Publications by authors named "Nazim Serdar Turhal"

31 Publications

Efficacy and tolerability of current treatments for hormone-refractory prostate cancer patients with visceral metastases.

Future Oncol 2021 May 26;17(13):1611-1624. Epub 2021 Feb 26.

Department of Medical Oncology, Dicle University Faculty of Medicine, Diyarbakır, Turkey.

To assess the efficacy and tolerability of the first-line treatment options for hormone-refractory prostate cancer patients with visceral metastases. The records of 191 patients diagnosed with hormone-refractory prostate cancer with visceral metastases were analyzed retrospectively. Docetaxel was administered to 61.2% (n = 117), abiraterone to 14.2% (n = 27) and enzalutamide to 9.4% (n = 18) as the first-line treatment. The median survival of the patients receiving docetaxel, abiraterone and enzalutamide as the first-line treatment during the hormone-refractory period was 15 (95% Cl: 12.9-17) months, 6 (95% Cl: 1.8-10.1) months and 11 (95% Cl: 0.9-23.1) months (p = 0.038), respectively. The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival.
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http://dx.doi.org/10.2217/fon-2020-1032DOI Listing
May 2021

Trastuzumab ± Capecitabine Maintenance After the First-Line Treatment of HER2-Positive Advanced Gastric Cancer: Retrospective Observational Real-Life Data of Turkish Oncology Group.

J Gastrointest Cancer 2021 Feb 4. Epub 2021 Feb 4.

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

Purpose: In the ToGA trial for HER2-positive advanced gastric cancer, cisplatin plus fluoropyrimidine was given for 6 cycles; trastuzumab was given until disease progression. However, there is a lack of real-life data about trastuzumab maintenance after 6 cycle chemotherapy. This study aims to present real-life data of trastuzumab ± capecitabine maintenance after 6 cycles of platinum, fluoropyrimidine, and trastuzumab in non-progressive patients.

Methods: This is a retrospective multicenter study of the Turkish Oncology Group. A total of 35 HER2-positive, inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma patients being non-progressive at the end of 6 cycle chemotherapy and being given trastuzumab ± capecitabine as maintenance treatment were included from sixteen oncology centers. Baseline characteristics, objective tumor responses, progression free and overall survival data, and toxicities were determined.

Results: About 68% of the patients were given CF, and 32% were given FOLFOX with trastuzumab as the first-line treatment. The best response in 6 cycle chemotherapy was complete 8 (22%), partial 24 (68%), and stable disease 3 (8%). All patients had trastuzumab maintenance (median cycle 13; range 7-51), and 49% of the patients had capecitabine with trastuzumab (median capecitabine cycle 6; range 2-30). The median PFS of the patients was 12.0 months (95% CI 10.3-13.7), and median OS was 17.4 months (95% CI 15.2-19.5). There were 2 patients with grade 1 cardiotoxicity.

Conclusion: Trastuzumab maintenance ± capecitabine after 6 cycles of trastuzumab plus combined chemotherapy treatment revealed efficacy and safety in non-progressive HER2-positive advanced gastric cancer.
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http://dx.doi.org/10.1007/s12029-021-00594-1DOI Listing
February 2021

Clinical features and outcomes of COVID-19 in patients with solid tumors: Turkish National Registry Data.

Int J Cancer 2020 Dec 7. Epub 2020 Dec 7.

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

We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30-day mortality. Median age was 61 (range: 18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one COVID-19-directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy-seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95% CI 3.3-13.7, P < .001), lymphocytopenia (OR 3,1, 95% CI 1,6-6,1, P = .001) and thrombocytopenia (OR 3,4 95% CI 1,5-8,1, P = .005) were found to be associated with increased 30-day mortality. Relatively lower mortality compared to Western countries and China mainly results from differences in baseline risk factors but may also implicate the importance of intensive supportive care.
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http://dx.doi.org/10.1002/ijc.33426DOI Listing
December 2020

Combination of trastuzumab and taxane-containing intensified chemotherapy in first-line treatment of HER2-positive advanced gastric cancer.

Tumori 2020 Nov 9:300891620969823. Epub 2020 Nov 9.

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

Purpose: Taxane-containing combinations are recommended for the first-line therapy of advanced gastric cancer. It is not known which chemotherapy regimen is the best with trastuzumab for HER2-positive patients. The aim of this study was to compare taxane-containing intensified chemotherapy versus standard chemotherapy in combination with trastuzumab in the first-line treatment of HER2-positive advanced gastric adenocarcinoma.

Methods: This study is a retrospective multicenter study of the Turkish Oncology Group. A total of 130 HER2-positive patients with inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma being given chemotherapy plus trastuzumab as the first-line treatment were included from 16 different oncology centers. Trastuzumab combination with intensified chemotherapy including taxane or standard chemotherapy was compared in terms of progression-free survival (PFS), overall survival (OS), and toxicity.

