bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of a biomarker signature that predicts upgrading or upstaging in patients with low-risk prostate cancer.
Authors: Erho Nicholas , Vergara Ismael A. , Buerki Christine , Ghadessi Mercedeh , Crisan Anamaria , Sierocinski Thomas , Haddad Zaid , Zimmermann Benedikt , Harko Sebastian , Sosu-Sedzorme Worlanyo , Triche Timothy J. , Davicioni Elai
Published: February 2017

37

Background: More than 90% of patients diagnosed with organ-confined prostate cancer (PCa) choose upfront definitive treatment (e.g., radical surgery) even though many are excellent candidates for delayed therapy (i.e., active surveillance [AS]). Therefore, patients may suffer from the adverse effects of treatment without gaining any benefit. Biomarker signatures that predict tumour aggressiveness are promising tools for identification of patients suited for AS. In this study, we use a transcriptome-wide assay to develop a biomarker signature for patients assessed as low risk at diagnosis who are upgraded or upstaged following radical prostatectomy (RP). Methods: Gene expression data of 56 RP samples from the Memorial Sloan Kettering Oncogenome Project (GSE21034) which met the low risk criteria (i.e., biopsy Gleason score (GS) ≤ 6, clinical stage T1 or T2A, and pre-operative PSA (pre-op PSA) ≤ 10 ng/ml) were used to develop the signature. Of these tumors, 31 underwent upgrading or upstaging (defined by pathological GS ≥ 7 or a pathological tumor stage > T3A). In the training set (n = 29) a median fold difference filter (MFD > 1.4) was applied to select features. The top 16 t-test ranked features were modelled with a K-nearest-neighbor (KNN) classifier (k = 3) which predicts upgrading/upstaging events. Results: The KNN was applied to the test set (n = 27) and achieved an area under the receiver operating characteristic curve (AUC) of 0.93, significantly better discrimination than pre-op PSA (AUC = 0.52) or tumor stage (AUC = 0.63). Compared to the null model’s accuracy of 56%, the KNN correctly predicts 81% (p-value < 0.005) of the upgrading/upstaging events. In multivariable analysis with pre-op PSA, tumor stage, and age at diagnosis, the KNN remained the only significant (p < 0.05) factor with an odds ratio of 2.7. Conclusions: A 16 marker signature was identified from RP specimens and shown to accurately segregate true low risk patients from those which transitioned to higher risk. Validation studies of this signature in prospectively designed cohorts of active surveillance candidates are underway to determine if the molecular signature can improve treatment and management decisions for low risk PCa patients.
Detection of alpha-methylacyl-CoA racemase (AMACR), a biomarker of prostate cancer, in patient blood samples using a nanoparticle electrochemical biosensor.
Authors: Cooney Matthew M. , Thompson Cheryl L. , Lin Po-Yuan , Cheng Kai-Lun , McGuffin-Cawley James D. , Shieu Fuh-Sheng , Samia Anna C. , Gupta Sanjay , Liu Chung-Chiun
Published: February 2017

41

Background: A promising prostate cancer biomarker, alpha-methylacyl-CoA racemase (AMACR), has demonstrated the ability to distinguish cancer from healthy and benign cells with high sensitivity and specificity. However the lack of a good clinical assay has limited its translation into the clinic. Here we report on the development of a single use disposable biosensor for AMACR detection. Methods: This is a very inexpensive, small, single-use disposable sensor that requires only a drop of plasma and connects to a portable device. The biosensor utilizes the reaction of pristanic acid with a substrate that includes AMACR to produce Trans-2,3-dehydropritanayl-CoA plus H2O2. The biosensor utilizes iridium oxide nanoparticle catalyst to oxidize the H2O2 produced in the above metabolic pathway. Thus the oxidation of H2O2 yields a measurable current to quantify AMACR in the sample. This is the first in vitro assay method for AMACR based on this reaction mechanism. Results: In our study including plasma from 9 healthy males, 10 patients with high grade prostatic intraepithelial neoplasia and 5 prostate cancer patients we show 100% accuracy in separating prostate cancer patients from controls as well as those with benign prostate conditions. Conclusions: Our data provides strong evidence for the ability of this biosensor to perform as a reliable assay for prostate cancer detection and diagnosis.
Correlation of elevated ALCAM shedding with patient outcome in colorectal cancer.
Authors: Hansen Amanda Georgia , Freeman Tanner , Washington Mary Kay , Fan Kang-Hsien , Shyr Yu , Beauchamp R. Daniel , Zijlstra Andries
Published: February 2017

