Veli Berk

Protective effects of nebivolol against anthracycline-induced cardiomyopathy: A randomized control study

BACKGROUNDnWe aimed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients.nnnMETHODSnIn this small, prospective, double-blind study, we randomly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5mg daily (n=27) or placebo (n=18). Echocardiographic measurements and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were obtained at baseline and at 6-month of chemotherapy.nnnRESULTSnBoth studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline. At 6-month, the left ventricular (LV) end-systolic and end-diastolic diameters increased in the placebo group (LVESD: 29.7 ± 3.4 to 33.4 ± 4.5mm; LVEDD: 47.2 ± 3.8 to 52.0 ± 4.6mm, p=0.01 for both) but remained unchanged in the nebivolol group (LVESD: 30.4 ± 3.5 to 31.0 ± 3.6mm, p=0.20; LVEDD: 47.0 ± 4.4 to 47.1 ± 4.0mm, p=0.93). The placebo group also had lower LVEF than the nebivolol group (57.5 ± 5.6% vs. 63.8 ± 3.9%, p=0.01) at 6-month. NT-pro-BNP level remained static in the nebivolol group (147 ± 57 to 152 ± 69 pmol/l, p=0.77) while it increased in the placebo group (144 ± 66 to 204 ± 73 pmol/l, p=0.01).nnnCONCLUSIONSnProphylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients.

Protective effects of spironolactone against anthracycline-induced cardiomyopathy

The protective effect of beta‐blockers, ACE inhibitors, and ARBs on anthracycline cardiotoxicity has already been demonstrated, but the effect of aldosterone antagonism, which inhibits the last step of the renin–angiotensin–aldosterone system (RAAS), was questioned. This study sought to investigate whether spironolactone protects the heart against anthracycline‐induced cardiotoxicity.

Outcome of non-metastatic male breast cancer: 118 patients

Studies concerning adjuvant systemic therapy and prognosis in male breast carcinoma (MBC) are limited. We aimed to evaluate outcome of the changing practices of adjuvant systemic treatment and survival in operable MBC patients over the last two decades. The medical records of 148 MBC patients followed between the years 1986 and 2009 at 7 cancer center were evaluated retrospectively. One hundred and eighteen operable non-metastatic patients had sufficient data were included the study. One hundred and eighteen operable MBC were found to be eligible. Median age was 60 (range 29–83) years. Thirty-two percent of the patients had T3-4 tumors. Half of the patients had axillary lymph node-positive disease. The proportion of positivity of estrogen receptor(ER), progesterone receptor (PgR), and HER2 status were 82.9, 75.8, and 23.4%, respectively. Only, 7 patients had triple negative (TN). Adjuvant hormonotherapy was advised for 76.8% whereas adjuvant chemotherapy for 73.7% of the patients. Median follow-up was 40.9xa0months (range 3.8–186xa0months). Locoregional and/or distant recurrence developed in thirty-eight patients (32.2%). Twenty-three patients died during the follow-up period. Five-year disease-free survival (DFS) was found to be 60%, whereas overall survival (OS) was 82%. Larger tumor size and lymph node positivity were statistically significant poor prognostic factors for OS. Although statistical insignificant, patients with HER2-positive tumors have worse DFS (52 vs. 120xa0months, log rank Pxa0=xa0.73) and OS (85 vs. 144xa0months, log rank Pxa0=xa0.30) than HER2-negative ones. Although the frequency of the use of adjuvant systemic therapy in MBC has been increasing and survival rates improving for the last decades, lymph node status and tumor size are still the most important determining factors for prognosis. There is a need for further prognostic information in men with HER2-positive or TN breast cancer.

Is the Pretreatment Neutrophil to Lymphocyte Ratio an Important Prognostic Parameter in Patients with Metastatic Renal Cell Carcinoma

BACKGROUNDnTyrosine kinase inhibitor is a standard treatment for mRCC. The NLR, an index of systemic inflammation, is associated with outcome in several cancer types. To study the association of pretreatment NLR with PFS and overall survival (OS) of patients treated with VEGF-targeted therapy.nnnPATIENTS AND METHODSnWe retrospectively studied an unselected cohort of patients with mRCC, who were treated with TKIs. Kaplan-Meier and log-rank analyses were employed on PFS and OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance.nnnRESULTSnA total of 100 patients with mRCC who had early progressed after first-line therapy with interferon-α were included in this retrospective multicenter study conducted at 4 centers between February 2008 and December 2011. The median of the NLR was 3.04 and patients were divided into 2 higher and lower NLR groups according to median of NLR. Median PFS was 9 versus 11 months in patients with baseline NLR > 3.04 versus ≤ 3.04 (P = .009). The median OS was 16 months versus 29 months, in patients with NLR > 3.04 versus ≤ 3.04, respectively (P = .004). In the whole group OS was independently associated with higher NLR (hazard ratio [HR], 2.406; P = .004), PFS more than 6 months (HR, 4.081; P = .0001), and sex (HR, 2.342; P = .040). On the other hand in the higher NLR group (HR, 1.107; P = .009) Memorial Sloan-Kettering Cancer Center score (HR, 3.398; P = .0001) was associated with PFS.nnnCONCLUSIONnIn patients with mRCC treated with VEGF-targeted therapy, pretreatment NLR, the duration of PFS might be associated with OS. This should be investigated prospectively.

