Publications by authors named "Ibrahim Gullu"

46 Publications

Thyroid gland metastasis mimicking thyroid carcinoma in a lung cancer patient and dramatic response to crizotinib: A case report.

Tuberk Toraks 2021 Mar;69(1):98-101

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

Metastasis of lung adenocarcinoma to the thyroid is extremely rare. Since treatment for primary thyroid cancer and non thyroid malignancy is totally different, precise diagnosis is clinically important.
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http://dx.doi.org/10.5578/tt.20219912DOI Listing
March 2021

A novel agnostic tumor: NTRKoma.

J Oncol Pharm Pract 2021 Mar 9:1078155221996049. Epub 2021 Mar 9.

Department of Medical Oncology, 37515Hacettepe University Cancer Institute, Ankara, Turkey.

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http://dx.doi.org/10.1177/1078155221996049DOI Listing
March 2021

Can Levamisole be used in the treatment of COVID-19 patients presenting with diarrhea?

J Infect Dev Ctries 2020 Aug 31;14(8):844-846. Epub 2020 Aug 31.

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China, on Jan 7, 2020. Over the following months, the virus rapidly spread throughout the world. Coronavirus Disease 2019 (COVID-19) can involve the gastrointestinal tract, including symptoms like nausea, vomiting and diarrhea and shedding of the SARS-CoV-2 in feces. Angiotensin-converting enzyme 2 (ACE2) protein, which has been proven to be a cell receptor for SARS-CoV-2, is expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells. According to the literature, rates of COVID-19 patients reporting diarrhea were between 7 - 14%. Diarrhea in the course of COVID-19 disease can cause dehydration and hospitalization. Although no antiviral drug was specifically designed for the treatment of diarrhea, several molecules could have beneficial effects by reducing viral replication. In this letter, we discussed the Levamisole, which is an anthelmintic agent with immunomodulatory effects, could be used effectively both for antiviral therapy and especially in COVID-19 patients with diarrhea.
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http://dx.doi.org/10.3855/jidc.13101DOI Listing
August 2020

Cancer incidence in Behçet's disease.

Ir J Med Sci 2020 Nov 8;189(4):1209-1214. Epub 2020 May 8.

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

Background: Previous studies demonstrated an increased cancer risk in autoimmune diseases. Behçet's disease (BD) was also reported to be associated with an increased risk of cancer, although the data is limited.

Aims: In this study, we aimed to assess cancer incidence in a large cohort of BD patients and to compare with the data of the same age and gender groups.

Methods: The study cohort consisted of BD patients of > 18 years of age who were prospectively recorded in the Hacettepe University Vasculitis Center. Data on any cancer was collected from the patient files. Cancer incidence was compared with age- and gender-specific cancer incidence rates of the normal population retrieved from the 2014 Turkish National Cancer Registry (TNCR) data using standardized incidence rates (SIR).

Results: Totally, 451 adult cases with BD were included. The median age of the cohort was 43 (20-75), and 52.5% of the patients were males. Eleven cancer cases were observed during a median of 124 months follow-up. Behçet's disease was associated with an increase in cancer risk compared with expected counts in the corresponding age and sex group (SIR 2.84, 95% CI 1.50-4.94, p < 0.001). Patients with papulopustular lesions had a trend toward a decreased risk of cancer (p = 0.060), and patients using azathioprine had a significantly decreased cancer risk (p = 0.031).

Conclusion: This study revealed BD patients had approximately three times increased cancer risk compared with corresponding age and sex groups. Besides the routine care, increased attention for cancer surveillance is required in the follow-up of BD patients.
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http://dx.doi.org/10.1007/s11845-020-02244-0DOI Listing
November 2020

The Synergistic Effect of Immune Checkpoint Blockade and Radiotherapy in Recurrent/Metastatic Sinonasal Cancer.

Cureus 2018 Oct 29;10(10):e3519. Epub 2018 Oct 29.