46

Background: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is a cell-cell adhesion protein that has been highlighted as a putative biomarker for the progression of many cancers, including colorectal cancer (CRC). Current prognosis for CRC patients predominantly rely on pathologic staging classification. Although TNM staging successfully stratifies high-risk patients, there is significant variability in the rate of disease progression within each stage. Previous studies evaluating ALCAM as a biomarker for predicting colorectal cancer patient survival have published conflicting and inconclusive results. The aim of this present study was to investigate the prognostic value of ALCAM shedding, quantified using a dual stain that detects both the extracellular and the intracellular domains in formalin-fixed tissue, in colorectal patients. Methods: A novel dual-immunohistological detection of ALCAM shedding was performed on tissue microarrays constructed from 75 colorectal primary tumors and 9 healthy control specimens. Tissue was assessed by CellProfiler image analysis to obtain quantitative estimates of ALCAM shedding, defined as the detection of the intracellular domain the absence of the extracellular domain of ALCAM. Two tailed p values ≤ 0.05 were considered to be statistically significant. Results: ALCAM shedding was elevated in 33/79 (41.8%) of tissue from CRC patients compared to healthy controls (p=0.0239). Univariate analysis of CRC patients, stages I-IV, revealed a statistical significance correlating high ALCAM shedding with worse overall survival (p=0.0401). Moreover, ALCAM shedding is a predictor of overall survival (p=0.432) and more notably, disease-specific survival in stage II patients (p=0.0098). Conclusions: Detection of ALCAM shedding allows for stratification of patients according to their risk for poor long-term outcome. Considering that ALCAM is altered in a number of malignancies, the clinical correlation of ALCAM shedding to patient outcome is likely to extend beyond CRC to other cancers.
Examining the reliability of surrogate tissue predictability of drug efficacy in reconstituted human 3D skin models containing melanomas.
Authors: Parekh Palak R. , Redon Christophe E. , Weyemi Urbain , Bonner William
Published: February 2017

49

Background: Melanoma has a poor survival rate in advanced stages due to the lack of efficacious approved treatments. However, melanoma’s dermal location enables the application of human skin models. These models mimic many important characteristics of skin in vivo and obviate the use of invasive procedures. Monitoring gamma-H2AX foci to assess DNA double-strand break (DSB) levels in reconstituted human 3D skin tissue harboring melanoma tumor cells may provide insights into important questions in cancer research. In addition to the differential toxicities of anti-cancer agents on the various cell types, we examine how the early drug response of normal tissues might serve as surrogates for predicting treatment efficacy on the tumors. Methods: Commercially available reconstituted 3D human skin tissue consists of dermal fibroblast and epidermal keratinocyte layers with malignant melanoma A375 cells which have been cultured to form a multilayer, highly differentiated epidermis containing various stages of cutaneous melanoma malignancy. Drugs representative of several different categories were studied, including bleomycin (a radiomimetic), camptothecin (a topoisomerase I inhibitor), temozolomide (a DNA alkylating agent), AZD6244 (a MEK inhibitor), Vorinostat (a HDAC inhibitor) and cisplatin (a DNA intercalatingagent). DNA DSB levels were monitored by gamma-H2AX foci formation and apoptosis by TUNEL assay. Tumor growth was monitored by H&E staining. Results: A wide range of responses in both tumor and normal tissue by various drugs were observed, including tumor regression and normal tissue toxicity. The early responses of normal tissues depended on the treatment, providing insights into the use of surrogate tissues as predictors of drug efficacy and later tumor regression. Conclusions: Measuring DNA DSB damage in reconstituted 3D skin tissue is an attractive model for studying the efficacy and toxicity of genotoxic drugs against melanoma. If validated, such models would help reduce the use of animals for preclinical studies.
Hypothesis-free biomarker discovery platform evolving into a companion diagnostic using bioinformatics.
Authors: Pedersen Gitte
Published: February 2017

52

Background: Cancer drug discovery is hypothesis driven focused on addressing specific mechanisms; however the patient’s individual tumor harbor much more diversity and therefore the biomarkers behind the hypothesis are often insufficient in explaining the differences in individual drug response. A Danish Private Public Partnership is developing biomarkers for cancer prognostics under a $30 million grant. The Danish National Biobank was established by another $20 million grant and hosts approximately 15 million biological samples associated with cradle-to-grave electronic medical records. Methods: Proposing a hypothesis-free biomarker-discovery platform using intelligent target-filtering technology integrated with sequencing short reads on a small chip addressing the sample prep and data analysis bottlenecks in current sequencing platforms. By using bioinformatics on existing sequence data it is possible to optimize the proposed strategy and develop novel diagnostic applications. The intelligent target-filtering process generates a single-stranded tag library. Because the tags are single stranded, it is possible to detect all possible tags using a universal high-throughput platform. The cost per sample is low, the content/test very high, and hypotheses free. This approach represents a paradigm shift in the biomarker-discovery process, saving significant time and money while increasing the probability of success. The diagnostic becomes a bioinformatics exercise that allows the drug discovery company to optimize the definition of responders. Results: The result of the digital gene expression experiment was compared to RNA-seq and Affymetrix whole genome array. Conclusions: The platform offers a more cost-effective way of providing an open and hypothesis free platform compared to sequencing. The platform also offers cost-effective open-ended solution for such diverse applications as expression profiling, genome wide methylation profiling, genome wide duplication/deletion analysis, environmental microbiome profiling, and single gene mutation detection with only relatively minor adjustments in how the single stranded tags are extracted from the sample.
Moving next-generation sequencing into the clinical realm: Detection of somatic mutations in cancer by targeted amplicon sequencing.
Authors: Lih Chih-Jian , Forbes Thomas , Mehaffey Michele , Sause Eric , Sims David , McGregor Paul , Conley Barbara A. , Kummar Shivaani , Williams Paul M.
Published: February 2017

