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.

Prognostic role of inflammatory biomarkers in metastatic breast cancer.

PURPOSE: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer. METHODS: This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (ß2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). CONCLUSION: Serum CRP, ferritin and ß2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

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

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

The effect of renin-angiotensin-system inhibition on survival and recurrence of N3+ breast cancer patients.

PURPOSE: The purpose of this study was to evaluate the association between the rennin-angiotensin system (RAS) inhibition and the risk of breast cancer (BC) recurrence and progression in N3 positive patients. METHODS: The medical records of patients treated for N3 positive BC in Hacettepe Cancer Institute between 2005 and 2012 were evaluated. Angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) users were defined as patients who took these medications for at least 6 months in no evidence of disease (NED) stage after the initial diagnosis. The primary and secondary outcome was disease-free survival (DFS) and overall survival (OS). Kaplan-Meier and Cox proportional hazard models were used. RESULTS: A total of 218 pathologic N3 BC patients were included. Follow up ranged from 12 to 212 months (median 49.58). Thirty one patients used ACE inhibitors/ARBs. Univariate analysis showed BC recurrence was lower and OS was higher among patients who used ACE inhibitors/ ARBs, however without reaching statistical significance (p=0.38 and p=0.24, respectively). RAS inhibition was associated with reduced risk of pathologic N3 BC recurrence. CONCLUSION: To the best of our knowledge this is the second study showing that the use of ACE inhibitors/ARBs may be effective in N3 BC. Because of the limited therapeutic options in BC, new drugs or new therapeutic modalities should be considered. In the future, studies with long-term follow-up may be helpful for their implication in clinical practice.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

Impact of inflammatory markers on the prognosis of patients with operable breast cancer.

PURPOSE: To investigate the effect of inflammatory markers on the prognosis of patients with operable breast cancer. METHODS: This study was conducted on breast cancer patients followed up between December 2009 and December 2012 at the Division of Medical Oncology, Department of Internal Medicine, Hacettepe University Medical School. A total of 704 patients with stages I to III disease whose inflammatory markers were assessed at the time of diagnosis were included the study. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, ferritin, ß2 microglobulin (ß2-M), and lactate dehydrogenase (LDH) levels were evaluated as inflammatory markers. RESULTS: The median age at diagnosis was 50 years (range 25-92). Of the patients 42.8% were premenopausal and 48.2 % postmenopausal. Invasive ductal carcinoma was the most common histology (76.5 %). Serum ferritin, LDH, ß2-M, ESR, and CRP were higher than the normal values in 1.0, 4.3, 9.5, 32.4 and 36.4 % of the patients, respectively. Serum albumin levels were lower than the normal values in 1.7 % of the patients. The median patient follow-up period was 22 months (range 3-227). During follow-up, metastatic disease developed in 31 patients (4.4%) and 11 patients (1.56%) died due to disease progression. Two-year overall survival (OS) and disease free survival (DFS) rates were not statistically different among patients with normal and abnormal values with respect to albumin, ferritin, LDH, ß2-M, CRP, and ESR. CONCLUSION: Our study is the first study to investigate the effect of inflammatory markers on the prognosis of operable breast cancer patients. We showed that inflammatory markers such as ESR, CRP, ferritin, ß2-M, albumin and LDH have no effect on prognosis.

Survival of Patients With Metastatic Rectum Cancer Who Underwent Metastasectomy Following Conversion Chemotherapy Sans Pelvic Radiotherapy: A Turkish Oncology Group Study.

BACKGROUND: The management of early rectal cancer is different from that of colon cancer in terms of radiotherapy (RT) requirements or neoadjuvant treatment. It is not clear how the course of rectal cancer differs from that of the colon in a metastatic setting or how it should be approached differently. This study aimed to evaluate outcomes after combining downsizing chemotherapy (CTx) with rescue surgery. METHODS: Eighty-nine patients (57 men and 32 women) diagnosed with metastatic rectal cancer with resectable disease after systemic CTx were included in the study. All patients underwent surgery for the primary mass and metastasis, but none received radiation therapy before or after surgery. Survival curves for overall survival (OS) and progression-free survival (PFS) were generated using the Kaplan-Meier method and compared with the log-rank test for subgroups. RESULTS: The median follow-up time was 28.8 (17.6-39.4) months. During the follow-up, 54 (60.7%) patients died and 78 (87.6%) patients had a PFS event. Cancer relapsed in 72 (80.9%) patients. Median OS was 35.2 (95% CI: 28.5-41.8) months, and median PFS was 17.7 (95% CI: 14.4-21) months. The five-year OS and PFS were 19% and 3.5%, respectively. Male sex (p=0.04) and a better Mandard score (p=0.021) were associated with a longer OS, while obesity was associated with a shorter PFS (p<0.001). CONCLUSION: Our study is the first to evaluate the effects of metastasectomy after conversion therapy in metastatic rectal cancer independent of colon cancer. As a result of the study, it was seen that the survival after metastasectomy in rectal cancer is worse than the colon cancer data known from previous studies.

Fluid rim sign: a new ultrasonographic sign of soft tissue aspergillosis.