Radiation Oncology, Hacettepe University Medical School, Ankara, TUR.

Treatment options for recurrent/metastatic sinonasal cancer (RMSNC) patients are limited. We present two cases with RMSNC treated with a combination of immune checkpoint blockade and hypo-fractionated stereotactic radiotherapy (HSRT).  Case 1 presented with RMSNC three months after the primary treatment. The patient progressed under first-line chemotherapy and pembrolizumab was offered. The disease progressed after the sixth cycle. We performed reirradiation with HSRT to the primary site. Case 2 presented with local recurrence eight years after the primary treatment for maxillary sinus cancer. He refused surgery and chemotherapy and was offered nivolumab treatment. After two doses, we performed reirradiation with HSRT. Case 1 showed regression at both the local and the metastatic sites after radiotherapy. The second patient's symptoms resolved completely three months after radiotherapy. The HSRT and immune checkpoint blockade combination is a promising treatment option for patients with RMSNC.
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http://dx.doi.org/10.7759/cureus.3519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318133PMC
October 2018

Human papillomavirus infection in patients with laryngeal carcinoma.

BMC Cancer 2018 Oct 20;18(1):1005. Epub 2018 Oct 20.

Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey.

Background: The aim of this study was to determine the HPV positivity rate in patients with laryngeal cancer, and to determine the effect of HPV positivity on survival. An additional aim was to determine if patients with HPV positive laryngeal cancer are more sensitive to chemotherapy and if such sensitivity differs according to chemotherapy protocol.

Methods: The study included laryngeal specimens obtained from 82 laryngeal cancer patients and 11 laryngeal specimens with normal laryngeal mucosa that were obtained from our hospital's paraffin block archives between 1995 and 2013. HPV was detected via chromogenic in situ hybridization (cISH) and confirmed via genotyping.

Results: HPV was not detected in any of the 82 laryngeal cancer patients' laryngeal specimens, nor in any of the 11 archived laryngeal specimens with normal laryngeal mucosa via cISH. Genotyping confirmed these findings; none of the HPV types studied were detected in any of the specimens. As none of the study samples were HPV positive, it was not possible to compare survival, recurrence, or chemotherapy sensitivity.

Conclusions: HPV infection is not a leading cause of laryngeal cancer; however, additional research on HPV positivity in patients with laryngeal cancer and its effect on recurrence, survival, and chemotherapy sensitivity is warranted.
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http://dx.doi.org/10.1186/s12885-018-4890-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195980PMC
October 2018

Primary gastric choriocarcinoma.

J BUON 2018 Mar-Apr;23(2):534

Dr.Abdurrahman Yurtaslan Training and Research Hospital, Dept of Medical Oncology, Ankara.

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August 2019

Modified docetaxel, cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study.

Curr Med Res Opin 2017 03 8;33(3):401-407. Epub 2016 Dec 8.

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

Aim: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC).

Methods: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2-6 cycles of mDCF chemotherapy which consisted of docetaxel 60 mg/m intravenously (IV) on day 1, cisplatin 60 mg/m IV on day 1, and 5-fluorouracil 600 mg/m IV for 5 days of continuous infusion, with cycles repeated every 21 days.

Results: The most common grade 3-4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3-8.6) and 11.5 (95% CI: 9.4-13.7) months, respectively.

Conclusions: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.
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http://dx.doi.org/10.1080/03007995.2016.1257984DOI Listing
March 2017

Detection of O6-methylguanine-DNA methyltransferase gene promoter region methylation pattern using pyrosequencing and the effect of methylation pattern on survival, recurrence, and chemotherapy sensitivity in patients with laryngeal cancer.

Pathol Res Pract 2016 May 26;212(5):456-62. Epub 2016 Feb 26.

Department of Preventive Oncology, Hacettepe University Cancer Institute, Sihhiye 06100, Ankara, Turkey.

