Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

The efficacy and reliability of sequential adjuvant anthracycline-based chemotherapy and weekly paclitaxel regimen in human epidermal growth factor receptor 2 negative breast cancer: A retrospective analysis of a multicentre study.

PURPOSE: To analyze the reliability and the effectiveness of chemotherapy and prognostic factors for survival in patients with HER2 (human epidermal growth receptor 2) negative early-stage breast cancer treated with adjuvant sequential anthracycline-based chemotherapy and paclitaxel. METHODS: This analysis retrospectively evaluated the medical records of 756 HER2 negative early-stage breast cancer patients who received adjuvant sequential anthracycline-based chemotherapy and weekly paclitaxel in 15 medical oncology centers in Turkey between 2008-2015. Estrogen receptor (ER), progesterone receptor (PR),HER2,age,tumor size and grade,nodal status,perineural and lymphatic invasion,disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: The median patient age was 50 years (22-82). Median follow up period was 46 months (13-82). The rates of recurrence and death detected in this period were 14.8% and 7.4%, respectively. Median OS and PFS were not reached in this period. Five-year DFS and OS rates were 87% and 89%, respectively. Age (OR:0.35,95%Cl 0.12-0.96, p=0.04), PR status (OR:0.44,95%Cl 0.18-1, p=0.05), lymphatic invasion (OR:2.6,95%Cl 0.97-7.4, p=0.05) were independent prognostic factors. Most common grade 3-4 toxicities were fatigue (6.7%), neutropenia (1.7%) and nausea (1.3%). Neutropenic fever developed in 1.8% of the patients and peripheral neuropathy in 16.9%. Dose reduction was necessary for 10% of the patients due to grade 3-4 toxicity, whereas postponement of chemotherapy was necessary for 7% of the patients. CONCLUSIONS: This multicentric retrospective study confirmed that sequential adjuvant therapy with anthracycline-based chemotherapy and paclitaxel for HER2 negative breast cancer is an effective and reliable regimen.

Can Inflammatory and Nutritional Serum Markers Predict Chemotherapy Outcomes and Survival in Advanced Stage Nonsmall Cell Lung Cancer Patients?

Purpose. To determine the values of prognostic nutritional and inflammatory markers in chemotherapy outcomes and survival in the patients with advanced nonsmall cell lung cancer (NSCLC) and also in the secondary malnutrition and cachexia. Methods. Twenty-five patients with diagnosis of aNSCLC were registered for the prospective study. Malnutrition was determined by the Subjective Global Assessment (SGA) and performance status by criteria of the Eastern Cooperative Oncology Group (ECOG). Before treatment, serum levels of albumin, prealbumin, vitamin D, zinc (Zn), C-reactive protein (CRP), IL-6, IL-1 ß, TNF-α, lipoprotein lipase (LPL), and the Glasgow Prognostic Score (GPS) were recorded. Patients were followed prospectively for treatment outcomes and survival. Results. Due to the deaths of 18 patients during the 4-month follow-up period, no adequate measurements of inflammatory and nutritional markers could be performed. However, seven patients completed the treatment period and evaluations of these markers could be performed during the three periods. Eighty-four percent of patients were male with a mean age of 63.3 ± 8.7 years. Evaluation of the malnutrition by SGA showed that 5 (20%) patients were well nourished (A), 12(48%) were moderately malnourished (B), and 8(32%) were severely malnourished (C). Low levels of serum albumin (<3.5g/dl), prealbumin (<20 mg/ml), 25-hydroxycholecalciferol (<30 ng/ml), and Zn (<70mg/ml) were detected in 15(60%), 17(68%), 24 (96%), and 22 (88%) patients, respectively. Elevated levels of CRP (≥10 mg/L), IL6 (≥18pg/ml), TNF-α (≥24pg/ml), IL-1ß (≥10pg/ml), and LPL (<12pg/ml) were found in 24 (96%), 11(44%), 9(36), 13(52%), and 11(44%) patients, respectively. Moderate and severe malnutrition, acute phase response, and reduced survival were determined in patients with NCSLC. In 7 patients that completed the treatment period, there was an association between elevated serum levels of IL-6, IL-1ß, TNF-α, CRP, and LPL and also the reduced serum levels of albumin, prealbumin, Zn, vitamin D, and GPS, respectively. Similarly, Friedman analysis indicated that prealbumin significantly increased (p=0.007) in the follow-up period. But the serum levels of CRP (mean 37.3±22.3; Wilcoxon test P=0.368) in the seven patients were lower than those of the 18 patients that expired (mean 75.82±56.2). Conclusion. Malnutrition and cachexia negatively influence oncological outcomes in patients with NSCLC. These nutritional/inflammatory markers may be useful for selection of high risk and reduced survival in patients with aNSCLC undergoing adjuvant chemotherapy.