Cytokeratin 5/6, c-Met expressions, and PTEN loss prognostic indicators in triple-negative breast cancer

In subgroups of breast cancer, the shortest disease-free and overall survival was observed in basaloid and human epidermal growth factor receptor-2 groups. CK5/6 expression is a marker used in diagnosing breast cancers in basaloid group and is associated with a poor prognosis. Similarly, loss of tumor suppressor gene PTEN and a high expression of c-Met has been associated with poor prognosis in breast cancer and many other cancers. In this study, we aimed to determine the effect of CK5/6 and c-Met expressions, and PTEN loss on the disease prognosis in triple-negative breast cancer patients. Ninety-seven patients pathologically diagnosed with triple-negative breast cancer were enrolled. The clinical and pathological characteristics of the patients were recorded. c-Met, PTEN, and CK5/6 expressions were evaluated with immunohistochemical methods from paraffin blocks. The median age of patients was 47xa0years. CK5/6 positivity was 50.5xa0%, PTEN loss was 44.3xa0%, and high c-Met expression was detected in 53.6xa0%. In multivariate analysis, predictors of the recurrence were loss of PTEN (HRxa0=xa02.99; Pxa0=xa00.004), high c-Met expression (HRxa0=xa02.05; Pxa0=xa00.06), CK5/6 expression (HRxa0=xa02.99; Pxa0=xa00.02), increase in the number of metastatic lymph nodes (HRxa0=xa01.11; Pxa0=xa00.001), and an increase in tumor size (HRxa0=xa01.226; Pxa0=xa00.01). Also, PTEN loss (HRxa0=xa02.43; Pxa0=xa00.05), CK5/6 expression (HRxa0=xa03.74; Pxa0=xa00.01), and N2–3 tumors compared to negatives (HRxa0=xa03.63; Pxa0=xa00.01) were associated with death. PTEN loss correlated with those of lymphovascular invasion. There was a correlation between CK5/6 expression and the number of metastatic lymph nodes. Also, a correlation was found among cancers with highly expressed levels of c-Met, T1–2 tumors, and high-grade tumors. The classical markers, lymph node involvement and tumor size, were found to be of prognostic value; however, high c-Met and CK5/6 expressions, and PTEN loss were found to increase risk of recurrence and death in patients with triple-negative breast cancer.

Treatment Regimen With Bevacizumab Decreases Mean Platelet Volume in Patients With Metastatic Colon Cancer

The risk of thromboemboli is increased in patients with cancer, and this is precipitated by the chemotherapeutic agents. Bevacizumab is an anti-vascular endothelial growth factor monoclonal antibody and has an importance in the treatment of metastatic colon cancer. The association between bevacizumab, which is demonstrated to increase the risk of thromboemboli, and mean platelet volume (MPV), which is a marker of thrombocyte function, has been investigated within study. A total of 74 patients with metastatic colon cancer were included in the study and the levels of platelets (PLTs), MPV, and platecrit (PCT) values were recorded in SPSS 16.0 program both at baseline and at the >third month. There were significant decreases in 3 parameters (PLT, MPV, and PCT) during the treatment period with bevacizumab (P = .009, P = .001, and P = .000, respectively). Unlike cases with thrombosis, there is a significant decrease in MPV in combination treatments with bevacizumab.

