Publications by authors named "Zafer Arik"

25 Publications

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Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy.

Support Care Cancer 2021 Mar 11. Epub 2021 Mar 11.

Department of Medical Oncology, Hacettepe University Cancer Institute, 06100 Sıhhıye, Ankara, Turkey.

Purpose: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. However, the association of VTE with immunotherapy remains poorly defined. We therefore evaluated the frequency of VTE in patients receiving immunotherapy and tried to determine predisposing factors.

Methods: A total of 133 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses.

Results: The median age was 60 (interquartile range (IQR) 48-66) years, and the median follow-up was 10.1 (IQR 5.8-18.5) months. Renal cell carcinoma (26.3%) and melanoma (24.1%) were most common diagnoses. Fifteen patients (11.3%) had an episode of VTE. Most of the VTEs were diagnosed as pulmonary emboli (10/15; 67%). Eighty percent (12/15) of these VTE cases were detected incidentally. Patients with a baseline ECOG performance status of 1 or more (29.3% of patients) had a significantly increased risk of venous thrombosis (ECOG ≥1 vs. 0, HR: 3.023, 95% CI: 1.011-9.039, p=0.048). Other factors, including patient age, tumor type, body mass index, baseline thrombocyte, neutrophil, and lactate dehydrogenase levels were not significantly associated with VTE risk.

Conclusions: In this study, we observed VTE development in more than 10% of immunotherapy-treated patients and increased VTE risk in patients with poorer ECOG status. With the asymptomatic nature of VTEs in most cases, a high index of suspicion level for VTE is required in patients treated with immunotherapy.
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http://dx.doi.org/10.1007/s00520-021-06139-3DOI Listing
March 2021

Frequency of germline BRCA1/2 mutations and association with clinicopathological characteristics in Turkish women with epithelial ovarian cancer.

Asia Pac J Clin Oncol 2021 Feb 25. Epub 2021 Feb 25.

Department of Gynecology and Obstetrics, Zekai Tahir Burak Women's Health Research and Education Hospital, Faculty of Medicine, University of Health Sciences, Ankara, Turkey.

Aim: This study aims to determine the frequency of germline BRCA 1/2 mutations in Turkish women with epithelial ovarian cancer (EOC) and evaluate its relationship with clinicopathological characteristics.

Methods: In this cross-sectional study, all women with recently diagnosed EOC presenting to Zekai Tahir Burak Women's Health Training and Research Hospital Medical Oncology Clinic between 2016 and 2019 were referred for BRCA testing. Peripheral blood samples were obtained from 76 patients applying to Medical Genetics and BRCA1/2 genes were sequenced using next-generation sequencing. The American College of Medical Genetics and Genomics 2015 criteria were followed for classification of genetic variants.

Results: Twenty-four women (31.6%) had pathogenic germline BRCA1/2 mutations. Of these, 17 patients (22.4%) harbored germline BRCA1 mutations and 7 (9.2%) had BRCA2 mutations. When we compared the patients with and without BRCA mutations, there was significant difference in terms of family history (41.7% vs 9.6%, respectively, P = .001). Among all patients, 15 (19.7%) had history of breast or ovarian cancer in first- or second-degree relatives. Germline BRCA1/2 mutations were detected in 66.7% of patients with family history, while these mutations were found in 22.9% of patients without family history (P = .001).

Conclusion: In this sample 31.6% of Turkish women with EOC harbored germline BRCA1/2 mutations, which seems higher compared to other ethnic groups except for the Ashkenazi Jews population. All women with EOC should be referred for BRCA testing regardless of family history, age at diagnosis, and histological subtype.
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http://dx.doi.org/10.1111/ajco.13520DOI Listing
February 2021

Evaluation of early unplanned readmissions and predisposing factors in an oncology clinic.

Support Care Cancer 2021 Jan 6. Epub 2021 Jan 6.

Department of Medical Oncology, Hacettepe University Cancer Institute, 06100, Sıhhiye, Ankara, Turkey.

