Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study.

BACKGROUND: There are insufficient predictive markers for renal cell carcinoma (RCC). METHODS: A total of 308 metastatic RCC patients were analyzed retrospectively. RESULTS: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35 months (p < .001) and 21.0 versus 11.36 months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. CONCLUSIONS: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

Aromatase inhibitor treatment for breast cancer: short-term effect on bone health.

AIM OF THIS STUDY: Aim of this study was to examine the effects of aromatase inhibitors (AIs), which are used in every phase of breast cancer treatment, on the bone mineral density (BMD) of patients with early-stage breast cancer. MATERIAL AND METHODS: Menopausal female patients who were diagnosed with stages 1-3 breast cancer and who were planned for anastrazole or letrozole as adjuvant therapy were examined. After the patients' BMD was measured, 45 patients without osteoporosis were included in the study. Six months after AI therapy started, the patients' BMD was measured again. RESULTS: In this study, we tried to show that there was a statistical difference in the BMD of 45 patients before and 6 months after treatment. Among all measurements (femur and lumbar T-scores), the femur Z-score (p = 0.52) was the only score that was not statistically significant. Statistical significance (p < 0.01) was detected in comparative analysis of the other measurements. According to this analysis, a significant loss of BMD was seen even in the first six months after AI treatment was introduced. CONCLUSIONS: Female patients with breast cancer are at higher risk for bone loss and fractures than healthy women. In this study, we showed the negative effects on BMD of aromatase inhibitor therapy, one of the main contributions to osteoporosis in women with breast cancer. This study is the first to quantify the short-term effect of AI treatment on BMD in postmenopausal women with breast cancer.

Evaluation of cardiotoxicity via speckle-tracking echocardiography in patients treated with anthracyclines.

BACKGROUND: The aim of this study was to examine the cardiac effects of anthracycline therapy based on speckle-tracking echocardiography (STE) and to identify patients at risk for cardiotoxicity. PATIENTS AND METHODS: The study included 35 breast cancer (BC) and 15 lymphoma patients who were treated with anthracycline-based chemotherapy. Conventional echocardiography and STE were performed 1 month prior to and 1 month after chemotherapy. Longitudinal strain analysis was performed via STE using automated functional imaging. RESULTS: The ejection fraction (EF) and the fractional shortening values were significantly lower in the lymphoma group. There was a positive correlation between anthracycline dose and subclinical heart failure (p = 0.024). There was an increase in the myocardial performance index in both groups. After therapy, STE showed regional decreases in the longitudinal strain values in the BC group, but the global strain values did not differ. In the lymphoma group, the apical long-axis, the 4-chamber, and the global longitudinal strain values were significantly lower after therapy (p = 0.002, 0.041, and 0.004, respectively). The long-axis and global longitudinal strain values were significantly lower in the lymphoma patients with normal EF values (p = 0.01 and 0.05, respectively). CONCLUSION: Cardiotoxicity during the early phase of anthracycline treatment can be detected via STE prior to the observation of systolic function deterioration.

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.

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).

The effect of tumor size on overall survival in patients with pT3 gastric cancer: experiences from 3 centers.

BACKGROUND: Although a number of studies have investigated whether tumor diameter is a prognostic factor in gastric cancer, no consensus was reached on its clinical importance. In this study, we aimed to determine the effect of tumor size on survival in patients with pT3 gastric cancer. PATIENTS AND METHODS: A total of 232 patients with pT3 gastric cancer, who underwent curative gastrectomy with D2 lymph node dissection, were retrospectively analyzed. Receiver operating characteristics analysis showed that the cutoff value for tumor size was 8 cm. On the basis of this cutoff point, patients were divided into 2 groups: small-size tumors (SST, ≤8 cm) and large-size tumors (LST, >8 cm). The prognostic significance of tumor size and the relationship between tumor size and other prognostic factors were evaluated. RESULTS: LST was detected in 44% of patients. Resection type, tumor site, lymph node metastasis, tumor differentiation, lymphatic vessel invasion, and blood vessel invasion were correlated with tumor size. The median survival of patients with SST was significantly better than that of patients with LST (107 vs. 18.2 months; p < 0.001). Multivariate analysis indicated that tumor size was an independent prognostic factor (p = 0.001; hazard ratio (HR): 0.43) as were resection type and blood vessel invasion. CONCLUSIONS: Our results show that tumor size is an important prognostic indicator in patients with pT3 gastric cancer, who underwent curative gastrectomy, and that the rate of LST increased with aggressiveness and stage of disease. Tumor size may be a useful and reliable prognostic factor for detection and staging in patients with gastric cancer, who have a poor prognosis after curative resection.

