tbuckley/cabot-search huggingface dataset:
MicroRNA in biofluids—Robust biomarkers for disease, toxicology, or injury studies: The case of minimally invasive colorectal cancer detection.
Authors: Peter Mouritzen, Søren Jensby Nielsen, Maria Wrang Teilum, Thorarinn Blondal, Ditte Andreasen, Niels Tolstrup
Journal: Journal of Clinical Oncology (2012)

20 Background: MicroRNAs function as post-transcriptional regulators of gene expression. Their high relative stability in common clinical source materials (FFPE blocks, plasma, serum, urine, saliva, etc.) and the ability of microRNA expression profiles to accurately classify discrete tissue types and specific disease states have positioned microRNAs as promising new biomarkers for diagnostic application. Furthermore microRNAs have been shown to be rapidly released from tissues into the circulation with the development of pathology. Methods: Thousands of biofluid samples were profiled including blood derived plasma/serum and urine using a genome-wide LNA-based microRNA qPCR platform, which has unparalleled sensitivity and robustness even in biofluids with extremely low microRNA levels. Only a single RT reaction is required to conduct full miRNome profiling thereby facilitating high-throughput profiling without the need for pre-amplification. Results: Normal reference ranges for circulating microRNAs were determined in several biofluids, allowing development of qPCR arrays containing only relevant microRNA subsets present in various biofluids together with tissue specific microRNA markers. Procedures were developed to control pre-analytical variables, for quality checking and qualifying biofluid samples in particular serum and plasma but also urine and other biofluids. An extensive QC system was implemented in order to secure technical excellence and reveal any unwanted bias in the dataset. We currently screen and validate microRNAs biomarkers for cancer with the aim of developing minimal invasive tests to be applied in early detection population screens. Conclusions: The qPCR panels support development of robust biomarkers in disease, toxicology, and injury studies. We will demonstrate how panels may be quickly and robustly applied in biomarker discovery/validation projects using the specific case early detection of colorectal cancer in blood. Close attention is required on pre-analytical parameters. Hemolysis and cellular contamination affect miRNA profiles in biofluids and control is required.
Effect of insurance status on receiving standard quality care treatment in patients with stage III colon cancer.
Authors: Samip R. Master, Lihong Liu, Hemangini Dhaibar, Glenn Morris Mills, Runhua Shi
Journal: Journal of Clinical Oncology (2016)

45 Background: NCCN (National comprehensive Cancer network) recommends adjuvant chemotherapy for stage 3 colon cancer patients. National Cancer Data Base (NCDB) data were analyzed to investigate the impact of insurance status on receiving standard quality of care with adjuvant chemotherapy for stage 3 colon cancer patients. Methods: Data was analyzed from 11,563 men and women, between ages 18-80 years, registered in the NCDB who were diagnosed with stage 3 colon cancer between 1998 and 2011 and had follow-ups to end of 2012. The primary predictor variable was payer status and the outcome variable was treatment received. Additional variables addressed and adjusted for included sex, age, race, Charlson Comorbidity index, education, income, distance traveled facility type and diagnosing/treating facility. Results: Among these 11,563 patients, the mean age at diagnosis was 60.3 years (median, 61 years). The mean ages at diagnosis were 53.3, 54.9, 53.9, 69.6, and 58.2 years for uninsured, private, Medicaid, Medicare and unknown payer status, respectively. In multiple logistic regression analysis, after adjusting for secondary predictor variables, payer status was a statistically significant predictor of not receiving adjuvant chemotherapy. Relative to privately insured patients, patients with Medicaid were 2.20 times, Uninsured were 2.16 times, Medicare was 1.76 times, and unknown insurance were 2.25 times more likely not to receive adjuvant chemotherapy, respectively. Compared to age group 18-49 years, patient with age group 50-64 years, 65-74 years and 75+ years were 1.59, 2.54 and 5.59 times more likely to not to received adjuvant chemotherapy, respectively. Of the factors analyzed, age, comorbidity index, insurance and distance travelled to treatment center were statistically significant predictors of a patient not receiving adjuvant chemotherapy. Conclusions: We observed that payer status has a statistically significant relationship with stage 3 colon cancer patients not receiving adjuvant chemotherapy. This remained true after adjusting for other predictive factors. Further research is necessary to investigate how the treatment disparities are associated with different types of insurance.
Long‐Term Tissue Culture of Adult Brain and Spleen Slices on Nanostructured Scaffolds
Authors: Sonja Kallendrusch, Felicitas Merz, Ingo Bechmann, Stefan G. Mayr, Mareike Zink
Journal: Advanced Healthcare Materials (2017)