Background: Unplanned readmission in the first 30 days after discharge is an important medical problem, although the data on cancer patients is limited. So we planned to evaluate the rates and causes of early readmissions and the predisposing factors.

Methods: Patients hospitalized in Hacettepe University Oncology services between August 2018 and July 2019 were included. The demographic features, tumor stages, regular drugs, last laboratory parameters before discharge, and readmissions in the first 30 days after discharge were recorded. The predisposing features were evaluated with univariate and multivariate analyses.

Results: A total of 562 hospitalizations were included. The mean age of the patients was 58.5 ± 14.5 years. Almost 2/3 of the hospitalizations were due to symptom palliation and infections. Eighty-three percent of the patients had advanced disease, and over 60% had an ECOG score of 2 and above. In the first 30 days after discharge, 127 patients were readmitted (22.6%). Advanced stage disease, presence of polypharmacy (5 or more regular drugs), hospitalization setting (emergency department (ED) vs. outpatient clinic), and hypoalbuminemia (< 3 gr/dL) were associated with a statistically significant increase in the risk of readmission. Among these factors, advanced-stage disease (HR: 2.847, 95% CI: 1.375-5.895), hospitalization from ED (HR: 1.832, 95% CI: 1.208-2.777), and polypharmacy (HR: 1.782, 95% CI: 1.173-2.706) remained significant in multivariate analyses.

Conclusions: In this study, 22% of cancer patients had early readmissions. The readmission risk increased in patients with advanced disease, hospitalization from ED, and polypharmacy. The optimal post-discharge plan may reduce readmissions in all oncology patients, with priority for these patient groups.
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http://dx.doi.org/10.1007/s00520-020-05927-7DOI Listing
January 2021

Perspectives, fears and expectations of patients with gynaecological cancers during the COVID-19 pandemic: A Pan-European study of the European Network of Gynaecological Cancer Advocacy Groups (ENGAGe).

Cancer Med 2021 01 18;10(1):208-219. Epub 2020 Nov 18.

Department of Surgery, Institute Gustave Roussy, Villejuif, France.

Background: The impact of the COVID-19 pandemic on European gynaecological cancer patients under active treatment or follow-up has not been documented. We sought to capture the patient perceptions of the COVID-19 implications and the worldwide imposed treatment modifications.

Methods: A patient survey was conducted in 16 European countries, using a new COVID-19-related questionnaire, developed by ENGAGe and the Hospital Anxiety & Depression Scale questionnaire (HADS). The survey was promoted by national patient advocacy groups and charitable organisations.

Findings: We collected 1388 forms; 592 online and 796 hard-copy (May, 2020). We excluded 137 due to missing data. Median patients' age was 55 years (range: 18-89), 54.7% had ovarian cancer and 15.5% were preoperative. Even though 73.2% of patients named cancer as a risk factor for COVID-19, only 17.5% were more afraid of COVID-19 than their cancer condition, with advanced age (>70 years) as the only significant risk factor for that. Overall, 71% were concerned about cancer progression if their treatment/follow-up was cancelled/postponed. Most patients (64%) had their care continued as planned, but 72.3% (n = 892) said that they received no information around overall COVID-19 infection rates of patients and staff, testing or measures taken in their treating hospital. Mean HADS Anxiety and Depression Scores were 8.8 (range: 5.3-12) and 8.1 (range: 3.8-13.4), respectively. Multivariate analysis identified high HADS-depression scores, having experienced modifications of care due to the pandemic and concern about not being able to visit their doctor as independent predictors of patients' anxiety.

Interpretation: Gynaecological cancer patients expressed significant anxiety about progression of their disease due to modifications of care related to the COVID-19 pandemic and wished to pursue their treatment as planned despite the associated risks. Healthcare professionals should take this into consideration when making decisions that impact patients care in times of crisis and to develop initiatives to improve patients' communication and education.
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http://dx.doi.org/10.1002/cam4.3605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753798PMC
January 2021

Lycopene sensitizes the cervical cancer cells to cisplatin via targeting nuclear factor- kappa B (NF-κB) pathway

Turk J Med Sci 2021 02 26;51(1):368-374. Epub 2021 Feb 26.

