Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Outcomes and clinicopathologic characteristics associated with disseminated tumor cells in bone marrow after neoadjuvant chemotherapy in high-risk early stage breast cancer: the I-SPY SURMOUNT study.

PURPOSE: Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45- cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes. METHODS: Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery. EPCAM+CD45- cells in 4 mLs of bone marrow aspirate were enumerated using immunomagnetic enrichment/flow cytometry (IE/FC). Patients with > 4.16 EPCAM+CD45- cells per mL of bone marrow were classified as DTC-positive. Tumor response was assessed using the residual cancer burden (RCB), a standardized approach to quantitate the extent of residual invasive cancer present in the breast and the axillary lymph nodes after NAC. Association of DTC-positivity with clinicopathologic variables and survival was examined. RESULTS: A total of 73 patients were enrolled, 51 of whom had successful EPCAM+CD45- cell enumeration. Twenty-four of 51 (47.1%) were DTC-positive. The DTC-positivity rate was similar across receptor subtypes, but DTC-positive patients were significantly younger (p = 0.0239) and had larger pretreatment tumors compared to DTC-negative patients (p = 0.0319). Twenty of 51 (39.2%) achieved a pathologic complete response (pCR). While DTC-positivity was not associated with achieving pCR, it was significantly associated with higher RCB class (RCB-II/III, 62.5% vs. RCB-0/I; 33.3%; Chi-squared p = 0.0373). No significant correlation was observed between DTC-positivity and distant recurrence-free survival (p = 0.38, median follow-up = 3.2 years). CONCLUSION: DTC-positivity at surgery after NAC was higher in younger patients, those with larger tumors, and those with residual disease at surgery.

Opioid Prescribing at Discharge in Opioid-Naïve Trauma Patients.

BACKGROUND: Opioid analgesics remain mainstay of treatment for trauma-related pain despite growing concerns for opioid dependency or misuse. The purpose of this study was to evaluate opioid prescribing at hospital discharge after traumatic injury. METHODS: This is a single-center, retrospective analysis of patients ≥18 years of age admitted for ≥24 hours with a primary diagnosis of traumatic injury. Those with alcohol use disorder, polysubstance abuse, chronic opioid use, or in-hospital mortality were excluded. The primary outcome was the incidence of patients prescribed opioids at discharge. Secondary outcomes included percent of patients who received nonopioids, intensive care unit (ICU) admission, and hospital length of stay (LOS). RESULTS: Of the 927 encounters, 471 were included. The mean age was 60 ± 23 years, and 62.0% were male. The majority were blunt trauma, and 49.9% were falls. Mean initial injury severity score (ISS) was 9 ± 7.2. Of the 70.4% of patients prescribed opioids, 39.4% were discharged on opioids. Age ≥30 years, ICU admission, ISS <9, or Charlson Comorbidity Index >1 was less likely to have opioids prescribed at discharge. Most received nonopioids (93.6%) and multimodal analgesia (84.3%). The median hospital and ICU LOS were 5 (3-9) and 2 (0-4) days, respectively. DISCUSSION: Only 39.4% had opioids prescribed at discharge. Opioid-reductive strategies may decrease in-hospital and discharge opioid prescribing. While opioid analgesics remain a mainstay of trauma-associated pain management, institution-wide opioid-sparing strategies can further reduce discharge opioid prescribing after trauma.