60

Background: Molecular targeted therapies are increasingly important in treating cancer patients; robust analytically validated clinical assays are required for patient selection in early-stage clinical trials. The goal of Molecular Characterization Laboratory (MoCha) is to develop clinical diagnostic assays using next generation sequencing methods to support clinical studies in DCTD (CTEP). Methods: We developed a custom assay for somatic mutation detection using Fluidigm access array technology for amplicon generation followed by sequencing with the Illumina Miseq. A panel of 62 amplicons covering 6 Kb genomic regions was designed to detect 92 DNA loci, including common therapeutically actionable targets, in 37 genes. Analytical studies were performed using genomic DNA samples from fresh or formalin fixed cancer cell-lines and a normal hapmap individual (CEPH). We subsequently applied this assay to characterize DNA samples from both tumor tissues and blood specimens from ovarian cancer patients. Results: The assay detected known variants in both frozen and fixed DNA samples reproducibly with high sensitivity and specificity (<2%). Using a series of positive control plasmid spikes mixed into a normal reference CEPH DNA at pre-defined copy number ratios, we verified the assay is sensitive to detect variants at 5% allelic frequency with a minimum 400 X coverage. We identified somatic mutations in TP53 and PIK3CA in a few patients, and a germ-line variant D1583N in ATM genes occurring in one-third of tested patients. Conclusions: We developed and validated a next generation sequencing assay suitable for patient selection for clinical trials. Plans are to correlate sequencing and clinical results when clinical data are available.
Prognostic and diagnostic significance of epigenetic alterations of p16 and DAPK1 promoter sequences in patients with epithelial ovarian carcinoma (EOC).
Authors: Mir Ab Rashid , Najar Imtiyaz Ahmad , Yadav Prasant , Javed Jamsheed , Zubari Mariyam , Farooq Shazia , Gandhi Gauri , Ray Prakash C. , Dholariya Sagar , Saxnena Alpana
Published: February 2017

62

Background: Novel strategies for early detection of EOC, the most common and second most lethal cancer in Indian women, are urgently needed. Silencing tumor suppressor genes via DNA methylation has established hypermethylation as one of the most frequent molecular alterations that may initiate and drive many types of human neoplasia including EOC. To determine the alterations of tumor suppressor gene DAPK1 and p16INK4A in EOC patients to explore the possibilities of identifying potential minimally invasive markers in blood of the patients, which could help in the clinical practice as a diagnostic and prognostic marker. Methods: Fifty EOC patients with primary epithelial ovarian cancer were selected for the study; these patients were followed for a median of 20 months. Genomic DNA extracted from fresh peripheral blood and serum followed by sodium bisulfate modification. The DAPK1 and p16 methylation was detected using methylation-specific PCR (MSP). The DAPK1 and p16 methylation status was correlated with age, stage,menopause, Ca125.5 and clinic pathological features. Results: The frequencies of DAPK1 and p16 methylation in EOC patients was found to be 68% and 84% respectively . Aberrant methylation of DAPK1 and p16 was associated with age at diagnosis (p = 0.043) .The significant association was seen with age,menopause. Patients with high methylation indices had poor prognosis (p<0.001, Hazards ratio=14.58) with age (p = 0.043), and tumor stage (p = 0.033). Aberrant methylation of DAPK1 and p16 was strongly associated with EOC patients (p = 0.037 respectively). Conclusions: our results that the methylated loci of TSGs (DAPK1 and p16) may be employed as clinically useful biomarkers for prognosis and diagnosis of EOC noninvasively using readily available body fluid by MS-PCR and proved to be efficient and cost-effective method.
A 19-gene prognostic GEP signature to determine metastatic risk associated with thymomas.
Authors: Gokmen-Polar Yesim , Goswami Chirayu Pankaj , Cook Robert W. , Oelschlager Kristen M. , Maetzold Derek , Vladislav Ioan Tudor , Shirar Kristen L. , Kesler Kenneth , Loehrer Patrick J. , Badve Sunil S.
Published: February 2017

68

Background: Therapeutic decisions for patients with thymomas are made on tumor stage as histologic classification is of limited prognostic value. A molecular prognostic tool may better predict the likelihood of metastasis in thymomas and enable better management of patients. Methods: Reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay for 23 genes (19 test and 4 reference genes) was performed on archival paraffin-embedded primary thymomas (n=36). The gene expression levels were used to compute gene expression profile (GEP) signature and classify tumors into low or high risk. The GEP was validated in an independent test set (n=75) of patients. Results: We developed and validated a 19-gene prognostic GEP signature for predicting metastatic behavior in thymomas. Using radial basis machine (RBM) modeling in the training set, both 5-year and 10-year MFS rates were 85% and 22% for predicted low risk and high risk of metastasis (p<0.0005, log-rank), respectively. For the validation set, 5-year MFS rates were 93% and 35% for predicted low and high risk patients (p<0.0018 log-rank), respectively. The 5-year MFS rates for Masaoka stage in the validation set were 53% and 41% for stage I/II and stage III/IV(p<0.0433 log-rank), respectively. In a multivariate Cox model, the GEP was the only independent predictor of metastasis free survival compared to age at diagnosis and stage (p=0.048). Conclusions: Using archival tissues, we identified and validated a 19-gene signature that predicts likelihood of metastases of thymomas more accurately than traditional staging. The signature provides insights for both patient stratification and targeted therapy.
Disruption of protocadherin function and correlation with metastasis and cancer progression in TCGA patients.
Authors: Shima James , Delaney Joseph , Umesh Anita , Park Jenny , Wall Gregory , Su Qiaojuan , Shekar Mamatha , Kupershmidt Ilya
Published: February 2017

