Change in Psoas Muscle Volume as a Predictor of Outcomes in Patients Treated with Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer.

Sarcopenia, or the age-related loss of skeletal muscle mass and function, has been investigated as a potential marker of adverse outcomes among surgical patients. Our aim was to assess for changes in psoas muscle volume (PMV) following administration of neoadjuvant chemotherapy (NAC) in patients with bladder cancer and to examine whether changes in PMV following NAC are predictive of perioperative complications, pathologic response or survival. During the period of 2009-2013, patients undergoing NAC and radical cystectomy (RC) at our institution with pre and post NAC cross sectional images available were included.

A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients With Metastatic Renal Cell Carcinoma.

Purpose Sunitinib is a standard initial therapy in metastatic renal cell carcinoma (mRCC), but chronic dosing requires balancing toxicity with clinical benefit. The feasibility and clinical outcome with intermittent sunitinib dosing in patients with mRCC was explored. Patients and Methods Patients with treatment-naïve, clear cell mRCC were treated with four cycles of sunitinib (50 mg once per day, 4 weeks of receiving treatment followed by 2 weeks of no treatment).

Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial.

Background: First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity. This study assessed atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatin-ineligible patients.

Methods: For this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible.

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis-Free Survival and Prostate Cancer-Specific Mortality.

Objectives/background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM).

Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions.

Immunobiology and immunotherapy in genitourinary malignancies.

Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g.

Efficacy and Safety of Gemcitabine Plus Either Taxane or Carboplatin in the First-Line Setting of Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

Although gemcitabine plus carboplatin (GCa) is the conventional first-line chemotherapy for cisplatin-ineligible metastatic urothelial carcinoma, its results are suboptimal. A meta-analysis evaluated the results of gemcitabine with either carboplatin or a taxane (GT). Literature was searched for studies including GT (paclitaxel or docetaxel) and GCa.

Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma.

Smoking has been linked to urothelial carcinoma (UC), but the implications on genomic profile and therapeutic response are poorly understood. To determine how smoking history impacts genomic profile and chemotherapy response, clinicopathologic data was collected for patients with metastatic UC (mUC) across 3 academic medical centers and comprehensive genomic profiling (CGP) was performed through a CLIA-certified lab. Unsupervised hierarchical clustering based on smoking status was used to categorize the frequency of genomic alterations (GAs) amongst current smokers (CS), ex-smokers (ES) and non-smokers (NS), and survival was compared in these subsets.

Low-Cost Intervention to Increase Influenza Vaccination Rate at a Comprehensive Cancer Center.

Influenza morbidity and mortality can be severe and costly. Vaccination rates remain suboptimal in cancer patients due to provider- and patient-related factors. The objective of this study was to evaluate whether low-cost provider- and patient-focused interventions would increase influenza vaccination rates at the University of Michigan Comprehensive Cancer Center (UMCCC).

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.

Background: Patients with metastatic urothelial carcinoma have few treatment options after failure of platinum-based chemotherapy. In this trial, we assessed treatment with atezolizumab, an engineered humanised immunoglobulin G1 monoclonal antibody that binds selectively to programmed death ligand 1 (PD-L1), in this patient population.

Methods: For this multicentre, single-arm, two-cohort, phase 2 trial, patients (aged ≥18 years) with inoperable locally advanced or metastatic urothelial carcinoma whose disease had progressed after previous platinum-based chemotherapy were enrolled from 70 major academic medical centres and community oncology practices in Europe and North America.

Contemporary Systemic Therapy for Urologic Malignancies in Geriatric Patients.

Current data on systemic therapy in geriatric populations with genitourinary malignancies are largely derived from retrospective analyses of prospectively conducted trials or retrospective reviews. Although extrapolation of these data to real-world patients should be cautious, patients aged 65 years or older with good functional status and minimal comorbidities seem to enjoy similar survival benefit from therapy as their younger counterparts. Chronologic age alone should generally not be used to guide management decisions.

The biological complexity of urothelial carcinoma: Insights into carcinogenesis, targets and biomarkers of response to therapeutic approaches.

Bladder cancer is a major cause of morbidity, mortality and health-related costs. Urothelial carcinoma is by far the most common histologic type of bladder cancer and may also arise from the upper urinary tract, e.g.

Clinical and therapeutic factors associated with adverse pathological outcomes in clinically node-negative patients treated with neoadjuvant cisplatin-based chemotherapy and radical cystectomy.

Purpose: Several disease characteristics have been identified as potential predictors for pathological node involvement (pN+) following radical cystectomy (RC). However, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). We endeavored to assess factors predicting adverse pathology in clinically node-negative patients treated with NAC and RC.