The air crescent sign is a well-known important diagnostic finding in invasive pulmonary aspergillosis. Herein we report a distinctive but rare ultrasonographic appearance in a patient with myositis secondary to Aspergillus flavus infection, which can be considered as the soft tissue counterpart of the air crescent sign.

Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer.

BACKGROUND: Trastuzumab emtansine (T-DM1), a novel drug developed for the treatment of HER2-positive breast cancer, is a human epidermal growth factor receptor (HER2) targeted antibody drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). It has been shown that, in preclinical studies, it has anti-tumor activity in trastuzumab refractory cancer cells. In this review, we aim to show the clinical data about trastuzumab-DM1 (T-DM1) therapy and to discuss the therapy advantages for the management of patients with HER2-positive breast cancer. SCOPE: T-DM1 showed positive results in clinical studies of HER2-positive metastatic breast cancer. PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to September 2012 by using the terms 'trastuzumab emtansine (T-DM1) and anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors. FINDINGS: The phase III randomized trial EMILIA has shown that T-DM1 provided objective tumor responses and significantly improved progression free survival and overall survival compared to lapatinib and capacitabine combination in HER2-positive metastatic breast cancer patients treated with a prior taxane and trastuzumab regimen. It is believed that T-DM1 will play a role in the management of patients with advanced and early stage HER2-positive breast cancer, but this awaits further study. In particular, the ongoing phase III trials MARIANNE and TH3RESA will further give information about the place of T-DM1 in the treatment algorithms for HER2-positive disease. CONCLUSION: The trials of T-DM1 as a single agent and in combination with other chemotherapies have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. There are ongoing studies of T-DM1 showing an increasing tendency towards moving the study of these agents to earlier stages of HER2-positive breast cancer.

Association between common risk factors and molecular subtypes in breast cancer patients.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer. METHODS: This cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis. RESULTS: Thousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15-1.74; p=0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01-2.25; p=0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03-2.13; p=0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83-1.88; p=0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47-0.97; p=0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53-1.04; p=0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93-5.17; p=0.04) and luminal A (OR 1.87, 95% CI 0.93-3.90, p=0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06-3.37; p=0.04 and OR 1.90 95% CI 1.00-3.61; p=0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43-0.95; p=0.02 and OR 0.50 95% CI 0.32-0.76; p=0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands. CONCLUSIONS: Reproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.

Association of breast cancer subtypes and body mass index.

AIMS AND BACKGROUND: Breast cancer is a heterogeneous disease with various pathological and molecular subtypes. This study aims to determine the association between BMI and the distribution of breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2/neu) expression in pre- and postmenopausal breast cancers. METHODS AND STUDY DESIGN: A total of 1847 female breast cancer patients were involved. After the exclusion of 457 patients due to missing subtype information (n = 400) or benign histology (n = 57), 1390 were included in the analyses. The histological type of the tumor, ER and PR expression, HER2/neu with immunohistochemistry and HER2/neu gene evaluation with interphase fluorescence in situ hybridization (if necessary), age, body weight, height and menopausal status at diagnosis were investigated retrospectively. The patients were stratified as having a normal body weight if BMI was ≤24.9 kg/m², as being overweight if BMI was between 25.0 and 29.9 kg/m², and as being obese if BMI was ≥30.0 kg/m². RESULTS: Median BMI was 28.7 kg/m² (17.6-55.6) in the postmenopausal and 25.6 kg/m² (16.4-51.1) in the premenopausal group (P <0.001). BMI at diagnosis did not differ significantly between the molecular subtypes (P = 0.12). Distribution of BMI strata was similar between the molecular subtypes both in pre- and postmenopausal breast cancer (P = 0.24 and P = 0.99, respectively). Premenopausal women with a BMI of ≥25.0 kg/m² showed a tendency towards ER- tumors when compared to premenopausal women with a BMI of <25.0 kg/m² (P = 0.009). CONCLUSIONS: The risk of specific breast cancer subtypes may not be associated with BMI in pre- and postmenopausal breast cancer. However, obesity might be related to an increased risk of premenopausal hormone receptor-negative breast cancer. Further studies are needed for clarification of the probable mechanisms in the pathogenesis of premenopausal hormone receptor-negative breast cancer.

Evaluation of cardiac safety of lapatinib therapy for ErbB2-positive metastatic breast cancer: a single center experience.

Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. In this observational single center study, all patients with ErbB2-positive MBC who were previously treated with anthracycline, taxanes, and trastuzumab in the adjuvant and/or metastatic setting were assigned to receive lapatinib at a dose of 1,250 mg per day continuously plus capecitabine at a dose of 2,000 mg/m(2) in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9 weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3-60) weeks. The median age was 48 (range 28-83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2 %) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8 %) had T wave negativity, 1 (3.8 %) had sinus tachycardia, 1 (3.8 %) had grade 1 (453 ms) QT prolongation, and 2 (7.7 %) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7 %) had increased BNP, 1 (3.8 %) had increased CK, and 1 (3.8 %) had increased CK-MB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK-MB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies.