bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated large-volume extraction of circulating, cell-free DNA to improve the sensitivity of tumor biomarker detection.
Authors: Nocon Annette , Horlitz Martin , Sprenger-Haussels Markus
Published: February 2017

19

Background: Because of its low concentration and high degree of fragmentation, the extraction and detection of tumor-derived circulating cell-free DNA (ccfDNA) is technically challenging. An optimized ccfDNA extraction method was developed and evaluated by comparison to an existing extraction protocol running on the QIAsymphony instrument and to a manual reference. Methods: 5mlEDTA plasma from healthy donors (with IRB approval) was processed. ccfDNA was bound to magnetic particles with novel surface chemistry and recovered in 150µl. As an alternative method, the “Virus cell-free 1000 protocol” using the QIAsymphony Virus/Pathogen Midi Kit was modified for the processing of higher sample volumes. ccfDNA was extracted from 4ml plasma and eluted in 90µl. The QIAamp Circulating Nucleic Acid (CNA) Kit served as a reference. ccfDNA yield was quantified by qPCR (66bp within the 18S rDNA). To determine the DNA fragment size-dependent recovery, another qPCR assay was run, quantifying four target sequences of different lengths within the APP gene. 5ml plasma was processed and eluted in 150µl. Results: The mean ccfDNA recovery (18S 66bp target; compared to the QIAamp CNA Kit) was 87% (N=6; +/-46%) for the newly developed automated extraction chemistry and 85% (N=6; +/-8%) for the modified extraction protocol. For the APP assay, ratios between the copy numbers of different target sizes were calculated. The mean ratios were: 67/476bp = 11 (N=12; +/-6.2), 180/476bp = 8.1 (N=12; +/-3.6) and 67/180bp = 1.4 (N=12; +/-0.3). Conclusions: The automated protocol versions led to an overall similar ccfDNA recovery compared to the QIAamp CNA Kit. Using the new extraction chemistry a generally improved recovery of tumor-derived circulating DNA is possible. This improvement leads to a higher sensitivity of tumor biomarker detection, which is, besides a high specificity, very important for the use of tumor biomarkers as non-invasive tool in cancer diagnosis and prognosis. The applications presented here are for research use only. Not for use in diagnostic procedures. This work has received funding from the European Union FP7 Programme under grant agreement no. 222916, SPIDIA project ( www.spidia.eu ).
Pre- and postoperative plasma concentrations of five novel candidate biomarker proteins in patients with high- and low-grade gliomas.
Authors: Holdhoff Matthias , Yovino Susannah G. , Savage William J. , Dulloor Pratima , Grossman Stuart A. , Everett Allen
Published: February 2017

21

Background: Current imaging techniques are unable to accurately measure tumor burden in gliomas, because they rely on blood-brain barrier (BBB) permeability that is altered following surgery, radiation, steroids, and antiangiogenic therapies. This often leads to misinterpretation of disease status and incorrect clinical decisions. The development of tumor-specific blood-based markers for gliomas is therefore critically important. This study evaluates the detectability of five novel protein biomarker candidates in the plasma of patients with gliomas: neurogranin, ICAM-5, beta-synuclein, brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP). These biomarker candidates were chosen because of their specificity for brain tissue. Methods: Pre- and postoperative plasma samples were obtained from patients with newly diagnosed gliomas with IRB approval. Plasma concentrations were measured in duplicates using an electrochemiluminescent immunoassay with a lower limit of quantification of >0.04ng/mL (GFAP) and >0.02 ng/mL (other markers). Results: Plasma levels were detectable for all 5 tested markers at baseline and postoperatively. Baseline levels were highly variable and postoperative GFAP levels were much higher than preoperative levels likely related to brain injury (see table). Conclusions: Five potentially useful protein markers have been identified in the plasma of patients with gliomas. Further studies are underway to assess the specificity of each marker and its ability to detect dynamic changes in tumor burden. [Table: see text]
Flow cytometric quantification of surface IGF-1R and intracellular p-AKT, p-S6, and p-ERK in Ewing sarcoma (EWS) cells.
Authors: DuBois Steven G. , Epling C. Lorrie , Tan Alice , Matthay Katherine K. , Sinclair Elizabeth
Published: February 2017