Aim: To determine the methylation pattern of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene in laryngeal cancer and normal laryngeal mucosa samples using pyrosequencing, and to determine the relationship between the methylation pattern of MGMT, and tumor stage, survival, recurrence, and chemosensitivity in patients with laryngeal cancer.

Materials And Methods: Laryngeal cancer and normal laryngeal mucosa specimens were obtained from our paraffin block archives, and then subjected to pyrosequencing. Different cut-off values were used to detect methylation. Clinicopathological data for the patients that provided specimens were obtained from archive records.

Results: When 5% was used as the cut-off value, 78% of the laryngeal cancer specimens (64 of 82), and 27.3% of normal laryngeal mucosa specimens (3 of 11) were considered methylated. When 10% was used as the cut-off value, 47% of the laryngeal cancer specimens (39 of 82), and none of the normal laryngeal mucosa specimens were considered methylated. There was not a significant relationship between the methylation status of MGMT, and clinicopathological parameters, including age, tumor stage, histopathological differentiation, chemoradiotherapy protocol used, recurrence, or disease-free survival.

Conclusion: Pyrosequencing is a reliable semiquantitative technique that can be used to detect the methylation pattern. Methylation was common in the laryngeal cancer specimens, but there was not a significant relationship between the methylation status of MGMT and clinicopathological parameters.
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http://dx.doi.org/10.1016/j.prp.2016.02.022DOI Listing
May 2016

Renal cell carcinoma metastatic to the tongue: a case report and review of the literature.

J Oral Maxillofac Surg 2015 Jun 8;73(6):1227-30. Epub 2015 Jan 8.

Professor, Department of Medical Oncology, Hacettepe University School of Medicine, Anakara, Turkey.

Renal cell carcinoma (RCC) metastatic to the head and neck region is quite rare. This report describes a case of RCC metastatic to the oral tongue presenting initially with a renal mass that evaded diagnosis by biopsy examination of the primary lesion and was eventually established as a papillary type RCC by lingual biopsy examination. The tongue mass progressed rapidly despite chemotherapy with interferon-α2b, caused difficulties with oral food intake, and thus necessitated removal by partial glossectomy. Treatment alternatives for lingual RCC metastasis include surgical resection for major functional impairment, risk of airway compromise, or massive hemorrhage. Radiotherapy might be useful and should be considered for specific patients. Lingual metastasis from RCC usually predicts poor survival.
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http://dx.doi.org/10.1016/j.joms.2014.12.031DOI Listing
June 2015

Comparison of three different induction regimens for nasopharyngeal cancer.

Asian Pac J Cancer Prev 2015 ;16(1):59-63

Department of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey E-mail :

Background: The standard treatment of local advanced nasopharyngeal cancer is chemoradiotherapy. There is a lack of data concerning induction therapy. In this study we retrospectively examined patients treated with induction therapy and chemoradiotherapy.

Materials And Methods: Locally advanced nasopharyngeal cancer patients treated between 1996 and 2013 in our clinic were included in the study. Three different induction regimens were administered to our patients in different time periods. The regimen dosages were: CF regimen, cisplatin 50mg/m2 1-2 days, fluorouracil 500mg/m2 1-5 days; DC, docetaxel 75mg/m2 1 day, cisplatin 75mg/m2 1 day; and DCF, docetaxel 75mg/m2 1 day, cisplatin 75mg/m2 1 day, 5-Fu 750mg/m2 1-5 days. Most of the patients were stage III (36.4%) and stage IV (51.7%).

Results: Median follow-up time was 50 months (2-201 months). Three-year progression-free survival (PFS) was 79.3%, and 5-year PFS 72.4% in all patients. Three-year overall survival (OS) was 87.4% and 5-year OS 76% in all patients. In terms of induction therapies, 3-year OS was 96.5% in the DCF group, 86.6% in the DC group and 76.3% in the CF group (p=0.03).

