bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

67 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

71 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

76 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

101 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

118 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]