23

Background: Targeting the IGF-1R pathway has shown preclinical and clinical evidence of activity in EWS. Markers predictive of response to IGF-1R inhibition are required. The aims of the current study were to quantify surface IGF-1R expression and intracellular signaling proteins by flow cytometry. Methods: Flow cytometry for CD99 and CD45 was used to detect bone marrow micrometastatic tumor cells as CD99+CD45- events in patients with localized EWS. Surface IGF-1R was quantified on tumor cells and normal marrow cells using a commercially available antibody. RD-ES EWS cells were spiked into control PBMCs and starved for 1 hour. Cells were then treated with saline control, rapamycin 10 ng/mL, ADW742 5 uM (small molecule IGF-1R inhibitor), or alpha-IR3 0.5 ug/mL (anti-IGF-1R antibody) and levels of pS6, pAKT, and pERK quantified by phospho-flow cytometry 60 minutes later. All results were expressed as the mean fluorescent intensity (MFI) of staining using arbitrary units. Results: We detected bone marrow micrometastatic tumor cells in marrow samples from 16 patients with EWS. We observed heterogeneous levels of IGF-1R tumor cell surface expression between patients (range of IGF-1R MFI = 0 – 3355). IGF-1R levels were higher in CD99+CD45- tumor cells compared to normal marrow cells (mean MFI 840 for CD99+CD45- tumor cells vs.190 for normal marrow cells; p = 0.005). In RD-ES cells spiked into PBMCs, treatment with rapamycin resulted in 1.32 fold increase in pAKT MFI compared to saline control. Treatment with ADW742 or alpha-IR3 did not impact pAKT MFI. Treatment with rapamycin resulted in a 0.52 fold decrease and a 1.20 fold increase in pS6 and pERK, respectively. Treatment with ADW742 or alpha-IR3 each resulted in similar decreases in both pS6 (0.75-0.87 fold) and pERK (0.67-0.82 fold). In PBMCs, modest changes in pS6 in rapamycin treated cells were observed, without changes in pAKT or pERK. Neither ADW742 nor alpha-IR3 modulated pS6, pAKT, or pERK signaling in PBMCs. Conclusions: Flow cytometry detects a range of surface IGF-1R expression on bone marrow micrometastatic EWS cells. Phospho-flow cytometry detects modulation of pAKT, pS6, and pERK in EWS cells treated with IGF-1R or mTOR inhibitors.
BMP9 as a potential biomarker for dalantercept efficacy against ALK1-mediated angiogensis in head and neck cancer.
Authors: Pearsall Scott , Solban Nicolas , Attie Kenneth M. , Sherman Matthew L. , Kumar Ravi
Published: February 2017

30

Background: Activin receptor-like kinase 1 (ALK1) is a type 1 receptor in the TGF-β superfamily. The ALK1 pathway plays a role in vascular development and pathological angiogenesis. Mutations affecting this pathway result in hereditary hemorrhagic telangiectasia, a disease characterized by failed vascular development and arteriovenous malformations. Therefore, disruption of this pathway in adults may help in conditions with pathological angiogenesis. Bone morphogenetic protein 9 (BMP9) is a ligand that binds with high affinity to ALK1 and stimulates endothelial cell sprouting during vessel maturation. BMP9 is upregulated in the RIP1-Tag2 murine model of vascular invasive carcinoma; treatment with a murine version of dalantercept (RAP-041) can inhibit tumor growth. Methods: Dalantercept (ACE-041) is a soluble receptor protein comprising the extracellular domain of ALK1 linked to an IgG1 Fc region, which functions as a ligand trap to inhibit endogenous BMP9 signaling. Results: In a phase I study of dalantercept in advanced solid tumors, three patients with squamous cell carcinoma of the head and neck (SCCHN) were enrolled. One SCCHN patient received 10 cycles (30 weeks) at 0.4 mg/kg and had a partial response (32.5% decrease in target lesion size). A second SCCHN patient received 11 cycles (33 weeks) at 1.6 mg/kg and had a 28.9% decrease in lesion size. A third SCCHN patient had progressive disease after 1 cycle at 0.8 mg/kg. Dalantercept was generally well-tolerated. Common AEs included fatigue, peripheral edema, nausea, anemia, headache, anorexia, and dyspnea. Analysis of archived tumor samples from SCCHN patients demonstrated that 25% had high BMP9 expression and 44% had medium levels of expression. Conclusions: A phase II study to evaluate the efficacy, safety and pharmacodynamics (PD) of dalantercept in SCCHN is ongoing. The primary objective is ORR. Secondary objectives include PFS, OS, safety, tolerability and pharmacokinetics. Exploratory analyses in this study will examine BMP9 expression in archived and fresh tumor biopsies as well as serum levels of BMP9 and other markers; association of biomarkers with response to therapy will be examined as potential companion diagnostics.
A fully automated capillary western system for absolute quantitation of endogenous PKC proteins: An approach to correlate protein quantity with function.
Authors: Chen Jin-Qiu , Heldman Madeleine , Herrmann Michelle , Kedei Noemi , Blumberg Peter , Goldsmith Paul
Published: February 2017

31

Background: The human prostate cell line LNCaP and the human myelocytic leukemia cell line U937 differ dramatically in their responses to the two protein kinase C (PKC) targeted ligands phorbol 12-myristate 13-acetate (PMA) and bryostatin 1 and show complex differences in the patterns of transcriptional responses that they induce. Quantitation of relative abundance of individual PKC isoforms in the two cell lines may help to link the downstream effects of the two compounds to these isoforms. Methods: Simple Western is a capillary-based automated Western system recently developed by ProteinSimple. All steps following sample preparation are fully automated in the Simple Western system, including sample loading, size-based protein separation, immunoprobing, washing, detection and data analysis. Simple Western is gel-free and blot-free, uses less amount of samples, and produces highly quantitative, reproducible information that cannot be generated using regular Western assays. Using the Simple Western system, we developed a method for absolute quantitation of endogenous proteins in cell lysates and quantified PKC isoforms in LNCaP and U937 cells. Results: PKC isoforms were measured at levels of picogram or sub-picogram per nanogram cell lysate. PKC delta was identified as the dominant PKC isoforms in both cell lines. In LNCaP cells, PKC delta expression is ~20-fold higher than PKC alpha, ~40-fold higher than PKC epsilon, and at least 20-fold higher than PKC beta. In U937 cells, PKC delta expression is similar to PKC beta, at least 200 fold higher than PKC alpha, and ~50-fold higher than PKC epsilon. Conclusions: The Simple Western system, with its high-quality data quantitation and excellent assay reproducibility, allowed us to detect both the relative abundance of the PKC isoforms and their absolute quantitation in the tested cells. It circumvents the problem that antibodies of different affinities for different proteins yield a misleading impression of relative abundance and it provides an approach to accurately correlate protein quantities with their function.
Elevated pretreatment serum activin A and progression-free and overall survival in trastuzumab-treated metastatic breast cancer.
Authors: Zubritsky Lindsey , Leitzel Kim , Ali Suhail M. , Köstler Wolfgang , Fuchs Eva-Maria , Costa Luis , Knight Robert D. , Laadem Abderrahmane , Sherman Matthew L. , Lipton Allan
Published: February 2017

