scholarly journals Precision cancer therapy by molecular profiling – A Theoretical Study

2021 ◽  
Author(s):  
V. Sah
Keyword(s):  
Large Scale ◽  
Clinical Decision Making ◽  
Single Cell Analysis ◽  
Clinical Decision ◽  
Molecular Profiling ◽  
Outcome Analysis ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Next Generation Sequencing Technology ◽  
Genomic Studies

The amount of druggable tumor-specific molecular aberrations has increased significantly over the last decade, with biomarker-matched therapies demonstrating a major survival advantage in many cancer forms. Therefore, molecular pathology has been critical not just for tumor detection and prognosis, but also for clinical decision-making in everyday practice. The advent of next-generation sequencing technology and the proliferation of large-scale tumor molecular profiling services through universities worldwide have transformed the area of precision oncology. When systematic genomic studies become more accessible in clinical and laboratory environments, healthcare professionals face the difficult challenge of outcome analysis and translation. This study summarizes existing and future methods to implementing precision cancer medicine, outlining the obstacles and possible strategies for facilitating the understanding and maximization of molecular profiling findings. Beyond tumor DNA sequencing, we discuss innovative molecular characterization techniques such as transcriptomics, immunophenotyping, epigenetic profiling, and single-cell analysis. Additionally, we discuss present and future uses of liquid biopsies for evaluating blood-based biomarkers such as circulating tumor cells and nucleic acids. Finally, the shortcomings of genotype-based treatments give insight into opportunities to extend personalized medicine beyond genomics.

scholarly journals Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer

2021 ◽  
Author(s):  
Irene Casanova-Salas ◽  
Alejandro Athie ◽  
Paul C. Boutros ◽  
Marzia Del Re ◽  
David T. Miyamoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Qualitative Analysis ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Liquid Biopsies

scholarly journals Clinician checklist for assessing suitability of machine learning applications in healthcare

2021 ◽  
Vol 28 (1) ◽  
pp. e100251
Author(s):  
Ian Scott ◽  
Stacey Carter ◽  
Enrico Coiera
Keyword(s):  
Machine Learning ◽  
Large Scale ◽  
Clinical Decision Making ◽  
Improve Patient Care ◽  
Clinical Decision ◽  
Routine Care ◽  
Machine Learning Algorithms ◽  
Clinical Settings ◽  
Machine Learning Applications ◽  
Key Issues

Machine learning algorithms are being used to screen and diagnose disease, prognosticate and predict therapeutic responses. Hundreds of new algorithms are being developed, but whether they improve clinical decision making and patient outcomes remains uncertain. If clinicians are to use algorithms, they need to be reassured that key issues relating to their validity, utility, feasibility, safety and ethical use have been addressed. We propose a checklist of 10 questions that clinicians can ask of those advocating for the use of a particular algorithm, but which do not expect clinicians, as non-experts, to demonstrate mastery over what can be highly complex statistical and computational concepts. The questions are: (1) What is the purpose and context of the algorithm? (2) How good were the data used to train the algorithm? (3) Were there sufficient data to train the algorithm? (4) How well does the algorithm perform? (5) Is the algorithm transferable to new clinical settings? (6) Are the outputs of the algorithm clinically intelligible? (7) How will this algorithm fit into and complement current workflows? (8) Has use of the algorithm been shown to improve patient care and outcomes? (9) Could the algorithm cause patient harm? and (10) Does use of the algorithm raise ethical, legal or social concerns? We provide examples where an algorithm may raise concerns and apply the checklist to a recent review of diagnostic imaging applications. This checklist aims to assist clinicians in assessing algorithm readiness for routine care and identify situations where further refinement and evaluation is required prior to large-scale use.