Results: There were 108 patients in the standard and 22 patients in the intensified chemotherapy group. PFS of the standard and intensified group were 5.6 months (95% confidence interval [CI] 4.8-6.4) and 5.3 months (95% CI 2.6-8), respectively ( = 0.70). OS of the standard and intensified group were 11.1 months (95% CI 8.3-13.9) and 15.2 months (95% CI 12.7-17.7), respectively ( = 0.03). Repeated analysis excluding patients given any previous therapy revealed similar results. The intensified group had more fever and febrile neutropenia.

Conclusion: Trastuzumab combination with intensified chemotherapy provides better OS in first-line treatment of HER2-positive advanced gastric cancer. Further large-scale studies should be performed in HER2-positive patients.
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http://dx.doi.org/10.1177/0300891620969823DOI Listing
November 2020

Does primary tumor localization has prognostic importance in seminoma patients?: Turkish Oncology Group Study.

J BUON 2020 Mar-Apr;25(2):1130-1135

Health Sciences University, Gülhane Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey.

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients.

Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study.

Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007).

Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.
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February 2021

Imaging and clinical correlates with regorafenib in metastatic colorectal cancer.

Cancer Treat Rev 2020 Jun 4;86:102020. Epub 2020 Apr 4.

Institut Jules Bordet, 121 Boulevard de Waterloo, 1000 Brussels, Belgium. Electronic address:

In colorectal cancer (CRC), imaging is important in determining tumor stage, selecting treatment strategies, and in assessing response to therapy. However, some challenges remain with established imaging techniques, such as computed tomography, and with some commonly used response criteria, such as Response Evaluation Criteria in Solid Tumors, which measures change in size of several target lesions instead of change in tumor morphology or metabolic function. In addition, these assessments are not typically conducted until after 8 weeks of treatment, meaning that potential non-responders are often not identified in a timely manner. Regorafenib, an oral tyrosine kinase inhibitor indicated for the treatment of metastatic CRC, blocks the activity of several protein kinases involved in angiogenesis, oncogenesis, metastasis, and tumor immunity. Timely differentiation of regorafenib responders from non-responders using appropriate imaging techniques that recognize not only changes in tumor size but also changes in tumor density or vasculature, may reduce unnecessary drug-related toxicity in patients who are unlikely to respond to treatment. This review discusses the latest developments in computed tomography, magnetic resonance imaging, and positron emission tomography tumor imaging modalities, and how these aid in identifying patients with metastatic CRC who are responders or non-responders to regorafenib treatment.
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http://dx.doi.org/10.1016/j.ctrv.2020.102020DOI Listing
June 2020

Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study.

Surg Oncol 2018 Sep 30;27(3):485-489. Epub 2018 May 30.

Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey. Electronic address:

Purpose: We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC).

Methods: We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens.

Results: The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients.

Conclusion: Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.
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http://dx.doi.org/10.1016/j.suronc.2018.05.032DOI Listing
September 2018

Role of clinical oncology pharmacist in determination of pharmaceutical care needs in patients with colorectal cancer.

Eur J Hosp Pharm 2018 Mar 10;25(e1):e17-e20. Epub 2017 Mar 10.

Department of Internal Medicine, Division of Medical Oncology, Marmara University Medical School, Istanbul, Turkey.

Objective: To determine and evaluate the pharmaceutical care needs and quality of life of patients with colorectal cancer.

Methods: 36 Patients with colorectal cancer eligible for chemotherapy after surgery were included in the study. The patients were followed up during 3 courses of chemotherapy and individual pharmaceutical care plans were developed. The quality of life of patients was evaluated before and after the third course of chemotherapy.

Results: The incidence of drug-related problems (DRPs) in chemotherapy-treated patients was reduced in the 3rd course as compared with 1st course (63.9% vs 75%, respectively; n=36; p>0.05). The clinical oncology pharmacist gave 147 recommendations to patients, which were followed in 98% (n=144) of cases. 91.7% (n=132) of the recommendations of clinical oncology pharmacists solved the drug-related problems; however, the remaining 8.3% (n=12) did not solve the problems and the patients were referred to a doctor for further investigations. The symptom-related quality of life of patients related to anaemia, diarrhoea and neurotoxicity was reduced after the third course of chemotherapy (p<0.05).

Conclusions: The pharmaceutical care provided by the clinical oncology pharmacist has an important role in the identification and resolution of DRPs. Evaluation of symptom-related quality of life is important for the monitoring of patients receiving chemotherapy.
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http://dx.doi.org/10.1136/ejhpharm-2016-001188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457159PMC
March 2018

Bevacuzimab May Be Less Effective in Obese Metastatic Colorectal Cancer Patients.

