Phase 2 study of pembrolizumab in patients with advanced rare cancers.

Background: Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.

Methods: In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies.

Identification of pharmacodynamic biomarkers and common molecular mechanisms of response to genotoxic agents in cancer cell lines.

Purpose: Genotoxic agents (GAs) including cisplatin, doxorubicin, gemcitabine, and topotecan are often used in cancer treatment. However, the response to GAs is variable among patients and predictive biomarkers are inadequate to select patients for treatment. Accurate and rapid pharmacodynamics measures of response can, thus, be useful for monitoring therapy and improve clinical outcomes.

Pheochromocytoma-Induced Takotsubo Cardiomyopathy.

Pheochromocytoma, a rare catecholamine-secreting tumor, typically manifests itself with paroxysmal hypertension, tachycardia, headache, and diaphoresis. Less often, symptoms related to substantial hemodynamic compromise and cardiogenic shock occur. We report the case of a 66-year-old woman who presented with abdominal pain.

D3Oncoprint: Stand-Alone Software to Visualize and Dynamically Explore Annotated Genomic Mutation Files.

Purpose: Advances in next-generation sequencing technologies have led to a reduction in sequencing costs, which has increased the availability of genomic data sets to many laboratories. Increasing amounts of sequencing data require effective analysis tools to use genomic data for biologic discovery and patient management. Available packages typically require advanced programming knowledge and system administration privileges, or they are Web services that force researchers to work on outside servers.

PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study.

Background: The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men.

Methods: A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline.

On the Design of Combination Cancer Therapy.

Combination therapy programs are the hallmark of the successful treatment of all forms of human malignancies. In this issue of Cell, Palmer and Sorger present data suggesting that cell culture results indicative of synergistic anticancer drug interactions rarely translate clinically and that the results of combination therapies in mouse models or human clinical trials, even if successful, are best explained by the independent activities of the individually administered drugs.

Predictors of operative time during radical retropubic prostatectomy and robot-assisted laparoscopic prostatectomy.

Objectives: To better predict operative time using patient/surgical characteristics among men undergoing radical retropubic prostatectomy or robot-assisted laparoscopic prostatectomy in order to achieve more efficient operative scheduling and potentially decrease costs in the Veterans Health System.

Methods: We analyzed 2619 men treated with radical retropubic prostatectomy (n = 2005) or robot-assisted laparoscopic prostatectomy (n = 614) from 1993 to 2013 from six Veterans Affairs Hospitals in the Shared Equal Access Regional Cancer Hospital database. Age, body mass index, race, biopsy Gleason, prostate weight, undergoing a nerve-sparing procedure or lymph node dissection, and hospital surgical volume were analyzed in multivariable linear regression to identify predictors of operative time and to quantify the increase/decrease observed.

Does Peak Urine Flow Rate Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from REDUCE.

Purpose: We determined whether decreased peak urine flow is associated with future incident lower urinary tract symptoms in men with mild to no lower urinary tract symptoms.

Materials And Methods: Our population consisted of 3,140 men from the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial with mild to no lower urinary tract symptoms, defined as I-PSS (International Prostate Symptom Score) less than 8. REDUCE was a randomized trial of dutasteride vs placebo for prostate cancer prevention in men with elevated prostate specific antigen and negative biopsy.

The association between sexual function and prostate cancer risk in US veterans.

Sexual dysfunction and prostate cancer are common among older men. Few studies explored the association between these two illnesses. We examined whether sexual function is associated with prostate cancer risk among older men.

OpenGeneMed: a portable, flexible and customizable informatics hub for the coordination of next-generation sequencing studies in support of precision medicine trials.

Trials involving genomic-driven treatment selection require the coordination of many teams interacting with a great variety of information. The need of better informatics support to manage this complex set of operations motivated the creation of OpenGeneMed. OpenGeneMed is a stand-alone and customizable version of GeneMed (Zhao et al.

Efficiency of Prostate Cancer Diagnosis by MR/Ultrasound Fusion-Guided Biopsy vs Standard Extended-Sextant Biopsy for MR-Visible Lesions.

Background: Use of magnetic resonance (MR) imaging to improve prostate biopsy efficiency is rapidly gaining in popularity. The aim of this study was to assess the biopsy efficiency of MR/ultrasound (MR/US) fusion-guided ("targeted") biopsies vs extended-sextant 12-core ("standard") biopsies for overall and high-grade prostate cancer detection.

Methods: From August 2007 to February 2014, 1003 men were enrolled in a prospective trial comparing the diagnostic yield of targeted and standard prostate biopsies performed during the same session.

Amount, Source, and Quality of Support as Predictors of Women's Birth Evaluations.

Background: This paper examines the separate effects of the perceived amount, source, and quality of support during labor and delivery on women's positive and negative evaluations of their birth experiences.

Methods: Data come from the Listening to Mothers I and II (LTM) surveys (n = 2,765). Women's perception of support was regressed separately onto indices of positive and negative words that women associated with their labor and delivery.

Does Prostate Size Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from the REDUCE Trial.

Background: It has been shown that increased prostate size is a risk factor for lower urinary tract symptom (LUTS) progression in men who currently have LUTS presumed due to benign prostatic hyperplasia (BPH).

Objective: To determine if prostate size is a risk factor for incident LUTS in men with mild to no symptoms.

Design, Setting, And Participants: We conducted a post hoc analysis of the REDUCE study, which contained a substantial number of men (n=3090) with mild to no LUTS (International Prostate Symptom Score [IPSS] <8).

Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy.

Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy.

Materials And Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics.

Analytical Validation and Application of a Targeted Next-Generation Sequencing Mutation-Detection Assay for Use in Treatment Assignment in the NCI-MPACT Trial.

Robust and analytically validated assays are essential for clinical studies. We outline an analytical validation study of a targeted next-generation sequencing mutation-detection assay used for patient selection in the National Cancer Institute Molecular Profiling-Based Assignment of Cancer Therapy (NCI-MPACT) trial (NCT01827384). Using DNA samples from normal or tumor cell lines and xenografts with known variants, we assessed the sensitivity, specificity, and reproducibility of the NCI-MPACT assay in five variant types: single-nucleotide variants (SNVs), SNVs at homopolymeric (HP) regions (≥3 identical bases), small insertions/deletions (indels), large indels (gap ≥4 bp), and indels at HP regions.

Do all men with pathological Gleason score 8-10 prostate cancer have poor outcomes? Results from the SEARCH database.

Objective: To determine whether there are subsets of men with pathological high grade prostate cancer (Gleason score 8-10) with particularly high or low 2-year biochemical recurrence (BCR) risk after radical prostatectomy (RP) when stratified into groups based on combinations of pathological features, such as surgical margin status, extracapsular extension (ECE) and seminal vesicle invasion (SVI).

Materials And Methods: We identified 459 men treated with RP with pathological Gleason score 8-10 prostate cancer in the SEARCH database. The men were stratified into five groups based on pathological characteristics: group 1, men with negative surgical margins (NSMs) and no ECE; group 2, men with positive surgical margin (PSMs) and no ECE; group 3, men with NSMs and ECE; group 4, men with PSMs and ECE; and group 5, men with SVI.

Adverse pathology and undetectable ultrasensitive prostate-specific antigen after radical prostatectomy: is adjuvant radiation warranted?

Objectives: To determine if men with adverse pathology but undetectable ultrasensitive (<0.01 ng/mL) PSA are at high-risk for biochemical recurrence (BCR), or if there is a subset of patients at low-risk for whom the benefit of adjuvant radiation therapy might be limited.

Patients And Methods: We evaluated 411 patients treated with RP from 2001 to 2013 without adjuvant radiation who had an undetectable (<0.

GeneMed: An Informatics Hub for the Coordination of Next-Generation Sequencing Studies that Support Precision Oncology Clinical Trials.

We have developed an informatics system, GeneMed, for the National Cancer Institute (NCI) molecular profiling-based assignment of cancer therapy (MPACT) clinical trial (NCT01827384) being conducted in the National Institutes of Health (NIH) Clinical Center. This trial is one of the first to use a randomized design to examine whether assigning treatment based on genomic tumor screening can improve the rate and duration of response in patients with advanced solid tumors. An analytically validated next-generation sequencing (NGS) assay is applied to DNA from patients' tumors to identify mutations in a panel of genes that are thought likely to affect the utility of targeted therapies available for use in the clinical trial.

The association of exercise with both erectile and sexual function in black and white men.

Introduction: There is growing interest in using exercise to treat. Although many studies have highlighted the relationship between better erectile function and exercise, black men have been underrepresented in the literature.

Aims: This study aims to determine whether or not exercise is associated with better erectile as well as sexual function in black men and define a minimum exercise threshold for which better erectile/sexual function is seen in a cross-sectional study.

Use of serial multiparametric magnetic resonance imaging in the management of patients with prostate cancer on active surveillance.

Introduction: We evaluated the performance of multiparametric prostate magnetic resonance imaging (mp-MRI) and MRI/transrectal ultrasound (TRUS) fusion-guided biopsy (FB) for monitoring patients with prostate cancer on active surveillance (AS).

Materials And Methods: Patients undergoing mp-MRI and FB of target lesions identified on mp-MRI between August 2007 and August 2014 were reviewed. Patients meeting AS criteria (Clinical stage T1c, Gleason grade ≤ 6, prostate-specific antigen density ≤ 0.

Application of molecular profiling in clinical trials for advanced metastatic cancers.

There is growing interest in the application of molecular profiling, including sequencing, genotyping, and/or mRNA expression profiling, to the analysis of patient tumors with the objective of applying these data to inform therapeutic choices for patients with advanced cancers. Multiple clinical trials that are attempting to validate this personalized or precision medicine approach are in various stages of development and execution. Although preliminary data from some of these efforts have fueled excitement about the value and utility of these studies, their execution has also provoked many questions about the best way to approach complicating factors such as tumor heterogeneity and the choice of which genetic mutations to target.

Clinical implications of a multiparametric magnetic resonance imaging based nomogram applied to prostate cancer active surveillance.

Purpose: Multiparametric magnetic resonance imaging may be beneficial in the search for rational ways to decrease prostate cancer intervention in patients on active surveillance. We applied a previously generated nomogram based on multiparametric magnetic resonance imaging to predict active surveillance eligibility based on repeat biopsy outcomes.

Materials And Methods: We reviewed the records of 85 patients who met active surveillance criteria at study entry based on initial biopsy and who then underwent 3.

Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer.

Importance: Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard extended-sextant biopsy or the 2 modalities combined are not well understood.

Objective: To assess targeted vs standard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer.

Randomized Trial of Oral Cyclophosphamide and Veliparib in High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers, or BRCA-Mutant Ovarian Cancer.

Purpose: Veliparib, a PARP inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase I trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase II trial to determine the response rate of veliparib in combination with cyclophosphamide compared with cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC).

Experimental Design: Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles.