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Surgical resection remains the only potentially curative therapy for pancreatic ductal adenocarcinoma (PDAC). There is paucity of literature about morbidity and mortality in older patients with PDAC undergoing pancreaticoduodenectomy. This retrospective analysis evaluates the in-hospital 30-day mortality of this population utilizing the Nationwide Inpatient Sample (NIS) database.All US patients hospitalized for pancreaticoduodenectomy (Whipple procedure) were included. Data was obtained from the NIS provided by the Agency for Healthcare Research and Quality. Pancreaticoduodenectomy diagnoses were identified using Clinical Classifications Software codes based on ICD-9 between 2007 and 2010. Univariable and multivariable analyses were performed using the logistic model, weighted chi-square test, and generalized linear model.A total of 6149 patient discharges for pancreaticoduodenectomy were identified. Mean age was 64.9 years (SD ± 12.3); 21% of patients were ≥ 76 years of age. Majority were White (N = 5257, 77.9%) with a male:female ratio of 1. Patients aged 76 and older (OR: 1.76; 1.36-2.28; p .001), Hispanics (OR: 1.40; 0.92-2.13; p = .12), and high comorbidity score (OR: 5.70; 3.44-9.46; p .001) were found to be associated with a higher risk of 30-day in-hospital mortality. In the multivariable analysis, advanced age (76) remained a significant predictor of longer in-hospital length of stay (OR: 1.09; 1.04-1.14; p .001) and 30-day in-hospital mortality (OR 1.46; 1.07-2.00; p = .016). The 30-day in-hospital mortality rate for all patients across all years was 3.24%, for patients76 years 4.11% and for patients76 years 2.77%. Patients who underwent surgery at teaching hospitals (OR: 0.61; 0.42-0.88; p = .008) had a lower risk of 30-day in-hospital mortality compared to non-teaching hospitals.In-hospital 30 day mortality was higher in selected older patients with PDAC undergoing pancreaticoduodenectomy. Mortality was lower at high volume and teaching centers. Further stringent selection criteria are needed to decrease mortality in the older population.

Oncogenic mutations in B-type Raf kinase (BRAF) occur in 7-10% of metastatic colorectal cancers (mCRC). Despite recent improvements in survival in the general population of patients with mCRC, patients with BRAF-mutant mCRC continue to have poor response to most systemic therapies, and prognosis remains poor. There is a substantial unmet need for novel therapeutic strategies to treat patients with BRAF-mutant mCRC. This review outlines the epidemiology, molecular pathogenesis, prognosis, and mechanisms of treatment resistance of BRAF-mutated CRC. Additionally, this review highlights novel therapeutic strategies aimed at enhancing response and improving outcomes.

Silencing of tumor suppressor and DNA repair genes through methylation plays a role in cancer development, growth and response to therapy in colorectal and pancreatic cancers. Heat shock protein 90 (HSP90) regulates transcription of DNA methyltransferase enzymes (DNMT). In addition, DNMTs are client proteins of HSP90. The aim of this study is to evaluate the effects of HSP90 inhibition on DNA methylation in colorectal and pancreatic cancer cell lines. Our data shows that inhibition of HSP90 using ganetespib resulted in downregulation of mRNA and protein expression of DNMT1, DNMT3A, and DNMT3B in HT-29 and MIA PaCa-2 cell lines. This in turn was associated with a drop in the fraction of methylated cytosine residues and re-expression of silenced genes including MLH-1, P16 and SPARC. These effects were validated in HT-29 tumors implanted subcutaneously in mice following in vivo administration of ganetespib. This work demonstrates the effectiveness of ganetespib, an HSP90 inhibitor in modulating DNA methylation through downregulation of DNMT expression.

Background Left ventricular assist devices are increasingly being used in patients with advanced heart failure as both destination therapy and bridge to transplant. We aimed to identify histomorphometric, structural and inflammatory changes after pulsatile- and continuous-flow left ventricular assist device placement. Methods Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by Western blot. Results Decellularization of the aortic tunica media was observed in patients receiving continuous-flow support. Both device types showed an increased inflammatory response after left ventricular assist device placement with variable T-cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. Conclusions Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous-flow left ventricular assist and associated with aortic media decellularization. The present findings help to explain the progressive aortic root dilation and vascular dysfunction in patients after continuous-flow device placement.

Mismatch repair–deficient (dMMR) colorectal cancer (CRC) is caused by Lynch syndrome (LS) in 3% and sporadic inactivation of MLH1 by hypermethylation (MLH1-hm) in 12% of cases. It is not clear whether outcomes between LS-associated and MLH1-hm CRC differ. The objective of this study was to explore differences in clinical factors and outcomes in these two groups. Patients with dMMR CRC identified by immunohistochemistry staining and treated at a single institution from 1998 to 2012 were included. MLH1-hm was established with BRAF mutational analysis or hypermethylation testing. Patients’ charts were accessed for information on pathology, germ-line MMR mutation testing, and clinical course. A total of 143 patients had CRC associated with LS (37 patients, 26%) or MLH1-hm (106 patients, 74%). Patients with LS were younger, more often male, presented more often with stage III disease, and had more metachronous disease than patients with MLH1-hm tumors. There was no difference in cancer-specific survival (CSS) between the groups; overall survival was longer in patients with LS, but this difference was minimal after adjusting for age and stage at diagnosis. CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis. Genet Med 18 9, 863–868.

Combinations of fluoropyrimidines with oxaliplatin or irinotecan plus a biologic agent are standard treatments for metastatic colorectal cancer (mCRC). Recent approvals of first-line cetuximab, second-line ziv-aflibercept, and regorafenib as salvage therapy have increased the complexity of the treatment armamentarium. To define optimal regimens, we systematically reviewed combination chemotherapy trials (N=83). Descriptive analyses focusing on fluoropyrimidine formulation, oxaliplatin vs irinotecan combinations, and compatibility with biologics indicated the following: infusional 5-fluorouracil (5-FU) yielded better efficacy and safety than bolus 5-FU. Capecitabine had similar outcomes and better safety than 5-FU with oxaliplatin but not irinotecan. First-line oxaliplatin and irinotecan appeared equivalent. Antiangiogenics, such as bevacizumab and ziv-aflibercept, and epidermal growth factor receptor-targeted monoclonal antibodies cetuximab and panitumumab further improved efficacy. The treatment landscape for mCRC has become complex, and we are approaching individualized therapy based on predictive factors, including KRAS mutational status. Appropriate administration of chemotherapy/biologic combinations is critical.

Heart failure (HF) is associated with the derangement of muscle structure and metabolism, contributing to exercise intolerance, frailty, and mortality. Reduced handgrip strength is associated with increased patient frailty and higher morbidity and mortality. We evaluated handgrip strength as a marker of muscle function and frailty for prediction of clinical outcomes after ventricular assist device (VAD) implantation in patients with advanced HF.Handgrip strength was measured in 72 patients with advanced HF before VAD implantation (2.3 ± 4.9 days pre-VAD). We analyzed dynamics in handgrip strength, laboratory values, postoperative complications, and mortality. Handgrip strength correlated with serum albumin levels (r = 0.334, P = .004). Compared with baseline, handgrip strength increased post-VAD implantation by 18.2 ± 5.6% at 3 months (n = 29) and 45.5 ± 23.9% at 6 months (n = 27). Patients with a handgrip strength25% of body weight had an increased risk of mortality, increased postoperative complications, and lower survival after VAD implantation.Patients with advanced HF show impaired handgrip strength indicating a global myopathy. Handgrip strength25% of body weight is associated with higher postoperative complication rates and increased mortality after VAD implantation. Thus, the addition of measures of skeletal muscle function underlying the frailty phenotype to traditional risk markers might have incremental prognostic value in patients undergoing evaluation for VAD placement.