J Gastrointest Cancer 2019 Jun;50(2):214-220

Department of Medical Oncology, Anadolu Medical Center, Istanbul, Turkey.

Purpose: The purpose of this study was to investigate whether obesity affects survival in metastatic colorectal cancer (mCRC) patients treated with bevacizumab combined with chemotherapy.

Methods: A total of 563 patients with mCRC who had received first-line chemotherapy in combination with bevacizumab were studied. Patients were grouped as obese (BMI levels > 30) or non-obese (BMI levels < 30). Progression-free survival (PFS) and overall survival (OS) were analyzed. Primary tumor location was also investigated in terms of PFS and OS.

Results: The median age of the patients was 59 years. The non-obese group had longer PFS than the obese group (P = 0.030). The 2-year survival rate of the non-obese group was also significantly higher (P = 0.036). The median PFS of non-obese patients was significantly longer in Kras wild-type patients (10.1 vs. 8.1 months, P = 0.010). Among patients with left-sided primary tumor location, median PFS and OS were significantly higher in the non-obese group (PFS non-obese, 11.5 months; obese, 8.8 months; P = 0.002) (OS non-obese, 29.4 months; obese, 21.4 months; P = 0.026).

Conclusions: Efficacy of bevacizumab may be lower in obese patients. Among patients with Kras wild-type left-sided tumors treated with bevacizumab-based regimens, the prognosis could be worse for obese patients than that for non-obese patients. There is a need for prospectively designed studies of obese patients to prove the efficacy and dosages of bevacizumab in treatment of mCRC.
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http://dx.doi.org/10.1007/s12029-017-0047-2DOI Listing
June 2019

Prognostic factors for survival in metastatic renal cell carcinoma patients with brain metastases receiving targeted therapy.

Tumori 2018 Dec 9;104(6):444-450. Epub 2018 May 9.

17 Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul - Turkey.

Background: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy.

Patients And Methods: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed.

Results: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy.

Conclusions: The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.
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http://dx.doi.org/10.5301/tj.5000635DOI Listing
December 2018

Multidisciplinary training of cancer specialists in Europe.

Eur J Cancer 2017 09 10;83:1-8. Epub 2017 Jul 10.

Department of Oncology, Odense University Hospital, Odense, Denmark. Electronic address:

The best care for patients with cancer is most likely to be achieved when decisions about diagnosis, staging and treatment are made at multidisciplinary and multiprofessional meetings, preferably when all the professional expertise relevant to the patient's condition is gathered together. Questionnaires were sent to National Societies of Radiation Oncology and Medical Oncology concerning similarities and differences in training programs and multidisciplinary care in member states in Europe. Results indicated wide variation in training systems and practice. Data were lacking for Surgery because Surgical Oncology is not recognised as a speciality in the EU and most specialist training in cancer surgery is organ based. A period of time in cross-disciplinary training in each of the other two disciplines for all trainees in Medical Oncology, Radiation Oncology and Surgical Oncology (including all surgeons training in cancer surgery) is recommended. This is likely to improve the value of multidisciplinary meetings and may result in improved patient care. The Expert Group on Cancer Control of the European Commission has endorsed this recommendation.
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http://dx.doi.org/10.1016/j.ejca.2017.05.043DOI Listing
September 2017

Tendency of cancer patients and their relatives to use internet for health-related searches: Turkish Oncology Group (TOG) Study.

J BUON 2016 May-Jun;21(3):714-9

Department of Medical Oncology, Kahramanmaras Necip Fazil City Hospital, Kahramanmaras, Turkey.

Purpose: This study aimed to reveal the habits of using internet by cancer patients and their relatives to access health-related information and services in Turkey.

Methods: An 18-item questionnaire survey was applied in cancer patients and their relatives.

Results: A total of 1106 patients (male, 37.3%, and female, 62.7%) and their relatives were included in the study. The responders had been using internet to obtain health information about oncological diseases, once a month (34.2%), 1-2 times a week (27.4%) or 2-3 times a month (21.9%). After diagnosis of cancer was made, participants more frequently (64.4%) investigated health-related issues, while 64.9% of them considered internet as an important search tool, and 16.7% of them had thought to give up cancer therapy under the influence of internet information. Some (33.1%) participants had used herbal medicine, and 16.7% of them had learnt these herbal products from internet. Still 12.7% of them had not questioned the accuracy of internet information, while 26.9% of them indicated that they had not shared the internet information about cancer with their physicians, and 13 % of them searched information in internet without asking their physicians.

Conclusion: Cancer patients and their relatives showed a higher tendency to use health-related internet information which may mislead them, and can result in treatment incompliance. Health professionals should offer evidence-based information to the patients and their relatives through internet.
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December 2016

Changes in lifestyle upon diagnosis of cancer or other chronic illnesses: A Turkish Oncology Group study.