Multianalyte Prognostic Signature Including Circulating Tumor DNA and Circulating Tumor Cells in Patients With Advanced Pancreatic Adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis. Multianalyte signatures, including liquid biopsy and traditional clinical variables, have shown promise for improving prognostication in other solid tumors but have not yet been rigorously assessed for PDAC. MATERIALS AND METHODS: We performed a prospective cohort study of patients with newly diagnosed locally advanced pancreatic cancer (LAPC) or metastatic PDAC (mPDAC) who were planned to undergo systemic therapy. We collected peripheral blood before systemic therapy and assessed circulating tumor cells (CTCs), cell-free DNA concentration (cfDNA), and circulating tumor KRAS (ctKRAS)-variant allele fraction (VAF). Association of variables with overall survival (OS) was assessed in univariate and multivariate survival analysis, and comparisons were made between models containing liquid biopsy variables combined with traditional clinical prognostic variables versus models containing traditional clinical prognostic variables alone. RESULTS: One hundred four patients, 40 with LAPC and 64 with mPDAC, were enrolled. CTCs, cfDNA concentration, and ctKRAS VAF were all significantly higher in patients with mPDAC than patients with LAPC. ctKRAS VAF (cube root; 0.05 unit increments; hazard ratio, 1.11; 95% CI, 1.03 to 1.21; P = .01), and CTCs ≥ 1/mL (hazard ratio, 2.22; 95% CI, 1.34 to 3.69; P = .002) were significantly associated with worse OS in multivariate analysis while cfDNA concentration was not. A model selected by backward selection containing traditional clinical variables plus liquid biopsy variables had better discrimination of OS compared with a model containing traditional clinical variables alone (optimism-corrected Harrell's C-statistic 0.725 v 0.681). CONCLUSION: A multianalyte prognostic signature containing CTCs, ctKRAS, and cfDNA concentration outperformed a model containing traditional clinical variables alone suggesting that CTCs, ctKRAS, and cfDNA provide prognostic information complementary to traditional clinical variables in advanced PDAC.

PSMA-targeting TGFß-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial.

Chimeric antigen receptor (CAR) T cells have demonstrated promising efficacy, particularly in hematologic malignancies. One challenge regarding CAR T cells in solid tumors is the immunosuppressive tumor microenvironment (TME), characterized by high levels of multiple inhibitory factors, including transforming growth factor (TGF)-ß. We report results from an in-human phase 1 trial of castration-resistant, prostate cancer-directed CAR T cells armored with a dominant-negative TGF-ß receptor (NCT03089203). Primary endpoints were safety and feasibility, while secondary objectives included assessment of CAR T cell distribution, bioactivity and disease response. All prespecified endpoints were met. Eighteen patients enrolled, and 13 subjects received therapy across four dose levels. Five of the 13 patients developed grade ≥2 cytokine release syndrome (CRS), including one patient who experienced a marked clonal CAR T cell expansion, >98% reduction in prostate-specific antigen (PSA) and death following grade 4 CRS with concurrent sepsis. Acute increases in inflammatory cytokines correlated with manageable high-grade CRS events. Three additional patients achieved a PSA reduction of ≥30%, with CAR T cell failure accompanied by upregulation of multiple TME-localized inhibitory molecules following adoptive cell transfer. CAR T cell kinetics revealed expansion in blood and tumor trafficking. Thus, clinical application of TGF-ß-resistant CAR T cells is feasible and generally safe. Future studies should use superior multipronged approaches against the TME to improve outcomes.

Association of women leaders in the C-suite with hospital performance.

BACKGROUND: Women comprise 50% of the healthcare workforce, but only about 25% of senior leadership positions in the USA. No studies to our knowledge have investigated the performance of hospitals led by women versus those led by men to evaluate the potential explanation that the inequity reflects appropriate selection due to skill or performance differences. METHODS: We conducted a descriptive analysis of the gender composition of hospital senior leadership (C-suite) teams and cross-sectional, regression-based analyses of the relationship between gender composition, hospital characteristics (eg, location, size, ownership), and financial, clinical, safety, patient experience and innovation performance metrics using 2018 data for US adult medical/surgical hospitals with >200 beds. C-suite positions examined included chief executive officer (CEO), chief financial officer (CFO) and chief operating officer (COO). Gender was obtained from hospital web pages and LinkedIn. Hospital characteristics and performance were obtained from American Hospital Directory, American Hospital Association Annual Hospital Survey, Healthcare Cost Report Information System and Hospital Consumer Assessment of Healthcare Providers and Systems surveys. RESULTS: Of the 526 hospitals studied, 22% had a woman CEO, 26% a woman CFO and 36% a woman COO. While 55% had at least one woman in the C-suite, only 15.6% had more than one. Of the 1362 individuals who held one of the three C-suite positions, 378 were women (27%). Hospital performance on 27 of 28 measures (p>0.05) was similar between women and men-led hospitals. Hospitals with a woman CEO performed significantly better than men-led hospitals on one financial metric, days in accounts receivable (p=0.04). CONCLUSION: Hospitals with women in the C-suite have comparable performance to those without, yet inequity in the gender distribution of leaders remains. Barriers to women's advancement should be recognised and efforts made to rectify this inequity, rather than underusing an equally skilled pool of potential women leaders.

