scholarly journals A Retrospective Comparison of In Silico Pharmaceutical Recommendations with Tumor Board Recommendations in Pediatric Oncology

2020 ◽  
Vol 3 ◽  
Author(s):  
Jacob Turner ◽  
Travis Johnson ◽  
Bryan Helm ◽  
Karen Pollock ◽  
Kun Huang
Keyword(s):  
Pediatric Population ◽  
Gene List ◽  
High Impact ◽  
Negative Regulator ◽  
Tumor Board ◽  
Adolescent Male ◽  
Treatment Recommendation ◽  
Gene Interactions ◽  
Variant Annotation ◽  
Chemotherapy Agents

Background and Hypothesis:  The objective of this study was to analyze available whole genome sequencing from an adolescent male patient diagnosed with osteosarcoma (OS) in 2014. OS is a primary bone malignancy that most commonly affects the pediatric population. Precision medicine techniques provide new opportunities to improve treatment of OS patients. Pharmaceutical annotation tools such as PharmacoDB and DGIdb can help indicate chemotherapy agents that may benefit patients based on their molecular profiles. We hypothesize that these tools can indicate genome-specific chemotherapy agents for OS after genomic data has been aligned and analyzed.     Project Methods:  A PDX pipeline and retrospective study were performed that identified and compared pharmaceutical treatment options from software tools with the chemotherapy provided. Gene alignment and variant calling were used to process and analyze DNA sequencing data; germline and somatic mutations were also identified. Ensembl VEP was used for variant annotation. PharmacoDB and DGIdb were then applied to identify potentially beneficial medications.    Results:  Gene variant annotation indicated 54 potentially high impact mutations. Of these, DGIdb identified 15 drug-gene interactions. PharmacoDB identified no drugs that target any of the genes containing the 54 high impact mutations. For the entire mutated gene list, DGIdb identified 398 drug-gene interactions. After gene set enrichment, DGIdb identified medications targeting genes of pathways such as “O-glycan processing” and “Diseases of glycosylation”. Potentially harmful variants in the NPRL3 gene were identified. Because NPRL3 is a component of the Gator1 complex that serves as a negative regulator of mammalian target of rapamycin complex 1 (mTORC1), the identified variants in NPRL3 could have played a role in the patient’s OS.    Potential Impact:  This study will foster future collaborations to evaluate the pharmaceutical tool recommendations for this patient’s derived cell lines. These efforts will determine the efficacy of and identify improvements for computational treatment recommendation systems. 

scholarly journals The UCSC Genome Browser database: 2018 update

2017 ◽  
Vol 46 (D1) ◽  
pp. D762-D769 ◽  
Author(s):  
Jonathan Casper ◽  
Ann S Zweig ◽  
Chris Villarreal ◽  
Cath Tyner ◽  
Matthew L Speir ◽  
...  
Keyword(s):  
Ucsc Genome Browser ◽  
Genome Browser ◽  
Gene Interactions ◽  
Command Line ◽  
Web Interface ◽  
Variant Annotation ◽  
The Past ◽  
Ucsc Genome Browser Database ◽  
Genome Assemblies ◽  
Command Line Version

Abstract The UCSC Genome Browser (https://genome.ucsc.edu) provides a web interface for exploring annotated genome assemblies. The assemblies and annotation tracks are updated on an ongoing basis—12 assemblies and more than 28 tracks were added in the past year. Two recent additions are a display of CRISPR/Cas9 guide sequences and an interactive navigator for gene interactions. Other upgrades from the past year include a command-line version of the Variant Annotation Integrator, support for Human Genome Variation Society variant nomenclature input and output, and a revised highlighting tool that now supports multiple simultaneous regions and colors.

scholarly journals CLRM-06. COMPARISON OF INDIVIDUALIZED ANTI-CANCER THERAPY REGIMENS RECOMMENDED BY A MULTIDISCIPLINARY MOLECULARLY-DRIVEN TUMOR BOARD IN A PEDIATRIC DIPG CLINICAL TRIAL (PNOC003) VERSUS THOSE SELECTED BY THE CNS-TAP TOOL

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv2-iv2
Author(s):  
Holly Roberts ◽  
Karthik Ravi ◽  
Allison Schepers ◽  
Bernard Marini ◽  
Cassie Kline ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Treatment Plan ◽  
Pilot Trial ◽  
Study Participant ◽  
Molecular Profiling ◽  
Individualized Treatment ◽  
Tumor Board ◽  
Treatment Recommendation ◽  
Patient Specific ◽  
Genomic Profiling

