RESUMEN
PURPOSE: Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity. PATIENTS AND METHODS: Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99mTc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer-specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction. RESULTS: The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS (P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7, higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase. CONCLUSION: Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.
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Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Receptores Androgénicos , Estudios Prospectivos , BiomarcadoresRESUMEN
CONTEXT: Patients with advanced cancer are at increased risk for multiple hospitalizations and often have considerable needs post-discharge. Interventions to address patients' needs after transitioning home are lacking. OBJECTIVES: We sought to demonstrate the feasibility and acceptability of a post-discharge intervention for this population. METHODS: We conducted a single-arm pilot trial (n=54) of a post-discharge intervention, consisting of a video visit with an oncology nurse practitioner (NP) within three days of discharge to address symptoms, medications, hospitalization-related issues, and care coordination. We enrolled English-speaking adults with advanced breast, gastrointestinal, genitourinary, or thoracic cancers experiencing an unplanned hospitalization and preparing for discharge home. The intervention was deemed feasible if ≥70% of approached patients enrolled and ≥70% of enrolled patients completed the intervention within three days of discharge. Two weeks after discharge, patients rated the ease and usefulness of the video technology on a 0-10 scale (higher scores indicate greater ease of use). NPs completed post-intervention surveys to assess protocol adherence. RESULTS: We enrolled 54 of 75 approached patients (77.3%). Of enrolled patients (median age=65.0 years), 83.3% participated in the intervention within three days of discharge. The median ease of participating in the intervention was 9.0 (IQR: 6.0-10.0) and the median usefulness of the intervention was 7.0 (IQR: 4.5-8.0). The majority of visits focused on symptom management (85.7%), followed by post-hospital medical issues (69.0%). CONCLUSION: An oncology NP-delivered intervention immediately after hospital discharge is a feasible and acceptable approach to providing post-discharge care for hospitalized patients with advanced cancer.
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Antagonistas de Andrógenos , Capacidad Cardiovascular , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Capacidad Cardiovascular/fisiología , Anciano , Ecocardiografía/métodos , Persona de Mediana EdadRESUMEN
PURPOSE: The androgen receptor (AR) mRNA splice variant AR-V7 has emerged as a predictive biomarker for response to AR-targeted therapies. There are currently no commercially available assays to detect AR splice variants. The branched chain RNA in situ hybridization (ISH) platform enables the highly sensitive detection of RNA transcripts in formalin-fixed, paraffin-embedded (FFPE) tissues. EXPERIMENTAL DESIGN: We designed a branched chain RNA ISH probe to target the unique cryptic exon CE3 of AR-V7 using multiple tiling probes. This automated ISH assay was applied to tumor tissue from two distinct clinical cohorts that we hypothesized would differ in AR-V7 status. RESULTS: We detected AR-V7 in all tumor samples from men with metastatic castration-resistant prostate cancer with tissue obtained after disease progression despite at least one subsequent line of hormonal therapy (abiraterone, enzalutamide, or bicalutamide; n = 12). We detected AR-V7 in just one tumor from men who had undergone prostatectomy for localized adenocarcinoma (n = 30; Gleason 4 + 5 = 9 in the AR-V7-positive sample). Given the apparent distinction between the above groups by AR-V7 signal, we analyzed pretreatment AR-V7 status as a predictive and prognostic biomarker in men with treatment-naïve metastatic disease. Patients with metastases but without detectable AR-V7 RNA at baseline had significantly longer overall survival (log-rank P = 0.044) and a trend toward superior progression-free survival (log-rank P = 0.055). CONCLUSIONS: Within an institutional cohort, the RNA ISH assay identified AR-V7 within FFPE tissue and may have prognostic value in metastatic castration-sensitive prostate cancer. These preliminary findings warrant further study in larger cohorts. Clin Cancer Res; 23(2); 363-9. ©2016 AACR.