38

Background: About half of HER2-positive metastatic breast cancer patients will respond tofirst-line trastuzumab-containing therapy, but most will progress within a year. Trastuzumab resistance remains a vexing clinical problem, and better predictive and prognostic biomarkers are needed. Activin A is a TGF-B superfamily member and regulates cell proliferation, apoptosis, differentiation, and immune response. Methods: Serum activin A was measured using ELISA (R&D Systems, Minneapolis, MN) in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) serum activin A analyses. Results: Pretreatment serum activin A levels averaged 2376 pg/ml, and had a median of 629 pg/ml and 25th and 75th quartile values of 406 and 1791 pg/ml, respectively. Patients who were hormone receptor negative had significantly higher activin A levels (median 1287 vs 450 pg/ml, p=0.002). Higher serum activin A was significant on a continuous basis for predicting reduced PFS to first-line trastuzumab-containing therapy (p<0.003), and for predicting shorter OS (p<0.0001). When analyzed using a dichotomous (median) cutpoint, the elevated serum activin A cohort had a significantly reduced PFS (HR 2.79, p <0. 002) (median 6.6 mo vs. 31.1 mo) and OS (HR 5.24, p <0.0001) (median 19.6 mo vs. median not reached). In multivariate analysis for PFS with other covariates (age, line of therapy, CA 15-3, and hormone receptor status), activin A was the only significant covariate (p=0.021). In multivariate analysis for OS, activin A (p=0.002) and CA 15-3 (p=0.03) remained significant as prognostic factors. Conclusions: Elevated pretreatment serum activin A predicts reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Activin A deserves further study as an adverse biomarker, and to select patients most likely to respond to activin A-targeted therapy.
The prognostic value of detection methylation level panel of gene in DNA circulating after and before treatment in patients with breast cancer.
Authors: Martínez-Galán Joaquina , Torres-Torres Blanca , Soberino Jesús , Ríos Sandra , González Rivas Cynthia S. , Ruiz Vozmediano Julia , Castillo Lucia , Delgado Juan Ramón
Published: February 2017

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Background: Objective of this study was to determine the concordance of promoter methylation of 14-3-3σ and ESR1 in circulating DNA of breast cancer patients with response and their association with clinicopathological parameters and disease prognosis. Methods: Plasmawas sampled prospectively from 110 patients diagnosed of breast cancer. A PCR quantitative technique was used to analyze the utility of circulating DNA with CpG island hypermethylation of ESR1, 14-3-3σ, Rar-B and APC genes promoter regions as breast cancer biomarkers. Results: The cutoff points for the genes methylated promoters were established from the ROC curves, selecting values that gave the maximal likelihood ratio. Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179); and presence of methylated 14-3-3σ was associated with T3-4 stage (p<0.05) and nodal positive status (p<0.05). Mean serum values of methylated genes before treatment was for ESR1:0.009µg/ml, 14-3-3σ:0.047µg/ml, Rar B:0.0001µg/ml and APC:0.012µg/ml. Mean serum values of methylated genes after treatment was for ESR1:0.003 µg/ml, 14-3-3σ:0.038µg/ml, Rar-B:0 µg/ml and APC:0.001µg/ml. In the light of the discriminatory power of ESR1 and 14-3-3σ and the finding that serum levels of methylated gene promoters changed after breast cancer treatment, post-treatment modifications in these two promoters were analyzed. We observed lower methylated ERS1,14-3-3-σ and APC values after surgery, respect pretreatment levels, but without an overall statistically significant difference.With a median follow-up of 8 years, we found that patients with a significant decrease of sera methylated levels of these genes after surgery had better time to progression an overall survival respect patients without this observation. Conclusions: These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation of specific gene promoters in DNA extracted from serum. Although numerous issues remain to be resolved, the quantitative measurement of circulating methylated DNA is a promising tool for cancer prognostic assessment.
Use of a novel patient-specific model of glioma growth kinetics to elucidate underlying biology as measured by gene expression microarray.
Authors: Trister Andrew Daniel , Bot Brian , Hawkins-Daarud Andrea , Fontes Kellie , Bridge Carly , Baldock Anne , Rockne Russ , Huang Erich , Swanson Kristin
Published: February 2017