J Health Psychol 2018 03 22;23(4):561-566. Epub 2016 Jul 22.

7 Hacettepe University, Turkey.

Cancer, like other chronic illnesses, changes the patients' way of living significantly. Although some may think, for instance, that religiousness would increase with the diagnosis of cancer, no previous studies have been performed in the Turkish society to confirm this. We, as the Turkish Oncology Group, conducted a survey in seven different oncology centres, representing a large majority of Turkey, to investigate how patients' lifestyles changed following a cancer diagnosis; we used dialysis patients as a chronic illness control group. The study findings showed how changes in spiritual practices are completely in line with what is observed in other chronic illnesses. These findings may help to address cancer patients' needs and facilitate resource allocation accordingly.
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http://dx.doi.org/10.1177/1359105316658968DOI Listing
March 2018

Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study.

Clin Genitourin Cancer 2016 08 2;14(4):e347-53. Epub 2016 May 2.

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

Background: We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma.

Patients And Methods: This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS).

Results: The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months.

Conclusion: This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma.
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http://dx.doi.org/10.1016/j.clgc.2016.04.021DOI Listing
August 2016

Benefit of Bevacizumab-Based Frontline Therapy in Patients with Metastatic Colorectal Cancer (mCRC): a Turkish Oncology Group Study.

J Gastrointest Cancer 2016 Sep;47(3):264-72

Department of Medical Oncology, Anadolu Medical Center, Istanbul, Turkey.

Background: Several chemotherapy regimens using bevacizumab have been developed. Our goal was to investigate regimens that have demonstrated significant clinical activity in patients with metastatic colorectal cancer (mCRC).

Materials And Methods: Six hundred and sixty six patients with mCRC who received first-line chemotherapy combination with bevacizumab were studied. Fluoropyrimidine (F) plus irinotecan (I)-based (FI-bev), F plus oxaliplatin (O)-based (FO-bev), and F-based (F-bev) treatment regimens were compared with respect to progression-free survival (PFS) and overall survival (OS).

Results: The median PFS of FI-bev (n = 414) was 10.9 months (95 % CI 10-11.8), of FO-bev (n = 211) was 9.4 months (95 % CI 8.3-10.4), and of F-bev (n = 41) was 9.5 months (95 % CI 5.9-13.1) (p = 0.089). The median OS of FI-bev was 26.3 months (95 % CI 21.7-30.9), of FO-bev was 27 months (95 % CI 24.3-29.7), and of F-bev was 23.3 months (95 % CI 12.7-33.9) (p = 0.102). In KRAS wild-type patients, the median PFS of FI-bev group was significantly longer than FO-bev group (10.5 vs. 9.1 months, p = 0.006). The FI-bev group had better OS than FO-bev group with borderline significance (p = 0.058). The FI-bev group had significantly longer OS than F-bev group. Patients who underwent metastasectomy or those with Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1 had longer PFS and OS independent of the type of chemotherapy regimen.

Conclusion: FI-bev may be the preferred frontline regimen for patients with KRAS wild-type mCRC. Metastasectomy and performance score were the strongest positive predictors of OS and PFS regardless of backbone chemotherapy regimen.
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http://dx.doi.org/10.1007/s12029-016-9823-7DOI Listing
September 2016

Prevalence of K-Ras mutations in hepatocellular carcinoma: A Turkish Oncology Group pilot study.

Mol Clin Oncol 2015 Nov 31;3(6):1275-1279. Epub 2015 Aug 31.

Department of Medical Oncology, Necmettin Erbakan University, Meram Faculty of Medicine, 42080 Konya, Turkey.

Hepatocellular carcinoma (HCC) is the fifth most common male-predominant type of cancer worldwide. There is no effective treatment regimen available for advanced-stage disease and chemotherapy is generally ineffective in these patients. The number of studies on the prevalence of K-Ras mutations in HCC patients is currently limited. A total of 58 patients from 6 comprehensive cancer centers in 4 metropolitan cities of Turkey were enrolled in this study. Each center committed to enroll approximately 10 random patients whose formalin-fixed paraffin-embedded tumor tissues were available for K-Ras, exon 2 genotyping. Two methods were applied based on the availability of adequate amounts of tumor DNA. In the first method, the samples were processed using TheraScreen. The genomic DNA was further used to detect the 7 most frequent somatic mutations (35G>A; 35G>C; 35G>T; 34G>A; 34G>C; 34G>T and 38G>A) in codons 12 and 13 in exon 2 of the K-Ras oncogene by quantitative polymerase chain reaction (PCR). In the second method, the genomic DNA was amplified by PCR using primers specific for K-Ras exon 2 with the GML SeqFinder Sequencing System's KRAS kit. The identified DNA sequence alterations were confirmed by sequencing both DNA strands in two independent experiments with forward and reverse primers. A total of 40 samples had adequate tumor tissue for the mutation analysis. A total of 33 (82.5%) of the investigated samples harbored no mutations in exon 2. All the mutations were identified via a direct sequencing technique, whereas none were identified by TheraScreen. In conclusion, in our patients, HCC exhibited a remarkably low (<20%) K-Ras mutation rate. Patients harboring K-Ras wild-type tumors may be good candidates for treatment with epidermal growth factor inhibitors, such as cetuximab.
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http://dx.doi.org/10.3892/mco.2015.633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665597PMC
November 2015

Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish Study.

J BUON 2015 Jul-Aug;20(4):1137-41

Acibadem University School of Medicine, Department of Medical Oncology, Istanbul, Turkey.

Purpose: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma.

Methods: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma.

Results: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <1mm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients).

Conclusion: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database.
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November 2015

Is perineural invasion (PN) a determinant of disease free survival in early stage colorectal cancer?

Hepatogastroenterology 2015 Jan-Feb;62(137):59-64

Background/aims: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy.

Methodology: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test.

Results: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect.

Conclusions: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.
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June 2015

PTEN loss is not associated with trastuzumab resistance in metastatic breast cancer.

J BUON 2014 Oct-Dec;19(4):900-5

Department of Medical Oncology, Sanliurfa State Hospital, Sanliurfa, Turkey.

Purpose: Although the clinical benefits of trastuzumab are well known, intrinsic or acquired resistance is a commonly encountered clinical condition. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensine homologue (PTEN). This study investigated the relationship between trastuzumab response and loss of PTEN in metastatic breast cancer patients.

Methods: Patients with histologically confirmed human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer, who were treated with trastuzumab were enrolled into the study. PTEN expression was immunohistochemically evaluated.

Results: The patient median age was 50 years. Of 38 patients, 6 (15.8%) showed PTEN loss. No statistically significant difference was found between trastuzumab response, overall survival (OS) and progression-free survival (PFS) and PTEN loss (p=0.538).

Conclusion: The activation of phosphatidylinositol 3-kinase (PI3K) pathway resulting from PTEN loss was not found to be correlated with trastuzumab response and survival. PTEN loss should not lead to exclusion of patients from the potential to benefit from trastuzumab administration.
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June 2018

Do high-risk features support the use of adjuvant chemotherapy in stage II colon cancer? A Turkish Oncology Group study.

Tumori 2014 Mar-Apr;100(2):143-8

Background: A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western populations. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer.

Methods: A total of 554 stage II colon cancer patients were retrospectively enrolled in the study. Three hundred fifty-three patients had received adjuvant chemotherapy (5-FU-LV, FOLFOX or FLOX) and 201 had received no adjuvant chemotherapy. T4 tumor stage, lymphovascular invasion, perineural invasion, bowel obstruction and/or perforation, <12 harvested lymph nodes, and poor differentiation were defined as high-risk factors.

Results: The median age of the patients was 62 years (range 26-88). The median disease-free survival (DFS) was 58.1 months (95% CI, 47.6 months to 68.5 months) in the non-treatment group and has not been reached in the treatment group (P <0.01). In univariate analysis, patient age >60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors. Adjuvant chemotherapy reduced the risk of recurrence with statistical significance (P <0.01). In multivariate analysis, patient age >60 years and T4 tumor stage were independent risk factors affecting DFS. In addition, adjuvant chemotherapy was an independent favorable prognostic factor for DFS (P <0.01).

Conclusions: Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other populations. Further prospective studies in colon cancer are needed to understand the differences in biology and risk factors between races.
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http://dx.doi.org/10.1700/1491.16397DOI Listing
July 2014

p95-HER2 and trastuzumab resistance in metastatic breast cancer; is immunohistochemistry appropriate?

J BUON 2014 Jan-Mar;19(1):245-9

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

Purpose: Unraveling the mechanisms underlying the resistance to trastuzumab is important for amending the prognosis of patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Experimentally, it has been shown that p95-HER2 positive breast tumors are resistant to trastuzumab. The aim of this study was to investigate the predictive and prognostic importance of p95-HER2 expression by immunohistochemistry in HER2-positive metastatic breast cancer patients treated with trastuzumab.

Methods: Only patients who had a histological diagnosis of HER2-positive metastatic breast cancer and who had received first line therapy containing trastuzumab were enrolled in the study. Immunohistochemistry was used to analyze p95-HER2 expression in the tissue blocks of the patients.