70

Background: Protocadherins (PCDH) are a large family of calcium-dependent cell–cell adhesion molecules involved in tissue morphogenesis. Inactivation of PCDH locus genes are implicated in a number of oncogenic processes—hypermethylation of the PCDH gamma locus is present in Wilms’ tumors and arises after tumor development and the epigenetic silencing of PCDHGA11 occurs in the course of parenchymal invasion by astrocytomas. Assessment of PCDH function may help guide treatment decisions and provide a marker for metastasis in specific cancers. Methods: Identification of altered PCDH locus genes in TCGA patient samples was performed using the NextBio Clinical platform which provides access to the genomic and clinical data available in the TCGA dataset. The NextBio Research platform was used to correlate curated public experimental data and identify deleterious genomic changes associated with the PCDH locus and disease. Results: A nearly 3-fold increase in the frequency of potentially detrimental somatic mutations in PCDHGB4 was observed in breast cancer patients with extensive lymph node metastases (N3) compared to those with a lower degree of lymph node metastasis (N0-N2) (p value = 0.015). No other cancers appeared to have genomic changes deleterious to PCDHGB4 function, including ovarian and uterine cancer. Using the NextBio Research platform, breast cancer was found to be the 3rd most correlated disease with PCDHGB4, strongly correlating with RNA downregulation, DNA hypermethylation, and copy number loss. Other deleterious genomic changes in the PCDH locus were identified in ovarian (PCDHG), renal (PCDHA), and lung (PCDHA) cancers. Conclusions: Using the NextBio Clinical and Research platforms to analyze available TCGA data, disruption of PCDH function was found to correlate with increased metastasis only in certain cancers and with specific locus-disease pairings. Examination of PCDH locus perturbations may provide insight into a patient’s risk of developing metastatic disease. Further examination of the tissue specific alteration in PCDH genes may also aid in identifying unique cell adhesion pathways leading to metastasis in distinct tissues.
Use of quantitative histomorphometrics to classify disease progression in HPV-positive squamous cell carcinoma.
Authors: Ali Sahirzeeshan , Lewis James S. , Madabhushi Anant
Published: February 2017

73

Background: Oropharyngeal squamous cell carcinoma (SCC) is now recognized as distinct because of its strong association with high-risk human papillomavirus (HPV) and favorable prognosis. Although these tumors have some specific morphologic features, none have been shown to predict prognosis, particularly on small specimens such as biopsies. Methods: We present a novel cluster cell graph (CCG) that is computationally efficient and provides an effective tool to quantitatively describe histopathologic images according to the spatial distribution and clustering of cells. CCG is generated by firstly automatically identifying all cells/nuclei within the histologic image and then identifying nuclear clusters. These clusters are then represented via a single node corresponding to center of mass of the cluster. Any pair of nodes is connected via a link if the probability of such an association is greater than a pre-defined threshold, the probability being calculated as a decaying function of the Euclidean distance between node pairs. Once links have been identified between cluster nodes, subgraphs are constructed as series of topological features defined on each node of the subgraph, i.e., local graph metrics (e.g. clustering coefficients and skewness of edge lengths). Results: We leverage CCG to capture structural characteristics of HPV-related (p16+) oropharyngeal SCC (oSCC) from formalin-fixed, paraffin-embedded tissue microarray images. A series of quantitative histomorphometric descriptors are extracted for each image and used to train a random forest (RF) classifier to distinguish patients with p16+ oSCC who develop disease progression from those that do not. Over 25 runs of 3-fold cross validation in a cohort of 140 studies (116 non-progressors and 26 progressors) the RF classifier yielded a mean accuracy of over 87% in distinguishing between progressors and non-progressors. Conclusions: The ability to quantitatively describe the spatial distribution/clustering of nuclei via CCG allows for building of classifiers that can distinguish between progressors and non-progressors in p16+ oSCC tissue images. The approach should be extensible to outcome prediction for other cancers as well.
Endobronchial ultrasound-guided transbronchial needle aspiration samples for multiple molecular analysis.
Authors: Chen Kezhong , Yang Fan , Zhao Hui , Wang Jun
Published: February 2017