Conclusions: There was no significant differences in response rate and PFS between the three regimens. OS in the DCF group was significantly higher than in the other groups. However, this study was retrospective and limited toxicity data were available; the findings therefore need to be interpreted with care.
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http://dx.doi.org/10.7314/apjcp.2015.16.1.59DOI Listing
October 2015

Long-term complications in Hodgkin's lymphoma survivors.

Tumori 2012 Sep-Oct;98(5):601-6

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

Background. Although patients with Hodgkin's lymphoma (HL) achieve prolonged survival, long-term complications are a major cause of morbidity and mortality among long-term survivors of HL. Methods. We retrospectively evaluated long-term complications in 336 HL survivors treated between January 1990 and January 2006 at the Department of Medical Oncology of the Hacettepe University Institute of Oncology who were >16 years old at presentation. All patients were regularly followed up every 3 months for the first 2 years after complete response, biannually for 3 years, and annually after 5 years. Results. Median follow-up was 8.5 years. The mean age (±SD) of the patients at the time of diagnosis was 35.7 ± 13.1 years. The male to female ratio was 61%/39%. During follow-up, 29 second malignancies (8.6%) were diagnosed in 28 patients with HL; 22 were solid tumors and 7 were hematological malignancies. Forty-seven (14.0%) of all patients with HL were found to have thyroid abnormalities. During follow-up, 54 (16.1%) patients developed cardiovascular complications. Overall, 29 (8.6%) patients developed late pulmonary toxicities. The cumulative number of chronic viral infections was 13 (3.9%). Conclusions. Long-term survivors of HL need to be properly followed up not only for disease control but also for evaluation of possible late morbidities to minimize the consequences.
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http://dx.doi.org/10.1700/1190.13201DOI Listing
February 2013

Ifosfamide and doxorubicin combination chemotherapy for recurrent nasopharyngeal carcinoma patients.

Asian Pac J Cancer Prev 2012 ;13(5):2225-8

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

Background: We assessed the efficacy and toxicity of ifosfamide and doxorubicin combination chemotherapy (CT) regimen retrospectively in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy.

Methods: A total of thirty patients who had received cisplatin based chemotherapy/chemoradiotherapy as a primary treatment received ifosfamide 2500 mg/m2 days 1-3, mesna 2500 mg/m2 days 1-3, doxorubicin 60 mg/m2 day 1 (IMA), repeated every 21 days. Eligible patients had ECOG PS<2, measurable recurrent or metastatic disease, with adequate renal, hepatic and hematologic functions.

Results: Median age was 47 (min-max; 17-60). Twenty six (86.7%) were male. Median cycles of chemotherapy for each patient were 2 (range:1-6). Twenty patients were evaluable for toxicity and response. No patient achieved complete response, with nine partial responses for a response rate of 30.0% in evaluable patients. Stable disease, and disease progression were observed in five (16.7%) and six (20.0%) patients, respectively. Clinical benefit was 46.7%. Median time to progression was 4.0 months. Six patients had neutropenic fever after IMA regimen and there were one treatment-related death due to tumor lysis syndrome in first cycle of the CT. No cardiotoxicity was observed after CT and treatments were generally well tolerated.

Conclusion: Ifosfomide and doxorubicin combination is an effective regimen for patients with recurrent and metastatic NPC. For NPC patients demonstrating failure of cisplatin based regimens, this CT combination may be considered as salvage therapy.
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http://dx.doi.org/10.7314/apjcp.2012.13.5.2225DOI Listing
January 2013

Increased mean corpuscular volume of erythrocytes during capecitabine treatment: a simple surrogate marker for clinical response.

Tumori 2011 Nov-Dec;97(6):711-6

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

Aims And Background: Capecitabine, as all fluoropyrimidines, interferes with vitamin metabolism and may thus have an impact on hematopoiesis. It is metabolized to its active form 5-fluoruracil by the enzyme thymidine phosphorylase, which exists in higher concentrations in tumor tissue and liver than in normal tissues. In the study, we investigated the changes in mean corpuscular volume (MCV) of red blood cells and the possible correlation of these changes with the clinical outcome of capecitabine treatment in women with metastatic breast cancer.