Comparative Analysis of Patients with Robotic Hiatal Hernia Repairs with and without Collis Gastroplasty.

INTRODUCTION: After extensive mediastinal dissection fails to achieve adequate intra-abdominal esophageal length, a Collis gastroplasty(CG) is recommended to decrease axial tension and reduce hiatal hernia recurrence. However, concerns exist about staple line leak, and long-term symptoms of heartburn and dysphagia due to the acid-producing neoesophagus which lacks peristaltic activity. This study aimed to assess long-term satisfaction and GERD-related quality of life after robotic fundoplication with CG (wedge fundectomy technique) and to compare outcomes to patients who underwent fundoplication without CG. Outcomes studied included patient satisfaction, resumption of proton pump inhibitors (PPI), length of surgery (LOS), hospital stay, and reintervention. METHODS: This was a single-center retrospective analysis of patients from January 2017 through December 2018 undergoing elective robotic hiatal hernia repair and fundoplication. 61 patients were contacted for follow-up, of which 20 responded. Of those 20 patients, 7 had a CG performed during surgery while 13 did not. There was no significant difference in size and type of hiatal hernias in the 2 groups. These patients agreed to give their feedback via a GERD health-related quality of life (GERD HRQL) questionnaire. Their medical records were reviewed for LOS, length of hospital stay (LOH), and reintervention needed. Statistical analysis was performed using SPSS v 25. Satisfaction and need for PPIs were compared between the treatment and control groups using the chi-square test of independence. RESULTS: Statistical analysis showed that satisfaction with outcome and PPI resumption was not significantly different between both groups (P > .05). There was a significant difference in the average ranks between the 2 groups for the question on postoperative dysphagia on the follow-up GERD HRQL questionnaire, with the group with CG reporting no dysphagia. There were no significant differences in the average ranks between the 2 groups for the remaining 15 questions (P > .05). The median LOS was longer in patients who had a CG compared to patients who did not (250 vs. 148 min) (P = .01). The LOH stay was not significantly different (P > .05) with a median length of stay of 2 days observed in both groups. There were no leaks in the Collis group and no reoperations, conversions, or blood transfusions needed in either group. CONCLUSION: Collis gastroplasty is a safe option to utilize for short esophagus noted despite extensive mediastinal mobilization and does not adversely affect the LOH stay, need for reoperation, or patient long-term satisfaction.

THSB2 as a prognostic biomarker for patients diagnosed with metastatic pancreatic ductal adenocarcinoma.

Patients newly diagnosed with metastatic pancreatic ductal adenocarcinoma generally have poor survival, with heterogeneous rates of progression. Biomarkers that could predict progression and/or survival would help inform patients and providers as they make care decisions. In a previous retrospective study, we discovered that circulating thrombospondin-2 (THBS2) could, in combination with CA19-9, better distinguish patients with PDAC versus healthy controls. Here we evaluated whether THBS2 levels, previously not known to be prognostic, were associated with outcome in 68 patients at time of diagnosis of metastatic PDAC. Specifically, we interrogated the association of THBS2 level, alone or in combination with CA19-9, with progression by 90 days and/or survival to 180 days. The results indicate that elevated THBS2 levels alone, at the time of a metastatic PDAC diagnosis, can identify patients with a shorter time to death and thus help patients and providers when planning treatment.

Pseudoaneurysm of the Abdominal Aorta at the Celiac Trunk After Penetrating Trauma.