Background The benefit of immune checkpoint blockade in mCRC is currently limited to mismatch repair (MMR) deficient tumours. Increasing evidence suggests that the vascular endothelial growth factor (VEGF) pathway plays a role in cancer immune evasion. Co-targeting the PD-1/PD-L1 and VEGF axes may result in clinical activity in mCRC. Methods 133 patients (pts) were randomized 2:1 to receive C/B/P (Arm A) or C/B/A (Arm B), stratifying by ECOG and RAS. Pts had progressed on 5-FU, oxaliplatin, irinotecan, bevacizumab, and anti-EGFR therapy (if RAS wt). Prior anti-PD-1/PD-L1 therapy was not permitted. Doses were C 850 or 1000 mg/m² d1-14, B 7.5 mg/kg d1, and A 1200 mg d1 in 21 day cycles. Primary endpoint was progression free survival (PFS). 110 events were required to detect PFS hazard ratio (HR) of 0.65 at 1-sided α = 0.1 with 80% power. Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety/tolerability. Primary and secondary efficacy analyses were performed using modified intent to treat analysis (mITT). Results Analysis includes 46 pts (Arm A) and 82 pts (Arm B) with median age 58 yo, 40% female, 47% ECOG 0. As of 4/12/19, median follow-up was 12.35 months (mo). Proficient MMR or microsatellite stable (MSS) is present in 86.7% vs 85.7%. In mITT analysis, median PFS is 3.3 mo (2.1-6.2) vs 4.4 mo (4.1-6.4) with a HR of 0.725 (0.491-1.07), 1-sided log-rank p-value 0.051. In MSS only pts, HR for PFS is 0.67 (0.44-1.03). ORR is 4.35% (0.5-14.8) vs 8.54% (3.5-16.8), p = 0.5. The 12 mo OS is 43% (29-63) vs 52% (42-65), HR 0.94 (0.56-1.56), p = 0.4. Most common grade > = 3 related adverse events are hypertension (7% vs 9%), hand-foot syndrome (4% vs 6%), and diarrhea (2% vs 7%). Conclusions The study reached its prespecified primary endpoint and the addition of A to CB results in a significantly longer PFS. No new or increased safety signals are identified. Further investigation in a larger phase III study may be warranted. This is the first positive study co-targeting PD-1/PD-L1 and VEGF axes in mCRC and correlative analyses may help identify predictors of benefit. Clinical trial identification NCT0287319. Legal entity responsible for the study ACCRU. Funding Genentech Roche. Disclosure H.J. Lenz: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb. P.M. Boland: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Hemispherx; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Isofol Medical; Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): Athenex; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Clinical Genomics. A.B. Nixon: Research grant / Funding (self): Seattle Genetics; Research grant / Funding (self): MedPacto; Research grant / Funding (self): Genentech Roche; Advisory / Consultancy, Research grant / Funding (self): Tracon Pharma; Research grant / Funding (self): Acceleron Pharma; Research grant / Funding (self): Leadiant Biosciences; Research grant / Funding (self): Sanofi-Aventis; Advisory / Consultancy: Eli Lilly. H. Hurwitz: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech Roche. M.G. Fakih: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Amgen; Advisory / Consultancy: Array; Advisory / Consultancy: Bayer; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Novartis. All other authors have declared no conflicts of interest.