Methods And Study Design: Data from 75 metastatic breast cancer patients were analyzed retrospectively. Capecitabine was used at a dose of 2500 mg/m² daily for 14 days of every 3-week period. Mean corpuscular volume of red blood cells and other parameters of complete blood count were recorded at the beginning of the treatment, in the ninth week, and periodically thereafter.

Results: Mean age was 51.5 ± 10.8 and 61.3% of the patients were premenopausal. Capecitabine was administered as the median 3rd line (min-max: 1-9) treatment and a median of 6 cycles (min-max: 1-24) for metastatic breast cancer. Median ΔMCV level (post-treatment values at ninth week - baseline) was 8. ΔMCV was ≥8 in 37 patients and <8 in 38 patients. The 35 of the 37 patients with ΔMCV level ≥8 and 25 of the 38 patients with ΔMCV level <8 had clinical benefit (complete response + partial response + stable disease) from capecitabine treatment (P = 0.02). However, the difference between progression-free survival of the patients with ΔMCV levels higher than 8 and those with ΔMCV levels lower than 8 according to Kaplan-Meier survival analysis was not statistically significant (6.7 and 4.3 months, respectively, P = 0.26). Additionally, median ΔMCV level was 9.1 (min-max: -2.4 to 24.9) among patients who had clinical benefit and 5.90 (min-max: -0.8 to 12.3) among nonresponders (P = 0.016).

Conclusions: Capecitabine increases the mean corpuscular volume levels of red blood cells by a yet unidentified mechanism. Early increment of mean corpuscular volume levels is higher than 8, i.e. by the 9th week, might predict clinical benefit from the treatment.
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http://dx.doi.org/10.1700/1018.11086DOI Listing
April 2012

A retrospective comparison of robotic stereotactic body radiotherapy and three-dimensional conformal radiotherapy for the reirradiation of locally recurrent nasopharyngeal carcinoma.

Int J Radiat Oncol Biol Phys 2011 Nov 22;81(4):e263-8. Epub 2011 Apr 22.

Hacettepe University, Faculty of Medicine, Department of Radiation Oncology, Ankara, Turkey.

Purpose: We assessed therapeutic outcomes of reirradiation with robotic stereotactic radiotherapy (SBRT) for locally recurrent nasopharyngeal carcinoma (LRNPC) patients and compared those results with three-dimensional conformal radiotherapy (CRT) with or without brachytherapy (BRT).

Methods And Materials: Treatment outcomes were evaluated retrospectively in 51 LRNPC patients receiving either robotic SBRT (24 patients) or CRT with or without BRT (27 patients) in our department. CRT was delivered with a 6-MV linear accelerator, and a median total reirradiation dose of 57 Gy in 2 Gy/day was given. Robotic SBRT was delivered with CyberKnife (Accuray, Sunnyvale, CA). Patients in the SBRT arm received 30 Gy over 5 consecutive days. We calculated actuarial local control and cancer-specific survival rates for the comparison of treatment outcomes in SBRT and CRT arms. The Common Terminology Criteria for Adverse Events v3.0 was used for toxicity evaluation.

Results: The median follow-up was 24 months for all patients. Two-year actuarial local control rates were 82% and 80% for SBRT and CRT arms, respectively (p = 0.6). Two-year cancer-specific survival rates were 64% and 47% for the SBRT and CRT arms, respectively (p = 0.4). Serious late toxicities (Grade 3 and above) were observed in 21% of patients in the SBRT arm, whereas 48% of patients had serious toxicity in the CRT arm (p = 0.04). Fatal complications occurred in three patients (12.5%) of the SBRT arm, and four patients (14.8%) of the CRT arm (p = 0.8). T stage at recurrence was the only independent predictor for local control and survival.