75

Background: We assessed the usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to detect EGFR, K-ras, ALK mutations from malignant mediastinal nodes of patients with NSCLC. Methods: From February 2010 to April 2012, 81 specimens diagnosed with lung adenocarcinoma by EBUS were used for molecular analysis. Needle puncture site for the EBUS was standard 22G needle, once cytology pathology diagnosed adenocarcinoma, at the same site with the conventional needle puncture method to obtain adequate biopsy specimen for further analysis. The tissue was fixed in 10% formalin. When histologic diagnosis confirmed adenocarcinoma, the FFPE tissue was extracted DNA to detect EGFR mutation by both amplification refractory mutation system (ARMS) and direct sequencing. Partial specimens also extracted DNA or RNA to detect K-ras and ALK mutation. Results: 80/81 specimens were successfully extracted DNA, 52 were male and 28 were female, mean age of 62.9 years (34 to 82 years). Somatic mutations of the EGFR gene were detected in 37 of 80 cases (46.3%), 22 cases of exon 19 mutation,14 cases of exon 21 mutation, and 1 of T790M mutation in ARMS. The result have some difference in direct sequening. In the patients who requested other biomarkers analysis, 6 had K-ras mutations and 2 had ALK mutations.7 patients with EGFR mutations had a radical surgery after neoadjuvant chemotherapy, tumor specimens were tested again with EGFR gene mutation, the same result as the preoperative test results. Conclusions: EBUS-TBNA mediastinal lymph node biopsy in the detection of EGFR, K-ras, and ALK mutations in tissue samples was feasible, through the highly sensitive methods, higher detection rate was available, the result can be used as evidence of personalized treatment of lung cancer.
High-throughput glycomics for discovery of cancer biomarkers.
Authors: Nakahara Taku , McCarthy Diane , Miura Yoshiaki , Asada Hidehisa
Published: February 2017

9

Background: While the importance of glycosylation in many cancers is well established, the use of glycomics in biomarker research has lagged behind genomics and proteomics. This is due, in part, to the lack of practical platforms capable of analyzing clinically relevant sample numbers. To address these challenges, we have developed a novel glycomics technology (the GlycanMap platform) that combines a high-throughput assay with custom bioinformatics and rapidly provides both biomarker candidates and information on the underlying biology. Methods: N-glycans were enzymatically released from their parent glycoproteins and captured on chemoselective beads. After washing to remove non-glycan components, purified glycans were derivatized to stabilize labile sialic acids and released from the beads. The steps described above were automated on a 96-well format robotics system to maximize throughput and reduce variability and can be performed in less than 24 hours. Released glycans were analyzed by MALDI-TOF MS using internal standards to facilitate quantitation. In addition to comparing individual glycans between groups, glycan changes were also analyzed with respect to known glycan biosynthetic pathways. Results: The automated assay was compatible with multiple biological sample types, including serum/plasma, tissue, and cell lysates. Human serum was used to assess assay performance and yielded 50-60 glycans with CVs of 10-15% and good linearity. The lower limit of detection was approximately 100 nM. The assay was applied to drug-treated colon cancer cells (HCT116) and revealed significant (> 2-fold) changes in 17 glycans. Projection of these glycan changes on the known N-glycan pathway showed that the most significant changes occurred in the medial-Golgi. Conclusions: We have developed and optimized a high-throughput glycomics platform to facilitate large-scale biomarker studies and assured its practical performance in terms of sensitivity, repeatability, and linearity. Application of this assay to drug-treated colon cancer cells demonstrated that projection of individual glycan changes against known glycan pathways provided additional information about biological mechanism and relevance.
MDR1 gene expression in peripheral blood as a marker of treatment response in lung cancer.
Authors: Luque Raquel , Gonzalez Flores Encarnacion , Delgado Juan Ramon , Melguizo Consolación , Prados Jose Carlos , Gonzalez Astorga Beatriz , Ortiz Raul , Sánchez Toro Carmen , Valdivia Javier , Aránega Antonia
Published: February 2017

96

Background: Non-small cell lung cancer (NSCLC) is sometimes chemoresistant and does not respond to treatment; several factors are involved in the development of chemoresistance, such as multidrug resistance (MDR) phenotype, mainly. Methods: We studied MDR1 gene expression in peripheral blood PMN of 23 patients with NSCLC, advanced stages in most of the cases, who had not received treatment previously, before (hour 0) and after (hour 6) paclitaxel-carboplatin treatment. RNA was obtained from PMN pellet by means of the protocol of trizol. RNA was checked with agarose gels, and later RT-PCR technique was carried out using specific primers. Expression levels were randomly distributed, so that overexpression under 3 was considered low level of expression, and overexpression above 4 was considered high level of expression. Results: After treatment, we found overexpression of MDR1 in 22 patients. High levels were found in 11 patients, and low levels were observed in the other 11 patients. No relation was found between this fact and the treatment response or survival rate. No significant differences in expression were found in the other variables: gender, tobacco habit, weight loss at the diagnosis, tumour staging, and tumor histology. Conclusions: We can conclude that MDR1 expression in peripheral blood is not a predictive factor for treatment response nor a prognostic factor of the disease. Despite these results, further studies are necessary on molecular biology of NSCLC in order to try to establish subgroups of patients based on genetic profiles, in which the use of microarrays could be very useful.
Utilization of intensive care resources due to better communication of end-of-life issues.
Authors: Chen Allen Ray Sing , Kane Joyce M. , Kasecamp Barbara , Cottrell Candace , Apostol Colleen C. , Billing Lynn , List Donald C. , Jones Richard J. , Fetting John H.
Published: February 2017