Background HER2 (ERBB2) amplification is present in 5-10% of patients (pts) with KRAS and NRAS (RAS) WT mCRC. Tucatinib (Seattle Genetics, Bothell, WA) is a potent, highly selective oral tyrosine kinase inhibitor of the HER2 receptor. In patient-derived xenograft models of HER2+ mCRC, the combination of tucatinib and trastuzumab showed significantly greater antitumor activity compared with tucatinib or trastuzumab alone. Here we present initial results from a trial of tucatinib and trastuzumab in pts with HER2 amplified mCRC. Methods MOUNTAINEER is a multicenter open-label single-arm phase II trial. Pts with RAS WT mCRC had HER2 amplification/overexpression by NGS, FISH, or IHC (3+ or 2+ and amplified by FISH). Prior treatment with 5FU, oxaliplatin, irinotecan, and an anti-VEGF antibody was required. Prior anti-HER2 therapy was excluded. Pts received tucatinib 300mg PO bid and standard doses of trastuzumab (IV, Q3 weeks). The primary endpoint was objective response rate (ORR) per RECIST v1.1. Using a 2-Stage Fleming design, this study compared ORR of 20% (null) vs 40% (alt) in 10 or 25 evaluable pts (1-sided α = 0.11; β=.16). At least 8 responses were needed to meet the primary efficacy endpoint. Results As of 26 April 2019, 26 pts enrolled, and 22 pts completed ≥1 evaluation of response. 16/26 pts (62%) were male. Median age= 52.5 (range 24-70). The primary tumor site of origin included right colon (N = 4), left colon/rectum (N = 17), transverse colon (N = 3), and overlapping (N = 2). Among 22 evaluable pts, ORR= 55% (CR/PR= 12; SD = 5; PD = 5). Clinical benefit rate (CR+PR+SD≥4 months) = 64%. At a median follow-up of 10.6 months, median PFS= 6.2 months (95% CI 3.5-NE). Median OS = 17.3 months (95% CI 12.3-NE). Median duration of response has not been reached. There were 2 (9%) grade 3 treatment-related adverse events (TRAEs) and no grade 4/5 TRAEs. The most common TRAEs were AST elevation (48%; all G1), ALT elevation (30%; all G1), and diarrhea (26%; G1/G2/G3=4%/17%/4%). Conclusions The combination of tucatinib and trastuzumab is well tolerated and has met its primary efficacy endpoint. Based on these results, further expansion of the MOUNTAINEER trial in pts with HER2 amplified mCRC is justified. Updated results will be presented. Clinical trial identification NCT03043313. Legal entity responsible for the study Academic and Community Cancer Research United. Funding Seattle Genetics. Disclosure J.H. Strickler: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): Chugai; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: OncoMed; Advisory / Consultancy: Celgene; Advisory / Consultancy: Proteus Digital Health; Advisory / Consultancy: Chengdu Kanghong Biotechnology Ltd; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Leap Therapeutics. A. Cercek: Advisory / Consultancy: Bayer; Advisory / Consultancy: Proteus; Research grant / Funding (institution): Seattle Genetics. C. Wu: Research grant / Funding (institution): Vaccinex; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Lycera; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): FLX Bio. J. Hubbard: Research grant / Funding (institution): Seattle Genetics; Honoraria (institution), Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Treos Bio; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Senhwa pharmaceuticals. N. Kemeny: Research grant / Funding (institution): Amgen. P.M. Boland: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Hemispherx; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Isofol Medical; Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): Athenex; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Clinical Genomics. K. Ng: Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Tarrex Biopharma; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Trovagene; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Pharmavite; Research grant / Funding (institution): Consano. T. Bekaii-Saab: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Seattle Genetics. All other authors have declared no conflicts of interest.

Hypoalbuminemia has been recognized as a prognostic indicator in patients with heart failure. We aimed to investigate the association of hypoalbuminemia with postoperative mortality in patients undergoing left ventricular assist device (LVAD) implantation. We studied 272 consecutive patients undergoing LVAD implantation from 2000 to 2010 at our institution. Preoperative clinical characteristics and laboratory variables associated with mortality were analyzed. Postoperative survival of patients with preoperative hypoalbuminemia (

Background Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab. Methods Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models. Results A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02–1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed. Conclusions Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients.