Conclusion: Our robotic SBRT protocol seems to be feasible and less toxic in terms of late effects compared with CRT arm for the reirradiation of LRNPC patients.
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http://dx.doi.org/10.1016/j.ijrobp.2011.02.054DOI Listing
November 2011

Demographic and clinico-pathological characteristics in patients with triple-negative and non-triple-negative breast cancer.

Med Oncol 2011 Dec 21;28 Suppl 1:S75-9. Epub 2010 Oct 21.

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

We investigate retrospectively the demographic and clinico-pathological characteristics of patients with triple-negative breast cancer (TNBC) compared to those with non-TNBC. Patients with breast cancer diagnosed from 1981 to 2008 in our clinic were retrospectively analyzed. Patient demographics including survival data and tumor characteristics were obtained from charts. A total of 795 patients were assessed in the study, including 140 patients (17.6%) with TNBC and 655 patients (82.4%) with non-TNBC. Patients with non-TNBC were further classified into 3 groups according to hormone receptor (HR) and HER-2 status. Median age was 49 (range 38-60 years) and similar between patients with TNBC and non-TNBC. Patients with TNBC had an increased likelihood of a higher histological grade III compared with HR(+) HER-2(-) subgroup (P > 0.001) and lower stage compared with HR(+)/HER2(+) and HR(-)/HER2(+) subgroups (P < 0.001 and P = 0.002, respectively). In patients with TNBC, the disease-free survival (DFS) rate was 66% at 5 years. In subgroup analysis of non-TNBCs, 5-year-DFS rates of the patients in HR(+)/HER2(-), HR(+)/HER2(+) and HR(-)/HER2(+) subgroups were 59, 66, and 57%, respectively. There was no significant difference between the TNBC and non-TNBC subgroups (P = 0.238). In multivariate analysis, nodal involvement (RR = 2.8, 95% CI: 0.99-8.3, P = 0.052) and the presence of lymphovascular invasion (RR = 3.2, 95% CI: 1.1-9.2, P = 0.029) were significantly associated with increased recurrence risk in patients with TNBC. Although there are differences in patient and tumor features, patients with TNBC had similar clinical course with those with non-TNBC.
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http://dx.doi.org/10.1007/s12032-010-9715-9DOI Listing
December 2011

Salvage reirradiaton with stereotactic body radiotherapy for locally recurrent head-and-neck tumors.

Int J Radiat Oncol Biol Phys 2011 Sep 2;81(1):104-9. Epub 2010 Aug 2.

Department of Radiation Oncology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.

Purpose: In this study, we present our results of reirradiation of locally recurrent head-and-neck cancer with image-guided, fractionated, frameless stereotactic body radiotherapy technique.

Methods And Materials: From July 2007 to February 2009, 46 patients were treated using the CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey. All patients had recurrent, unresectable, and previously irradiated head-and-neck cancer. The most prominent site was the nasopharynx (32.6%), and the most common histopathology was epidermoid carcinoma. The planning target volume was defined as the gross tumor volume identified on magnetic resonance imaging and computed tomography. There were 22 female and 24 male patients. Median age was 53 years (range, 19-87 years). The median tumor dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median of five (range, one to five) fractions.

Results: Of 37 patients whose response to therapy was evaluated, 10 patients (27%) had complete tumor regression, 11 (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local disease control was achieved in 31 patients (83.8%). The overall survival was 11.93 months in median (ranged, 11.4-17.4 months), and the median progression free survival was 10.5 months. One-year progression-free survival and overall survival were 41% and 46%, respectively. Grade II or greater long-term complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%) patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding from carotid arteries. We discovered that this fatal syndrome occurred only in patients with tumor surrounding carotid arteries and carotid arteries receiving all prescribed dose.