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Background: Gliomas are heterogeneous diseases with a wide distribution of growth kinetics that can be estimated prior to treatment and that are prognostic for patient outcome after treatment. Coherent molecular data sets have been made available through cooperative projects such as REMBRANDT and TCGA. We apply our novel patient specific method of measuring the net proliferation and diffusion rate from routinely available preoperative MRI sequences on patients included in these publicly available data sets to assess the underlying biology with imaging. Methods: The normalized microarray data from REMBRANDT (n=475) was used to discover a set of genes differentially expressed among GBM patients when compared with lower grade gliomas (n=853). 647 of these genes were also assessed with probesets in TCGA (n=466). Of these 466 patients, 84 also had preoperative MRI imaging available through The Cancer Imaging Archive (TCIA), for which net diffusion (D) proliferation (ρ) were estimated. Differential gene expression comparing these patients was performed. Results: 37 genes were differentially expressed with D. Genes implicated in cell adhesion, ECM maintenance and the production of focal adhesions are negatively correlated with D. Genes positively correlated with D are related to cell motility and pseudopodia formation. When considering ρ, 20 genes were found to be differentially expressed. A subset of these genes is related to hypoxia and therapy resistance. Some genes are also increased after radiation in cell-lines. Clustering on these genes revealed two classes; one with a survival advantage (p=0.0002). Conclusions: This work demonstrates the potential to assess underlying differences in biology in a heterogeneous disease through patient specific assessment of routinely available imaging. We find that more diffuse tumors will under-express genes involved in focal-adhesions and production of ECM, while they express genes in pathways related to motility and pseudopodia formation. Furthermore, tumors with high ρ are seen to express genes related to treatment resistance, which may explain worse survival in these patients. Future work will verify these markers in model organisms.
Neoadjuvant ipilimumab in locally/regionally advanced melanoma: Clinical outcome and biomarker analysis.
Authors: Tarhini Ahmad A. , Edington Howard , Butterfield Lisa H. , Shuai Yongli , Lin Yan , Rao Uma N. , Kirkwood John M.
Published: February 2017

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Background: Neoadjuvant ipilimumab (Ipi) for stage IIIB-C melanoma may improve the clinical outcome and provide access to pre/post Ipi blood. Methods: Pts were treated with Ipi (10mg/kg IV q3wks x 2 doses) bracketing definitive surgery. Tissue samples were obtained at baseline and at surgery (wk ≥ 6) and serum/PBMC collected at baseline, 6 wks, 3, 6, 9, 12 mos and/or progression. Flow cytometry was used to monitor the host immune response in blood and evaluable tumor. IHC for select markers was also performed. Baseline and wk-6 serum cytokines were tested by xMAP multiplex technology (Luminex Corp). Results: 31 pts were enrolled, 6 had stage IIIB (N2b, N2c), and 25 IIIC (N3) melanoma. Worst toxicities (N=31 pts) included grade 3 diarrhea/colitis (5 pts; 16%), hepatitis (2; 6%), rash (1; 3%), lipase (2; 6%), all manageable. Median f/u was 19 mos: among 29 evaluable pts, median PFS was 12.9 mos, 95% CI = (7.4,-). Only 2 pts died. Peripherally, a significant increase in circulating T-regs (CD4+CD25hi+ Foxp3+; p=0.02 CD4+CD25hi+CD39+; p=0.001) from baseline to 6 wks was observed. Significant decreases in circulating MDSCs, were observed in monocytic HLA-DR+/low/CD14+ MDSC (p<0.0001). Greater increases in T-regs were associated with improved PFS (p=0.034; HR=0.57). Spontaneous in vivo cross-presentation was observed resulting in Th1CD4+ and CD8+ antigen specific T-cell immunity (gp-100, MART-1, NY-ESO-1 peptides). Significant fold increase (3-10-fold) in CD3+/CD4+/INF-γ+ antigen specific T cells was seen only in pts who were progression free at 6 mos. Baseline serum IL-17 correlates with grade 3 diarrhea (p=0.02). In tumor, Tregs appeared higher at wk 6 in PD group while the opposite in clinical benefit group (p=0.09). In tumor, Ipi induced TIL T-cell activation as evidenced by CD69 in the absence of other in vitro stimulation and induced T cell memory (CD45RO+) and not naïve (CD45RO-). By IHC, there was significant increase in CD8+ TIL after ipilimumab (p=0.02). Conclusions: Neoadjuvant ipi exhibited promising clinical activity and significantly modulated the host effector and suppressor immune response. Functional studies and prediction modeling analyses of biomarker findings are ongoing.
Alteration of candidate circulating microRNA cancer biomarkers by blood sample processing.
Authors: Cheng Heather H. , Yi Hye Son , Tewari Muneesh , Pritchard Colin C.
Published: February 2017

