms of survival. Results. In our study, 31 (23.4%) of a total of 132 patients received rechallenge pemetrexed plus platinum treatment. There was no statistically significant difference between median progression-free survival of patients who received pemetrexed plus cisplatin or gemcitabine plus cisplatin in the first-line therapy [5 months vs. 8 months (HR = 1.43; 95% CI 0.59–3.45; p = 0.376)]. In the second-line treatment, patients who received rechallenge pemetrexed plus platinum therapy had statistically significantly higher median PFS than those who received gemcitabine plus platinum [6 months vs. 4 months (HR = 0.46; 95% CI 0.22–0.94; p = 0.011)] due to a previous good response. In the second-line treatment, median overall survival was 15 months with gemcitabine plus platinum and 29 months with pemetrexed plus platinum rechallenge (p = 0.007). Conclusions. This study demonstrated that the pemetrexed plus platinum regimen was more effective than gemcitabine plus platinum in the second-line treatment in terms of both progression-free and overall survival in patients who had previously benefited from pemetrexed-based chemotherapy and had not progressed up to 6 months after first-line treatment.
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    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) Karaçin, Cengiz; Öksüzoğlu, Berna; Demirci, Ayşe; Baytemür, Naziyet Köse; Yılmaz, Funda; Kalkan, Ziya; Keskinkılıç, Merve
    Background 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 efectiveness of systemic treatments after CDKi and whether there is a survival diference 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 frst-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 efective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after frst-line CDKi compared to monotherapy ET.
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    Evaluation Of Cancer And Non-Cancer Patients Receiving Palliative Care Service İn Terms Of Hospitalization Times And Overall Survival During Hospitalization: A Single-Center Experience
    (Veysi AKPOLAT, 2021) Kalkan, Ziya; Ebinç, Senar; Kalkan, Tuğba Tezer; Urakçı, Zuhat; Oruç, Zeynep
    Objective: In the last 20 years, palliative care has gained a place within the health system worldwide. Our aim is to review the demographic characteristics of patients hospitalized in palliative care centers, to investigate the factors influencing hospitalization times of patients with cancer and non-cancer diagnoses and the median in-hospital survival. Results: A total of 428 patients, comprising 237 (55.4%) males and 191 (44.6%) females were included in the study. Median patient age was 75 (18-105) years. In terms of hospitalization times, there were no significant differences between genders (p=0.79) and diagnoses (malignant/non-malignant); however, there was a statistically significant difference between survival statuses (died/discharged) and patients who died had longer hospitalization times (16 days versus 12 days) (p=0.008). When age, gender, hospitalization type and diagnosis were compared with regard to median in-hospital survival in multivariate analysis, the diagnosis (non-malignant/malignant) was an independent factor indicating median in-hospital survival (HR:2.08, 95% CI:(1.47-2.94), p
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    Evaluation of factors predicting the effectiveness of regorafenib in the treatment of metastatic colorectal cancer
    (Aves Yayıncılık, 2022) Ebinç, Senar; Oruç, Zeynep; Urakçı, Zuhat; Kalkan, Ziya; Kaplan, Muhammet Ali; Küçüköner, Mehmet; Işıkdoğan, Abdurrahman
    Objective: Regorafenib is a multikinase inhibitor, the effectiveness of which was demonstrated in metastatic colorectal cancer. This study aimed to investigate the factors that could predict the effectiveness of regorafenib. Materials and Methods: This study retrospectively reviewed the clinical characteristics, tumor characteristics, and previous therapies in 62 patients who presented to our center between 2016 and 2020 and used regorafenib for metastatic colorectal cancer. The effects of the investigated variables on the response obtained with regorafenib use were evaluated. Results: This study included a total of 62 patients diagnosed with metastatic colorectal cancer, of whom 30 (48.4%) were males and 32 (51.6%) were females. Patients' median age at diagnosis was 49 years (1868). Regorafenib therapy yielded a disease control rate of 64% [complete response = 0, partial response= 14 (28%), and stable disease = 18 (36%)]. Objective response was obtained in 28% of patients [complete response = 0 and partial response = 14 (28%)]. Progression-free survival was 4 months. The evaluation of the effects of patients' age, sex, performance status, previous treatments, metastatic sites, and RAS mutation status on the disease control rate and progression-free survival did not determine any positive or negative effects on progression-free survival. However, left-sided tumors had a positive effect on disease control rate (69.8% vs. 28.6%, P =.029). and previous use of cetuximab had a negative effect on disease control rate [76.5% vs. 37.5% (P =.007)]. Conclusion: In our study, tumor localization and previous cetuximab use were found to be correlated with the disease control rate in patients on regorafenib. However, the need for novel biomarkers that will predict the effectiveness of regorafenib in metastatic colorectal cancer treatment persists.