Conclusions: Stereotactic body radiotherapy is an appealing treatment option for patients with recurrent head-and-neck cancer previously treated with radiation to high doses. Good local control with considerable 1-year survival is achieved with a relatively high rate of morbidity and related mortality.
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http://dx.doi.org/10.1016/j.ijrobp.2010.04.027DOI Listing
September 2011

FDG-PET/CT in the evaluation of epithelioid hemangioendothelioma of the liver: the role of dual-time-point imaging. A case presentation and review of the literature.

Ann Nucl Med 2010 Aug 23;24(7):549-53. Epub 2010 Apr 23.

Department of Nuclear Medicine, Gazi University, Ankara, Turkey.

A 46-year-old man with liver lesions referred to us as having "metastases of a malignant mesenchymal tumor" underwent PET/computerized tomography (CT) imaging for the localization of the primary tumor and determination of the extent of disease. No pathological FDG uptake was observed in PET/CT images obtained after 60 min, following FDG injection but delayed PET/CT images demonstrated intense FDG uptake at the liver masses. Since the PET/CT findings were discordant with the initial diagnosis, the pathology specimen was reevaluated and with certain immunohistochemical examinations, the final histopathological decision was changed to epithelioid hemangioendothelioma (EHE). In this report, we discuss the FDG uptake pattern in a patient with hepatic EHE and emphasize the importance of dual-time-point hepatic FDG-PET/CT imaging.
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http://dx.doi.org/10.1007/s12149-010-0379-5DOI Listing
August 2010

Comparative study of the immunohistochemical detection of hormone receptor status and HER-2 expression in primary and paired recurrent/metastatic lesions of patients with breast cancer.

Med Oncol 2011 Mar 23;28(1):57-63. Epub 2010 Jan 23.

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

Recent studies have shown some degrees of discordance in ER, PR and HER-2 immunohistochemical expression between primary and recurrent/metastatic lesions (RML). Analysis was made on 78 patients with MBC whose ER, PR and/or HER-2 status were known both on the tissue samples of primary and RML. Among the RML sites, 29.5% were locoregional, 70.5% were distant metastatic sites. Among 75 patients with known ER expression on both primary and RML, 36% (n = 27) showed discordance on ER expression. Among 72 patients with known PR expression on both primary and RML, 54.2% (n = 39) showed discordance on PR expression. Among 61 patients with known HER-2 expression on both primary and RML, 14.7% (n = 9) showed discordance on HER-2 expression. No differences were observed when we compared patients who have discordant ER and HER-2 status with patients who have concordant results between the primary tumor and paired RML with respect to site of biopsy (locoregional vs distant metastasis) and prior therapies (chemotherapy and endocrine therapy). As these discordant results make changes in treatment decision, a biopsy of the metastatic lesion could be recommended in patients with MBC when feasible. Larger series are needed to identify the potential effect of prior therapies and site of metastasis on discordant results.
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http://dx.doi.org/10.1007/s12032-010-9418-2DOI Listing
March 2011

Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

J Natl Med Assoc 2008 May;100(5):521-6

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

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.
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http://dx.doi.org/10.1016/s0027-9684(15)31298-0DOI Listing
May 2008

Renal safety of zoledronic acid administration beyond 24 months in breast cancer patients with bone metastases.

Med Oncol 2008 15;25(3):356-9. Epub 2008 Jan 15.

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

Zoledronic acid (ZA) delays the onset or reduces the incidence of skeletal complications in breast cancer patients with bone metastases. However, there are few data on the long-term renal safety of ZA. We retrospectively evaluated 43 breast cancer patients with bone metastases who received ZA more than 24 months. The following parameters measured prior to first ZA use and after the last dose of ZA administration were compared: serum creatinine (SCr), blood urea nitrogen (BUN), alkaline phosphatase (ALP), calcium (Ca), and phosphorous (P). Forty-three breast cancer patients with documented bone metastases were evaluated. Median age at the start of treatment was 53 years (range 37-77). Median overall duration of ZA administration was 36 months (25-62). There were no statistically significant differences in the pre- and post-treatment levels of SCr, BUN, Ca and P. However, ALP levels after long-term ZA administration were decreased significantly (P<0.05). More than 24 months of ZA administration did not adversely affect the renal function. ZA can be used safely in breast cancer patients with bone metastases beyond 2 years.
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http://dx.doi.org/10.1007/s12032-008-9045-3DOI Listing
December 2008

Concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer.