8

Background: Circulating, cell-free microRNAs (miRNAs) are promising candidates as cancer biomarkers due to their association with cancer, stability in plasma and serum, and easy and sensitive detection using standard PCR-based methods. However, little is known about optimal conditions for collecting and processing blood specimens for miRNA biomarker measurements, or what effects blood processing has on miRNA levels. We systematically evaluated the effect of specimen processing differences on miRNA expression levels, an essential step in developing circulating miRNAs as robust cancer biomarkers. Methods: Matched plasma and serum samples drawn at a single timepoint from 3 healthy individuals were processed with increasing stringency to remove platelets (PLTs) and cell debris by differential centrifugation or 0.22µM filtration to produce: PLT-rich plasma, standard plasma, PLT-poor plasma, filtered plasma, serum, and filtered serum samples. PLTs were quantified by Coulter Counter. MiRNA expression profiling of differently processed samples was performed using Exiqon miRCury LNA qPCR panels with TaqMan qPCR confirmation. Results: Of 369 miRNAs profiled for expression after increasingly stringent sample processing, 150 (41%) showed a difference in cycle threshold (ΔCt) of ≥5 (≥30-fold), and 23 miRNAs showed a ΔCt of ≥10 (≥1,000-fold). For example, expression of miR-142-3p, a proposed biomarker for lung and esophageal cancers, ranged from a Ct of 19.9±2.4 to 30.8±0.8 (1,800-fold difference, p<10-5). A minority of miRNAs (34/369) showed a ΔCt ≤2 (≤4-fold) between differently processed samples, suggesting expression of this subset is relatively unaffected by processing differences. Differences attributable to processing were reproducible, with a majority of miRNAs with ΔCt ≥5 overlapping between the 3 individuals. Conclusions: Blood-sample processing substantially and reproducibly affects about half of circulating miRNAs, while a minority of miRNAs are relatively unaffected. In pursuing circulating miRNAs as cancer biomarkers, focusing efforts on miRNAs less affected by processing and ensuring adherence to standardized processing protocols will minimize confounding effects.
Evaluating systems of care.
Authors: Duggan Goldstein Sarah Ford , Wisner Jennifer , Flamm Carole Redding
Published: February 2017

100

Background: Blue Cross and Blue Shield Association (BCBSA) is an association of 38 independent, locally operated Blue Cross and/or Blue Shield Plans (each, a BCBS Company). BCBSA and the 38 Blue Companies developed the Blue Distinction (BD) Program, a hospital based quality recognition program with clinical focus on six areas of specialty care, including complex and rare cancers. In 2010, BCBSA and 7 BCBS companies engaged in a pilot study with 25 systems of cancer care, to examine the feasibility of measuring key components of quality that were developed with input from a national multidisciplinary expert panel. Breast and/or colon cancer programs were examined on a range of settings, to understand similarities and differences between systems of cancer care in various regions across the country. Methods: A series of structured discussions and a three-part survey were used to gather information about systems of cancer care. The surveys explored various structures and processes of care that support multidisciplinary, coordinated, evidence-based and patient-centered care across the continuum of care. Results: A diverse group of established multidisciplinary systems of cancer care [n =17 responses (68%)] participated, representing tertiary, community, urban, and rural settings from various regions. Approximately one-third of the responding systems provided written treatment plans or written treatment summaries to patients, and less than one-half had formal processes for comprehensive survivorship care. A majority provided patient navigators, care coordination, or case management services, and a similar majority communicated with the primary care provider at identified points in course of patient’s treatment (e.g., initial assessment, change in treatment, completion of treatment). Conclusions: The pilot study identified gaps in oncology care, similar to those found by the Institute of Medicine (National Cancer Policy Board, Institute of Medicine, and National Research Council. Ensuring Quality Cancer Care. Washington, DC: The National Academies Press, 1999) and others. Opportunities exist for oncology stakeholders to promote quality improvement efforts to narrow these gaps and to improve the quality of cancer care.
Elective chemotherapy admission pilot and work-flow improvements to reduce excess days.
Authors: Miano Wendy Rowehl , Silverman Paula , Colella Frank , McQuigg Bernadette , Hines Heather , Ciarallo Santina , Whittington Lalena , Belcher Sarah
Published: February 2017

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Background: The Inpatient (Inpt) Oncology Service at University Hospitals Seidman Cancer Center, a large urban academic NCI Comprehensive Cancer Center was charged with identifying opportunities to link patient (pt) quality improvement and decreased length of stay (LOS) in pts admitted for elective chemotherapy (EC). Historically, EC admissions were delayed due to pt variables, inpt bed availability, and chemotherapy order entry errors. Often chemotherapy was not initiated until late evening on day of admission, resulting in increased LOS. Safety concerns associated with late starts included fewer pharmacy resources, lower nurse/pt ratio, and no onsite APRN. Methods: A 2-month pilot was conducted, using an intervention group (IG) and control (C) group representing usual care (UC). The IG group was a subset with oropharyngeal pts and C group, all other EC admissions. Pre-registration and bed placement processes were reviewed. Workflow changes for IG included chemotherapy order set entered in electronic medical record 48 hours before admission, labs drawn day before admission, and weekly huddle including admitting, inpt and outpatient (Outpt) teams to review upcoming week’s admissions. IG pts were pre-scheduled for am admission. Inpt oncology services incorporated admissions into morning workflow. Census was taken above cap to accommodate IG patients. Time parameters were tracked from point of pt arrival in Admitting to initiation of EC. Results: There were 32 pts in the 2-month pilot study; 14 in the IG and 9 in UC. Mean admit time was 0900 (range 0730-1030) for IG and 1200 noon (range 1000-1600) for UC. Initiation of EC before 1500 occurred in 93% of IG compared to 11% of UC pts. This resulted in an average decreased LOS for IG of 1.1 day compared to UC. Pt and family comments included appreciation of predictable admit time and LOS. Conclusions: Because of the 8-week pilot success, these EC workflow changes have been implemented across Oncology services. Weekly huddles and coordination of clinical services across inpt and outpt settings continue to show advantage of proactive planning and troubleshooting before the day of EC admission. More importantly, EC pt safety and experience has improved with these work-flow changes.
Outcome assessment of an oral chemotherapy management clinic: A preliminary report.
Authors: Wong Siu-Fun , Nguyen Cham Phuong , Bounthavong Mark , Bechtoldt Kezia , Hernandez Elvin
Published: February 2017

