Complete response as an intermediate end point in patients receiving salvage systemic therapy for urothelial carcinoma.

Background: The complete remission (CR) rate with salvage systemic therapy for urothelial carcinoma (UC) is unclear, and its value as an intermediate end point and association with survival are unknown.

Materials And Methods: Data from phase II trials of salvage chemotherapy and/or biologic agents were pooled. Data regarding response, overall survival (OS), progression-free survival (PFS), time from prior chemotherapy, hemoglobin, performance status, and liver metastasis status were collected.

Cisplatin-based first-line therapy for advanced urothelial carcinoma after previous perioperative cisplatin-based therapy.

Background: Outcomes with cisplatin-based first-line therapy for advanced UC after previous perioperative cisplatin-based chemotherapy are unclear. In this study we evaluated outcomes with a focus on the effect of time from previous cisplatin-based perioperative chemotherapy.

Patients And Methods: Data were collected for patients who received cisplatin-based first-line therapy for advanced UC after previous perioperative cisplatin-based therapy.

Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases.

While de-escalation of bisphosphonates from 4 to 12-weekly dosing has been shown to be clinically non-inferior to standard dosing, there is evidence the de-escalation is associated with increased bone turnover biomarkers. Here we evaluated the effect of de-escalated dosing on a panel of biomarkers and determined their association with incidence of skeletal related events (SREs) in breast cancer patients with 'low risk' bone metastases. As part of a pilot randomized trial, women with baseline C-telopeptide levels <600 ng/L after >3 months of 3-4 weekly pamidronate were randomized to continue pamidronate every 4 weeks or de-escalation to 12-weekly treatment.

Cognitive function and fatigue after diagnosis of colorectal cancer.

Background: Cognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC).

Patients And Methods: We evaluated CRC patients with stage I-III disease before or after surgery, participants with limited metastatic disease and healthy controls (HC).

Factors associated with publication of randomized phase iii cancer trials in journals with a high impact factor.

Background: Impact factor (if) is often used as a measure of journal quality. The purpose of the present study was to determine whether trials with positive outcomes are more likely to be published in journals with higher ifs.

Methods: We reviewed 476 randomized phase iii cancer trials published in 13 journals between 1995 and 2005.

A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance.

Background: In active surveillance (AS) patients: (i) To compare the ability of a multiparametric MRI (mpMRI)-ultrasound biopsy system to detect clinically significant (CS) prostate cancer with systematic 12-core biopsy (R-TRUSBx), and (ii) To assess the predictive value of mpMRI with biopsy as the reference standard.

Methods: Seventy-two men on AS prospectively underwent 3T mpMRI . MRI-ultrasound fusion biopsy (UroNavBx) and R-TRUSBx was performed.

Impact of the number of prior lines of therapy and prior perioperative chemotherapy in patients receiving salvage therapy for advanced urothelial carcinoma: implications for trial design.

Background: The differential impact of the number of prior lines of therapy and the setting of prior therapy (perioperative or metastatic) is unclear in advanced urothelial carcinoma.

Patients And Methods: Ten phase II trials of salvage chemotherapy, biologic agent therapy, or both, enrolling 731 patients, were available. Data on the number of prior lines of therapy and the setting of prior therapy were required in addition to known previously recognized prognostic factors: time from prior chemotherapy, hemoglobin level, performance status, and liver metastasis status.

Long-term impacts on macroinvertebrates downstream of reclaimed mountaintop mining valley fills in Central Appalachia.

Recent studies have documented adverse effects to biological communities downstream of mountaintop coal mining and valley fills (VF), but few data exist on the longevity of these impacts. We sampled 15 headwater streams with VFs reclaimed 11-33 years prior to 2011 and sampled seven local reference sites that had no VFs. We collected chemical, habitat, and benthic macroinvertebrate data in April 2011; additional chemical samples were collected in September 2011.

Phase 1 trial design: is 3 + 3 the best?

Background: Concerns have been recognized about the operating characteristics of the standard 3 + 3 dose-escalation design. Various innovative phase 1 trial designs have been proposed to address the issues and new challenges posed by molecularly targeted agents. However, in spite of these proposals, the conventional design is still the most widely utilized.

Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial.

Purpose: Obesity is associated with poor outcomes in women with operable breast cancer. Lifestyle interventions (LIs) that help women reduce their weight may improve outcomes.

Patients And Methods: We conducted a multicenter randomized trial comparing mail-based delivery of general health information alone or combined with a 24-month standardized, telephone-based LI that included diet (500 to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of moderate-intensity physical activity per week) goals to achieve weight loss (up to 10%).