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    Evaluation of Immunotherapy and Targeted Therapies in the Treatment of Metastatic Malignant Melanoma
    (2022) Kaplan, Muhammet Ali; Kalkan, Ziya; Tunç, Sezai; İleri, Serdar; Oruç, Zeynep; Ebınc, Senar; Urakçı, Zuhat
    Objectives: The prognosis of metastatic malignant melanoma is poor. In this study, we aim to evaluate the response rates, PFS and OS times obtained with Nivolumab, Ipilimumab and Dabrafenib plus Trametinib in the treatment of advanced malignant melanoma, as well as the side effect profiles of these three agents. Methods: This study included 58 patients diagnosed with advanced malignant melanoma who received Nivolumab, Ipilimumab or Dabrafenib plus Trametinib therapy between January 2010 - March 2021 and had follow-up at our clinic. Response rates, survival times and side effects associated with each of the three treatment arms were evaluated. Nivolumab, Ipilimumab and Dabrafenib plus Trametinib were compared with regard to effectiveness and tolerability. Results: The Nivolumab, Ipilimumab and Dabrafenib plus Trametinib treatment arms, included 34 (58.6%), 13 (22.4%) and 11 (19%) patients, respectively. The comparison of Nivolumab, Ipilimumab and Dabrafenib plus Trametinib yielded, respectively; ORR (53%, 38.5%, 72.8%), mPFS (7 months, 3 months, 9 months) (p=0.57), mOS (12 months, 16 months, 15 months) (p=0.85). Conclusion: In this study that we conducted with real life data, we confirmed that Nivolumab, Ipilimumab and Dab rafenib plus Trametinib have different effectiveness adn manageable side effect profiles in the treatment of advanced malignant melanoma.
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    Evaluation of the effectiveness and tolerability of sunitinib and pazopanib in the first line treatment of metastatic renal cell carcinoma
    (Via Medica, 2022) Ebinc, Senar; Kalkan, Ziya; Oruc, Zeynep; Urakci, Zuhat; Kucukoner, Mehmet; Kaplan, Muhammet Ali; Isikdogan, Abdurrahman
    Introduction. It is known that sunitinib and pazopanib are effective in the first-line and subsequent treatment of metastatic renal cell carcinoma (mRCC). This study aims to investigate the effectiveness and tolerability of sunitinib and pazopanib in the first-line treatment of mRCC. Material and metbods. This study included 78 patients followed up in our clinic due to a diagnosis of mRCC, who received pazopanib or sunitinib treatment between 2006 and 2020. Along with clinical and laboratory findings, survival times obtained with each treatment and medication side effects were assessed. Sunitinib and pazopanib were compared in terms of effectiveness (ORR, PFS and OS) and tolerability. Results. The patients' median age at diagnosis was 55 years (25-81). In the first-line treatment, 54 patients (69.2%) received sunitinib and 24 (30.8%) received pazopanib. The comparison of sunitinib and pazopanib yielded an ORR of 66.7% vs. 45.8% (p = 0.08), PFS of 24 months vs. 19 months (p = 0.66) and OS of 27 months vs. 30 months (p = 0.73), respectively. The most common side effect was hypothyroidism in those on sunitinib (25.9%) and nausea-vomiting in those on pazopanib (41.7%). In our study, hemoglobin >= 13 g/dL, an ECOG PS of 0-1 and the occurrence of hypothyroidism as a medication side effect were found to be predictive factors of PFS for both agents. An International Metastatic RCC Database Consortium score corresponding to the poor risk group was associated with a poor PFS. Conclusions. This study, which provides current real-world data, confirms that sunitinib and pazopanib have similar effectiveness and side-effect profiles in the first-line treatment of mRCC.