We report the case of a 33-year-old man who had received multiple gunshot wounds to the abdomen; consequently, he was diagnosed with a traumatic dissection of the abdominal aorta at the level of the superior mesenteric artery (SMA) extending to just below the renal arteries with a posterior pseudoaneurysm of the aorta. He had wounds in the right upper quadrant and in the left lower back. He demonstrated signs of peritonitis for which he was taken to the operating room for exploratory laparotomy. A right common iliac to SMA bypass with a 7-mm ringed polytetrafluoroethylene (PTFE) graft was created. The celiac trunk was then ligated, and through the right groin sheath, a thoracic endograft stent (Cook Medical, Bloomington, IN) was inserted at the level of the thoracic aorta with resolution of the blood flow to the aorta, visceral and iliac arteries, as well as retrograde flow into the bypass graft. The literature on traumatic abdominal aortic pseudoaneurysm was reviewed, and based on that, we believe this report describes a unique case of a traumatic aortic pseudoaneurysm at the level of the celiac trunk, as well as our operative approach.

Optimization of Sources of Circulating Cell-Free DNA Variability for Downstream Molecular Analysis.

Circulating cell-free DNA (ccfDNA) is used increasingly as a cancer biomarker for prognostication, as a correlate for tumor volume, or as input for downstream molecular analysis. Determining optimal blood processing and ccfDNA quantification are crucial for ccfDNA to serve as an accurate biomarker as it moves into the clinical realm. Whole blood was collected from 50 subjects, processed to plasma, and used immediately or frozen at -80°C. Plasma ccfDNA was extracted and concentration was assessed by real-time quantitative PCR (qPCR), fluorimetry, and droplet digital PCR (ddPCR). For the 24 plasma samples from metastatic pancreatic cancer patients, the variant allele fractions (VAF) of KRAS G12/13 pathogenic variants in circulating tumor DNA (ctDNA) were measured by ddPCR. Using a high-speed (16,000 × g) or slower-speed (4100 × g) second centrifugation step showed no difference in ccfDNA yield or ctDNA VAF. A two- versus three-spin centrifugation protocol also showed no difference in ccfDNA yield or ctDNA VAF. A higher yield was observed from fresh versus frozen plasma by qPCR and fluorimetry, whereas a higher yield was observed for frozen versus fresh plasma by ddPCR, however, no difference was observed in ctDNA VAF. Overall, our findings suggest factors to consider when implementing a ccfDNA extraction and quantification workflow in a research or clinical setting.

Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy.

Although the majority of patients with metastatic non-small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS: Patients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded. RESULTS: Among 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P < .001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P < .001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95% CI, 0.13 to 0.50) and overall survival (hazard ratio, 0.27; 95% CI, 0.12 to 0.64) compared with molecular nonresponders. CONCLUSION: Molecular response assessment using circulating tumor DNA may serve as a noninvasive, on-therapy predictor of response to pembrolizumab-based therapy in addition to standard of care imaging in mNSCLC. This strategy requires validation in independent prospective studies.

Combining radiomic phenotypes of non-small cell lung cancer with liquid biopsy data may improve prediction of response to EGFR inhibitors.

Among non-small cell lung cancer (NSCLC) patients with therapeutically targetable tumor mutations in epidermal growth factor receptor (EGFR), not all patients respond to targeted therapy. Combining circulating-tumor DNA (ctDNA), clinical variables, and radiomic phenotypes may improve prediction of EGFR-targeted therapy outcomes for NSCLC. This single-center retrospective study included 40 EGFR-mutant advanced NSCLC patients treated with EGFR-targeted therapy. ctDNA data included number of mutations and detection of EGFR T790M. Clinical data included age, smoking status, and ECOG performance status. Baseline chest CT scans were analyzed to extract 429 radiomic features from each primary tumor. Unsupervised hierarchical clustering was used to group tumors into phenotypes. Kaplan-Meier (K-M) curves and Cox proportional hazards regression were modeled for progression-free survival (PFS) and overall survival (OS). Likelihood ratio test (LRT) was used to compare fit between models. Among 40 patients (73% women, median age 62 years), consensus clustering identified two radiomic phenotypes. For PFS, the model combining radiomic phenotypes with ctDNA and clinical variables had c-statistic of 0.77 and a better fit (LRT p = 0.01) than the model with clinical and ctDNA variables alone with a c-statistic of 0.73. For OS, adding radiomic phenotypes resulted in c-statistic of 0.83 versus 0.80 when using clinical and ctDNA variables (LRT p = 0.08). Both models showed separation of K-M curves dichotomized by median prognostic score (p < 0.005). Combining radiomic phenotypes, ctDNA, and clinical variables may enhance precision oncology approaches to managing advanced non-small cell lung cancer with EGFR mutations.