Objectives This study evaluated the Model for End-Stage Liver Disease (MELD) score and its modified versions, which are established measures of liver dysfunction, as a tool to assess heart transplantation (HTx) urgency in ambulatory patients with heart failure. Background Liver abnormalities have a prognostic impact on the outcome of patients with advanced heart failure. Methods We retrospectively evaluated 343 patients undergoing HTx evaluation between 2005 and 2009. The prognostic effectiveness of MELD and 2 modifications (MELDNa [includes serum sodium levels] and MELD-XI [does not include international normalized ratio]) for endpoint events, defined as death/HTx/ventricular assist device requirement, was evaluated in our cohort and in subgroups of patients on and off oral anticoagulation. Results The MELD and MELDNa scores were excellent predictors for 1-year endpoint events (areas under the curve: 0.71 and 0.73, respectively). High scores (>12) were strongly associated with poor survival at 1 year (MELD 69.3% vs. 90.4% [p < 0.0001]; MELDNa 70.4% vs. 96.9% [p < 0.0001]). Increased scores were associated with increased risk for HTx (hazard ratio: 1.10 [95% confidence interval: 1.06 to 1.14]; p < 0.0001 for both scores), which was independent of other known risk factors (MELD p ¼ 0.0055; MELDNa p ¼ 0.0083). Anticoagulant use was associated with poor survival at 1 year (73.7% vs. 86.4%; p ¼ 0.0118), and the statistical significance of MELD/MELDNa was higher in patients not receiving oral anticoagulation therapy. MELD-XI was a fair but limited predictor of the endpoint events in patients receiving oral anticoagulation therapy. Conclusions Assessment of liver dysfunction according to the MELD scoring system provides additional risk information in ambulatory patients with heart failure. (J Am Coll Cardiol 2013;61:2253–61) a 2013 by the American College of Cardiology Foundation

Repeated oral stimulation with solutions of 2 ppm capsaicin increased time to maximum intensity, but yielded a decrease in sequential mouth-burn intensity due to a rising minimum irritation rating between stimuli. Two response patterns were observed: for 18 subjects mouth-burn increased, while 14 subjects showed depression upon repeated stimulation. Because of across-subject variability, there was little correlation between parotid salivary response and perceived sensory responses. Capsaicin-stimulated salivary flow was significantly higher than flow stimulated by distilled water in 9 high-flow subjects, but not in 14 low-flow subjects. Oral adaptation to capsaicin may attenuate parotid salivary response, although eaters and noneaters of chili peppers did not differ significantly in their perception of mouth-burn or in salivary flow.

Oral rinsing with different solutions significantly reduced mouth-burn of capsaicin solutions in both eaters and noneaters of chili peppers. Cold solutions (5 degrees C) were more effective in reduction of mouth-burn than solutions at 20 degrees C. Sucrose solutions (10%) at 20 degrees C and whole milk at 5 degrees C were equally effective while 5% ethanol was no more effective in mouth-burn reduction than water at 20 degrees C. Reduction of mouth-burn by sucrose was not dose dependent. Noneaters of chili peppers experienced a slightly greater reduction of mouth-burn from sucrose solutions than eaters. Oral rinsing with sweetened milk containing 0 and 10% fat, of varying globule size, resulted in similar degree of mouth-burn reduction. The first (control) sample was rated higher in intensity than subsequent ones, suggesting desensitization, which appears to be due to the interaction of stimulation of chemo-, mechano-, thermo- and gustatory receptors.

Purpose Galectin-3 (gal-3) is a novel biomarker implicated in cardiac fibrosis and is shown to correlate with the severity of heart failure (HF) and to independently predict mortality in HF. We investigated if hemodynamic improvement after left ventricular assist device (LVAD) implantation affects gal-3 levels. Methods and Materials Plasma samples were acquired from patients at time of LVAD implantation (HMII or Heartware, n=57), at 3 (n=17) and 6 months post-LVAD (n=14), and at explantation (n=23), as well as from healthy age and gender matched controls (n=30). Gal-3 was measured using a commercially available ELISA assay (BG Medicine, Waltham, MA). Data was analyzed with Prism 5. Events rates were calculated using the Kaplan-Meier method. Results At time of LVAD implantation, HF patients had significantly higher gal-3 levels compared to controls (29.2±14 ng/ml vs. 13±9 ng/ml; p figure 1 ] Conclusions Gal-3 levels are associated with HF state and predict survival on LVAD support. Distinct dynamics in gal-3 levels occur in patients following LVAD implantation with an initial decrease but subsequent increase. Gal-3 may serve as a new biomarker for risk assessment of patients before LVAD implantation.