1

Background: Advanced life support resources are required for optimal care of patients undergoing curative therapy, but their use in patients with terminal disease does not improve patient outcomes. In 2007, our cancer center established the Duffey Pain and Palliative Care team, and one important goal was to help our physicians improve at discussing end-of-life issues with patients. We hypothesized that if this effort was effective, it would result in less utilization of intensive care unit (ICU) management among patients who die in the center. Methods: All inpatient deaths were systematically tabulated and code status displayed at the multidisciplinary Morbidity and Mortality review twice per quarter, beginning in July 2006. Utilization of ICU care, defined as ventilator or dialysis support, was identified from billing data and confirmed by chart review. Survival to discharge among patients who received ICU care was monitored as a component of our patient safety dashboard. Results: From 2008 through 2011, 525 oncology patients died while hospitalized in the cancer center. During this period, among patients who died, there was a gradual increase in no-code status, election of comfort care, or withdrawal of ICU support, from 81% to 95% (OR 1.14 per quarter, p<0.0001). Although the proportion of patients who received any ICU care during their terminal hospitalization did not change, the duration of such care decreased: the proportion with mechanical ventilation for over 14 days decreased from 10% to 5% (OR 0.93 per quarter, p<0.05). There was no decrease in the survival-to-discharge of patients who received ICU care. Conclusions: A multidisciplinary team approach to improve discussion of end-of-life issues, combined with regular feedback to cancer center staff regarding code status at death, resulted in significant changes in patient and family decisions about management at the end of life over a four-year interval. These changes have reduced utilization of ICU care during terminal hospitalizations with no reduction in the survival-to-discharge of all patients who receive ICU care. We propose appropriate establishment of code status and survival-to-discharge of ICU patients as measures of quality oncology care.
Changes in adjuvant endocrine therapy over one year among postmenopausal women with early-stage breast cancer initiating aromatase inhibitors.
Authors: LaMorte Danielle Lindsay , Hartmann Katherine E. , Abramson Vandana Gupta , Mayer Ingrid A. , Peacock Nancy Walker , Cella David , Castel Liana Desharnais
Published: February 2017

11

Background: Aromatase inhibitors (AIs) are standard of care for adjuvant endocrine therapy (AET) to prevent recurrence of early stage breast cancer in postmenopausal women. Previous AET adherence research has focused on the 25-96% adherence observed with, but more information is needed about AI adherence, especially regarding the role of arthralgia (joint pain or stiffness) in AET changes. Our objective was to understand AET changes within a year of AI initiation. Methods: We examined AET switching (either to another AI or to tamoxifen), overall changes in AET (including switching and temporary or permanent discontinuation), and physician- and patient-reported arthralgia, using data abstracted from medical records and self-administered surveys among 93 patients initiating AI. We conducted Chi-square and Wilcoxon univariate analyses. Results: Anastrazole was initially prescribed to 64 patients (69%), letrozole to 28 patients (30%), and exemestane to 1 patient. A year after AI initiation, 64 patients (69%) had no change in AET. Among the 29 patients (31%) who had an AET change, 14 switched to at least one other AI, 11 switched to tamoxifen, 9 temporarily discontinued AET, and 7 entirely discontinued AET (categories not mutually exclusive). Average time to first AET switch was 182.7 days. Average number of AET switches was 1.4. Arthralgia was the most common reason for AET changes, noted in the records of 19 patients (66% of those who changed AET). Patients who changed AET reported more severe arthralgia (median pain from 0-10 among 8 joint groups =1.4, interquartile range [IQR]=0.3-2.6) at week 12 than those who did not (median=0.3, IQR=0-1.1), p=0.03. A higher proportion (46%) of the 28 patients who initiated with letrozole changed AET due to arthralgia, compared with 20% of the 64 patients who initiated with anastrazole (p=0.01). Conclusions: A substantial proportion of women initiating AI change AET over one year. Arthralgia appears to play a key role in AET changes, particularly for letrozole as compared with anastrazole. More longitudinal patient-reported arthralgia data are needed to guide clinical decision making about AI initiation and AET changes.
Evaluating survivorship cancer care through quality improvement programs.
Authors: Palos Guadalupe R. , Zandstra Fran , Russell Ludivine , Flores Jacklyn J. , Gilmore Katherine R. , Rodriguez Maria Alma
Published: February 2017