Randomised, phase II, placebo-controlled, trial of fulvestrant plus vandetanib in postmenopausal women with bone only or bone predominant, hormone-receptor-positive metastatic breast cancer (MBC): the OCOG ZAMBONEY study.

Biomarkers of bone turnover, including urine N-telopeptide (uNTx), have been used as surrogate measures of response to bone-targeted therapies. Vascular endothelial growth factor (VEGF) levels correlate with extent of bone metastases. We assessed whether vandetanib, an inhibitor of VEGF, epidermal growth factor receptor and RET signalling, improved uNTx response when added to fulvestrant (F) in breast cancer patients with bone metastases.

Prognostic impact of the neutrophil-to-lymphocyte ratio in men with metastatic castration-resistant prostate cancer.

Background: We retrospectively evaluated the prognostic impact of neutrophil-lymphocyte ratio (NLR) as a marker for inflammatory and immune state in men with progressive metastatic castration resistant prostate cancer (mCRPC) following docetaxel.

Methods: The SUN-1120 phase III trial comparing prednisone combined with sunitinib (n = 584) or placebo (n = 289) for mCRPC following docetaxel-based chemotherapy was evaluated. The arms were combined for analysis, since no difference was observed in the primary endpoint of overall survival (OS).

Concurrent chemoradiotherapy for men with locally advanced penile squamous cell carcinoma.

Background: Outcomes with concurrent chemoradiotherapy for penile squamous cell carcinoma (PSCC) are unclear, and only anecdotal reports have been published. This study was a retrospective analysis of patients who received concurrent chemotherapy and radiotherapy for PSCC.

Patients And Methods: Individual patient-level data were obtained from 5 institutions for outcomes with concurrent chemoradiotherapy for PSCC.

Targeting integrin α6 stimulates curative-type bone metastasis lesions in a xenograft model.

Laminin-binding integrin receptors are key mediators of epithelial cell migration and tumor metastasis. Recent studies have demonstrated a role for the α6 integrin (ITGA6/CD49f) in maintaining stem cell compartments within normal bone marrow and in residency of tumors metastatic to bone. In this study, we tested a function-blocking antibody specific for ITGA6, called J8H, to determine if preexisting cancer lesions in bone could be slowed and/or animal survival improved.

Assessing the necessity of including a crossover period with dual reporting when changing total prostate-specific antigen methods.

Objectives: Options are limited for the laboratory when changing analytical methods for tumor markers. Standardization between methods should alleviate this burden. Our objective was to assess the necessity of dual reporting for total prostate-specific antigen (tPSA) when changing methods that have been calibrated against the World Health Organization PSA reference material.

A phase II, multicentre trial evaluating the efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal-related events.

The optimal frequency of intravenous (IV) bisphosphonate administration is unclear. We thus performed a study evaluating the effects of switching from 3-4 to 12 weekly therapy in patients with biochemically defined low-risk bone metastases. Patients with serum C-telopeptide (CTx) levels ≤600 ng/L after ≥3 months of 3-4 weekly IV pamidronate were switched to 12 weekly therapy for 48 weeks.

Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy.

Purpose: To determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative breast cancer in a randomized controlled trial (RCT).

Patients And Methods: Formalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out.

Tolerability and efficacy of docetaxel in older men with metastatic castrate-resistant prostate cancer (mCRPC) in the TAX 327 trial.

Objective: Prostate cancer is a disease of older men. Weekly docetaxel (DPq1w) is often favored over the standard three-weekly regimen (DPq3w) due to concerns about safety and tolerability in this population.

Materials And Methods: Two subgroup analyses of TAX 327 were conducted.

Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.

Background: Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease.

Cost effectiveness of a survivorship care plan for breast cancer survivors.

Purpose: Survivorship care plans (SCPs) are recommended for patients who have completed primary treatment and are transitioning to routine follow-up care. However, SCPs may be costly, and their effectiveness is unproven. The study objective was to assess the cost effectiveness of an SCP for breast cancer survivors transitioning to routine follow-up care with their own primary care physician (PCP) using data from a recent randomized controlled trial (RCT).

Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer.

Objective: To investigate the association of radiographic progression defined by Prostate Cancer Working Group (PCWG)-2 guidelines and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC).

Patients And Methods: Two trials that used PCWG-2 guidelines to define progression were analysed: a randomized phase II trial (n = 221) comparing first-line docetaxel-prednisone plus AT-101 or placebo, and a phase III trial (n = 873) comparing prednisone plus sunitinib or placebo after docetaxel-based chemotherapy. Cox proportional hazards regression models were used to estimate the association of radiographic progression with OS.