Department of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Background/aim: Lycopene is associated with anticancer effects in various tumor types. However, the exact underlying mechanisms of action of lycopene in human cervical cancer remain to be determined. This study aimed to determine anticancer efficacy and mechanism of lycopene in human cervical carcinoma (HeLa) cells.

Materials And Methods: HeLa cells were treated with cisplatin (1 μM) alone, lycopene (10 μM) alone, and in combination for 72 h. The cell viability of HeLa cells was assessed via MTS assay. Western blot was used to analyze the expression levels of the nuclear factor-kappa B (NF-κB), B-cell-associated X protein (Bax), nuclear factor erythroid 2-related factor (Nrf2), and B-cell lymphoma 2 (Bcl-2).

Results: We found that lycopene acts as a synergistic agent with cisplatin in preventing the growth of HeLa cells. The rates of HeLa cells’ viability were 65.6% and 71.1% with lycopene and cisplatin treatment alone compared to the control group, respectively (P < 0.001). The inhibitory effect of cisplatin was enhanced with lycopene addition by declining the cell viability to 37.4% (P < 0.0001). Lycopene treatment significantly increased Bax expression (P < 0.0001) and decreased Bcl-2 expression (P < 0.0001) in HeLa cells. Furthermore, lycopene markedly activated the Nrf2 expression (P < 0.001) and suppressed the NF-κB signaling pathway (P < 0.0001).

Conclusion: Lycopene increases the sensitization of cervical cancer cells to cisplatin via inhibition of cell viability, up-regulation of Bax expression, and down-regulation of Bcl-2 expression. Furthermore, the anticancer effect of lycopene might be also associated with suppression of NF-κB-mediated inflammatory responses, and modulation of Nrf2-mediated oxidative stress. The results of the present study suggest that lycopene and concurrent cisplatin chemotherapy might have a role in improving the treatment of cervical cancer.
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http://dx.doi.org/10.3906/sag-2005-413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991865PMC
February 2021

COVID-19 pandemic: changes in cancer admissions.

BMJ Support Palliat Care 2020 Jul 14. Epub 2020 Jul 14.

Department of Medical Oncology, Cancer Institute, Hacettepe University, Ankara, Turkey.

Background: COVID-19 pandemic could create a collateral damage to cancer care denoting disruptions in care due to a significant burden on healthcare and resource allocations. Herein, we evaluate the early changes in the inpatient and outpatient oncology clinics to take a snapshot of this collateral damage at Hacettepe University Cancer Institute.

Methods: Patients applying the outpatient clinic and outpatient palliative care (OPC) clinic for the first time and patients admitted to inpatient wards in the first 30 days after the first case of COVID-19 in Turkey were evaluated. These data were compared with data from the same time frame in the previous 3 years.

Results: The mean number of daily new patient applications to the outpatient clinic (9.87±3.87 vs 6.43±4.03, p<0.001) and OPC clinic (3.87±1.49 vs 1.13±1.46, p<0.001) was significantly reduced compared with the previous years. While the number of inpatient admissions was similar for a month frame, the median duration of hospitalisation was significantly reduced. The frequency of hospitalisations for chemotherapy was higher than in previous years (p<0.001). By comparison, the rate of hospitalisations for palliative care (p=0.028) or elective interventional procedures (p=0.001) was significantly reduced.

Conclusion: In our experience, almost all domains of care were affected during the pandemic other than patients' systemic treatments. There were significant drops in the numbers of newly diagnosed patients, patients having interventional procedures and palliative care services, and these problems should be the focus points for the risk mitigation efforts for prevention of care disruptions.
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http://dx.doi.org/10.1136/bmjspcare-2020-002468DOI Listing
July 2020

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

J Obstet Gynaecol 2021 Apr 29;41(3):414-420. Epub 2020 Apr 29.

Department of Radiation Oncology, Hacettepe University Medical School, Ankara, Turkey.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statement The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous. This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups. Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.
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http://dx.doi.org/10.1080/01443615.2020.1737661DOI Listing
April 2021

Defining the Optimal Regimen for Stage III Colon Cancer: Concerns with Study Design.