A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma.

Background: Epidermal growth factor receptor overexpression is associated with poor outcomes in urothelial carcinoma (UC). Cetuximab (CTX) exhibited an antitumor effect in in vivo UC models. The efficacy of gemcitabine/cisplatin (GC) with or without CTX in patients with advanced UC was evaluated.

Double-blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma.

Background: Angiogenesis contributes to the progression of urothelial carcinoma (UC). In the current study, the authors investigated the role of maintenance sunitinib in patients with advanced UC.

Methods: Patients with locally recurrent/metastatic UC and adequate organ function who achieved stable disease or a partial or complete response after 4 to 6 chemotherapy cycles were randomized to sunitinib at a dose of 50 mg/day (28 days on and 14 days off) or placebo.

Evaluation of the antitumor activity of dacomitinib in models of human bladder cancer.

Members of the human epidermal growth factor receptor (HER) family play a significant role in bladder cancer progression and may underlie the development of chemotherapy resistance. Dacomitinib is an irreversible tyrosine kinase inhibitor with structural specificity for the catalytic domains of epidermal growth factor receptor (EGFR), HER2 and HER4 that has exhibited vigorous efficacy against other solid tumors. We evaluated the antitumor activity of dacomitinib in human bladder cancer cell lines expressing varying levels of HER family receptors.

A phase II trial of neoadjuvant nab-paclitaxel, carboplatin, and gemcitabine (ACaG) in patients with locally advanced carcinoma of the bladder.

Objective: To assess the activity of neoadjuvant nab-paclitaxel, carboplatin, gemcitabine (ACaG) followed by cystectomy in patients with muscle-invasive urothelial carcinoma of the bladder.

Methods: Patients who were candidates for cystectomy received nab-paclitaxel 260 mg/m(2) on day 1, carboplatin area under the curve 5 on day 1, and gemcitabine 800 mg/m(2) on days 1 and 8, every 21 days for 3 cycles. The first 3 patients received nab-paclitaxel 100 mg/m(2) weekly and were not included in the efficacy analysis of evaluable patients.

Transcriptional corepressors in cancer: emerging targets for therapeutic intervention.

The normal cell transcriptional process entails a high degree of combinatorial effects and time-dependent "flexibility" to translate cellular signaling into differential gene expression levels. Transcriptional corepressors can function as histone-modifying enzymes to regulate epigenetic events, modulate chromatin structure, and hence control transcriptional activity. Various corepressor complexes have been described; qualitative and quantitative alterations of corepressors can crucially influence the transcriptional output of both normal and malignant cells.

Urethral cancer.

Urethral carcinoma is a rare tumor with predominantly poor survival. Both the disease and its treatment can affect both sexual and urinary function. The natural history of urethral carcinoma varies, therefore the appropriate application of surgery, radiation, and chemotherapy remain unknown.

Predicting response to hormonal therapy and survival in men with hormone sensitive metastatic prostate cancer.

Androgen deprivation is the cornerstone of the management of metastatic prostate cancer. Despite several decades of clinical experience with this therapy there are no standard predictive biomarkers for response. Although several candidate genetic, hormonal, inflammatory, biochemical, metabolic biomarkers have been suggested as potential predictors of response and outcome, none has been prospectively validated nor has proven clinical utility to date.

Urothelial carcinomas: a focus on human epidermal receptors signaling.

Bladder cancer is a common malignancy and a frequent cause of cancer-related death worldwide. The benefit from current chemotherapy has reached a relative plateau, thus identification of molecular targets for better therapy is a high priority. Human epidermal receptors constitute a family of receptor tyrosine kinases, which appear to be implicated in cellular transformation and can be over-expressed in a variety of solid tumors.

Immunotherapy of kidney cancer.

Renal cell carcinoma (RCC) accounts for 4% of all new cancer cases in males and 3% in females in the US. Compared to other solid tumors, it does not respond to traditional management modalities, such as chemotherapy and radiation therapy. However, it appears to be an immune-responsive tumor and several immunotherapeutic strategies have been investigated in the management of RCC with variable degrees of success.

Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas.

The pathogenesis of colorectal carcinoma (CRC) is a complex process that involves the recruitment of both genetic and epigenetic mechanisms. Recent studies underline the cardinal role of small, noncoding RNA molecules, called microRNAs (miRs), in the pathobiology of numerous physiological and pathological processes, including oncogenesis. MiR biogenesis and maturation is mainly regulated by the nuclear ribonuclease Drosha and the cytoplasmic ribonucleases Dicer and Ago2.