Association of plasma cell-free DNA with survival in patients with IDH wild-type glioblastoma.

BACKGROUND: We aimed to determine whether plasma cell-free DNA (cfDNA) concentration is associated with survival in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM). METHODS: Pre-operative and post-chemoradiotherapy blood samples were prospectively collected from patients with newly diagnosed IDH wild-type GBM. Patients underwent surgical resection or biopsy and received adjuvant radiotherapy with concomitant temozolomide. Cell-free DNA (cfDNA) was isolated from plasma and quantified using SYBR Green-based q polymerase chain reaction (qPCR). RESULTS: Sixty-two patients were enrolled and categorized into high vs. low cfDNA groups relative to the pre-operative median value (25.2 ng/mL, range 5.7-153.0 ng/mL). High pre-operative cfDNA concentration was associated with inferior PFS (median progression-free survival (PFS), 3.4 vs. 7.7 months; log-rank P = .004; hazard ratio [HR], 2.19; 95% CI, 1.26-3.81) and overall survival (OS) (median OS, 8.0 vs. 13.9 months; log-rank P = .01; HR, 2.43; 95% CI, 1.19-4.95). After adjusting for risk factors, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, pre-operative cfDNA remained independently associated with PFS (HR, 2.70; 95% CI, 1.50-4.83; P = .001) and OS (HR, 2.65; 95% CI, 1.25-5.59; P = .01). Post-hoc analysis of change in cfDNA post-chemoradiotherapy compared to pre-surgery (n = 24) showed increasing cfDNA concentration was associated with worse PFS (median, 2.7 vs. 6.0 months; log-rank P = .003; HR, 4.92; 95% CI, 1.53-15.84) and OS (median, 3.9 vs. 19.4 months; log-rank P < .001; HR, 7.77; 95% CI, 2.17-27.76). CONCLUSIONS: cfDNA concentration is a promising prognostic biomarker for patients with IDH wild-type GBM. Plasma cfDNA can be obtained noninvasively and may enable more accurate estimates of survival and effective clinical trial stratification.

Feeling offended by clients: The experiences of doctoral student therapists.

Ten doctoral student therapists (8 White, 5 female) in 1 counseling psychology doctoral program located in the Mid-Atlantic United States were interviewed for approximately 1 hour each about their experiences of feeling offended by a client during an individual psychotherapy session. Interview data were analyzed with consensual qualitative research (CQR). Trainee therapists typically felt offended related to their sociocultural identities (e.g., being a woman, LGBTQ+, racial-ethnic minority), felt frozen after the events and uncertain about how to respond, wished they had handled the events differently, and struggled when clients expressed opinions or beliefs that ran counter to their own values. Trainees had difficulty maintaining an empathic, nonjudgmental therapeutic stance where they could both value the client and maintain their own sense of integrity and beliefs about social justice and multiculturalism. Implications for training, practice, and research are provided. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed too late for effective therapy. The classic strategy for early detection biomarker advancement consists of initial retrospective phases of discovery and validation with tissue samples taken from individuals diagnosed with disease, compared with controls. Using this approach, we previously reported the discovery of a blood biomarker panel consisting of thrombospondin-2 (THBS2) and CA19-9 that together could discriminate resectable stage I and IIa PDAC as well as stages III and IV PDAC, with c-statistic values in the range of 0.96 to 0.97 in two phase II studies. We now report that in two studies of blood samples prospectively collected from 1 to 15 years prior to a PDAC diagnosis (Mayo Clinic and PLCO cohorts), THBS2 and/or CA19-9 failed to discriminate cases from healthy controls at the AUC = 0.8 needed. We conclude that PDAC progression may be heterogeneous and for some individuals can be more rapid than generally appreciated. It is important that PDAC early-detection studies incorporate high-risk, prospective prediagnostic cohorts into discovery and validation studies.Prevention Relevance: A blood biomarker panel of THBS2 and CA19-9 detects early stages of pancreatic ductal adenocarcinoma at diagnosis, but not when tested across a population up to 1 year earlier. Our findings suggest serial sampling over time, using prospectively collected samples for biomarker discovery, and more frequent screening of high-risk individuals.