Prognostic factors for survival in patients with metastatic malign melanoma treated with ipilimumab: Turkish Oncology Group study.

PURPOSE: Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. METHODS: We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan-Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. RESULTS: The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm3) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. CONCLUSION: Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed.

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

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.

Retrospective evaluation of premenopausal hormone-sensitive breast cancer patients treated with adjuvant gonadotropin-releasing hormone analogue: Anatolian Society of Medical Oncology (ASMO) study.

AIM: The goal of this study is to evaluate possible factors affecting the survival of patients treated with gonadotropin-releasing hormone (GnRH) analogues. METHODS: Demographic characteristics, treatment modalities, overall survival (OS) and the possible factors affecting the survival a total of 554 premenopausal breast cancer patients in Turkey evaluated retrospectively. RESULTS: The median duration of GnRH analogues use was 22 ± 13.6 (range, 1-87) months. Patients were divided into three groups according to the duration of GNRH analogues use; 4-12 months (Group A), 13-24 months (Group B) and ≥25 months (Group C). Overall, 530 patients were analyzed; 23.2%, 45.8%, 30.9% of the patients were in Group A, B and C, respectively. The median follow-up duration was 34 ± 30.3 (range, 4-188) months. The OS in patients ≤35 years of age was found to be significantly longer than that of patients >35 years of age in Group B (log rank, P = 0.023). The disease-free survival of the patients in Group A was significantly shorter than that of patients in Group C (log rank, P = 0.003). The OS of Group A patients was significantly shorter in comparison to that of Group B and Group C patients (log rank, P = 0.000) and the OS of Group B patients was significantly shorter than Group C (log rank, P = 0,000). CONCLUSION: There is currently no definite data on the optimal duration of GnRH analogues use. One of the important results of this study that will provide an insight to the future studies is the improvement gained in OS by the increase in the duration of GnRH analogues use.

Attitudes of cancer patients after diagnosis: How cancer affects social life? A Turkish Oncology Group study.

PURPOSE: Each year, 12.7 million people learn that they have cancer and 8.2 million people die of cancer worldwide. Cancer is a major public health issue which causes fundamental changes in the lives of patients and their families. The purpose of this study was to evaluate the lives of patients after diagnosis and determine the changes in their lifestyles. METHODS: Between September 2013 to December 2013, a questionnaire consisting of 22 questions was administered during a face to face interview to patients at 13 different Oncology Units in Turkey. Each patient was queried during the administration of his/her chemotherapy. Eight of the questions featured independent choices, and 14 had dependent (multiple) choices. RESULTS: A total of 1300 patients were included in the study. Of patients 9.5% were 71 years of age and older which was the oldest age group. The mean patient age was 54.6±13.8 years. Of the whole group of patients 58.5% were female and 41.5% male. After diagnosis, 64% of the patients reported that they were complying with guidelines for a healthy lifestyle and 80% said that they were eating healthier food. At the time they filled in the questionnaire, more than half of the patients (57.3%) felt optimistic about their disease. CONCLUSIONS: Diagnosis of cancer may change the patients' dietary and reading habits, social relationships, activities and more importantly, their point of life view.

Tissue expression of human epididymal secretory protein 4 may be useful in the differential diagnosis of uterine cervical tumors.

OBJECTIVES: Human Epididymal Secretory Protein 4 was firstly described as an epididymis-specific protein but more recently it has been demonstrated to be a putative serum tumor marker for different malignancies, especially ovarian epithelial cancers. The aim of this study is to investigate the association between tissue Human Epididymal Secretory Protein 4 expression and the clinicopathological features of uterine cervical tumors. MATERIAL AND METHODS: This retrospective study was designed to evaluate the differences of tissue expressions of Human Epididymal Secretory Protein 4 protein in a spectrum of cervical neoplasms. One hundred and seven patients recently diagnosed as having cervical intraepithelial neoplasm or invasive squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma based on pathology databases. RESULTS: Decreased or negative Human Epididymal Secretory Protein 4 expressions were determined in both normal cervical epithelia and in intraepithelial carcinomas, while increased HE4 expression was observed in invasive tumors. CONCLUSIONS: This study demonstrated that altered expression of Human Epididymal Secretory Protein 4 may involve in tumorigenesis in the uterine cervix. Our findings also suggested the presence of a correlation between Human Epididymal Secretory Protein 4 expression and the invasive potential of uterine tumors. Therefore it may be thought that the tissue expression of HE4 can be used to differentiate high grade intraepithelial tumors from carcinomas.

Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).

PURPOSE: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. METHODS: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. RESULTS: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). CONCLUSIONS: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.

The mean platelet volume may predict the development of isolated bone metastases in patients with breast cancer: a retrospective study of the Young Researchers Committee of the Turkish Oncology Group (TOG).

PURPOSE: To determine the predictive value of the mean platelet volume (MPV) and the MPV/platelet count ratio on the development of isolated bone metastasis in patients with breast cancer. METHODS: A total of 121 previously untreated female patients with isolated bone metastases from breast cancer (group 1) were included in this retrospective cohort study. The patients enrolled in this study had similar age, biological subtypes, and duration of follow-up after diagnosis. Group 1 was compared with both 71 previously untreated women with breast cancer with no metastases at all (group 2) and 39 healthy women (group 3). Demographic data, laboratory tests and histological features of all of the patients in groups 1 and 2 were recorded and the study variables from each of the three groups were compared. RESULTS: In group 1, the cut-off value (9.2 fL) for the MPV was determined and patients were stratified into 4 subgroups. The MPV was higher in group 1 than in either group 2 or group 3. Group 1 patients had a MPV of 8.8±3.1 fL (mean 5.1, range: 6.1-15.6) and the cut-off value for MPV was 9.2 fl. For patients in group 1, the MPV distribution was stratified into 4 groups as follows: group A included MPV values <6.08 fL, in group B values ranged from 6.09 to 8.46 fL, group C included values from 8.47 to 10.05 fL, and group D included patients with MPV values >10.06 fL. MPV and the presence of lymphovascular invasion were found to be independent risk factors for the development of isolated bone metastases. CONCLUSION: We concluded that MPV can be used to predict the development of isolated bone metastases.

The association of clinicopathological features and survival in colorectal cancer patients with kras mutation status.

BACKGROUND: KRAS mutations have a significant role in the consecutive activation of RAS.RAF.MEK.ERK pathway in colorectal cancer.Approximately 30.35% of sporadic colorectal cancers have KRAS mutation. While the predictive role of KRAS is commonly accepted at the present time, its prognostic role and association with different clinical and histopathological properties are currently unclear and inconsistent. The intent of this study, has been to evaluate the associations between KRAS gene mutations and clinicopathological features and survival times in Turkish colorectal cancer patients. MATERIALS AND METHODS: In this study, the file records of 115 metastatic colorectal cancer patients who applied to the Department of Medical Oncology between 2000 and 2011 were monitored; data on clinicopathological features and survival times were collected. DNA.sequencing method with PCR amplification from archival paraffin blocks were used for KRAS mutation status analysis. The associations between KRAS mutation status and clinicopathological features and survival times were compared statistically. RESULTS: While a significant association hadbeen determined between KRAS mutation status and tumor localization, there was no determined significant association with other clinicopathological properties. Similarly, there was no association between KRAS mutation status and survival parameters. CONCLUSIONS: As a result, the effect of KRAS mutation status on clinicopathological features, survival time and prognosis is unclear.

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab.

PURPOSE: The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab. METHODS: Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively. RESULTS: Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER- and PR-) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33-8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33-8.71) were significant risk factors for development of brain metastasis as the first site of recurrence. CONCLUSIONS: In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER- and PR-) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.

Pretreatment Serum Albumin Level is an Independent Prognostic Factor in Patients with Stage IIIB Non-Small Cell Lung Cancer: A Study of the Turkish Descriptive Oncological Researches Group.

BACKGROUND: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. MATERIALS AND METHODS: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. RESULTS: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was 3.2±1.7 g/dL (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. CONCLUSIONS: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

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

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.

Differences in the ARID-1 alpha expressions in squamous and adenosquamous carcinomas of uterine cervix.

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. This retrospective study was designed to evaluate the differences in tissue expressions of ARID1A in a spectrum of cervical neoplasms. Cervical intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were identified in 100 patients recently diagnosed as cervical neoplasms based on pathology databases. In this series, there were 29 low- and 29 high-grade cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15 adenosquamous carcinomas. Mean age of the patients was 47.8 ± 13 years (20-80 years). It was determined that the expression of ARID1A was statistically significantly down-regulated in adenosquamous carcinomas when compared with non-invasive or invasive squamous cell carcinomas (p = 0.015). Lower levels of the ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low- or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell carcinomas (18.5%). Our findings have demonstrated the presence of a correlation between ARID1A expression and adenomatous differentiation of uterine squamous cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the pathogenesis of cervical adenosquamous carcinomas.