Long-term tissue culture of adult mammalian organs is a highly promising approach to bridge the gap between single cell cultures and animal experiments, and bears the potential to reduce in vivo studies. Novel biomimetic materials open up new possibilities to maintain the complex tissue structure in vitro; however, survival times of adult tissues ex vivo are still limited to a few days with established state-of-the-art techniques. Here, it is demonstrated that TiO2 nanotube scaffolds with specific tissue-tailored characteristics can serve as superior substrates for long-term adult brain and spleen tissue culture. High viability of the explants for at least two weeks is achieved and compared to tissues cultured on standard polytetrafluoroethylene (PTFE) membranes. Histological and immunohistochemical staining and live imaging are used to investigate tissue condition after 5 and 14 d in vitro, while environmental scanning electron microscopy qualifies the interaction with the underlying scaffold. In contrast to tissues cultured on PTFE membranes, enhanced tissue morphology is detected in spleen slices, as well as minor cell death in neuronal tissue, both cultured on nanotube scaffolds. This novel biomimetic tissue model will prove to be useful to address fundamental biological and medical questions from tissue regeneration up to tumor progression and therapeutic approaches.
Increasing hand hygiene compliance using a solution session.
Authors: Duke Rohe, Cheryl Perego, Polly Williams, Cindy Zabka, Julie Foster, Lisa McLemore, David Yao
Journal: Journal of Clinical Oncology (2012)

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.
Tau PET imaging: present and future directions
Authors: Laure Saint-Aubert, Laetitia Lemoine, Konstantinos Chiotis, Antoine Leuzy, Elena Rodriguez-Vieitez, Agneta Nordberg
Journal: Molecular Neurodegeneration (2017)

Abnormal aggregation of tau in the brain is a major contributing factor in various neurodegenerative diseases. The role of tau phosphorylation in the pathophysiology of tauopathies remains unclear. Consequently, it is important to be able to accurately and specifically target tau deposits in vivo in the brains of patients. The advances of molecular imaging in the recent years have now led to the recent development of promising tau-specific tracers for positron emission tomography (PET), such as THK5317, THK5351, AV-1451, and PBB3. These tracers are now available for clinical assessment in patients with various tauopathies, including Alzheimer's disease, as well as in healthy subjects. Exploring the patterns of tau deposition in vivo for different pathologies will allow discrimination between neurodegenerative diseases, including different tauopathies, and monitoring of disease progression. The variety and complexity of the different types of tau deposits in the different diseases, however, has resulted in quite a challenge for the development of tau PET tracers. Extensive work remains in order to fully characterize the binding properties of the tau PET tracers, and to assess their usefulness as an early biomarker of the underlying pathology. In this review, we summarize recent findings on the most promising tau PET tracers to date, discuss what has been learnt from these findings, and offer some suggestions for the next steps that need to be achieved in a near future.
Relationship of drain amylase and anastomotic leak after esophagectomy.
Authors: Joshua S. Hill, Erin Marie Hanna, Susie C. Hurley, Mark Reames, Jonathan C. Salo
Journal: Journal of Clinical Oncology (2013)