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    Factors influencing HER2 discordance in nonmetastatic breast cancer and the role of neoadjuvant therapy
    (Future Medicine Ltd, 2022) Ebinc, Senar; Oruc, Zeynep; Sezgin, Yasin; Karhan, Ogur; Bilen, Erkan; Yerlikaya, Halis; Kalkan, Ziya
    Plain language summary HER2 is an important and targetable molecule in breast cancer. In the early stages of breast cancer, a treatment modality called neoadjuvant therapy, which now includes anti-HER2 therapies, is administered before surgery in order to achieve disease regression and make the patient suitable for a more minor operation. In breast cancer, HER2 status may be positive in the initial biopsy specimen and negative in the surgical specimen. HER2 status plays an important role in treatment decisions. In this study, we investigated the factors causing HER2 status to change in early-stage breast cancer. This study has a retrospective design and includes 400 female patients with early-stage breast cancer. The results of the study identified the factors causing HER2 status to change to negative as receipt of neoadjuvant therapy, small tumor size and younger age. Objective: The rates of and the factors influencing HER2 discordance in patients receiving neoadjuvant therapy for breast cancer are investigated. Methods: This study retrospectively examines the rates of HER2 and hormone receptor discordance between the biopsy and postoperative resection specimens of 400 female early-stage breast cancer patients. Results: One hundred and thirty-three (33.3%) patients had received neoadjuvant therapy. The rate of HER2 discordance between biopsy and resection specimens was 1.7% in the control group and 5.3% in the neoadjuvant therapy group (p = 0.018). The rate of HER2 discordance was higher in younger patients and in patients with T1 tumors in the neoadjuvant therapy group. Conclusion: Neoadjuvant therapy, age <40 years and smaller tumor size were independent risk factors for HER2 discordance.
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    Factors influencing the prognosis in Braf wild-type metastatic malignant melanoma and the role of novel inflammation indices
    (Galenos Publ House, 2023) Ebinc, Senar; Kalkan, Ziya; Oruc, Zeynep; Sezgin, Yasin; Urakci, Zuhat; Kucukoner, Mehmet; Kaplan, Muhammet Ali
    Background and Design: This study aims to investigate the prognostic factors in BRAF wild-type metastatic cutaneous melanoma and the prognostic role of inflammation indices.Materials and Methods: Metastatic BRAF wild-type cutaneous melanoma patients who presented to our clinic between 2011 and 2021 were enrolled. To investigate their prognostic roles, age, gender, performance status, first immunotherapy regimen received by the patient, metastatic sites, and seven inflammation indices [C-reactive protein (CRP)/albumin ratio (CAR), neutrophil lymphocyte ratio (NLR), prognostic nutritional index (PNI), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and advanced lung cancer inflammation index (ALI) and hemoglobin, albumin levels, lymphocyte and platelet counts (HALP)] were studied.Results: Fourty-seven patients, consisting of 22 (46.8%) females and 25 (53.2%) males, were included in this study. Mean patient age was 54 (18-88) years. In our study, there were 16 (34%) patients with liver metastasis, 17 (36.2%) patients with lung metastasis, and 9 (19.1%) patients with brain metastasis. As immunotherapy, 34 (72.3%) patients had received Nivolumab, while 13 (27.7%) patients had received Ipilimumab therapy. When the relationships of the prognostic variables with overall survival were inspected in univariate and multivariate analyses, brain metastasis was found to be an independent prognostic factor (p=0.02). Lung metastasis approached the threshold of statistical significance in univariate analysis (p=0.09) and liver metastasis in multivariate analysis (p=0.07). The seven inflammation indices examined in the analyses [CAR, NLR, PNI, PLR, SII ALI and HALP] were found to have no prognostic role in both univariate and multivariate analyses.Conclusion: Our study determined that brain metastasis is an independent poor prognostic factor in BRAF wild-type metastatic melanoma. Prognostic roles of the CAR, NLR, PNI, PLR, SII ALI and HALP indices could not be demonstrated.