Clin Colorectal Cancer 2020 09 6;19(3):e71-e72. Epub 2020 Mar 6.

Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, Turkey.

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http://dx.doi.org/10.1016/j.clcc.2020.02.011DOI Listing
September 2020

Efficacy of Pazopanib in patients with metastatic uterine sarcoma: A multi-institutional study.

J BUON 2019 Nov-Dec;24(6):2327-2332

University of Health Sciences, Zekai Tahir Burak Women's Health Training and Research Hospital, Ankara, Turkey.

Purpose: Uterine sarcoma accounts for 3-9% of uterine malignant tumors and has poor prognosis. Pazopanib is an oral multi-kinase inhibitor and the only tyrosine kinase inhibitor which has been approved for metastatic soft tissue sarcoma. In the present study we aimed to evaluate the efficacy of pazopanib in metastatic uterine sarcoma.

Methods: The data of 28 metastatic uterine sarcoma patients receiving pazopanib therapy, who were followed in four oncology centers in Ankara, Turkey between May 2013 and June 2018, were retrospectively analyzed. Patients over 18 years, ECOG performance status ≤ 2, receiving at least one line of chemotherapy for metastatic disease, measurable disease at diagnosis, and histologically proven uterine high grade sarcoma were the inclusion criteria. Progression-free survival (PFS), overall survival (OS), and response rates to pazopanib were retrospectively evaluated.

Results: The median age was 53 years (range, 26-76). The majority of the patients had uterine leiomyosarcoma (LMS) (n=25, 89.3%), 2 (7.1%) had undifferentiated uterine sarcoma (UUS), and 1(3.6%) had high grade endometrial stromal sarcoma (ESS). The most common site of metastasis was lung (n: 21, 75%). The median time for pazopanib therapy was 5 months (0.6-28.3). In 22 patients (78.5%), pazopanib was discontinued due to disease progression, while 2 patients (7.1%) quitted therapy owing to toxicity. Partial response was achieved in 4 patients (14.3%), while 17 (60.7%) had stable disease. Median PFS was 5.2 months (95% CI 2.8-7.5) and median OS was 11.4 months (95% CI 3.4-19.5).

Conclusion: In the present study aiming to assess the real-life outcome of pazopanib-treated patients, we found that pazopanib is efficient in metastatic uterine sarcoma, and our results correspond to the literature.
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June 2020

Effectiveness of low-dose oral etoposide treatment in patients with recurrent and platinum-resistant epithelial ovarian cancer.

J Obstet Gynaecol 2017 Jul 21;37(5):649-654. Epub 2017 Mar 21.

a Department of Medical Oncology , Ankara Numune Education and Research Hospital , Ankara , Turkey.

The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment. The overall response rate was 19.2% and clinical benefit rate was 40.4% [PR (19.2%), SD (21.2%)]. Median overall survival (OS) and progression-free survival (PFS) was 9.95 months (95%CI, 0.2-19.7 months) and 3.2 months (95%CI 2.6-3.8 months), respectively. Grade III-IV haematologic and non-haematologic adverse events were observed in 7 (13.4%) patients. We consider that oral etoposide (50 mg/day, days 1-14, every 3 weeks) is an effective treatment with a manageable adverse effect profile in recurrent platinum-resistant EOC patients. Impact statement What is already known on this subject: Oral etoposide is an effective option for recurrent EOC patients at a dose of 50-100 mg/m/day (1-21 days, every 28 days) regimen. However, it has a high toxicity rate. What the results of this study add: Oral etoposide at a dose of 50 mg/kg (1-14 days, every 21 days) is an effective treatment with a manageable toxicity profile in platinum- resistant ovarian cancer patients when it is used as ≤4th-line palliative setting. What the implications are of these findings for clinical practice and/or further research: We need trials evaluating the effect of low-dose oral etoposide combination with bevacizumab or other chemotherapy agents (irinotecan and gemcitabine) in platinum-resistant EOC patients.
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http://dx.doi.org/10.1080/01443615.2017.1290056DOI Listing
July 2017

Molecular subtypes in patients with inflammatory breast cancer; a single center experience.