118 Background: Esophagectomy is considered the only curative approach in patients with esophageal cancers without locally advanced or metastasis. Anastomotic leak can lead to significant morbidity and mortality. CT esophagram (CTE) is a sensitive method of evaluating for leak; however this test carries with it financial cost and radiation exposure. This study evaluates the utility of drain amylase in the prediction of anastomotic leak. Methods: Fifty-nine patients underwent esophagectomy between 3/10 and 8/12; serial drain amylases and CTE were obtained in 50. Leak was defined by extravasation of contrast or the presence of empyema on CTE. Elevated drain amylase was defined as any level &gt; 400 IU/L. Chi-square and descriptive statistics were performed and the sensitivity of drain amylase &gt;400 IU/L in predicting leak was calculated. Results: A minimally invasive esophagectomy was performed in 47, and an open Ivor-Lewis in 2 and a minimally invasive Ivor-Lewis in 1. Stapled intra-thoracic anastomoses were performed in 47, 3 had a cervical anastomoses. Average age was 61 years and 84% were males. Leak occurred in 6 patients (12.5%). One patient with a late leak was excluded from analysis as they did not have concurrent drain amylase values. This patient had low amylase levels and a normal CTE, though later presented with leak. The overall peri-operative mortality rate was 4.2% (2/48). Mortality in the non-leak and leak cohorts were 0% &amp; 33%. Drain amylase was an accurate marker of anastomotic leak. Of 6 patients with an elevated drain amylase, 5 had an anastomotic leak (sensitivity 83.3%). 40/41 patients with low drain amylase had no leak. Using a cut-off value of 400 IU/L, the negative predictive value of drain amylase in predicting leak after esophagectomy was 97.6% (95%CI; 85.6, 99.9). Conclusions: Drain amylase is a simple and inexpensive test that has excellent sensitivity and negative prediction for the detection of anastomotic leak after esophagectomy. To our knowledge, this is the first study to demonstrate this finding. Routine evaluation of drain amylase may safely replace CTE in the management of patients after esophagectomy, thus reducing radiation exposure and overall cost.
Identifying targets for outpatient palliative care wait times in Ontario.
Authors: Victoria Zwicker, Sandy Buchman, Denise Marshall, Sara Urowitz
Journal: Journal of Clinical Oncology (2014)

258 Background: A wait time indicator is being developed for outpatient palliative care services for cancer patients in Ontario. Once developed, this indicator will become the first palliative performance measure for Regional Cancer Centres (RCCs) across the province. The wait time indicator will serve as one measure of accessibility, a key dimension of health care quality. However, in order to create this indicator, it is first necessary to identify targets against which current performance can be compared. Methods: A systematic review of the academic literature was conducted to a) identify existing palliative care wait time standards, and b) to gather evidence on how delays in care impact patient outcomes. An environmental scan was also conducted to identify wait time standards and benchmarks used in other Canadian provinces or territories. In addition, existing palliative care triaging tools and wait time standards from Ontario RCCs were collected. A consensus panel comprised of palliative clinicians, patient and family advisors, and administrators was convened to articulate a maximum acceptable wait time and a provincial target for the percentage of patients who should be seen within the maximum acceptable wait time. Results: The environmental scan and literature review found no existing standards or benchmarks for outpatient palliative care services. However, there are a number of triaging tools and wait time standards in use at Ontario RCCs for these services. Taking these tools and standards into consideration, the consensus panel identified a wait time benchmark and a provincial target for Ontario RCCs. Conclusions: This foundational work will help to highlight gaps and variation in timely access to palliative care services in Ontario. The benchmarks and targets identified through this process as well as the methods used can be useful for other jurisdictions seeking to measure and improve wait times for these services. Next steps include ensuring that data is of sufficient quality, identifying incremental improvement targets for the province based on current performance, and further refining the implementation of a palliative care wait time indicator for quality improvement.
Analysis of real-world treatment adherence in a cohort of 2,395 patients with metastatic renal cell carcinoma (mRCC).
Authors: Jay Margolis, Nicole Princic, Justin Doan, Gregory Lenhart, Robert J. Motzer
Journal: Journal of Clinical Oncology (2016)

