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BACKGROUND: No clear guidelines exist for management of breast cancer brain metastases (BCBM). OBJECTIVE: We assessed the relationship between patient and tumor characteristics, treatment, and overall survival (OS). METHODS:We conducted a retrospective review of 196 patients who received brain radiation for BCBMbetween 2009-2013 at Mayo Clinic. Primary tumor characteristics were collected, including simplified molecular subtype. Other characteristics included patient's ECOG, number of brain lesions at BCBM diagnosis, and treatment received, including neurosurgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). The primary endpoint was OS from time of BCBM diagnosis. RESULTS: Single-variable analysis revealed patients with HER2+ breast cancer had improved OS (HR = 0:6, p = 0:008). Compared to patients with 1-3 brain lesions, the risk of death in patients with leptomeningeal disease was 2.5-fold higher (p = 0:003). Worsening ECOG status was associated with worsening OS. Patients who received SRS and WBRT had improved OS (HR = 0:37, p < 0:001) compared to patients receiving WBRT alone. CONCLUSIONS: Patients with the best OS had an ECOG of 0, HER2+ disease, and 1-3 brain lesions. The best OS was associated with the combination of neurosurgery and radiation therapy. A comprehensive treatment plan including neurosurgical evaluation and radiation therapy should be considered for patients with BCBM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lymph lymph node metastasis from melanoma ≤0.50 mm (ultrathin) is an infrequent event. However, because many newly diagnosed melanomas are ultrathin, a significant proportion of patients who present with lymph node disease have an ultrathin melanoma. The authors hypothesized that ultrathin melanomas that present with lymph node metastasis represent biologically aggressive lesions with a worse prognosis. METHODS: The Surveillance, Epidemiology, and End Results registry data were queried to identify patients with cutaneous melanoma who presented with lymph node metastasis diagnosed between 1998 and 2008. Hazard ratios (HRs) from Cox proportional hazards regression models were used to compare disease-specific survival (DSS) between various tumor depths. RESULTS: In total, 6134 patients with lymph node-positive melanoma were identified and stratified according to tumor depth, including 588 (10%) with a tumor depth ≤0.50 mm, 519 (8%) with a tumor depth from 0.51 to 1.00 mm, 1669 (27%) with a tumor depth from 1.01 to 2.00 mm, 1871 (31%) with a tumor depth from 2.01 to 4.00 mm, and 1487 (24%) with a tumor depth >4.00 mm; and the respective 5-year DSS rates were 63%, 76%, 75%, 60%, and 43%. Multivariable analysis confirmed a similar trend in HRs for DSS: The HR was 1.00 for a tumor depth ≤0.50 mm (reference category) and 0.64 ( P < .001), 0.65 ( P < .001), 0.95 ( P = .57), and 1.42 ( P < .001) for tumor depths of 0.51 to 1.00 mm, 1.01 to 2.00 mm, 2.01 to 4.00 mm, and >4.00 mm, respectively. This association of tumor depth with DSS persisted for N1 and N2 disease but not for N3 disease. CONCLUSIONS: Ultrathin melanoma (≤0.50 mm) was identified as a marker of poor prognosis in the setting of lymph node metastasis. These results may improve recommendations for adjuvant therapy, surveillance protocols, and risk stratification for clinical trials. Cancer 2013. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little is known about the prognostic impact of body mass index (BMI) and obesity on patients with locally advanced kidney cancer. Previous studies suggest that clinical/pathological stage, the proximal extent of the tumour thrombus, direct vascular wall invasion, and preoperative performance status may all constitute important prognostic factors within this patient population. The present study shows that a patient's metastatic status, higher level of tumour thrombus, and lower BMI all constitute adverse predictors of overall survival in patients who have RCC with inferior vena cava tumour thrombus. OBJECTIVE To determine which clinical variables, including body mass index (BMI), predict overall survival (OS) after nephrectomy with inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC) with tumour thrombus., PATIENTS AND METHODS After institutional review board