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    Investigation of the Clinicopathological Characteristics and Survival Outcomes of Patients Refusing Surgery Post-Neoadjuvant Therapy in Rectal Cancer
    (2022) Topuk, Savas; Kaplan, Muhammet Ali; Urakçı, Zuhat; Kalkan, Ziya; Küçüköner, Mehmet; Işıkdoğan, Abdurrahman; Oruç, Zeynep
    Objectives: In locally advanced rectal cancer, the standard treatment approach consists of post-neoadjuvant surgery and adjuvant chemotherapy. In this study, we aimed to evaluate the clinicopathological characteristics of patients receiving neoadjuvant therapy for a diagnosis of rectal cancer and to compare the survival outcomes of patients who underwent surgery and patients who refused the surgical approach after neoadjuvant therapy, regardless of response status. Methods: Our study included patients who presented to our clinic and underwent neoadjuvant therapy for locally advanced or oligometastatic rectal carcinoma between 2011 and 2021. Patients who did not complete neoadjuvant therapy or progressed on treatment were excluded. Patient data were retrospectively reviewed using the hospital records system. Results: Our study analyzed data from a total of 123 patients, consisting of 98 (79.7%) patients in the surgery arm and 25 (20.3%) patients in the refusal arm. In our study, 65 (52.8%) patients were female and 58 (47.2%) patients were male. Median age at diagnosis was 53 years (20-86). Most of the patients (75.6%) had stage-III disease. Regarding response to neoadjuvant therapy; complete response was obtained in 16.3% (n=20), partial response was obtained in 71.5% (n=88), stable disease was obtained in 12.2% (n=15) of the patients. After neoadjuvant therapy, 20.3% of the patients had refused surgery and started follow-up. Of the 98 (79.7%) operated patients, 77 (26.6%) had been treated with a low anterior resection and 21 (17.1%) with an abdominoperineal resection. During follow-up, 29.3% (n=36) of the patients showed recurrence or progression. While progression-free survival could not be reached for operated patients, patients refusing surgery had a median recurrence free survival of 32 months (6.3-57.6) (Log-rank p=0.003). Median overall survival was 144 months (46.3-241.6) in operated patients as opposed to 41 (23.0-58.9) months in those refusing surgery (Log-rank p<0.001). Operated patients and patients refusing surgery had three-year survival rates of 64.9% vs 40% (p=0.023) and five-year survival rates of 45.4% vs 16% (p=0.007), respectively. Conclusion: We determined that, in rectal cancer, both the overall survival and progression/recurrence-free survival outcomes of patients refusing surgery were poorer than those in the surgery arm, regardless of response status.
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    Neoadjuvant Therapy and Factors Influencing Survival in Locally Advanced Non-Small Cell Lung Cancer
    (Springernature, 2023) Ebinc, Senar; Oruc, Zeynep; Kalkan, Ziya; Teke, Fatma; Onat, Serdar; Urakci, Zuhat; Kaplan, Muhammet Ali
    Aim: We aimed to investigate the effectiveness of neoadjuvant therapy (NAT) and clinicopathological characteristics in locally advanced non-small cell lung cancer (NSCLC) (IIIA-IIIB), as well as the influence of the post-NAT treatment modalities on survival. Materials and methods: This study included patients who presented to the Dicle University Medical Oncology Clinic and received NAT for a diagnosis of locally advanced NSCLC between 2004 and 2020. Clinicopathological and radiological data of the 57 patients whose data could be retrieved from the hospital archive system were retrospectively reviewed. Patients' overall survival (OS) and failure-free survival (FFS) times and the factors influencing these times were evaluated. Results: This study included a total of 57 patients consisting of five (8.8%) females and 52 (91.2%) males. The median patient age at diagnosis was 58 (30-75) years. All patients had received four courses of chemotherapy during the neoadjuvant period. When the factors influencing OS were evaluated, the post-NAT modality was found to have a statistically significant effect on survival. FFS times were 12, 13, and 16 months in the chemotherapy, chemoradiotherapy, and surgery arms, respectively (log-rank p=0.035). FFS was longer in those who underwent surgery (Hazard ratio (HR): 0.33, 95 % CI: 0.14-0.77, (p=0.01)). OS times were 20, 21, and 55 months in the chemotherapy, chemoradiotherapy, and surgery arms, respectively (log-rank p=0.05). OS was longer in the arm undergoing surgery compared to the other arms (HR: 0.36, 95% CI: 0.14-0.87, (p=0.02)). Five-year survival rates for the chemotherapy, chemoradiotherapy, and surgery arms were 14.3%, 21.4%, and 40%, respectively. Conclusions: This study shows that achieving an operable status is the most important indicator of survival and that patients undergoing surgery have a marked advantage in OS and FFS compared with patients receiving chemoradiotherapy or palliative chemotherapy.