Demographical and Clinical Features of Marginal Zone Lymphomas: A Retrospective Study of Turkish Oncology Group (TOG).

Marginal zone lymphomas (MZLs) are rare and indolent subtypes of non-Hodgkin lymphomas, and their clinical behaviours are heterogeneous. The aim of this study was to evaluate the clinical and prognostic characteristics of MZL. In this multicentre retrospective study, we analyzed demographical, clinical and prognostic features of 64 MZL patients. The median age was 54.0 and 78.1% of the patients had extra-nodal disease at presentation. Most of the patients were treated with chemotherapy. The 5 years and 10 years overall survival (OS) rates were 74.5% and 62.1%, respectively. The analysis of factors associated with OS showed that ECOG performance score was an important prognostic factor, with 133.0 months (95% CI 49.3-216.5) versus 18.0 months (95% CI 12.1-23.7) for ECOG 0-1 and 2-3, respectively (p = 0.011). Prognosis of MZL is favorable and ECOG performance score was found associated with OS. Further detailed studies with large patient numbers are needed to clarify the clinical features and treatment management of MZLs.

The prognostic value of ß-catenin and LEF-1 expression in patients with operable gastric carcinoma.

AIM: The aim of this study is to evaluate the prognostic value of ß-catenin and LEF-1 expression in patients with operable gastric cancer that receive adjuvant treatment and the relationship between demographic and histopathological variables. MATERIAL AND METHOD: In this study, 82 gastric cancer patients treated with adjuvant treatment after surgery and followed in the Medical Oncology Department of Kocaeli University were included. ß-catenin and LEF-1 expression were examined by immunuhistochemical analysis in paraffin embedded tumor tissues of the patients. RESULTS: Median age was 56 (26-81) and follow up was 19 months (4-61). Performance status (ECOG) were 0-1 in all patients. Male/female ratio was 53/29 (64.6/35.4%). The median disease free survival (DFS) time was 17 months (SE: 3 95% CI: 11-23) and 3 years DFS rate was 39.7%. The median overall survival (OS) time was 28 months (SE: 4 95% CI: 20-36) and 3 years OS rate was 41.2%. There was no statistical correlation between ß-catenin and LEF-1 expression and age, gender, performance status, tumor localization, T and N stage, lymphovascular, perinoral invasion, grade and operation type (>0.005). According to univariate analysis, we did not find significant effect of age, gender, T stage, lymphovascular, perinoral invasion, grade and operation type on overall survival (p>0.005). Good performance status (ECOG 0), tumor infiltration without diffuse type like linitis plastica, and lower N stage had positive effect on survival respectively (p=0.04, 0.033 and 0.005). CONCLUSION: In this study group, we found that only N stage was an independent prognostic factor (<0.005). Demographic features of the patients, histopathological characteristics other than N stage, ß-catenin and LEF-1 prognostic effects have not been shown.

XELIRI plus bevacizumab compared with FOLFIRI plus bevacizumab as first-line setting in patients with metastatic colorectal cancer: experiences at two-institutions.