Results: The study was performed on 38 patients aged between 30 and 84 years. In 14 patients (36.8%), p95-HER2 was positive, whereas it was negative in the remaining 24 patients (63.2%). There was no significant correlation between p95-HER2 expression and overall survival, response to trastuzumab, and progression-free survival (PFS).

Conclusion: Unlike previous reports, there was no correlation between the p95-HER2 expression and resistance to trastuzumab. It may be argued that an analysis using immunohistochemistry is inadequate for determining p95- HER2. In order to ascertain whether immunohistochemistry is an appropriate method, studies with larger patient groups are needed.
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May 2014

An international survey of practice patterns and difficulties in cancer pain management in Southeastern Europe: a Turkish & Balkan Oncology Group common initiative.

J BUON 2013 Oct-Dec;18(4):1082-7

Medical Oncology Department, Diyarbakir Training and Research Hospital, Diyarbakir, Turkey.

Purpose: While pain is highly prevalent in cancer patients and its management is universally challenging, it is more commonly undertreated in the developing world. Southeastern European countries have limited resources and manpower to allocate for delivery of effective care for cancer-related pain. The purpose of this study was to explore the practice methods and the barriers to effective pain management in Southeastern Europe.

Methods: We conducted a Web-based survey using a specially designed questionnaire among physicians practicing in member countries of the Balkan Union of Oncology (BUON).

Results: A representative from each of the member countries of BUON (including Armenia and Georgia) and close to 100 physicians from 8 countries responded. The majority (89%) of respondents were medical oncologists and had been practising for 10 years on average. For pain assessment, only 35.4% of the physicians used a formal pain scale. Of the respondents 34.1% were not able to reach the optimal doses of narcotic medications while managing cancer pain, mostly due to concerns about toxicity, such as constipation and nausea. Most physicians listed their inability to consult sub-specialists to seek assistance for improving pain management cases as one of the major difficulties in day-to- day clinical practice, along with lack of time.

Conclusions: The limitations faced by our respondents seem to be related mostly to the shortcomings of the respective health care systems, along with the need for more experience and knowledge about the titration of pain medications and dealing with toxicities.
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March 2014

Personality traits in cancer patients.

Asian Pac J Cancer Prev 2013 ;14(8):4515-8

Department of Internal Medicine, Division of Oncology, Marmara University Medical Faculty, Istanbul, Turkey E-mail :

Background: This study was planned to investigate the personality traits of cancer patients in different treatment settings, and to correlate the demographics with the personality features.

Materials And Methods: A total of 237 patients referred either to Marmara University School of Medicine (MUSM) Oncology Outpatient Unit or to the private office of the faculty between March 10th and April 22nd, 2010 were enrolled in the study. The Big Five Mini Test was used to evaluate the 40 personality traits of the patients.

Results: The study group consisted of 98 males (41.35%) and 139 females (58.65%) with a mean age of 51. Out of the 237, 73.9% had an educational level beyond the junior high school, and 47.3% of all patients reported a positive family history for cancer. A significant difference in terms of reconcilability, extraversion, and responsibility was observed between patients admitting to the university outpatient clinic and the private office (p<0.05). Reconcilability and extraversion were found to differ between genders significantly (p<0.05). The description of the patients by him/herself or by relatives displayed a significant difference in terms of openness (p<0.05). Parameters such as educational level, family history of cancer, age and marital status showed no relevance to their characters. No discordance was observed between the self-analysis of the patient and the patient's relatives.

Conclusions: Patients with cancer are typically highly reconcilable and responsible, moderately stable, open and extraverted.
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http://dx.doi.org/10.7314/apjcp.2013.14.8.4515DOI Listing
May 2014

Metastasis to paranasal sinuses and orbita of breast cancer with a rare metachronous tumor of the uterine cervix.

J Craniofac Surg 2013 Jan;24(1):e64-5

Department of Radiation Oncology, Division of Medical Oncology, School of Medicine, Marmara University, Istanbul, Turkey.

Breast cancer metastases are rarely seen in paranasal sinuses or orbit with a poor prognosis, and these cases were published as case reports. Moreover, metachronous tumors following breast cancer diagnosis are somewhat common, but uterine cervix is infrequent in them. In the present case, we report a 61-year-old female patient who had a biopsy-proven metastatic breast cancer to paranasal sinuses and orbita. She also had a cervical uterine cancer which is also unusually diagnosed following breast cancer. Palliative radiotherapy to paranasal sinuses (30 Gy) achieved a good response. However, she died due to leptomeningeal progression.
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http://dx.doi.org/10.1097/SCS.0b013e3182700748DOI Listing
January 2013

Daily life of a Turkish medical oncologist.

J Oncol Pract 2012 May;8(3):164-6

Marmara University, Istanbul, Turkey.