112

Background: The Institute of Medicine noted cancer survivors’ care may be improved by providing each with a cancer survivorship care plan (CSCP). Recently, numerous versions of CSCPs have emerged; however, evidence-based processes to evaluate their use and quality in providing personalized survivorship care have yet to be implemented. Here, we describe our efforts to use the approach recommended by the American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative (QOPI) to track and report the compliance rate for using electronic CSCPs in our survivorship clinics. Methods: The criteria used to conduct our audit evolved from the QOPI template, which included selection of survivors seen in 7 different out-patient survivorship clinics within a specific 6-month period, identification of denominators and numerators unique to each clinic, and determination of the number of records to audit based on the number of full-time providers in each clinic. Next, we established the target condition, method(s) used for data collection, appropriate measures, and other criteria used in the QOPI. All data were obtained from our CSCPs’ mined data, institutional electronic medical records, and scheduling systems. Results: From December 1, 2011, to May 31, 2012, we conducted an electronic medical records audit to determine the compliance rate for issuing survivorship care plans in 7 clinics. The survivorship clinics included breast, colorectal, endocrine (thyroid), genitourinary, gynecology, head/neck, and melanoma. A total of 3,274 electronic medical records were reviewed. 40 providers issued a total of 2,761 electronic CSCPs within 30 days of the arrived appointment. The compliance rate per clinic ranged from 64.5% to 94.7% (X=84.5%). Conclusions: We found the QOPI process to be user-friendly and applicable to our compliance monitoring effort. All data were extracted from electronic tools, thus ensuring the processes used were reliable, reproducible, and reasonably consistent across clinics. Further examination is warranted to determine characteristics of clinics with high- vs. low-compliance rates and their impact on survivors’ outcomes as related to specific CSCP recommendations.
Implementation and evaluation of a tobacco cessation program in an outpatient oncology center.
Authors: Hensing Thomas A. , Brockstein Bruce , Carro George W. , Gavin Shannon Maureen
Published: February 2017

117

Background: Tobacco use is the leading preventable cause of premature death in the United States and has a causal link to various cancer types. Continued tobacco use after a cancer diagnosis may decrease survival, reduce treatment efficacy, prolong/increase treatment toxicity, and increase the risk for recurrence. The combination of support from trained professionals and appropriate medications increases the chances of quitting successfully. In the literature, the advice of a physician improves quit rates to about 10% and the combination of tobacco cessation medication and behavioral support can increase the rate to 20-35%. There is a lack of data on the impact of a tobacco cessation program integrated into a cancer center. The objective of this project is to implement and prospectively evaluate a tobacco cessation program in a hospital-based outpatient cancer center across three treatment sites. Methods: A multidisciplinary group at the cancer center was established to oversee the development and implementation of the program including: pharmacist training to become a certified Tobacco Treatment Specialist, electronic medical record documentation tool establishment, and development of patient education tools. The pharmacist provided one-on-one counseling for each referred patient. Assessment of the 3, 6, and 12 month quit rates was performed. Results: The tobacco cessation program at the cancer center has been available for approximately one year to all patients and their family members. Of the 67 patients referred to the tobacco cessation program, 27 (40%) patients followed through with the referral and met with the tobacco treatment specialist. The 3, 6, and 12 month quit rates are 68%, 50%, and 50%, respectively. Conclusions: The tobacco cessation program at the cancer center is evolving into a successful program. The quit rates of the program have exceeded those reported in the literature. The accessibility of the tobacco cessation program has enhanced the comprehensive care provided to the patients at the cancer center.
Breast imaging boot camp: A mammography quality improvement initiative.
Authors: Dupuy Danielle , Miller Louise , Weldon Christine B. , Orsi Jennifer M. , Macarol Terry , Murphy Anne Marie , Trosman Julia R.
Published: February 2017

138

Background: In mammography, compression, and positioning are key quality factors. ACR standards suggest that compression should ensure that a breast is taut (drawn tight with no slack). In environmental scans, semi-structured interviews with cross discipline providers from Chicago mammography facilities, we found wide variation in radiology technologist’s understanding of standard compression and views. Optimal compression was reported from 12-45 lbs and some sites reported that four views are taken regardless of breast size. This discovery led to a mammography technologist training program as a quality improvement intervention. Methods: The Chicago Breast Cancer Quality Consortium contracted with Louise Miller, AART, CRT, and RTRM to lead a Breast Imaging Boot Camp and partnered with 4 hospitals to carry out the training. There were three components of the boot camp: a 1-day seminar for all mammography technologists, 1 day of hands on training for a limited number of techs and a train the trainer component where selected techs went through a 3-day intensive program with the goal of preparing them to provide ongoing education to the Chicago mam-tech community. A preliminary tool was developed and used randomly by radiologists during the training to examine the amount of tissue in the image from one year to the next, the presence or absence of an Inter-mammary fold and cleavage. Results: More than 120 radiology technologists attended a day-long seminar, 10 received hands on training, 4 of the 10 were trained to be future trainers. Participants rated their overall impression of the day-long seminar between 4 and 5 on a 5-point scale. During the hands-on training, radiologists assessing the images commented on significant improvements in image quality from the previous year’s mammogram. A quantitative evaluation process has been developed to examine the efficacy of the training and measure impact on mammography quality. This evaluation involves a 3 month and 1-year assessment that will take place in September of 2012 and again in May of 2013. Results of first evaluation will be available for presentation. Conclusions: Results from the evaluation will help review effectiveness of technologists post-training techniques and identify areas to improve.
Increasing hand hygiene compliance using a solution session.
Authors: Rohe Duke , Perego Cheryl , Williams Polly , Zabka Cindy , Foster Julie , McLemore Lisa , Yao David
Published: February 2017