J BUON 2015 Jan-Feb;20(1):35-9

Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, Turkey.

Purpose: The purpose of this study was to investigate the frequency and prognosis of inflammatory breast cancer (IBC) according to molecular subtypes.

Methods: Demographic data were examined for 78 patients diagnosed with IBC among breast cancer patients monitored in our clinic. Patients were staged according to the 2010 AJCC guidelines. Physical examination and radiographic findings classified on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) guidelines were employed in the evaluation of clinical response to systemic therapy. Subtype analysis was performed in patients with IBC and subtypes were compared. Patients were divided on the basis of metastatic or non metastatic status and survival analysis was performed on the basis of molecular subtypes.

Results: Distribution analysis of molecular subtypes revealed a lower incidence of luminal A and a higher incidence of both HER 2 (+) and triple negative breast cancer in IBC. Molecular subtypes had no effect on survival in the non metastatic (p=0.61) and metastatic patient group (p=0.08).

Conclusion: This study showed that IBC frequency is higher in HER2 overexpressing and triple negative subtypes. No survival differences were noticed in relation to molecular subtypes in IBC patients.
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April 2015

Which sequence best protects the heart against trastuzumab and anthracycline toxicity? An electron microscopy study in rats.

Anticancer Res 2015 Feb;35(2):857-64

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

Background/aim: Two effective cytotoxic agents, doxorubicin and trastuzumab, are associated with potentially life-threatening cardiotoxicity. The present study was designed to investigate cardiotoxicity aggravated by the timing of administration of trastuzumab and doxorubicin in rats.

Materials And Methods: Twenty-four rats were randomly assigned to one of four groups. These received one of the following treatment drug regimens administered via intraperitoneal injection: (i) 0.9% saline control (n=6); (ii) doxorubicin (5 mg/kg) on day 1 then trastuzumab 10 mg/kg on day 15 (n=6); (iii) trastuzumab 10 mg/ kg on day 1 then doxorubicin (5 mg/kg) on day 15 (n=6) or (iv) doxorubicin (5 mg/kg) on day 1 and trastuzumab 10 mg/ kg on day 1 (n=6). On the 30th day, the hearts were processed for pathological analysis by electron microscopy.

Results: Electron microscopy revealed an ultrastructurally normal heart tissue in the control group. At electron microscopic examination of the tissue samples in the second and fourth group, a mild degree of dilation was observed in the peri-nuclear cisternae of some heart muscle cells. In the third group, pathological changes were detected in mitochondria. These exhibited prominent cristae, which also showed a mild degree of ultrastructural pathology in mitochondria.

Conclusion: Based on electron microscopy findings, sequential administration of anthracycline first, followed by trastuzumab is safer in terms of cardiotoxicity, while the most toxic schedule for the rat heart was trastuzumab first, followed by anthracycline.
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February 2015

Evaluation of the effect of comorbidity on survival in pancreatic cancer by using "Charlson Comorbidity Index" and "Cumulative Illness Rating Scale".

Wien Klin Wochenschr 2014 Jan 19;126(1-2):36-41. Epub 2013 Nov 19.

Department of Medical Oncology, Kahramanmaras Sutcu Imam University Faculty of Medicine, 46000, Merkez, Kahramanmaras, Turkey,

Background: Effect of comorbidity on the treatments that patients receive is not clear, as healthy elderly patients and the elderly with less comorbid diseases are included in the studies. In the present study, the effect of comorbidity on the survival was evaluated using Charlson Comorbidity Index (CCI) and Cumulative Illness Rating Scale (CIRS).

Material And Method: The general features and comorbid diseases of the pancreatic cancer patients were retrospectively screened from the patient files using the automated system. CCI and CIRS were used as the comorbidity indices.