Abstract Genetic sequencing of diffuse intrinsic pontine gliomas (DIPG) has revealed genomic heterogeneity, fueling an interest in individualized targeted therapies. A feasibility study, PNOC003: Molecular Profiling for Individualized Treatment Plan for DIPG (NCT02274987), was completed within the Pacific Pediatric Neuro-Oncology Consortium in which a multidisciplinary tumor board reviewed molecular and genomic profiling of each participant’s tumor to make targeted therapy recommendations. Separately, our team developed the Central Nervous System Targeted Agent Prediction (CNS-TAP) tool, which combines pre-clinical, clinical, and CNS penetration data with patient-specific genomic information to derive numeric scores for anticancer agents to objectively evaluate these therapies for use in patients with CNS tumors. We hypothesized that agents highly-scored by CNS-TAP would overlap with agents recommended by the PNOC003 tumor board. For each study participant, we retrospectively utilized the genomic profiling report to identify actionable alterations and incorporated these data into CNS-TAP to find the highest-scoring agents. We compared these CNS-TAP-recommended agents with recommendations from the tumor board for each of the 28 PNOC003 participants. Overall, 93% of patients (26/28) had at least one agent recommended by both the tumor board and CNS-TAP. Additionally, 38% of all agents (36/95) chosen by the tumor board were also selected by CNS-TAP. When only molecularly targeted anticancer agents were included in a sub-analysis, 60% of agents (34/57) were recommended by both methods. At present, we are prospectively evaluating the CNS-TAP tool within PNOC008: A Pilot Trial Testing the Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan in Children and Young Adults with High-Grade Glioma (NCT03739372). The CNS-TAP tool recommendations are shared during the PNOC008 molecular tumor board meetings once a consensus treatment recommendation has been reached. Subsequent analyses will focus on any adjustments in therapy decisions within the tumor board that result from the CNS-TAP tool output.

scholarly journals Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1151
Author(s):  
Rouven Hoefflin ◽  
Adriana Lazarou ◽  
Maria Elena Hess ◽  
Meike Reiser ◽  
Julius Wehrle ◽  
...  
Keyword(s):  
Treatment Adherence ◽  
Objective Response ◽  
Tumor Board ◽  
Treatment Recommendation ◽  
Comprehensive Cancer Center ◽  
Precision Oncology ◽  
Single Center ◽  
Clinical Routine ◽  
Molecular Tumor Board ◽  
Over Time

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time.

Outcomes and applicability of a deep learning virtual tumor board (DLVTB) in community-dwelling colorectal cancer (CRC) patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18635-e18635
Author(s):  
Aakash Desai ◽  
Arturo Loaiza-Bonilla ◽  
Cagatay Culcuoglu ◽  
Kristin Johnston ◽  
Selin Kurnaz
Keyword(s):  
Clinical Trial ◽  
Deep Learning ◽  
Clinical Practice ◽  
Natural Language ◽  
Community Dwelling ◽  
Tumor Board ◽  
Treatment Recommendation ◽  
Evidence Based ◽  
Precision Oncology ◽  
Report Generation

e18635 Background: With almost 85% of patients treated outside NCI-designated cancer centers, providing comprehensive, state-of-the-art cancer care to millions of patients in the U.S. remains a significant challenge. We aimed to combine cutting edge AI based technology of DLVTB with high value-added services to provide evidence-based care management recommendations and implementation support to the patients and physicians in the community. To further demonstrate the feasibility, reproducibility, scalability, and benefits of DLVTB, we evaluated key outcomes from incorporating DLVTB in a cohort of 35 patients with advanced colorectal adenocarcinoma (CRC). Methods: Our core-enabling technology is a deep learning based Natural Language Understanding Engine that employs (1) natural language processing for medical text digestion and structuring, (2) decision trees and multilayer perception models to produce evidence-based treatment protocols, and (3) natural language based report generation. The technology platform is combined with human support from oncology sub-specialists to deliver a comprehensive Interpretive Report with a prioritized list of recommendations for each patient. These recommendations are operationalized by a case management team to ensure care implementation and monitoring of outcomes. Results: Thirty-five patients with CRC were referred for incorporation of DLVTB into clinical practice. Median age of patients was 57 years with 68.6% males. About 88.6% of the patients were Stage IV and 82.9% were treated by community practice oncologists. Median time since diagnosis was 17 months (1-73 months). Overall, DLVTB-cohort demonstrated an increase in median Overall Survival of 12 months per patient in comparison with historical cohorts. More specifically, DLVTB recommended initial and/or additional biomarker testing for 71% of the patients with further precision oncology-guided treatment recommendation (e.g. an EGFR inhibitor) for 80% of the patients. 63% of the patients were eligible for at least one clinical trial. 58% of the trials identified were within proximity (≤50 miles) of the patient’s primary residence. Thus, DLVTB was able to identify a trial that did not require extensive travel, provided eligibility and actionability closer to the point-of-care. 14% of the DLVTB evaluated patients subsequently enrolled in the recommended clinical trial, far surpassing the national average (3%). Moreover, DLVTB recommended treatments achieved on average savings of $39,194 per patient which is 35% of the average drug cost per patient. Conclusions: Our results demonstrate the feasibility and benefits of incorporating DLVTB into clinical practice. The utilization of DLVTB as a clinical trial enrollment tool and an engine for development of pathways resulting in improved clinical outcomes, in a cost-effective, and innovative care delivery model.

