scholarly journals Clingen Cancer Somatic Working Group – standardizing and democratizing access to cancer molecular diagnostic data to drive translational research

2017 ◽  
Author(s):  
Subha Madhavan ◽  
Deborah Ritter ◽  
Christine Micheel ◽  
Shruti Rao ◽  
Angshumoy Roy ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Cancer Biology ◽  
Large Scale ◽  
Treatment Decisions ◽  
Molecular Diagnostic ◽  
Patient Specific ◽  
Sequence Variants ◽  
Complementary Sequence ◽  
Treatment Information ◽  
Research Organizations

AbstractA growing number of academic and community clinics are conducting genomic testing to inform treatment decisions for cancer patients (1). In the last 3–5 years, there has been a rapid increase in clinical use of next generation sequencing (NGS) based cancer molecular diagnostic (MolDx) testing (2). The increasing availability and decreasing cost of tumor genomic profiling means that physicians can now make treatment decisions armed with patient-specific genetic information. Accumulating research in the cancer biology field indicates that there is significant potential to improve cancer patient outcomes by effectively leveraging this rich source of genomic data in treatment planning (3). To achieve truly personalized medicine in oncology, it is critical to catalog cancer sequence variants from MolDx testing for their clinical relevance along with treatment information and patient outcomes, and to do so in a way that supports large-scale data aggregation and new hypothesis generation. One critical challenge to encoding variant data is adopting a standard of annotation of those variants that are clinically actionable. Through the NIH-funded Clinical Genome Resource (ClinGen) (4), in collaboration with NLM’s ClinVar database and >50 academic and industry based cancer research organizations, we developed the Minimal Variant Level Data (MVLD) framework to standardize reporting and interpretation of drug associated alterations (5). We are currently involved in collaborative efforts to align the MVLD framework with parallel, complementary sequence variants interpretation clinical guidelines from the Association of Molecular Pathologists (AMP) for clinical labs (6). In order to truly democratize access to MolDx data for care and research needs, these standards must be harmonized to support sharing of clinical cancer variants. Here we describe the processes and methods developed within the ClinGen’s Somatic WG in collaboration with over 60 cancer care and research organizations as well as CLIA-certified, CAP-accredited clinical testing labs to develop standards for cancer variant interpretation and sharing.

scholarly journals Effect of a Multidisciplinary-Assisted Resident Diabetes Clinic on Resident Knowledge and Patient Outcomes

2013 ◽  
Vol 5 (1) ◽  
pp. 145-149 ◽  
Author(s):  
Margaret C. Lo ◽  
Morganna Freeman ◽  
M. Cecilia Lansang
Keyword(s):  
Patient Outcomes ◽  
Large Scale ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Patient Specific ◽  
Team Approach ◽  
Diabetes Knowledge ◽  
Diabetes Clinic ◽  
Practice Behavior ◽  
Patients With Diabetes

Abstract Background Despite the rising prevalence of diabetes, there is a paucity of diabetes curricula in residency training. The multidisciplinary diabetes team approach is underused in residency education. Objective To assess the feasibility of an innovative multidisciplinary resident diabetes clinic (MRDC) in enhancing (1) resident diabetes knowledge via a Diabetes Awareness Questionnaire, and (2) subsequent process and patient outcomes in patients with diabetes via a Diabetes Practice Behavior Checklist. Methods From October 2008 to February 2010, 14 internal medicine residents managed patients with uncontrolled diabetes in a weekly half-day MRDC for 1 month (total 4–5 half-day sessions/resident), with a collaborative team of internists, diabetes educators, an endocrinologist, and a pharmacist. The curriculum included didactic sessions, required readings, and patient-specific case discussions. A 20-question Diabetes Awareness Questionnaire was administered to each resident prerotation and postrotation. Records of 47 patients with diabetes in the residents' own continuity clinics (not the MRDC) were audited 6 months before and after the MRDC for Diabetes Practice Behavior Checklist measures (glycated hemoglobin, blood pressure, low-density lipoprotein cholesterol, retinal referral, foot exam, microalbumin screen). Pre-MRDC and post-MRDC data were compared via paired t test. Results The MRDC residents exhibited a modest increase in mean (SD) scores on the Diabetes Awareness Questionnaire (before, 8.2 [2.8]; after, 10.9 [2.8]; P  =  .02) and a modest mean (SD) performance increase in overall process outcomes from the Diabetes Practice Behavior Checklist (before, 74% [18%]; after, 84% [18%]; P  =  .004). No improvements occurred in patient outcomes. Conclusions Multidisciplinary diabetes teaching may be useful in fostering certain resident knowledge and performance measures but may not alter clinical outcomes. Further large-scale, longitudinal studies are needed to understand the effect of our curriculum on residents' diabetes knowledge and future practice behavior.

Comparison of treatment plans feasible through AI enabled multidisciplinary online tumor board solution versus NCCN-based clinical decision support system (CDSS).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 816-816
Author(s):  
Bhawna Sirohi ◽  
Sushil Beriwal ◽  
C. S. Pramesh ◽  
Supriya Chopra ◽  
Mahesh Goel ◽  
...  
Keyword(s):  
Large Scale ◽  
Treatment Plan ◽  
Specific Treatment ◽  
Treatment Decisions ◽  
Added Value ◽  
Tumor Board ◽  
Patient Specific ◽  
Clinical Scenarios ◽  
Tumor Boards ◽  
Treatment Plans

816 Background: Multidisciplinary tumor boards at Academic Medical Centers (AMC) maximize cancer outcomes. Guidelines based CDSS are alternatives to determine care pathways. Since 2015, 300 AMC cancer experts in USA and India use an AI enabled online tumor board solution, “NAVYA,” to scale low cost access to multidisciplinary expertise, on 1-2 minutes of expert time per decision (ASCO 2017). Methods: GI patients who used NAVYA between 5/1/15-8/31/19 were analyzed. Actionable treatment plans generated by NAVYA were compared to NCCN. Actionable treatment plans include chemotherapy protocols (doses, frequencies), radiation protocols (sites, fractions), etc. Inactionable specialty level decisions (CT-RT vs. surgery) lack specificity. Results: 1302 patients (4638 treatment decisions) were analyzed: 61% (794) male, 80% between age 45 to 75, mostly with Colon, Pancreas, Gallbladder, Rectum, or Stomach cancer; 49.7% non-metastatic. Cohort was comparable to GLOBOCAN estimates. In 82.2% (3812/4638) decisions, NAVYA added value beyond NCCN. First, in 4.5% (212/4638), NAVYA recommended a patient-specific treatment plan that was not part of NCCN. Second, in 3.2% (148/4638), NAVYA recommended treatments plan for clinical scenarios not covered by NCCN, (for eg. 3rd line therapies). Third, in 74.5% (3452/4638), NAVYA used patient specific criteria including resource constraints and patient preference to choose a treatment plan amongst the multiple pathways provided by NCCN and added actionable treatment details. Conclusions: Guideline based CDSS are insufficient to make the vast majority of actionable treatment decisions. Scaling rapid access to multidisciplinary experts is critical. Leapfrogging existing guidelines based CDSS, NAVYA online tumor board makes actionable expert treatment plans possible at a large scale.

scholarly journals Quality Control in 3D Printing: Accuracy Analysis of 3D-Printed Models of Patient-Specific Anatomy

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 1021
Author(s):  
Bernhard Dorweiler ◽  
Pia Elisabeth Baqué ◽  
Rayan Chaban ◽  
Ahmed Ghazy ◽  
Oroa Salem
Keyword(s):  
Wall Thickness ◽  
Large Scale ◽  
Fused Deposition Modeling ◽  
Vascular Anatomy ◽  
3D Models ◽  
Patient Specific ◽  
Stl File ◽  
Fused Deposition ◽  
3D Printed ◽  
The Mean

As comparative data on the precision of 3D-printed anatomical models are sparse, the aim of this study was to evaluate the accuracy of 3D-printed models of vascular anatomy generated by two commonly used printing technologies. Thirty-five 3D models of large (aortic, wall thickness of 2 mm, n = 30) and small (coronary, wall thickness of 1.25 mm, n = 5) vessels printed with fused deposition modeling (FDM) (rigid, n = 20) and PolyJet (flexible, n = 15) technology were subjected to high-resolution CT scans. From the resulting DICOM (Digital Imaging and Communications in Medicine) dataset, an STL file was generated and wall thickness as well as surface congruency were compared with the original STL file using dedicated 3D engineering software. The mean wall thickness for the large-scale aortic models was 2.11 µm (+5%), and 1.26 µm (+0.8%) for the coronary models, resulting in an overall mean wall thickness of +5% for all 35 3D models when compared to the original STL file. The mean surface deviation was found to be +120 µm for all models, with +100 µm for the aortic and +180 µm for the coronary 3D models, respectively. Both printing technologies were found to conform with the currently set standards of accuracy (<1 mm), demonstrating that accurate 3D models of large and small vessel anatomy can be generated by both FDM and PolyJet printing technology using rigid and flexible polymers.

