Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer

Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institution study was a pooled analysis of AR status, determined by droplet digital PCR, on pre-treatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in AR-gain [hazard ratio (HR)=1.61, 95% confidence interval (CI)=1.08-2.39, p=0.018), but not PFS (HR=1.04, 95%CI 0.74-1.46, p=0.8), nor PSA response [odds ratio (OR)=1.14, 95%CI=0.65-1.99, p=0.7)]. We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 7 chemotherapy-naïve, abiraterone/enzalutamide-treated patients with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR=0.27,95%CI=0.11-0.68, p=0.005) and PFS (HR=0.28, 95%CI=0.12-0.64, p=0.002). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal (HR=1.93, 95%CI=1.19-3.12, p=0.008) and a suggestion favoring docetaxel for AR-gained patients (HR=0.53, 95%CI=0.24-1.16, p=0.11). These data suggest that AR-normal patients should receive abiraterone/enzalutamide and AR-gained docetaxel. This treatment selection merits prospective evaluation in a randomized trial. // Patient summary: We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR-gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker

Gastric and colon metastasis from breast cancer: case report, review of the literature, and possible underlying mechanisms

J Carlos Villa Guzmán,1 J Espinosa,1 R Cervera,1 M Delgado,2 R Patón,3 JM Cordero García41Department of Medical Oncology, 2Department of Pathology, 3Department of Gastroenterology, 4Department of Nuclear Medicine, University Ciudad Real General Hospital, Ciudad Real, Spain Abstract: Gastrointestinal metastases from breast cancer are not common. We present a 58-year-old female diagnosed with lobular breast cancer some years before whose relapses were gastric and colonic mucosal. Simultaneous metastases are extremely rare. To our knowledge, no cases of initial dual affectation have been reported. The patient also showed gastritis by Helicobacter pylori. Invasive lobular breast carcinoma is the most frequent special type of breast cancer and carries some specific molecular alterations such as loss of expression of E-cadherin. Although underlying mechanisms of metastasization are not entirely known, chemokines as well as inflammatory events seem to be implicated in this process. Interaction between chemokines and their receptors frequently induces cell migration. We hypothesize that H. pylori, inflammatory cells, and chemokines may create a favorable environment attracting tumor cells. Keywords: chemokines, gastrointestinal metastases, H. pylori, lobular carcinom

Utilidad de una consulta de diagnóstico rápido de cáncer de pulmón en el Hospi- tal General de Ciudad Real

Resumen: Objetivo: Describir los resultados conseguidos en una consulta de diagnóstico rápido de cáncer de pulmón (CDR-CP). Comparar estos mismos datos con los pacientes evaluados mediante la sistemática habitual (NCDR-CP). Material y métodos: Se incluyeron los pacientes con CP diagnosticados en la CDR desde octubre 2014 hasta mayo de 2016. Se registró el tiempo desde la primera consulta hasta el inicio del tratamiento, datos de hospitalización, sexo, edad, hábito tabáquico, estadio, tipo histológico y tratamiento. Se han comparado estos mismos datos con los pacientes de CP valorados mediante la NCDR desde enero 2013 hasta mayo 2016. Resultados: Se diagnosticaron de CP 67 pacientes (45,3%) mediante la CDR. Más del 80% de los casos cumplieron las recomendaciones existentes. Al comparar estos datos con la NCDR (n=81; 54,7%), se encontraron diferencias significa- tivas en los ingresos hospitalarios (69,1% vs 14,5%; p<0,001) a favor de la CDR. En relación con las demoras terapéu- ticas hubo más pacientes en la CDR que cumplían con los tiempos acordados en las guías clínicas existentes (80,6% vs 64,6%; p =0,04). Conclusión: Una CDR-CP permite realizar, en la gran mayoría de los casos, los estudios de manera ambulatoria, en un plazo de tiempo acorde con las recomendaciones existentes y con una mejor optimización de los recursos sanitarios en comparación con la NCDR. Resume: Objective: To describe the results achieved of the Rapid Diagnostic Consultation of LC (RDC-LC) since its inception in 2014. To compare these same data with the patients evaluated by the standard system (NRDC-LC). Material and methods: Included patients diagnosed with LC in the RDC from October 2014 to May 2016. The time interval was collected from the first visit to the RDC up to start of treatment, data for hospitalizations, sex, age, smoking habit, staging, origin, histology, treatment. We compared these same data with LC patients who did not partake in the RDC and were diagnosed between January 2013 and May 2016. Results: We diagnosed 67 (45,3%) patients with LC through the RDC. Most patients, more than 80%, started treatment within the period of time recommended by clinical guidelines. When these results were compared with the NRDC group (n=81; 54,7%) differences were found in the hospitalizations in favor the RDC (69,1% vs 14,5%; p<0,001). According to therapeutic delays, there were more patients in the CDR who got the deadlines required in the current clinical guidelines (80,6% vs 64,6; p =0,04). Conclusion: Thanks to RDC-LC, most patients have begun treatment within the period of time recommended by clinical guidelines with health resources being correctly adjusted to the number of hospitalizations

Randomized phase III trial of erlotinib versus docetaxel in patients with advanced squamous cell non-small cell lung cancer failing first line platinum-based doublet chemotherapy stratified by Veristrat good versus Veristrat poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung trial.

INTRODUCTION Docetaxel and erlotinib are registered second-line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the Veristrat test in second-line therapy of NSCLC, classifying patients as either Veristrat "good" or "poor". EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely due to low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial. METHODS EMPHASIS-lung is a randomized phase III multicenter trial exploring the differential activity of second-line erlotinib versus docetaxel on progression-free survival (PFS) in Veristrat good versus poor patients with squamous cell NSCLC. RESULTS A total of 80 patients were randomized, with 72.5% categorized as Veristrat good. Patient characteristics were balanced between Veristrat status and treatment groups. Median PFS under docetaxel and erlotinib in the Veristrat good cohort was 4.1 and 1.6 months respectively, and 1.9 and 2.1 months in the Veristrat poor cohort. Median overall survival (OS) under docetaxel and erlotinib in the Veristrat good cohort was 7.8 and 8.4 and 4.4 and 5.2 months in the Veristrat poor cohort. An additional exploratory analysis was performed, where 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis contributing with 45 PFS and 41 OS events. CONCLUSION The final analysis of EMPHASIS-lung did not show differential activity on PFS for erlotinib versus docetaxel stratified by Veristrat status. Similarly, in the combined analysis, no significant treatment by Veristrat status interaction was observed (interaction P=0.24 for PFS and 0.45 for OS, stratified by study)

Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100 000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. METHODS We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. FINDINGS 292 982 (95% UI 261 017-327 792) maternal deaths occurred in 2013, compared with 376 034 (343 483-407 574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland. INTERPRETATION Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa. FUNDING Bill &amp; Melinda Gates Foundation