517 Background: Given recent European data highlighting the importance of real-world dose intensity(Cancer Med 2014; 3(6): 1517-26.), we sought to investigate real-world adherence in patients with mRCC from a US perspective. Methods: In this retrospective cohort study, patients with newly diagnosed mRCC were selected from the MarketScan Commercial and Medicare Supplemental administrative claims databases based on an index event from 1/1/2006 to 3/31/2014. First line (1L) therapy was defined as first prescription record post-index for any approved mRCC therapy; change in line of therapy was defined as a therapy switch. Adherence was measured using the medication possession ratio (MPR) during each and all lines. MPR was defined as total days of supply during the treatment period divided by total treatment period until the start of last treatment. Nonadherence was defined as an MPR &lt;80%. Results: A total of 2,395 mRCC patients were identified as initiating 1L therapy. Across all treatments the mean MPR was 0.77 ± 0.20, which increased over time from 0.73 in 2006 to 0.81 in 2013. More than 50% of patients were nonadherent. During 1L, patients treated with sunitinib had significantly lower mean MPR compared with most other treatments (table). Adherence was higher during 2L (0.85 ± 0.18) vs 1L (0.80 ± 0.19). A larger proportion of patients who initiated therapy with temsirolimus were adherent compared with those who initiated with sunitinib (62% vs 38%). Additional analyses are being conducted to address adherence with alternative dosing schedules. Conclusions: Over half of treated mRCC patients were found to be nonadherent to therapy. Adherence was significantly better with IV administered temsirolimus relative to the reference oral therapy, sunitinib. Real-world analysis of treatment adherence provides information for clinicians in monitoring and optimizing targeted therapy. [Table: see text]
Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-refractory patients with EGFR-positive advanced and/or metastatic colorectal cancer: Evaluation of the efficacy and safety based on <i>KRAS</i> mutation status (T- CORE0801).
Authors: H. Shimodaira, H. Soeda, M. Gamoh, H. Andoh, T. Yamaguchi, M. Watanabe, H. Isobe, T. Sudo, S. Kato, C. Ishioka
Journal: Journal of Clinical Oncology (2011)

573 Background: Activating mutation of the KRAS gene is a predictive biomarker for loss of efficacy to anti-EGFR antibody therapy. However, this was mainly established by the evidences of Caucasian studies. Then, this prospective study investigated the role of KRAS mutations on efficacy and safety to cetuximab plus irinotecan in Japanese patients with metastatic colorectal cancer (mCRC). Methods: We conducted a prospective study to analyze objective response to cetuximab plus irinotecan in molecularly defined KRAS wild-type (WT) or mutant subgroups of chemotherapy-refractory mCRC. KRAS mutations were detected by direct sequence on DNA from formalin-fixed, paraffin-embedded tissue of patients treated in 11 centers in Japan. Additional EGFR related genes such as BRAF, PIK3CA etc. and antibody-dependent cellular cytotoxicity related polymorphism in FCγRIIa and RIIIa genes were also examined. Results: Forty-three patients were enrolled. KRAS mutations were found in 31.7% of 41 eligible patients. Response rate (RR) to cetuximab plus irinotecan, the primary endpoint of the study, was 17.9% and 0% for the patients with tumor harboring WT and mutant KRAS, respectively. No significant differences in toxicity were observed between the KRAS WT and mutant groups. Detail statistical analyses are ongoing. Conclusions: We confirmed that KRAS status is a useful predictive maker for the efficacy to cetuximab plus irinotecan therapy in Japanese mCRC patients, even though the response rate in the KRAS WT group was lower than expected. [Table: see text]
Is there a "trial effect" on outcome of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib?
Authors: Daniel Keizman, Maya Ish-Shalom, Natalie Maimon, Maya Gottfried, Roberto Pili, Hans J. Hammers, Mario A. Eisenberger, Victoria J. Sinibaldi, Ben Boursi, Rony Weitzen, Henry Hayat, Avivit Peer, Avivit Neumann, Svetlana Kovel, Avishay Sella, Wilmosh Mermershtain, Keren Roubinov, Michael Anthony Carducci, Raanan Berger
Journal: Journal of Clinical Oncology (2013)