Risk factors influencing mortality related to Stenotrophomonas maltophilia infection in hematology–oncology patients

Stenotrophomonas maltophilia infection is of concern in patients with cancer. Antibiotics active against S. maltophilia are rarely used in the treatment of febrile neutropenia, making it important to identify the factors influencing mortality in cancer patients with S. maltophilia infection. The objective of this study was to analyze the clinical characteristics and outcomes of cancer and hemopathic patients with S. maltophilia infection and assess the factors influencing the mortality. The microbiology laboratory records of Erciyes University, Faculty of Medicine Hospital were reviewed to retrospectively identify patients with S. maltophilia infection between January 2007 and June 2011. A total of 38 patients (25 male, 13 female) were eligible for the study. The median age of the patients was 53xa0years. The underlying disease was hematological malignancy and disorders in 76.3xa0% (29 cases), solid tumors in 15.8xa0% (six cases), aplastic anemia in 7.9xa0% (three cases), while 18.4xa0% (seven cases) were hematopoietic stem cell transplantation (HSCT) recipients. An indwelling central venous catheter was used in 32 cases (84.2xa0%). Twenty-seven patients (71.1xa0%) were neutropenic at the onset of infection. Nine patients (23.7xa0%) were receiving corticosteroid therapy. The overall 14-day mortality rate was 50xa0%. Three of the patients received empirical antibacterial treatment, and three HSCT recipients received trimethoprim–sulfamethoxazole prophylaxis, which is active against S. maltophilia. Severe sepsis (OR 13.24, 95xa0% confidence interval (CI) 1.62–108.57) and the duration of the treatment (OR 0.73, 95xa0% CI 0.60–0.90) were related to death based on logistic regression analysis findings. In immunocompromised hematology–oncology patients with severe sepsis, S. maltophilia should be considered as a possible cause of infection, and should be given effective empirical antibiotic treatment immediately; the antimicrobial spectrum may be narrowed according to results of antibiotic susceptibility test.

Results of Adjuvant FOLFOX Regimens in Stage III Colorectal Cancer Patients: Retrospective Analysis of 667 Patients

Objective: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. Methods: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. Results: The median age of the patients was 56 years (range 17–78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1–79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. Conclusion: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Predictive factors for the development of brain metastases in patients with malignant melanoma: a study by the Anatolian society of medical oncology.

AbstractBackgroundThe development of brain metastases (BMs) was associated with poor prognosis in melanoma patients. Patients with BMs have a median survival of <6xa0months. Melanoma is the third most common tumor to metastasize to the brain with a reported incidence of 10–40xa0%. Our aim was to identify factors predicting development of BMs and survival.nPatients and methodsWe performed a retrospective analysis of 470 melanoma patients between 2000 and 2012. The logistic regression analyses were used to identify the clinicopathological features of primary melanoma that are predictive of BMs development and survival after a diagnosis of brain metastases.ResultsThere were 52 patients (11.1xa0%) who developed melanoma BMs during the study period. The analysis of post-BMs with Kaplan–Meier curves has resulted in a median survival rate of 4.1xa0months (range 2.9–5.1xa0months). On logistic regression analysis site of the primary tumor on the head and neck (pxa0=xa00.002), primary tumor thickness (Breslow >4xa0mm) (pxa0=xa00.008), ulceration (pxa0=xa00.007), and pathologically N2 and N3 diseases (pxa0=xa00.001) were found to be significantly associated with the development of BMs. In univariate analysis, tumor thickness and performance status had a significant influence on post-BMs survival. In multivariate analysis, these clinicopathologic factors were not remained as significant predictive factors.ConclusionsOur results revealed the importance of primary tumor characteristics associated with the development of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic ≥N2 disease were found to be significant predictors of BMs development.

Bevacizumab-containing Chemotherapy is Safe in Patients with Unresectable Metastatic Colorectal Cancer and a Synchronous Asymptomatic Primary Tumor

OBJECTIVEnSurgical resection of asymptomatic primary colorectal cancer in patients presenting with synchronous unresectable metastatic disease is controversial. Concerns and controversies remain over combining cytotoxic chemotherapy with bevacizumab in this patient population.nnnMETHODSnWe identified medical records of 99 patients with synchronous metastatic primary colorectal cancer who received chemotherapy with bevacizumab as their initial treatment. The incidence of subsequent use of surgery and surgical outcomes were recorded. Patients were also assessed for overall survival.nnnRESULTSnPatients who received bevacizumab-containing chemotherapy for synchronous metastatic primary colorectal cancer were divided into the non-surgery and surgery groups according to the resection status of their asymptomatic primary tumor. In the non-surgery group, two patients (4.4%) underwent additional surgery, while three patients (5.7%) required surgery for rectovesical fistula in the surgery group. The median overall survival was 17 months for the non-surgery group (95% CI: 10.6-23.3 months) and 23 months for the surgery group (95% CI: 21.3-24.6 months; P = 0.322).nnnCONCLUSIONSnThis study utilizing chemotherapy with bevacizumab did not result in an increased rate of morbidity related to the unresected primary tumor. Survival is not compromised by leaving the primary colon tumor intact.