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    Predictive and prognostic effect of ABO blood group on immune checkpoint inhibitors
    (Ios Press, 2022) Ergun, Yakup; Esen, Selin Akturk; Bardakci, Murat; Ucar, Gokhan; Kalkan, Ziya; Urakci, Zuhat; Seyran, Erdogan
    BACKGROUND: The relationship of the ABO blood group system with the immune response is known, but its relationship with immune checkpoint inhibitors (ICIs) has not been clearly investigated until now. OBJECTIVE: In this study, the relationship between different blood groups and nivolumab treatment response in patients with advanced malignant melanoma was investigated. METHODS: The data of patients who used nivolumab for advanced malignant melanoma between April 2018 and April 2021 were retrospectively reviewed. RESULTS: A total of 73 patients were included in the study. In the progression-free survival (PFS) analysis according to blood groups, it was 3.9 months, 16.1 months, 20.0 months and 3.0 months for A, B, AB and O, respectively ( p = 0.1). Overall survival (OS) analysis according to blood groups was 5.1 months, 25.0 months, 20.0 months and 9.3 months for A, B, AB and O, respectively (p = 0.1). The B antigen group (B or AB) had significantly longer PFS and OS than the non-B antigen group (A or O) (16.1 vs. 3.5 months for PFS, respectively, p = 0.03; 20.0 vs. 7.4 months for OS, respectively, p = 0.02). CONCLUSIONS: The presence of B antigen provides a significant advantage in terms of survival in patients using ICIs for advanced melanoma.
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    Prognostic factors and the prognostic role of inflammation indices in malignant pleural mesothelioma
    (Bayçınar Tıbbi Yayıncılık, 2023) Ebinç, Senar; Oruç, Zeynep; Kalkan, Ziya; Karhan, Oğur; Urakçı, Zuhat; Küçüköner, Mehmet; Kaplan, Muhammet Ali; Işıkdoğan, Abdurrahman
    Background: In this study, we aimed to investigate the prognostic factors of malignant pleural mesothelioma and the prognostic value of inflammation indices in malignant pleural mesothelioma. Methods: Between January 2002 and December 2019, a total of 132 patients (74 males, 58 females; mean age: 55 years; range, 31 to 79 years) diagnosed with malignant pleural mesothelioma were retrospectively analyzed. Patients’ demographic data and laboratory results were recorded. The prognostic value of the following five inflammation indices was evaluated: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, C-reactive protein/albumin ratio, and prognostic nutritional index. Results: Of all patients, 81% (n=107) were aged 65 or older and 61.4% (n=81) had an epithelioid histology. Of 12 variables examined in the multivariate analysis for their relationship with survival, age ≥65 years, non-epithelioid subtype, and prognostic nutritional index <40 were found to be poor prognostic factors. Based on the score constructed from these factors, the good prognostic group (score 0-1) had a median overall survival of 21 months and a one-year survival rate of 77.9%, while the poor prognostic group (score 2-3) had a median overall survival of nine months and a one-year survival rate of 29.7%. Conclusion: Our study results indicate that age ≥65 years, prognostic nutritional index <40, and non-epithelioid histological subtype are poor prognostic factors of malignant pleural mesothelioma.