453 Background: Several studies have suggested the existence of a trial effect, in which for a given treatment, participation in a clinical trial is associated with a better outcome of cancer patients. The VEGFR inhibitor sunitinib is a standard treatment for mRCC. The effect of clinical trial participation on the outcome of sunitinib treatment in mRCC is poorly defined. We aimed to study the effect of clinical trial participation on outcome of mRCC patients treated with sunitinib. Methods: Records from 275 mRCC patients treated with sunitinib from 2004 to 2012 in 7 centers across 2 countries were reviewed. We compared the response rate, progression free survival, and overall survival, between clinical trial participants (n=49) and a matched cohort of non participants (n=49) who received standard therapy. Each patient participating in a clinical trial was individually matched with a non-participant by clinicopathologic factors. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by age (median 64), gender (male 67%), Heng risk (favorable 24%, intermediate 60%, poor 16%), ECOG performance status (0-1 92%), prior nephrectomy (92%), renal cell carcinoma histology (clear cell 80%), sunitinib induced hypertension (56%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants vs. non participants, objective response was partial response/stable disease 80% (n=39) vs. 73% (n=36), and progressive disease at first imaging evaluation within the first 3 months (mos) 20% (n=10) vs. 27% (n=13) (p = 0.63, OR 1.2). Median progression free survival was 10 vs. 11 mos (HR=0.96, p = 0.84), and median overall survival 23 vs. 24 mos (HR=0.97, p=0.89). Conclusions: In mRCC patient treated with sunitinib, the outcome of clinical trial participants was similar to matched non participants who received standard therapy.
Objective responses to chemotherapy in recurrent glioma: A prospective analysis from the German Glioma Network.
Authors: O. Baehr, B. Hentschel, E. Hattingen, S. Nussbaum, H. Berger, M. Tatagiba, J. C. Tonn, O. Schnell, M. Simon, T. Reithmeier, D. Krex, T. Pietsch, G. Reifenberger, O. Heese, M. Weller, J. Steinbach, M. Loeffler
Journal: Journal of Clinical Oncology (2011)

2037 Background: Outside of controlled trials, the occurrence of objective responses (OR) to chemotherapy in glioma patients is poorly characterized. Further, the predictive value of OR for progression-free survival (PFS) and overall survival (OS) in glioma patients is unclear. Methods: In this study we screened the German Glioma Network Database for patients that had received any chemotherapy for recurrent glioma from 2004-2008. Patients with a gross total resection of the recurrent tumor, patients receiving radiotherapy for the recurrent tumor and patients with spinal gliomas were excluded. 655 chemotherapies in 487 patients were identified. The prospectively documented responses to these chemotherapies were reevaluated in the 8 participating centers and 69 ORs (corresponding to OR in 10.5% of all chemotherapies) were identified (partial responses, PR or complete responses, CR, according to the original Macdonald criteria). For 52 of these (75.4% of all cases with OR) imaging data were evaluable for central neuroradiological review. 33 ORs (in 5.0% of all therapies) were confirmed. Results: Centrally confirmed ORs were most common in low-grade gliomas (10 ORs in 111 therapies; 9.0% RR) and in anaplastic gliomas (16 ORs in 201 therapies; 8.0% RR). In glioblastoma, 7 ORs in 333 therapies were detected for a 2.1% RR. The chemotherapy regimens most likely resulting in an OR were temozolomide 5d/28d (5 ORs in 50 therapies, 10.0% RR) and dose-dense temozolomide protocols (6 ORs in 75 therapies, 8.0% RR). In therapies using temozolomide without detailed specification of the protocol RR was 4.2% (7 out of 166). Response rates were 5.3% for nitrosureas (14 out of 263), 1.7% for imatinib/hydroxyurea (1 out of 60) and 0.0% for others (0 out of 41). Conclusions: To date, this prospective study from the German Glioma Network cohort is the largest series investigating chemotherapy-induced ORs in glioma patients. Ongoing analyses include evaluation of the predictive value of OR for PFS and OS, the importance of biomarkers and patient variables by comparison of patients achieving OR with those who had stable disease or progressive disease.