approval, a retrospective analysis of all patients ( N= 100) undergoing nephrectomy and IVC thrombectomy for RCC from 1989 to 2010 were reviewed. One patient was excluded owing to missing clinical information leaving 99 patients in the study cohort., Patients were placed into one of two subgroups, based on their preoperative BMI (BMI ≤30 kg/m2 or BMI >30 kg/m2)., Complications, blood loss, level of tumour thrombus, side of tumour and follow-up data were tabulated., RESULTS Fifty-six patients had a BMI ≤30 kg/m2 and 43 patients had a BMI >30 kg/m2. Intraoperative complications occurred in 14% of those with BMI >30 kg/m2 and 5.4% of those with a BMI ≤30 kg/m2 ( P= 0.171)., On multivariate analysis, a higher thrombus level (III/IV vs I/II) and the presence of metastatic disease at time of diagnosis was associated with a worse OS ( P= 0.041 and P < 0.001, respectively)., The subgroup with a higher preoperative BMI had a significantly better OS (hazard ratio 0.42; 95% confidence interval 0.22-0.80, P= 0.009)., Similarly, our Kaplan-Meier survival analysis showed an improved OS in the patient cohort with a BMI >30 kg/m2 ( P= 0.016)., CONCLUSION Important predictors of outcome in patients undergoing nephrectomy with IVC thrombectomy for RCC with tumour thrombus include preoperative BMI, level of IVC tumour thrombus, and metastatic status at time of surgery. [ABSTRACT FROM AUTHOR]

Expression of ID1 (inhibitor of differentiation) has been correlate with the progression of a variety of cancers, but little information is available on its role in non-small cell lung cancer (NSCLC). Here we show that ID1 is induced by nicotinic acetylcholine receptor (nAChR) and epidermal growth factor receptor (EGFR) signaling in a panel of NSCLC cell lines and primary cells from the lung. ID1 induction was Src dependent and mediated through the α7 subunit of nAChR; transfection of K-Ras or EGFR to primary cells induced ID1. ID1 depletion prevented nicotine- and EGF-induced proliferation, migration, and invasion of NSCLC cells and angiogenic tubule formation of human microvascular endothelial cells from lungs (HMEC-Ls). ID1 could induce the expression of mesenchymal markers such as vimentin and fibronectin by downregulating ZBP-89, a zinc finger repressor protein. ID1 levels were elevated in tumors from mice that were exposed to nicotine. Further, human lung tissue microarrays (TMAs) showed elevated levels of ID1 in NSCLC samples, with maximal levels in metastatic lung cancers. Quantitative reverse transcription-PCR (RT-PCR) performed on patient lung tumors showed that ID1 levels were elevated in advanced stages of NSCLC and correlated with elevated expression of vimentin and fibronectin, irrespective of smoking history. [ABSTRACT FROM AUTHOR]

Cigarette smoking is a major risk factor in the development of non-small cell lung cancer (NSCLC), which accounts for 80% of all lung cancers. Nicotine, the major addictive component of tobacco smoke, can induce proliferation, invasion, and epithelial-to-mesenchymal transition (EMT) in NSCLC cell lines and promote metastasis of NSCLC in mice. Here, we demonstrate that the scaffolding protein β-arrestin-1 is necessary for nicotine-mediated induction of mesenchymal genes vimentin and fibronectin as well as EMT regulators ZEB1 and ZEB2. Nicotine induced changes in cell morphology and ablate tight junctions consistent with EMT; β-arrestin-1, but not β-arrestin-2, was required for these changes. β-Arrestin-1 promoted the expression of the mesenchymal genes, as well as ZEB1 and ZEB2, through the mediation of the E2F1 transcription factor; this required Src kinase activity. Stimulation of multiple NSCLC cell lines with nicotine led to enhanced recruitment of β-arrestin-1 and E2F1 on vimentin, fibronectin, and ZEB1 and ZEB2 promoters. Furthermore, there was significantly more b-arrestin-1 and E2F1 associated with these promoters in human NSCLC tumors, and β-arrestin-1 levels correlated with vimentin and fibronectin levels in human NSCLC samples. A549-luciferase cells lacking β-arrestin-1 showed a significantly reduced capacity for tumor growth and metastasis when ortho-topically implanted into the lungs of SCID-beige mice. Taken together, these studies reveal a novel role for β-arrestin-1 in the growth and metastasis of NSCLC. [ABSTRACT FROM AUTHOR]