Cyclic Breathing Simulations in Large Scale Models of the Lung Airway From the Oronasal Opening to the Terminal Bronchioles

2012 ◽  
Author(s):  
D. Keith Walters ◽  
Greg W. Burgreen ◽  
Robert L. Hester ◽  
David S. Thompson ◽  
David M. Lavallee ◽  
...  
Keyword(s):  
Steady State ◽  
Boundary Conditions ◽  
Large Scale ◽  
Whole Body ◽  
Patient Specific ◽  
Cfd Simulations ◽  
Reduced Order ◽  
Scale Models ◽  
Steady State Simulation ◽  
Conducting Zone

Computational fluid dynamics (CFD) simulations were performed for unsteady periodic breathing conditions, using large-scale models of the human lung airway. The computational domain included fully coupled representations of the orotracheal region and large conducting zone up to generation four (G4) obtained from patient-specific CT data, and the small conducting zone (to G16) obtained from a stochastically generated airway tree with statistically realistic geometrical characteristics. A reduced-order geometry was used, in which several airway branches in each generation were truncated, and only select flow paths were retained to G16. The inlet and outlet flow boundaries corresponded to the oronasal opening (superior), the inlet/outlet planes in terminal bronchioles (distal), and the unresolved airway boundaries arising from the truncation procedure (intermediate). The cyclic flow was specified according to the predicted ventilation patterns for a healthy adult male at three different activity levels, supplied by the whole-body modeling software HumMod. The CFD simulations were performed using Ansys FLUENT. The mass flow distribution at the distal boundaries was prescribed using a previously documented methodology, in which the percentage of the total flow for each boundary was first determined from a steady-state simulation with an applied flow rate equal to the average during the inhalation phase of the breathing cycle. The distal pressure boundary conditions for the steady-state simulation were set using a stochastic coupling procedure to ensure physiologically realistic flow conditions. The results show that: 1) physiologically realistic flow is obtained in the model, in terms of cyclic mass conservation and approximately uniform pressure distribution in the distal airways; 2) the predicted alveolar pressure is in good agreement with previously documented values; and 3) the use of reduced-order geometry modeling allows accurate and efficient simulation of large-scale breathing lung flow, provided care is taken to use a physiologically realistic geometry and to properly address the unsteady boundary conditions.

TMOD-29. STANDARDIZED GENERATION OF TUMOR-ORGANOIDS AS NOVEL DRUG SCREENING MODEL IN MENINGIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi221-vi222
Author(s):  
Gerhard Jungwirth ◽  
Tao Yu ◽  
Cao Junguo ◽  
Catharina Lotsch ◽  
Andreas Unterberg ◽  
...  
Keyword(s):  
Drug Screening ◽  
Cancer Biology ◽  
Drug Testing ◽  
Large Scale ◽  
Ex Vivo ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Drug Responses ◽  
Novel Drug ◽  
Tumor Organoids

Abstract Tumor-organoids (TOs) are novel, complex three-dimensional ex vivo tissue cultures that under optimal conditions accurately reflect genotype and phenotype of the original tissue with preserved cellular heterogeneity and morphology. They may serve as a new and exciting model for studying cancer biology and directing personalized therapies. The aim of our study was to establish TOs from meningioma (MGM) and to test their usability for large-scale drug screenings. We were capable of forming several hundred TO equal in size by controlled reaggregation of freshly prepared single cell suspension of MGM tissue samples. In total, standardized TOs from 60 patients were formed, including eight grade II and three grade III MGMs. TOs reaggregated within 3 days resulting in a reducted diameter by 50%. Thereafter, TO size remained stable throughout a 14 days observation period. TOs consisted of largely viable cells, whereas dead cells were predominantly found outside of the organoid. H&E stainings confirmed the successful establishment of dense tissue-like structures. Next, we assessed the suitability and reliability of TOs for a robust large-scale drug testing by employing nine highly potent compounds, derived from a drug screening performed on several MGM cell lines. First, we tested if drug responses depend on TO size. Interestingly, drug responses to these drugs remained identical independent of their sizes. Based on a sufficient representation of low abundance cell types such as T-cells and macrophages an overall number of 25.000 cells/TO was selected for further experiments revealing FDA-approved HDAC inhibitors as highly effective drugs in most of the TOs with a mean z-AUC score of -1.33. Taken together, we developed a protocol to generate standardized TO from MGM containing low abundant cell types of the tumor microenvironment in a representative manner. Robust and reliable drug responses suggest patient-derived TOs as a novel drug testing model in meningioma research.

scholarly journals Towards a large-scale model of patient-specific epileptic spike-wave discharges

2012 ◽  
Vol 107 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Peter Neal Taylor ◽  
Marc Goodfellow ◽  
Yujiang Wang ◽  
Gerold Baier
Keyword(s):  
Large Scale ◽  
Scale Model ◽  
Patient Specific ◽  
Large Scale Model ◽  
Spike Wave Discharges ◽  
Epileptic Spike ◽  
Spike Wave

scholarly journals Exploring the intersections: researchers and communication professionals' perspectives on the organizational role of science communication

2020 ◽  
Vol 24 (3) ◽  
pp. 207-226 ◽  
Author(s):  
Kaisu Koivumäki ◽  
Clare Wilkinson
Keyword(s):  
Science Communication ◽  
Large Scale ◽  
Institutional Environment ◽  
Structured Interviews ◽  
Content Type ◽  
Organizational Influences ◽  
Research Organizations ◽  
Funding Policies ◽  
Negative Impacts

PurposeThis paper reports on research exploring the intersections between researchers and communication professionals' perspectives on the objectives, funders and organizational influences on their science communication practices.Design/methodology/approachExamining one context, the inter-organizational BCDC Energy Research project based at five different research organizations in Finland, this paper presents data from semi-structured interviews with 17 researchers and 15 communication professionals.FindingsThe results suggest that performance-based funding policies that drive the proliferation of large-scale research projects can create challenges. In particular, a challenge arises in generating a shared sense of identity and purpose amongst researchers and communication professionals. This may have unintended negative impacts on the quality and cohesiveness of the science communication which occurs.Research limitations/implicationsThe study was exploratory in nature and focuses on one organizational and institutional environment. Further research with a wider number of projects, as well as funders, would be conducive to a greater understanding of the issues involved.Practical implicationsOn a practical level, this research suggests that the creation of clearer communications awareness and guidance may be helpful in some large-scale projects, particularly involving broad numbers of organizations, individual researchers and funders.Originality/valueThis is one of the first studies examining the perspectives of both researchers and communication professionals working over one project, drawing together a range of different institutional and disciplinary perspectives. The results highlight the importance of the influences of funding on science communication aims, assumptions, cultures and structures. The article articulates the need for further research in this area.

scholarly journals MR-Linac Radiotherapy – The Beam Angle Selection Problem

2021 ◽  
Vol 11 ◽  
Author(s):  
Rik Bijman ◽  
Linda Rossi ◽  
Tomas Janssen ◽  
Peter de Ruiter ◽  
Baukelien van Triest ◽  
...  
Keyword(s):  
Treatment Planning ◽  
Large Scale ◽  
Volumetric Modulated Arc Therapy ◽  
Patient Specific ◽  
Systematic Research ◽  
Plan Quality ◽  
Beam Angle ◽  
Clinical Workflow ◽  
Model Case ◽  
Angle Class

BackgroundWith the large-scale introduction of volumetric modulated arc therapy (VMAT), selection of optimal beam angles for coplanar static-beam IMRT has increasingly become obsolete. Due to unavailability of VMAT in current MR-linacs, the problem has re-gained importance. An application for automated IMRT treatment planning with integrated, patient-specific computer-optimization of beam angles (BAO) was used to systematically investigate computer-aided generation of beam angle class solutions (CS) for replacement of computationally expensive patient-specific BAO. Rectal cancer was used as a model case.Materials and Methods23 patients treated at a Unity MR-linac were included. BAOx plans (x=7-12 beams) were generated for all patients. Analyses of BAO12 plans resulted in CSx class solutions. BAOx plans, CSx plans, and plans with equi-angular setups (EQUIx, x=9-56) were mutually compared.ResultsFor x&gt;7, plan quality for CSx and BAOx was highly similar, while both were superior to EQUIx. E.g. with CS9, bowel/bladder Dmean reduced by 22% [11%, 38%] compared to EQUI9 (p&lt;0.001). For equal plan quality, the number of EQUI beams had to be doubled compared to BAO and CS.ConclusionsComputer-generated beam angle CS could replace individualized BAO without loss in plan quality, while reducing planning complexity and calculation times, and resulting in a simpler clinical workflow. CS and BAO largely outperformed equi-angular treatment. With the developed CS, time consuming beam angle re-optimization in daily adaptive MR-linac treatment could be avoided. Further systematic research on computerized development of beam angle class solutions for MR-linac treatment planning is warranted.

scholarly journals Variation in end-stage renal disease patient outcomes: what we know, what should we know, and how do we find it out?

1993 ◽  
Vol 3 (11) ◽  
pp. 1738-1747
Author(s):  
P Kurtin ◽  
A R Nissenson
Keyword(s):  
Patient Outcomes ◽  
Outcome Measure ◽  
Disease Patient ◽  
Patient Specific ◽  
Quality Cost ◽  
Current State ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

The size and expense of the ESRD program exceed all predictions made when the program was first initiated. Although the effectiveness of dialytic therapy is unquestioned, its value (quality/cost) is actively debated in this era of constricting resources. To better evaluate the quality of the ESRD program, it is essential to first define and quantitate the outcomes of dialytic care. Although mortality is a convenient outcome measure, it may be affected by many patient-specific as well as other factors that must be considered when evaluating and comparing new and existing technologies or advances. Quality of life is only beginning to be used in depth as an outcome measure, and much work is needed to standardize research methodology and thus move this area forward. The following review describes the current state of knowledge regarding outcomes of ESRD patients and proposes areas for future investigation, which should help increase the understanding of the value of the ESRD program to patients, providers, and payors.

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