Results: A total of 106 patients with pancreatic cancer were included in the study. The median overall survival rate was 9.0 [95 % confidence interval (CI): 6.7-11.3] months. The median overall survival rate was found as 9.4 (95 % CI: 6.7-12.1) months in the patients whose CCI score was ≤ 2 and was found as 6.2 (95 % CI: 4.0-8.3) months in the patients with CCI scores ≥ 3 (p = 0.05). The median overall survival rate was calculated as 9.8 (95 % CI: 6.3-13.4) months in the patients with CIRS scores ≤ 2 and was calculated as 8.3 (95 % CI: 6.0-10.6) months in the patients with CIRS scores ≥ 3 (p = 0.51). When surgery, radiotherapy, grading, and CCI score were evaluated using multivariate analysis, it was observed that only the treatment modality had a significant effect on the survival rate.

Conclusion: The results on the use of comorbidity indices are contradictory for the cancers with lower survival rates such as pancreatic cancer. New prognostic scales might be developed for this patient group by considering the side effects of chemotherapy.
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http://dx.doi.org/10.1007/s00508-013-0453-9DOI Listing
January 2014

Arrhythmias during and after zoledronic acid infusion patients with bone metastasis.

Med Oncol 2013 21;30(3):609. Epub 2013 May 21.

Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100 Sihhiye, Ankara, Turkey.

Zoledronic acid (ZA) is one of the important bisphosphonates which is widely used in bone metastatic cancer and osteoporotic patients. In a few studies, it has been reported that treatment with bisphosphonates was associated with an increased risk of atrial fibrillation. We aimed to evaluate the arrhythmias that developed during and immediately after infusion of the ZA. Fifty-two bone metastatic patients were included in the study group. All patients had 24-h Holter monitorization during the first dose ZA infusion day. All of the patients had 4-h basal cardiac rhythm records before ZA infusion and about 19 h after infusion. A short survey including demographic data and past medical history has been completed. None of patients had clinically important arrhythmias before ZA infusion. We divided arrhythmias into two groups as supraventricular and ventricular. We evaluated arrhythmias in pre-infusion, during infusion, and post-infusion periods. ZA was administered 4 mg intravenously (IV) in 15 min. Thirty-three of patients (63.5 %) were male and 19 (36.5 %) patients were female. Mean age of the patients was 53.9 ± 11.8 years. Most frequent cancers were breast (25 %) and lung cancer (15.3 %). Twelve (23 %) patients had history of mediastinal radiotherapy. In basal records, we detected that twenty-four (46 %) of patients had supraventricular premature complexes (SVPC) or ventricular premature complexes (VPC). Fifteen (28.8 %) of patients had SVPC and fourteen (26.9 %) had VPC during infusion period. After infusion period, 48 (92.3 %) of patients had SVPC and 41 (78.8 %) had VPC. Only 3 patients had no arrhythmia after infusion. Three patients had sinus arrhythmia and two had Mobitz type 2 atrioventricular blocks after infusion. One patient, who had no history of comorbidities and had SVPC in the basal records, developed atrial fibrillation that was refractory to medical cardioversion after 10 days of seventh dose of ZA infusion. In this study, we found that both SVPC and VPC increased in cancer patients treated with ZA. Furthermore, ZA may induce clinically important arrhythmias.
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http://dx.doi.org/10.1007/s12032-013-0609-5DOI Listing
April 2014

Association between common risk factors and molecular subtypes in breast cancer patients.

Breast 2013 Jun 14;22(3):344-50. Epub 2012 Sep 14.

Department of Medical Oncology, Ankara Oncology Research and Training Hospital, Ankara, Turkey.

Background: Breast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer.

Methods: This cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis.

Results: Thousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15-1.74; p=0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01-2.25; p=0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03-2.13; p=0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83-1.88; p=0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47-0.97; p=0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53-1.04; p=0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93-5.17; p=0.04) and luminal A (OR 1.87, 95% CI 0.93-3.90, p=0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06-3.37; p=0.04 and OR 1.90 95% CI 1.00-3.61; p=0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43-0.95; p=0.02 and OR 0.50 95% CI 0.32-0.76; p=0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands.