There are many changes occurring in the Turkish health care system, including but not limited to consolidation of public hospitals and administrative takeover of some university hospitals by the Ministry of Health. Because of its unique situation, Marmara University Hospital is at the center of these changes. The adaptation process will continue for another year or so, after which it is hoped that a better health care environment will have been created for patients with cancer in Turkey.
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http://dx.doi.org/10.1200/JOP.2011.000373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396804PMC
May 2012

Is subdivision of pT2 tumors superior to lymph node metastasis for predicting survival of patients with gastric cancer? Review of 224 patients from four centers.

Dig Dis Sci 2011 Nov 10;56(11):3226-34. Epub 2011 Jun 10.

Department of Medical Oncology, Dr.Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.

Background: The prognostic significance of the subclassification of pT2 tumors and the association of these categories with other clinicopathological factors in gastric cancer patients were investigated.

Methods: A total of 224 patients with pT2 gastric cancer who had undergone curative gastrectomy and lymph node dissection were retrospectively analyzed. The prognostic role of the subclassification of pT2 tumors was evaluated by univariate and multivariate analysis.

Results: Of 224 patients, 75 (33.5%) were classified as having pT2a tumors and 149 (66.5%) as having pT2b tumors. The prevalence of large-sized tumors (P < 0.003), lymph node involvement (P < 0.018), and lymphatic (P = 0.016), blood vessel (P = 0.001), and perineural invasion (P = 0.001) was significantly higher for pT2b tumors than for pT2a tumors. The rate of recurrence for pT2a cancers was significantly lower than that for pT2b cancers (P = 0.001).Median overall survival (OS) times and three-year OS of patients with a pT2b tumor were significantly worse than for patients with a pT2a tumor (P < 0.001).When patients were analyzed according to lymph node involvement, the prognosis of patients with pT2aN(1) cancers was significantly better than that of patients with pT2bN(1) (P < 0.001). Multivariate analysis indicated that the pT2 subdivision was an independent prognostic factor for OS (P = 0.006), as were pN stage, clinical stage, and recurrence.

Conclusion: Our results showed that subclassification of pT2 tumors into pT2a or pT2b was an important prognostic indicator for patients with pT2 gastric cancers who underwent curative gastrectomy. In the TNM staging system, subdivision of pT2 tumors should be undertaken routinely to detect gastric cancer patients who have a poor prognosis and to define patients more accurately in terms of their mortality after curative resection in accordance with the new 2010 AJCC TNM staging classification. This may also help as a guide to more appropriate therapy for tumors with subserosal invasion (old pT2b or new pT3).
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http://dx.doi.org/10.1007/s10620-011-1721-zDOI Listing
November 2011

Concomitant chemoradiotherapy with low-dose weekly gemcitabine for nonmetastatic unresectable pancreatic cancer.

Turk J Gastroenterol 2011 Feb;22(1):60-4

Departments of, Radiation Oncology, Marmara University School of Medicine, İstanbul.

Background/aims: This study aimed to demonstrate the efficacy and tolerability of low-dose weekly gemcitabine as a radiosensitizer in unresectable pancreatic cancer patients treated with chemoradiotherapy.

Methods: Twenty-four histologically confirmed pancreatic carcinoma patients (female/male: 10/14, median age: 60) were evaluated. Seven (29%) patients received gemcitabine either as a single agent or in combination prior to chemoradiotherapy. Concurrent 75 mg/m2 gemcitabine was infused weekly. Radiotherapy was delivered to the primary tumor and positive lymphatics with 3D-conformal radiotherapy to a total dose of 4500 cGy. Local progression-free survival, distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier method.

Results: Median follow-up was 36 weeks. Median local progression-free survival, distant metastasis-free survival and overall survival were 22 weeks (95% confidence interval [CI]: 5-59 weeks), 19 weeks (95%CI: 6.9-31 weeks) and 36 weeks (95%CI: 28-43 weeks), respectively. All patients completed radiotherapy as scheduled. Concurrent gemcitabine was given fully in 58.3% of patients. Gemcitabine was terminated in four (16.6%) patients due to grade 3 neutropenia (n=1), grade 3 nausea/vomiting (n=2) or patient's reluctance (n=1). Patients with local response and stable disease to chemoradiotherapy revealed a median survival of 39 weeks (95%CI: 30-47.9 weeks) compared to 36 weeks (95%CI: 9.7-62.2 weeks) in patients with locally progressive disease (p=0.52). Pain was improved in 50% of patients.

Conclusions: Weekly low-dose radiosensitizing gemcitabine is effective and safe in unresectable pancreatic cancer patients.
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http://dx.doi.org/10.4318/tjg.2011.0158DOI Listing
February 2011

Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey.

Med Oncol 2011 Jun 20;28(2):409-15. Epub 2010 Mar 20.

Marmara University Hospital, Istanbul, Turkey.

Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases had statistically significant impact on weight gain following adjuvant therapy in breast cancer patients (P = 0.000, P = 0.008, P = 0.015 and P = 0.017 respectively). This study shows that Turkish women with early breast cancer gain weight after adjuvant systemic therapy, in line with European and American counterparts. This increase in weight is maintained at least one year after adjuvant therapy. Given the adverse consequences of weight gain in terms of both breast cancer prognosis and general health, it is necessary to inform patients about this change and to develop strategies for weight maintenance during and after systemic therapy.
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http://dx.doi.org/10.1007/s12032-010-9463-xDOI Listing
June 2011

Neoadjuvant chemotherapy for locally advanced breast cancer: a single center experience.

Med Oncol 2010 Jun 2;27(2):454-8. Epub 2009 Jun 2.

Department of Medical Oncology, Dr Lütfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.

Neoadjuvant chemotherapy (NAC) is one of the treatment options for patients with locally advanced breast cancer (LABC). Preoperative chemotherapy potentially may reduce the extent of the surgery and offers the opportunity to assess the chemosensitivity of the tumor in vivo. Herein, we evaluated the results of NAC in Turkish LABC patients. We retrospectively analyzed 73 LABC patients. Anthracycline/taxane-based chemotherapy regimens were administered. Patients were stratified according to age, menopausal status, type of surgery, response to the treatment, histopathological properties, and survival. After 3-6 cycles of chemotherapy, patients were re-staged radiologically and surgery was performed in operable patients. Adjuvant chemotherapy was administered as needed. The median age was 45 (29-93) at the time of diagnosis. Sixteen percentage of patients were younger than 35 years of age and 45.2% were premenopausal. Median follow-up time was 20.2 months. Sixty-seven out of 73 patients responded to therapy (89%). Breast conserving surgery was possible in the 15% of the patients. In histopathological analysis, lymph node invasion was detected in 85%. The estrogen (ER) and progesterone (PR) receptor were positive in 78.1% and c-erb-B2 was positive in 17.5% of patients. The median disease-free survival (DFS) was 44 months (SE: 9; %95 CI: 27.1-60.8), overall survival (OS) was not reached at the time of analysis. Three-year DFS and OS were 58% and 91.9%, respectively. In a multivariate Cox regression analyses; no demographic or pathologic prognostic parameter predicted overall survival. In recent years, NAC in breast cancer has become a viable treatment option for patients with LABC. NAC is not commonly applied in Turkey. The response rate to NAC in Turkish breast cancer patients is encouragingly high. Broader efforts should be made to evaluate breast cancer patients preoperatively at tumor boards for proper treatment sequence.
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http://dx.doi.org/10.1007/s12032-009-9233-9DOI Listing
June 2010

Thrombin-activatable fibrinolysis inhibitor levels in patients with non-small-cell lung cancer.

Clin Lung Cancer 2008 Mar;9(2):112-5

Department of Biochemistry, Haseki Research and Training Hospital, Istanbul, Turkey.

Background: An increased incidence of thromboembolic events has been described in patients with cancer. Cancer cells are attributed with producing procoagulant substances such as cysteine protease and tissue factor to activate factor X and factor VII, respectively. However, there are limited data on the pathogenesis behind this hypercoagulability state, and the thrombin generation, fibrinolytic system, and coagulation inhibition system during cancer are largely obscure. In this study, we investigated the changes of different steps of coagulation pathway in patients with non-small-cell lung cancer (NSCLC) and compared the data with those of healthy controls.

Patients And Methods: Forty-four patients with NSCLC and 36 age-matched controls were recruited for this study. Prothrombin fragment 1 + 2 (F 1 + 2) were used as a marker of thrombin generation; thrombin-activatable fibrinolysis inhibitor (TAFI) immunologic activity level was measured for inhibition of the fibrinolytic system, and tissue factor pathway inhibitor (TFPI) activity was assessed for the coagulation inhibition system. In the patient group, the relationships between TAFI activity levels and patient parameters (age, sex, body mass index [BMI], histopathology, and stage) were evaluated.

Results: The TAFI activity, F 1 + 2 levels, and TFPI activity were significantly higher in patients with lung cancer than in subjects in the control group (P < .05; P < .0001; and P < .0001; respectively). However, there were no statistically significant associations between TAFI activity levels and patient age, sex, BMI, histopathology, or stage of disease (P > .05).

Conclusion: In this study, it was clearly shown that patients with lung cancer have hypercoagulable states and that the pathogenesis of thrombotic events in these patients is multifactorial. Increased TFPI is a reflection of thrombin activity in this patient group. Confirmatory studies with larger patient groups should be performed in this population.
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http://dx.doi.org/10.3816/clc.2008.n.017DOI Listing
March 2008