Skeletal Mass in Adolescent Male Athletes and Nonathletes: Relationships with High-Impact Sports

2011 ◽  
Vol 25 (12) ◽  
pp. 3439-3447 ◽  
Author(s):  
Ana L Dias Quiterio ◽  
Elvis A Carnero ◽  
Fátima M Baptista ◽  
Luís B Sardinha
Keyword(s):  
High Impact ◽  
Adolescent Male ◽  
Male Athletes ◽  
Skeletal Mass

scholarly journals Tumor Genomic Profiling Practices and Perceptions: A Survey of Physicians Participating in the NCI-MATCH Trial

2020 ◽  
pp. 1207-1216
Author(s):  
Alice Chen ◽  
Keith Flaherty ◽  
Peter J. O’Dwyer ◽  
Bruce Giantonio ◽  
Donna M. Marinucci ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Wait Time ◽  
Tumor Board ◽  
Patient Treatment ◽  
Treatment Recommendation ◽  
Genomic Profiling ◽  
Match Trial ◽  
Physician Participation ◽  
Therapy Choice ◽  
Tumor Profiling

PURPOSE To identify factors that may influence physician participation in tumor profiling studies and to assess the routine use of tumor profiling in clinical practice. METHODS Physicians in the National Cancer Institute–Molecular Analysis for Therapy Choice (NCI-MATCH) were invited to participate in an electronic survey consisting of 73 questions related to participation in genomic profiling studies, tumor profiling practices and education during usual patient care, and physician background and practice characteristics. RESULTS The survey response rate was 8.9% (171 surveys returned of 1,931 sent). A majority of respondents practiced in academic medical centers (AMCs). Participation in NCI-MATCH increased workload and cost but resulted in increased professional satisfaction, confidence in treatment recommendation, and subsequent use of tumor profiling. Barriers to patient participation included length of wait time for results and lack of a therapeutic option from the testing. Physicians who worked in AMCs reported a higher use of tumor profiling than did those who worked in non-AMC settings (43% v 18%; P = .0009). Access to a molecular tumor board was perceived as valuable by 56%. The study identified a need for educational materials to guide both physicians and patients in the field of genomic profiling. CONCLUSION Physicians who participate in NCI-MATCH perceive value to patient treatment that outweighs the additional effort required; survey results help identify barriers that may limit participation. The current findings have implications for the design of future genomic and other profiling studies.

scholarly journals New onset ANCA-associated vasculitis in an adolescent during an acute COVID-19 infection: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel D. Reiff ◽  
Chloe G. Meyer ◽  
Brittany Marlin ◽  
Melissa L. Mannion
Keyword(s):  
Case Reports ◽  
Pediatric Population ◽  
Adult Population ◽  
Pulmonary Nodules ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Pediatric Care ◽  
Adolescent Male ◽  
Care Providers ◽  
Healthy Adolescent ◽  
New Onset