147

Background: Few would argue that proper hand hygiene (HH) is vital for preventing nosocomial infection, yet compliance rates remain low and capturing its data is difficult. Methods: A homegrown "design" methodology called Solution Session which combines creative problem solving, GE WorkOut and an accountability maturity model was used to define problems, formulate ideas to increase HH compliance. From the session five subteams (addressing Compliance, Patient Education, Staff Education, Process and Automation) were enlisted to develop a holistic set of solutions to address HH compliance. Infection Control paid special attention to developing custom observation plans for each unit. One of the solutions, a homegrown web-based observation collection system, was created to collect and report compliance by individual and department level. The system of solutions were piloted on a unit that was already doing well (with a baseline compliance of 92%) and two struggling high acuity units (with baseline compliance at 54% and 50%). Results: The pilot unit that was doing well to begin with has averaged HH compliance rate 99% for over a 15 month period (n=105/month). The two struggling units have averaged 84% and 80% respectively (n= 60/month and n=24/month) over the same period. The operating room is the next candidate in line to employ this system. Conclusions: 1) Solutions are best designed by those affected. 2) People respond to data.Weekly reportsdisplay number of observations taken, compliance down to the department and individual level: powerful tools to start the self correction process. 3) Compliance is a marathon, not a sprint.
Cost of cancer care: The impact of disclosure on willingness to pay and treatment preferences.
Authors: Howe Rebecca , Hassett Michael J. , Wheelock Alyse , Thorsen Cristina M. , Kaplan Celia , Ozanne Elissa
Published: February 2017

15

Background: Little is known about patients’ views regarding the costs of cancer care and its effect on treatment selection. Even less is known about how patients view information about conflicts of interest, such as disclosure of a clinic’s profit from cancer therapy. In the setting of health care reform and rising costs, we sought to understand how out-of-pocket costs and disclosure of profit impact patient treatment preferences. Methods: Previous breast cancer patients were invited to complete a web-based survey that presented four scenarios outlining cancer care treatment benefits and risks (MRI, pegfilgrastim, cold cap, and chemotherapy drugs). Initially, respondents were asked their preference for each treatment over a standard of care alternative and their out-of-pocket willingness to pay. After providing information about first, the total cost per treatment and second, the profit to the clinic, respondents were asked if their preference changed. Results: 40 women responded, all whom had previous diagnoses of breast cancer. In each of the four scenarios, respondents were less interested in the treatment option after being informed about cost or disclosure of a clinic profit. While 45.5% of respondents said they consider costs all or most of the time, only 9.1% considered clinic profit. However, 66.7% of respondents said they would be less interested in a treatment if they knew their provider received a profit from the treatment. Conclusions: Patients are less likely to prefer treatments after disclosure of total cost and clinic profit data. Communication about the costs and profits associated with cancer care may be an essential component of informed decision making in an era of growing patient involvement and escalating health care costs. [Table: see text]
Value metrics of a nurse navigator patient support program within a multidisciplinary esophageal cancer clinic.
Authors: Ross Helen J. , Freese Joy , Ciafone Denise , Ashman Jonathan Ben , Rule William G. , Jaroszewski Dawn E. , Harold Kristi L. , Paripati Harshita , Crowell Michael , Pannala Rahul , Faigel Douglas , Ramirez Francisco , Bright Robert , Fleischer David
Published: February 2017

158

Background: Esophageal cancer patients (pts) require multidisciplinary management involving thoracic and general surgeons, medical and radiation oncologists, gastroenterologists and psychiatrists. Pts navigate complex medical discussions and endure challenges to nutrition, body image, swallowing mechanics, energy level and weight, mood, and performance status. Coordination of care is complicated by multiple sites of pt entry, complex scheduling requirements, and incomplete information at multidisciplinary consultation. A nurse navigator to coordinate the patient experience may optimize treatment and improve outcomes, quality of life and patient satisfaction. Methods: The nurse navigator evaluates all pt records prior to initial appointment and coordinates scheduling, records acquisition, testing and specialty appointments. The nurse navigator serves as a liaison with pts throughout the course of care and provides a patient navigation book (PNB) as a central source for patient-directed information and record keeping. Benchmarks compared before and after creation of the nurse navigator position include: (1) time from appointment request to multidisciplinary evaluation and start of treatment; (2) completeness of medical records and data (scans, pathology slides); (3) patient awareness of support services for themselves and caregivers; (4) utilization of the PNB; (5) number and frequency of interim hospitalizations and emergency room visits; (6) patient, caregiver, and physician satisfaction. Results: From January to July 2012, 27 gastroesophageal cancer pts have been followed by the nurse navigator. Most of these patients remain on active treatment, hence benchmark analysis is ongoing. Metrics thus far suggest improvement in time to treatment start and awareness of patient resources, use of the PNB and patient satisfaction. Conclusions: Esophageal cancer pts undergo complex and toxic multimodality therapy with curative intent. A dedicated nurse navigator may improve the patient experience, optimize adherence to guideline based therapy and appropriate timeframes and provide continuity to pts undergoing multidisciplinary treatment.