105

Background: Many oral chemotherapy (OC) drugs are used in the United States. The dosage regimens of OC increase the risks of nonadherence and drug interactions leading to potential adverse consequences affecting therapeutic outcomes and patient safety. A new OC management clinic was developed where patients (pts) receive comprehensive OC and concurrent medication (CM) education and symptom management services. Follow-up cares are provided to assure continual patient education, monitoring, and safety assessments. Currently there are no published data in OC clinic practice model and outcomes. We design this evaluation to measure the effectiveness of this practice model in patient care. Methods: Pts referred to the OC management clinic by the medical oncologists were enrolled. Pt demographics, depression scores, CMs, and types and outcome of interventions at initial, 3-day, 7-day, and 3-month follow-ups were collected. Adherence and persistence rates were monitored. Results: Retrospective cohort analyses were performed in 30 pts (9 males and 21 females, mean age 64.5). Majority of pts were college and high school graduates; social drinkers; non-smokers; with advanced stage cancer (stage III = 37%, IV = 27%); and no caregiver. Pts were predominately not depressed with Zung self-rating mean score of 36 (SD, 7.72) at baseline. The most common cancer diagnosis was breast (20%), followed by colon (17%), rectal (13%), and lung (6.7%). Capecitabine was the most common agent prescribed. Pts had an average 12.7 CMs and co-morbid conditions of hypertension (43%), chronic pain (43%), and diabetes (37%). Number and complexity of interventions (categories: adverse events (ADR), adherence, drug-interactions, medication error, symptom management) decreased over measured time periods. Complete resolution or improved response seen in 67% of interventions resulting in cost avoidance (49%). Optimal adherence (no missed dose) and persistence (completion of therapy) of OC were detected in at least 67% of patients. Conclusions: This evaluation demonstrated the effectiveness of OC management clinic in delivering early interventions, resulting in decreased incidence of ADR, non-adherence, drug interactions, and medication errors over time.
Distress management in a community oncology center.
Authors: Watts Lori , Camilo Nicolas , Thurston Nicole , Betts Michele , Zuckerman Dan Sayam
Published: February 2017

107

Background: NCCN and the Institute of Medicine recommend distress screening for all cancer patients. Surveys have found that 20% to 47% of newly diagnosed and recurrent cancer patients experience significant levels of distress. Less than half of distressed patients with cancer are actually identified and referred for psychosocial help. The development of screening tools, processes, appropriate timing, and systems for follow up on concerns is an ongoing challenge for many cancer programs. Mountain States Tumor Institute p,iloted a distress screen process as part of our work with NCCCP. Methods: From October 24, 2011, to April 30, 2012, 133 patients completed distress screens. Most frequently reported concerns included fatigue (50%), sleep changes (32%), and anxiety/worry (31%). 51% of patients reported three or more concerns. 90% of all patients reporting anxiety also reported fatigue or sleep problems. All patients who reported concerns were offered social work and other supports. Screens were reviewed by social workers and discussed at weekly multidisciplinary psychosocial care rounds by social workers, psychiatrist, nurse practitioners, and chaplains. A variety of interventions were used to respond to distress including symptom management, education and referrals to on-site social workers, chaplains, supportive care clinic, integrative medicine and psychiatry. Results: A task was created in Mosaiq Electronic Medical Record to cue Health Information Specialists to schedule patients for distress screening as close as possible to 45 days from first chemotherapy treatment. Patients completed screens before seeing their medical provider. The majority of patients screened received one or more interventions in follow-up. Conclusions: EMRs can be effective tools to cue scheduled screening of patient distress. The use of multidisciplinary psychosocial care rounds can effectively help clinics plan interventions to alleviate patient distress. The use of rounds can ensure staff from different disciplines are not duplicating efforts and can help determine appropriate timing of various psychosocial interventions. Project funded with Federal funds from the NCI, Contract No HHSN261200800001E.
The association between the transfer of emergency department boarders to inpatient hallways or off-service beds and the quality of oncology care.
Authors: Singh Simron , Trudeau Maureen E. , Imrie Kevin Robert , De Mendonca Ben , Fralick John , Cheung Matthew C.
Published: February 2017