Introduction The 5-year survival of pancreatic adenocarcinoma (PAC) with surgery alone is less than 10%, and with adjuvant chemotherapy increases to about 20%. The original GITSG adjuvant study demonstrated a survival benefit compared to surgery, and could have been attributed to the weekly IV bolus of 5FU for 2 years, in addition to chemoradiation. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that remain in G0 arrest, and kill them as they infrequently enter G1/S phase. To evaluate this hypothesis, we retrospectively evaluated patients at Georgetown University Hospital (GUH) who were treated with maintenance capecitabine, and compared to the patients who completed standard adjuvant gemcitabine at GUH and at the Ohio State University (OSU). Methods Patients in the Georgetown/Lombardi Cancer Center and the Ohio State University EMR were sought for PAC that was resected with curative intent, and had received standard adjuvant chemotherapy with or without chemoradiation. After 6 months of gemcitabine without recurrence, the study group received maintenance capecitabine for up to 2 years, and the control groups received no further therapy until disease relapse. Only patients with complete follow-up survival data were analyzed. Results 20 patients from GUH met the criteria as the maintenance group, and 58 and 14 patients from GUH and OSU respectively as the control group. In the maintenance group, capecitabine was usually given 1000mg orally twice a day, Monday through Friday following adjuvant therapy, for an indefinite period, up to 2 years. Patients received capecitabine for median duration of 12.5 months (2 to 24 months), and the median follow-up duration was 33 months (16 to 78 months). The median overall survival (OS) for the maintenance group was 48 months. The 2 year OS was 94%, and 5 year OS was 40%. The median recurrence free survival (RFS) was 39 months. The 2 year RFS was 67%, and the 5 year RFS was 25%. Common toxicities were mild hand-and-foot syndrome and fatigue. Four patients discontinued capecitabine due to toxicities: febrile neutropenia, severe fatigue, weight loss and diarrhea. The GUH control group was of comparable staging, and the median OS was 22 months, 2 year OS was 86.6%, 5 year OS rate was 16%, median RFS was 13 months, 2 year RFS was 19%. For the OSU control group, the median OS was 16.33 months, 2 yr OS was 35.7%, median RFS was 14.8 months, 2yr RFS was 20%. Conclusion In this retrospective controlled cohort study, capecitabine maintenance therapy following adjuvant therapy in resected PAC is associated with a significantly (p