Abstract Background SARS-CoV-2 has been found to be exquisitely adept at triggering autoimmunity and multiple new onset autoimmune diseases have been described as a post-infectious complication of COVID-19 infection in the adult population. Less has been described in the pediatric population, as infections are more likely to be asymptomatic and less severe. This case reports a previously healthy adolescent patient with new onset antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) diagnosed in the setting of acute COVID-19 infection. Case presentation A previously healthy adolescent male was diagnosed with COVID-19 pneumonia after presenting with infectious symptoms of fever, cough, congestion, and shortness of breath. After worsening of disease, he was found to have pulmonary nodules, atypical for COVID-19. Further imaging and laboratory workup showed elevated inflammatory markers, negative infectious testing, and positive antineutrophil cytoplasmic antibodies (ANCA) diagnostic for AAV. He was treated with pulse dose steroids followed by a prolonged taper and rituximab. Symptoms resolved and laboratory abnormalities improved over time. At six-month follow-up, lesions were much improved, laboratory markers were within normal limits, and patient remained asymptomatic off medications. Conclusions This case is one of the first in the pediatric population to describe new onset AAV presenting with an acute, symptomatic COVID-19 infection. There is increasing evidence for COVID-19 induced autoimmunity in the pediatric population and pediatric care providers should be on high alert for new onset autoimmune disease in children afflicted by COVID-19.

scholarly journals Uncommon Presentation of a Benign Nasopharyngeal Mass in an Adolescent: Comprehensive Review of Pediatric Nasopharyngeal Masses

2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Victor M. Duarte ◽  
Yuan F. Liu ◽  
Nina L. Shapiro
Keyword(s):  
Single Case ◽  
Pediatric Population ◽  
Tertiary Care ◽  
Adolescent Male ◽  
Comprehensive Review ◽  
Uncommon Presentation ◽  
Nasopharyngeal Mass ◽  
Tertiary Care Institution ◽  
High Index Of Suspicion ◽  
Nasopharyngeal Masses

Nasopharyngeal masses in the pediatric population are quite rare, and the majority of these are benign. In adolescent boys, there should be a high index of suspicion for juvenile nasopharyngeal angiofibromas. When malignant, the most common lesions encountered are rhabdomyosarcomas, carcinomas, and lymphomas. We report a single case from a tertiary care institution of an adolescent male with an unusual presentation of a benign nasopharyngeal mass and provide a comprehensive review of pediatric nasopharyngeal masses. Whenever possible, radiographic imaging should be obtained, in addition to biopsy, to assist in the diagnosis of pediatric nasopharyngeal masses.

scholarly journals The Genes of Pumpkin and Squash

HortScience ◽  
2005 ◽  
Vol 40 (6) ◽  
pp. 1620-1630 ◽  
Author(s):  
Harry S. Paris ◽  
Rebecca Nelson Brown
Keyword(s):  
Cucurbita Pepo ◽  
Gene List ◽  
Gene Interactions ◽  
Cucurbita Moschata ◽  
Fruit Characteristics ◽  
Important Species ◽  
New Gene ◽  
Sound Foundation ◽  
Allozyme Loci ◽  
Almost All

Pumpkin and squash (Cucurbita L. spp.) are important cucurbit crops and are grown in almost all arable regions of the world. The three economically important species, Cucurbita pepo L., Cucurbita moschata Duchesne, and Cucurbita maxima Duchesne are highly polymorphic in fruit characteristics, inspiring much research into their inheritance. A comprehensive list of genes for Cucurbita was last published more than a decade ago. This new gene list for pumpkin and squash includes descriptions of gene interactions and the genetic background of the parents that had been used for crossing to allow easy confirmation of previous work and provide a sound foundation for further investigation. This gene list includes 79 loci for phenotypic/morphological traits and 48 polymorphic allozyme loci. Linkage and mapping are discussed.

scholarly journals The Genes of Capsicum

HortScience ◽  
2006 ◽  
Vol 41 (5) ◽  
pp. 1169-1187 ◽  
Author(s):  
Deyuan Wang ◽  
Paul W. Bosland
Keyword(s):  
Molecular Markers ◽  
Genetic Background ◽  
Morphological Traits ◽  
Gene List ◽  
Physiological Traits ◽  
Gene Interactions ◽  
Chromosome Localization ◽  
New Genes ◽  
Action Mechanisms ◽  
The World

Pepper (Capsicum spp.) is one of the most cultivated vegetable and spice crops in the world. Capsicum genetics have been extensively studied, but the most recent Capsicum gene list was published more than a decade ago. Since then, new genes have been described. This updated gene list provides detailed descriptions of genes, including the genes' characteristics, the genetic background of the mutants/lines, action mechanisms of genes, gene interactions, molecular markers, and chromosome localization when available. This new list includes 292 genes for morphological traits; physiological traits; sterility; and resistance to diseases, nematodes, and herbicides, which includes the 92 genes that have not been previously described.

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