113

Background: Emergency department (ED) crowding is an important issue in the delivery of high-quality medical care. At our quaternary care hospital a policy was implemented to ease ED crowding by moving suitable admitted patients into inpatient hallway beds or off-service beds. This study assesses the impact of off service and hallway bed admissions on patient care and satisfaction. Methods: Retrospective and prospective data were collected from Jan 1 to Dec 31, 2011, on admissions to the oncology service via the ED. Patient care data was collected as follows: chest/abdominal exams performed at first MD visit, number of MD visits within 48 hours, time to antibiotic administration, time to complete vitals, and mean time spent in the ED. Satisfaction surveys were also given to all patients. Results: One hundred and eighteen patients were admitted to a hallway bed (HALL). A random sample of 90 patients were used for comparison in the on service (ON) and off service (OFF) groups. Among HALL patients, 4% percent discharged themselves against medical advice (0% of OFF and ON patients). MD visits within 48 hours were the same among all groups (mean=6). Forty-two percent of hallway patients had a chest/abdominal exam during the first MD visit (32% and 33% for OFF and ON patients, respectively). Time to first completion of vitals was 1:05 (hh:mm) for HALL patients (1:21 and 00:34 for OFF and ON patients, respectively). Time to antibiotic administration was 15:34 for hallway patients (23:59 and 12:35 for OFF and ON patients, respectively). More HALL patients expressed dissatisfaction with their hospital stay (16.7%) compared to OFF (0%) and ON patients (0%). Mean time for admitted patients in the ED awaiting their HALL bed was 9:14, considerably longer than for OFF patients (3:08) and ON patients (4:19). Conclusions: Admission of oncology patients in hallway or in off-service beds did not appear to compromise the timeliness or frequency of medical assessments. However, delays in nursing care (completion of vital signs and drug administration) were noted and patient satisfaction was decreased. Moreover, the policy did not meet its intent to reduce patient time spent in the ED.
Preliminary decision-tree analysis of costs to payors associated with a pancreatic multidisciplinary clinic.
Authors: Elnahal Shereef M. , Wild Aaron Tyler , Wang Hao , Wolfgang Christopher Lee , Pawlik Timothy M. , Herman Joseph M.
Published: February 2017

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Background: Multidisciplinary clinics (MDC) are well-established formats for delivering thorough oncologic evaluation and treatment. Although much evidence identifies an association between MDCs and superior clinical outcomes, their effect on total costs to payors is not well described. We performed a preliminary decision analysis of likely costs associated with a pancreatic MDC versus other settings, referring to known changes in diagnosis resulting from our pancreatic MDC (Pawlik, Ann Surg Oncol.2008; 15(8):2081-8). Methods: We extracted cost data from previous decision-analyses to determine expected cancer treatment costs for patients with resectable (Ljungman, World J Surg. 2011; 35:662-670), locally advanced (Murphy, Cancer. 2011;118:1119-1129), and metastatic disease (Attard. J Clin Oncol. 2012 [suppl 4; abstr 199]), using the most updated studies available. We then mapped these costs to a decision-analysis, modeling staging patterns that change after referral to the MDC. The expected cost of each disease stage was multiplied by its frequency of occurrence for both scenarios. A unique Markov analysis with consistent assumptions was not available at submission, but will be at the time of the meeting. Results: From the literature, an initial diagnosis of resectable disease was associated with the highest cost, and metastatic disease with the lowest. The percentage of patients managed for each disease stage in both clinic settings are indicated in the table. Because the MDC scenario resulted in a lower frequency of resectable and a higher frequency of metastatic staging at initial diagnosis, costs were 4.7% lower in the MDC scenario. Conclusions: In this preliminary analysis, the MDC showed potential to achieve up to 4.7% in cost-savings over treatment in conventional clinic settings, suggesting that the MDC setting for pancreatic cancer may be cost-saving to payors. [Table: see text]
Chlorhexidine bathing to reduce CLABSI in hematopoietic stem cell transplant and hematologic malignancy patients.
Authors: Reeber Christina , Bailey Kelly , Nemec Carrie , Salata Robert A. , Gonzalez Kathleen
Published: February 2017

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Background: At University Hospitals Seidman Cancer Center (UHSCC), adult patients with hematologic malignancies (HM) and those undergoing hematopoietic stem cell transplant (HSCT) require a central venous catheter nearly 100% of the time. According to the National Health Safety Network (NSHN), for permanent and temporary line days, the pooled mean infection rate in 2009 was 3.5 and 4.1, respectively. Catheter-associated bloodstream infections (CLABSI) lead to increased morbidity, mortality, length of stay, and cost. At UHSCC, the CLABSI rate for patients on the HM service from August 2010 through August 2011 was 8.0. Methods: It has been demonstrated that the use of Chlorhexidine (CHG) wipes has decreased the CLABSI rate in ICU and long term care patients. We were unable to identify literature evidence or medical centers currently using CHG bathing wipes in their cancer patients, specifically HSCT. A quality improvement project on the effectiveness of CHG bathing on the HSCT and HM populations commenced on April 2, 2012, at UHSCC. This study is also monitoring skin integrity to determine if there are adverse effects. Patient satisfaction is also being assessed. Results: Early results demonstrate a reduction in overall CLABSI rate to 4.3%, and no vancomycin resistant enterococcus (VRE) infections were observed since early April. Adverse effects on skin integrity have not been noted. An unanticipated obstacle is related to the “culture of bathing.” Specifically, caregivers and patients often do not understanding the importance of daily bathing as a key clinical intervention despite repeated education. The team continues to investigate this issue. Conclusions: CHG bathing appears to be an effective, well-tolerated, and minimally invasive intervention in preventing CLABSI in severely immunocompromised cancer patients. Unanticipated obstacles to implementing daily bathing have been encountered and are being addressed. During the course of this project, we also began tracking our CLABSI rate for the entire patient population on the HM HSCT nursing unit along with the service-based rate noted above.
Supervised exercise for cancer survivors during and after active therapy.
Authors: O’Rourke Mark Allen , Franco Regina A , Blackhurst Dawn W. , Trilk Jennifer C. , Hudson Matthew F. , Gluck William Larry
Published: February 2017