Evaluation of sleep disorders in cancer patients based on Pittsburgh Sleep Quality Index.

Insomnia, poor sleep quality and short sleep durations are the most common problems seen in cancer patients. More studies are needed about sleep disorders in cancer patients. In our study, we aimed to investigate the prevalence of sleep disorders and the impact of these problems on the quality of life in cancer patients. Pittsburgh Sleep Quality Index (PSQI) was given to a total of 314 patients. The psychometric evaluation of the Turkish version of PSQI in cancer patients revealed that 127 (40.4%) patients had global PSQI scores >5, indicating poor sleep quality. There was no statistically significant relationship between PSQI scores and sexuality, marital status, cancer stage and chemotherapy type (P > 0.05); while the patients with bone and visceral metastasis had much lower PSQI scores (P = 0.006). Patients with Eastern Cooperative Oncology Group performance scores of 3 or more had also significantly lower PSQI scores (P = 0.02). In conclusion, PSQI questionnaire may be used to evaluate the sleep disorders in cancer patients. Consistent use of multi-item measures such as PSQI with established reliability and validity would improve our understanding of difficulties experienced by cancer patients with chronic insomnia.

Perspectives and practical applications of medical oncologists on defensive medicine (SYSIPHUS study): a study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

Defensive medicine occasionally indulges unnecessary treatment requests to defend against lawsuits for medical errors and the use of unapproved medical applications. This study determines the attitudes and orientations of medical oncologists on defensive medicine. A cross-sectional survey was sent by e-mail to medical oncologists. The survey was designed to determine the participants' demographic characteristics and defensive medicine practices. The survey measured the attitudes about defensive medicine practices of the oncologists based on a five-point Likert scale (never, rarely, sometimes, often, and always). One hundred and forty-six of a total of 402 physicians serving in oncology were fully filled, and the rate of return invitation was 36 %. The majority of participants were male, with a duration of between 7 and 9 years of work as university hospital officials, and the mean age was 46 ± 9 (years). International guidelines were followed in the most common is NCCN, and the majority of respondents felt that the application of these guidelines improves their defensive medicine. All participants of defensive medicine who stand on the basis of the definition were found to be more afraid of complaints by patients' relatives. Physicians of 45 % was noted that applying defensive medicine. Among the participants were the most frequent checkups of positive defensive approach is defined as increasing or shortening the follow-up period, while avoiding high-risk patients were detected as described in the definition of negative defensive medicine. Both professional groups in both the positive and negative defensive medicine approach defensive medicine approach, academic tasks, work experience and job time, there was a significant correlation between the location. Made in single- and multi-variable analyses, positions were identified both positive and negative defensive medicine is an independent risk factor for direction. Improving the working conditions of young physicians to protect against medical error may require additional educational opportunities.

The preventive effect of oxytocin to Cisplatin-induced neurotoxicity: an experimental rat model.

Peripheral neurotoxicity is a frequent dose-limiting side effect of the chemotherapeutic agent cisplatin. This study was conducted to investigate the preventive effect of oxytocin (OT) on cisplatin-induced neurotoxicity in rats. Forty-four adult female rats were included in the study. Thirty-six rats were administered intraperitoneally (i.p.) single dose cisplatin 10 mg/kg and divided in to 3 groups. The first group (n=12) received saline i.p., whereas the second group (n=12) and the third group (n=12) were injected with 80 µg/kg and 160 µg/kg OT, respectively, for 10 days. The remaining 8 rats served as the control group. Electromyography (EMG) studies were recorded and blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA), tumor necrosis factor (TNF)-α, and glutathione (GSH) levels. EMG findings revealed that compound muscle action potential amplitude was significantly decreased and distal latency was prolonged in the nontreated cisplatin-injected rats compared with the control group (P<0.005). Also, nontreated cisplatin-injected rats showed significantly higher TNF-α and MDA levels and lower GSH level than control group. The administration of OT significantly ameliorated the EMG alterations, suppressed oxidative stress and inflammatory parameters, and increased antioxidative capacity. We suggest that oxytocin may have beneficial effects against cisplatin-induced neurotoxicity.

Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study.

The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) - Group-2 and sunitinib treatment group - Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student's t-test, analysis of variance (ANOVA) and Mann-Whitney's U-test. There was a significant increase in no-medication (water given) diabetic rat's ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats' ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat's ovary (Group-3) when compared with no-medication (water given) diabetic rat's ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.