Conclusions: Reproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.
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http://dx.doi.org/10.1016/j.breast.2012.08.005DOI Listing
June 2013

Demographic and clinico-pathological characteristics of breast cancer patients with history of oral alendronate use.

Med Oncol 2012 Dec 15;29(4):2601-5. Epub 2012 Mar 15.

Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100, Sihhiye, Ankara, Turkey.

Bisphosphonates are the most commonly used agents in the treatment of osteoporosis, and bisphosphonate therapy reduces the risk of skeletally related complications in patients with bone metastases due to malignancy. However, the effect of oral alendronate treatment on clinical and pathological properties of breast cancer has not been reported. Thus, we aimed to investigate retrospectively the demographic and clinico-pathological characteristics of new diagnosis of breast cancer patients with oral alendronate users for longer than 1 year, compared with non-users. Newly diagnosed breast cancer patients from 1998 to 2010 in our clinic were retrospectively analyzed. Patient's demographics, including survival data and tumor characteristics, were obtained from medical charts. Breast cancer patients who were taking oral alendronate more than 12 months at the time of breast cancer diagnosis were enrolled as an alendronate users (n=44), where the patients matched with the same age who were not taking oral alendronate were included as a control group (n=444). A total of 488 patients were included in this study. Forty-four patients received an oral alendronate treatment more than 1 year, and 444 patients were considered as non-users. Median age of both alendronate users and non-users was 57 (33-89). Lower incidence of histological grade III, T3-T4 tumor, and node positivity was seen in alendronate users but not statistically significant. A similar trend for lower incidence of triple negative and higher incidence ER (P=0.13), progesterone receptor (P=0.12), and HER2 positivity (P=0.21) was also seen in alendronate users but not statistically significant. Estimated median disease-free survival was 150 months in alendronate users where as 70 months in non-users (P=0.015). Five-year survival rate in alendronate users was 97.4%, whereas in non-users was 89.8% (P=0.13). The use of oral alendronate for longer than 1 year at the time of breast cancer diagnosis was associated with better clinico-pathological properties and significantly improved disease-free survival in breast cancer patients.
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http://dx.doi.org/10.1007/s12032-012-0209-9DOI Listing
December 2012

Is there an association between blood group and survival in pancreatic cancer?

Asian Pac J Cancer Prev 2012 ;13(12):6151-3

Department of Medical Oncology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.

Background: An association between the ABO groups and pancreatic cancer has been shown previously, group A being significantly commoner in affected patients. We conducted the present study to investigate the prognostic effect of ABO blood group on overall survival of pancreas cancer patients.

Methods: Patients who were diagnosed between 2005 and 2010 with pancreas cancer at Ankara Numune Education and Research Hospital were analyzed retrospectively. Patient demographics and ABO blood groups were obtained from medical charts.

Results: Fifty pancreas cancer patients with known ABO blood group were included, 26 (52%) group A, 12 patients (24%) group 0, 9 (18%) group B, and 3 (6%) group AB. Blood group A pancreas cancer patient median age was 61.5 (39-80) years, with the median age of the other blood groups (B, AB,O) being 55.5 (32-74) years (p=0.14). 18% of patients with blood group A and11%of the other blood group patients had metastasis (p=0.17) at the time of diagnosis. The median overall survival of blood group A pancreas patients was significantly lower than the other blood group patients, 7.6 (95%CI: 5.0-10.2) months versus 29.0 (95%CI: 0.0-68.8) months (p=0.05).

Conclusions: Acccording to previously published cohort studies a relation may exist between ABO blood groups and cancer of pancreas. In this study we observed that pancreas cancer patients with blood group A have significantly worse overall survival than other blood groups.
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http://dx.doi.org/10.7314/apjcp.2012.13.12.6151DOI Listing
April 2016

Isolated Testicular Metastasis of Gastric Cancer.

J Gastrointest Cancer 2012 Sep;43 Suppl 1:S64-6

Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100, Sihhiye, Ankara, Turkey.

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http://dx.doi.org/10.1007/s12029-011-9305-xDOI Listing
September 2012