BACKGROUND: Efficacy of chemotherapy plus bevacizumab has been shown in patients with metastatic colorectal cancer (mCRC) compared with chemotherapy alone. The aim of the present study was to evaluate the efficacy and safety of FOLFIRI or XELIRI regimens in combination with bevacizumab for mCRC patients in a first-line setting. MATERIALS AND METHODS: A total of 132 patients with previously untreated and histologically confirmed mCRC were included. They were treated with either FOLFIRI-Bevacizumab (Bev) or XELIRI-Bev according to physician preference. The efficacy and safety of the two regimens were compared. RESULTS: Between 2006 and 2010, 68 patients were treated with the XELIRI-Bev regimen, while the remaining 64 patients received the FOLFIRI-Bev regimen. The median age was 58.5 years (53.6 years in the FOLFIRI-Bev and 59.7 years in the XELIRI-Bev arm, p=0.01). Objective response rate was 51.6% for FOLFIRI-Bev versus 41.2% for XELIRI-Bev (p=0.38). At the median follow-up of 24.5 months, the median progression-free survival (PFS) was not different between two groups (14.2 months in FOLFIRI-Bev vs. not reached in the XELIRI-Bev, p=0.30). However, median overall survival time for the FOLFIRI-Bev arm was better than that for patients treated with XELIRI- Bev, but these differences was not statistically significant (37.8 months vs. 28.7 months, respectively, p=0.58). Most commonly reported grade 3-4 toxicities (FOLFIRI-Bev vs XELIRI-Bev) were nausea/vomiting (7.8% vs. 14.7%, p=0.27), diarrhea (10.9% vs 22.1%, p=0.10), hand-foot syndrome (0% vs 8.8%, p=0.02) and neutropenia (18.7% vs 27.9%, p=0.22). CONCLUSION: Our results showed that FOLFIRI-Bev and XELIRI-Bev regimens were similarly effective treatments in a first-line setting for patients with untreated mCRC, with manageable adverse event profiles.

Evaluation of the efficacy of aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life with functional living index emesis.

OBJECTIVE: Functional Living Index Emesis (FLIE) is developed to evaluate the relationship between emesis and it's effects on patient's daily life and is far more relevant to detect the effectiveness of antiemetic treatment compared with self-diary reports. In this study, the efficacy of oral neurokinin-1 antagonist aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life is evaluated with FLIE. STUDY DESIGN: Cross sectional study. MATERIAL AND METHODS: Sixty patients with Non-Small Cell Lung Cancer (NSCLC) receiving a chemotherapy regimen consisting of Cisplatin and Docetaxel were evaluated. The patients were prospectively randomized to two groups before the first cycle of chemotherapy. Patients in Group A (31 patients) received 3 daily doses of aprepitant along with oral ondansetron and dexamethasone. The patients in group B (29 patients) received only ondansetron and dexamathasone. The efficacy of both regimens was evaluated by a modified Turkish version of FLIE scale consisting of 18 questions. RESULTS: The number of patients with complete response was 31 in the whole group. Of these 18 patients (58%) were in Group A (Aprepitant) and 13 patients in group B (42%). Median FLIE score in group A was 24.97 (±12.45) while it was 38.1 (±26.987) in group B and the difference was statistically significant (p=0.022). Total score >20 was seen in only 5 of 31 patients in aprepitant group (16%) showing the significant efficiency of aprepitant on quality of life, while in group B, 13 of 29 patients (44%) had total scores >20 (p=0.02). CONCLUSION: Regarding these findings, it is certain to state that aprepitant in combination with other drugs optimizes protection against both nausea and vomiting compared to the prior standard of care, and must be recommended as first-line therapy for patients who are treated with moderately or highly emetogenic chemotherapy.

Ambulatory blood pressure and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease.

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. However, the association between ambulatory blood pressure and ED has not been investigated in these patients. Forty-one patients with ADPKD having well-preserved renal function were included in the study. Ambulatory blood pressure monitoring was performed in all patients. Patients were divided into dipper and non-dipper groups. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. The mean 24-hour systolic blood pressure was similar in both groups (125.5 +/- 10.7 mmHg in dippers and 121.2 +/- 14.3 in non-dippers, p > 0.05). There was also no significant difference between the mean 24-hour diastolic blood pressures in both groups (82.3 +/- 9.6 mmHg in dippers and 77.1 +/- 8.6 mmHg in non-dippers, p > 0.05). The nocturnal fall rate in systolic blood pressure was 11.1 +/- 1.2% in dippers and 0.98 +/- 0.9% in non-dippers (p = 0.001). The nocturnal fall rate in diastolic blood pressure was 14.0 +/- 0.9% in dippers and 3.8 +/- 0.8% in non-dippers (p = 0.001). Endothelial-dependent dilatation was significantly higher in dippers compared to non-dippers (6.22 +/- 4.14% versus 3.57 +/- 2.52%, p = 0.025). Non-dipper patients with ADPKD show significant ED, which has an important impact on cardiovascular morbidity and mortality.