Blood-based gene expression signature associated with metastatic castrate-resistant prostate cancer patient response to abiraterone plus prednisone or enzalutamide.

BACKGROUND: Precision medicine approaches for managing patients with metastatic castrate-resistant prostate cancer (mCRPC) are lacking. Non-invasive approaches for molecular monitoring of disease are urgently needed, especially for patients suffering from bone metastases for whom tissue biopsy is challenging. Here we utilized baseline blood samples to identify mCRPC patients most likely to benefit from abiraterone plus prednisone (AAP) or enzalutamide. METHODS: Baseline blood samples were collected for circulating tumor cell (CTC) enumeration and qPCR-based gene expression analysis from 51 men with mCRPC beginning treatment with abiraterone or enzalutamide. RESULTS: Of 51 patients (median age 68 years [51-82]), 22 received AAP (abiraterone 1000 mg/day plus prednisone 10 mg/day) and 29 received enzalutamide (160 mg/day). The cohort was randomly divided into training (n = 37) and test (n = 14) sets. Baseline clinical variables (Gleason score, PSA, testosterone, and hemoglobin), CTC count, and qPCR-based gene expression data for 141 genes/isoforms in CTC-enriched blood were analyzed with respect to overall survival (OS). Genes with expression most associated with OS included MSLN, ARG2, FGF8, KLK3, ESRP2, NPR3, CCND1, and WNT5A. Using a Cox-elastic net model for our test set, the 8-gene expression signature had a c-index of 0.87 (95% CI [0.80, 0.94]) and was more strongly associated with OS than clinical variables or CTC count alone, or a combination of the three variables. For patients with a low-risk vs. high-risk gene expression signature, median OS was not reached vs. 18 months, respectively (HR 5.32 [1.91-14.80], p = 0.001). For the subset of 41 patients for whom progression-free survival (PFS) data was available, the median PFS for patients with a low-risk vs high-risk gene expression signature was 20 vs. 5 months, respectively (HR 2.95 [1.46-5.98], p = 0.003). CONCLUSIONS: If validated in a larger prospective study, this test may predict patients most likely to benefit from second-generation antiandrogen therapy.

Physician-directed smoking cessation using patient "opt-out" approach in the emergency department: A pilot program.

OBJECTIVE: Using a physician-directed, patient "opt-out" approach to prescriptive smoking cessation in the emergency department (ED) setting, we set out to describe patient actions as they related to smoking cessation behaviors. METHODS: A convenience sample of smokers at 2 Pennsylvania hospital EDs who met inclusion/exclusion criteria were approached to participate in a brief intervention known as screening, treatment initiation, and referral (STIR) counseling that included phone follow-up. Demographic information, current smoking status, and specific physician prescription and follow-up recommendations were collected. Approximately 3 months later, patients were contacted to determine current smoking status and actions taken since their ED visit. RESULTS: One hundred six patients were approached and 7 (6.6%) opted out of the intervention. Patients who did not opt out were evaluated for appropriate use of smoking cessation-related medications; 35 (35.4%) opted out of the prescription(s) and 6 (6.1%) were not indicated. Twenty-one (21.2%) patients opted out of ambulatory referral follow-ups with primary care and/or tobacco treatment program; one (1.0%) was not indicated for referral. Nineteen (32.8%) patients who received prescription(s) for smoking cessation-related medications initially also followed the prescription(s). Seventeen (22.1%) patients participated in referral follow-up. CONCLUSION: In this small ED pilot, using the STIR concepts in an opt-out method, few smokers opted out of the smoking cessation intervention. About one-third of the patients declined prescriptions for smoking cessation-related medications and less than one-quarter declined ambulatory referrals for follow-up. These findings support a willingness of patients to participate in STIR and the benefits of intervention in this setting.