Med Oncol 2007 ;24(2):239-43

Dept. of Radiation Oncology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, 06100, Turkey. mcengiz@hacettepe

This study is designed to assess the toxicity and therapeutic effectiveness of concurrent gemcitabine and radiotherapy in patients with unresectable pancreatic cancer. Concurrent gemcitabine (400 mg/m2/wk) in six weekly cycles starting on d 1 of radiotherapy (50.4 Gy; 1.8 Gy/fraction/d; 5 d/wk) was prescribed on 22 patients with locally advanced pancreatic cancer. Patients were analyzed with regard to radiological response on computerized tomography, overall survival, and toxicity. Twelve (55%) patients completed the prescription of six gemcitabine cycles and 50.4 Gy radiotherapy; while 10 (45%) received one to five cycles of gemcitabine owing to neutropenia. All patients experienced abdominal discomfort during treatment and three patients required medical intervention. Other toxicities reported were nausea in 13 patients (60%), grade 3 vomiting in 3 (14%). Radiological response evaluations were as follows: complete, 2 (9%); partial, 9 (41%); stable, 7 (32 %); and progressive, 4 (18 %). Median survival was 8.7 mo. Combination of weekly gemcitabine (400 mg/m2) and radiotherapy provided response in 50% of the patients but was associated with severe toxicity resulting in incomplete delivery of the planned chemotherapy.
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http://dx.doi.org/10.1007/BF02698046DOI Listing
December 2007

Serum lactate dehydrogenase level is a prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

Cancer Invest 2007 Aug;25(5):315-21

Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey.

We investigated the treatment results and probable prognostic factors in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NCT) plus conventional radiotherapy (RT) or concomitant chemoradiotherapy (CCRT) at our hospital. We retrospectively evaluated 61 patients (48 males, 13 females) with locoregionally advanced NPC treated either with 2 cycles of NCT plus RT (Group A, 37 patients) or with three cycles of NCT plus CCRT (Group B, 24 patients) between September 1995 and October 2002. According to the AJCC 1997 classification system, 19 patients had Stage III disease and 42 had Stage IV. NCT consisted of cisplatin and 5-fluorouracil. Total RT doses were ranged between 59.4-71.6 Gy (median: 66.2 Gy). Concomitant cisplatin (75 mg/m(2)) was given on first days of Weeks 1, 4, 7 of CCRT. Patient sex, histopathologic subtype, T status, ECOG performance status, stage, serum lactate dehydrogenase (LDH) level, and cranial nerve involvement at diagnosis were comparable in the 2 groups. There were statistically significant differences between median follow-up times and N status for the 2 groups. Fifty-five (90.2 percent) patients completed all planned NCT. Univariate analysis revealed the pretreatment LDH level as the only statistically significant prognostic factor for disease-free survival (DFS) and overall survival (OS). Four-year DFS rates were 55.9 percent and 21.3 percent for patients with normal and high serum LDH levels, respectively (P = 0.04). Four-year OS rates were 68.7 percent and 28.5 percent for patients with normal and high serum LDH levels, respectively (P = 0.01). Multivariate analysis also revealed that high serum LDH level was the only independent risk factor that predicted OS. The relative risk was 2.43 (95%CI: 1.08-5.45) for patients with high serum LDH levels (P = 0.03). No independent risk factors associated with DFS were found for other prognosticators. Our study demonstrated that high serum LDH level is the only independent unfavorable risk factor for OS in patients with locoregionally advanced NPC who were treated with NCT plus RT or CCRT.
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http://dx.doi.org/10.1080/07357900701209103DOI Listing
August 2007