Aim: Reovirus is a naturally occurring virus that causes oncolysis in tumor cells with a Ras-activated pathway. It acts synergistically with taxanes. Since most pancreas cancer cells have downstream activated Ras we hypothesized that pts with MAP are susceptible to reovirus. Methods: We conducted an NCI-sponsored phase II study with a goal of 70 evaluable MAP pts randomized in a 1:1 allocation to paclitaxel [P (175 mg/m2)], carboplatin [C (AUC 5)] on day 1 with reovirus [R (3 x 1010 TCID50) iv] on days 1-5 {Arm A} vs P/C alone {Arm B} on day 1 of a 21-day cycle. The primary endpoint is progression-free survival (PFS). Secondary endpoints include safety, objective response rate (ORR), and overall survival (OS). Pts progressing on B were allowed to crossover to A. Eligible pts had no prior chemotherapy. Pre-treatment tissue was required for KRAS mutation status from DNA analysis. Analyses of immunomodulatory effects of therapy were performed. Results: Refer to Table 1 for key characteristics. Most common grade 3-4 toxicities include neutropenia (53%) and leucopenia (36%) with no overall difference between arms. In evaluable pts, ORR/SD was 22%/59% (A) and 21%/47% (B). To date, 81% have progressed, and median follow-up of 3.75 mo in event-free pts. PFS was similar in both arms (A: median 4.63 vs B: 5.1 mos; HR = 1.07, p = 0.81). The results held after sensitivity analyses and adjusting for factors such as KRAS. In 60 patients with KRAS analysis, a trend toward improved overall PFS in KRAS WT (6.0 mo) vs MT (4.3 mo); p = 0.20. In the KRAS MT group, an early limited differential in PFS between arm A (4.63 mo) vs B (4.34 mo); p = 0.73. 16 pts crossed over from B to A with 1 PR, 6 SD, 7 PD and 2 NA. Characteristic Arm A Arm B p-value Total N = 73 36 37 Age (Median, yrs) 61.5 66 0.055 ECOG PS (0/1), N 20/16 17/20 0.49 Baseline Ca 19-9 of > 59x ULN, % 53% 75% 0.14 KRAS Status ( MT), % 70% 77% 0.99 Pancreas Tumor Location, % Head Body Tail NS 22 36 22 22 27 38 19 14 Number of Metastatic Sites, % 1 2 >2 19 30 51 22 14 66 0.51 Conclusions: Reovirus can be administered safely in combination with P/C in pts with MAP. Both arms performed better than historical control, but R did not seem to improve outcome when added to P/C in MAP. This is the first report of P/C in MAP, which proved to have higher activity than anticipated, suggesting that similar to other disease settings, a relatively inexpensive taxane is an acceptable choice in MAP. A pharmaco-economic analysis is underway. Disclosure: T. Bekaii-Saab: Research Funding: Oncolytics Biotech; M.A. Villalona-Calero: Research Grant : Oncolytics Biotech. All other authors have declared no conflicts of interest.

Purpose Liver abnormalities have prognostic impact on the outcome of patients with advanced heart failure.We evaluated the Model of End-stage Liver Disease (MELD) score and its modified versions, established measures of liver dysfunction, as a tool to evaluate HTx urgency in ambulatory HF patients. Methods and Materials We retrospectively evaluated 343 patients undergoing HTx evaluation between 2005 and 2009. The prognostic effectiveness of MELD/MELDNa/MELD-XI for endpoint events defined as death/HTx/ventricular assist device (VAD) requirement was evaluated in our cohort and in subgroups of patients on and off oral anticoagulation. Results The MELD and MELDNa score were excellent predictors for 1 year endpoint events (AUC: 0.71 and 0.73, respectively). High scores (>12) were strongly associated with poor survival at one year (MELD: 69.3% vs. 90.4%, p Conclusions Assessment of liver dysfunction using the MELD scoring system provides additional risk information in patients with ambulatory heart failure.

judged as signs of possible LVAD indication. Lastly, in-hospital and 1-year outcome was analyzed and compared with outcome of LVAD implanted from 2007 to 2010 (C-LVAD). Results: 1244 pts were hospitalized for HF in one year. 191 were excluded due to age and 270 for other causes. 59 out of the remaining 783 pts had LVEF 0.35 and received inotropes, but only 38 (3%) were considered appropriate potential LVAD candidates after hospital chart review. Inhospital mortality was 5/38 (13%). Within 1-year, 8 pts underwent to heart transplant and 3 to LVAD with 10 surviving; 8/16 (50%) of medically managed pts died. In-hospital mortality after 2007-2010 C-LVAD implantation was 5/27 (18.5%). In 1-year, 3 pts were transplanted and only 1/20 pts remaining on LVAD died. Conclusions: Pts with HF characterized by low LVEF and the need for inotropes have a poor 1-year prognosis on medical therapy and would probably benefit from LVAD. The proportion of pts potentially candidates for LVAD is low with respect to the total population of HF, but the absolute number is high due to the prevalence of this syndrome.