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Background: Supervised exercise for cancer survivors can reduce symptoms and improve physical conditioning. This program evaluation reports the benefits of a nurse-supervised exercise program for cancer survivor participants both during and after active cancer therapy. Methods: The treating oncologist referred participants to the oncology rehabilitation program, called Moving On, either during or at the completion of active therapy. Participants enrolled in a 12-week program of supervised exercise for one hour, three days per week. Baseline and follow up evaluation included a patient reported fatigue score, on a scale from 1 to 10 (with higher scores indicating more fatigue), and the 6-minute walk test (6MWT), in feet. Results: In calendar 2011, 152 participants enrolled in the program and 91 completed all 12 weeks (completers). Participants were 71% female, 86% Caucasian, 14% African American, 68% enrolled on completion of active therapy, and 32% enrolled during active therapy. More than half were older than 60 years. More than half had cancer diagnoses other than breast cancer. A consistent decrease in fatigue and increase in exercise capacity was seen in subgroup analysis by gender, race, age, status on cancer therapy or after completion of therapy, and diagnosis. Conclusions: In this diverse group of cancer survivors, a program of 12 weeks of nurse-supervised exercise was feasible, substantially reduced fatigue, and increased exercise capacity. It is noteworthy that participants, both on active therapy and after, older and younger, and across diagnosis groups, experienced the benefits of the program. [Table: see text]
Reducing time to initiation of colon cancer adjuvant chemotherapy in a large community-based hospital.
Authors: Bochert Karen , Rentschler Brian , Powers Chris , Slezak Frederick , Mahesh Sameer A.
Published: February 2017

125

Background: Chemotherapy is standard of care after definitive surgery for stage III and certain subsets of stage II colon cancer (CC). A recent meta-analysis showed that for every 4 week delay in administering adjuvant chemotherapy relative survival decreases by 15%. At our institution, 24% of patients undergoing colon cancer surgery in 2010 subsequently received chemotherapy. On average, this process took 41 days from date of discharge to first chemotherapy (range 12-166 days). We sought to decrease this time to an average of 28 days. Methods: Previously, starting adjuvant chemotherapy was a step-wise process starting from the surgeon’s post operative visit to the medical oncologist’s office visit followed by port placement and finally, the commencement of chemotherapy. We instituted a program of concurrent scheduling of appointments by the colorectal cancer navigator (CRCN) upon availability of the pathology report. Primary end-point was time to start of chemotherapy from day of discharge (TTCD). Results: Twenty-three patients were eligible since inception of the program in September 2011. Of these, 5 declined entry and 2 were under the care of non-participating physicians, hence excluded from analysis. TTCD before and after implementation of the program are shown in the table. Two patients required financial assistance for capecitabine (C) that delayed TTCD to > 4 weeks. Results are shown after excluding those patients as well. Conclusions: Utilizing the CRCN to coordinate appointments for patients who required adjuvant chemotherapy significantly decreased the TTCD which might translate into better CC outcomes. [Table: see text]
Improving new patient access for patients with colorectal cancer.
Authors: Denton Kathy , Campbell Jessica
Published: February 2017

131

Background: Colorectal cancer is a common and lethal disease. The University of Texas MD Anderson Cancer Center has seen an increase in patients who want colorectal cancer treatment. This increase has had a negative result on the referral to appointment cycle time for new patients. Responding to this, Colorectal split from GI in 2010 and separate processes were developed. A performance improvement team was identified in September 2011 with the goal to decrease the referral to appointment cycle time for colorectal patients. Methods: The PI team Aim Statement was to facilitate patient access to the Colorectal Center by decreasing the days of referral to appointment by 10% within the first year. A retrospective study was conducted of the access data for the previous two years. A comprehensive 3-week audit of access center staff and processes was completed. A key component of project success was process standardization and staff education for the new patient communication. A physician designed and presented colorectal practice guidelines and education to the access staff to helped staff identify the correct first appointment type. Scripting was developed to establish clear patient expectations of their responsibilities obtaining medical records; the structure of the first visit; and to provide consistent answers to FAQ to improve access and the patient experience. Access teams were formed and new processes created for receiving and responding to first patient communication. Scheduling templates were revised to accommodate the increased patient volume. Staff work schedules were adjusted to accommodate the workload. There were also many “quick fixes” identified such as implementing separate fax/phone numbers for Colorectal and GI. Results: Within two years, new patient access time decreased from 19.48 days in fiscal year 2011 to 15.76 days in fiscal year 2012 through May 2012, a 19% decrease. The highest access month in fiscal year 2011 was 29 days and the lowest access month in fiscal year 2012 was 12.71 days, while realizing a 15% increase in referrals. Conclusions: The team realized success with the decrease in access time which provided a better quality patient experience. The next step is to further reduce access time by focusing on a different access process for local patients.