The Johns Hopkins Molecular Tumor Board Precision Oncology elective for Medical Oncology fellows.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11035-11035
Author(s):  
Kristen Marrone ◽  
Jessica Tao ◽  
Jenna VanLiere Canzoniero ◽  
Paola Ghanem ◽  
Emily Nizialek ◽  
...  
Keyword(s):  
Decision Making ◽  
Precision Medicine ◽  
Clinical Decision Making ◽  
Cancer Genomics ◽  
Medical Oncology ◽  
Clinical Decision ◽  
Tumor Board ◽  
Precision Oncology ◽  
Adaptive Expertise ◽  
Molecular Tumor Board

11035 Background: The accelerated impact of next generation sequencing (NGS) in clinical decision making requires the integration of cancer genomics and precision oncology focused training into medical oncology education. The Johns Hopkins Molecular Tumor Board (JH MTB) is a multi-disciplinary effort focused on integration of NGS findings with critical evidence interpretation to generate personalized recommendations tailored to the genetic footprint of individual patients. Methods: The JH MTB and the Medical Oncology Fellowship Program have developed a 3-month precision oncology elective for fellows in their research years. Commencing fall of 2020, the goals of this elective are to enhance the understanding of NGS platforms and findings, advance the interpretation and characterization of molecular assay outputs by use of mutation annotators and knowledgebases and ultimately master the art of matching NGS findings with available therapies. Fellow integration into the MTB focuses on mentored case-based learning in mutation characterization and ranking by levels of evidence for actionability, with culmination in form of verbal presentations and written summary reports of final MTB recommendations. A mixed methods questionnaire was administered to evaluate progress since elective initiation. Results: Three learners who have participated as of February 2021 were included. Of the two who had completed the MTB elective, each have presented at least 10 cases, with at least 1 scholarly publication planned. All indicated strong agreement that MTB elective had increased their comfort with interpreting clinical NGS reports as well as the use of knowledgebases and variant annotators. Exposure to experts in the field of molecular precision oncology, identification of resources necessary to interpret clinical NGS reports, development of ability to critically assess various NGS platforms, and gained familiarity with computational analyses relevant to clinical decision making were noted as strengths of the MTB elective. Areas of improvement included ongoing initiatives that involve streamlining variant annotation and transcription of information for written reports. Conclusions: A longitudinal elective in the JHU MTB has been found to be preliminarily effective in promoting knowledge mastery and creating academic opportunities related to the clinical application of precision medicine. Future directions will include leveraging of the MTB infrastructure for research projects, learner integration into computational laboratory meetings, and expansion of the MTB curriculum to include different levels of learners from multiple medical education programs. Continued elective participation will be key to understanding how best to facilitate adaptive expertise in assigning clinical relevance to genomic findings, ultimately improving precision medicine delivery in patient care and trial development.

Pathogenesis of Peritoneal Sclerosis

2005 ◽  
Vol 28 (2) ◽  
pp. 90-96 ◽  
Author(s):  
C. Pollock
Keyword(s):  
Peritoneal Dialysis ◽  
Large Scale ◽  
Clinical Decision Making ◽  
Inflammatory Cells ◽  
Clinical Decision ◽  
Cumulative Exposure ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Histological Data ◽  
The Individual

Peritoneal sclerosis is an almost invariable consequence of peritoneal dialysis. In most circumstances it is “simple” sclerosis, manifesting clinically with an increasing peritoneal transport rate and loss of ultrafiltration capacity. In contrast, encapsulating peritoneal sclerosis is a life threatening and usually irreversible condition, associated with bowel obstruction, malnutrition and death. It is unknown whether common etiological factors underlie the development of these 2 clinically and pathologically distinct forms of peritoneal sclerosis. The majority of studies to date have investigated factors that contribute to “simple” sclerosis, although it remains possible that similar mechanisms are amplified in patients who develop encapsulated peritoneal sclerosis. The cellular elements that promote peritoneal sclerosis include the mesothelial cells, peritoneal fibroblasts and inflammatory cells. Factors that stimulate these cells to promote peritoneal fibrosis and neoangiogenesis, both inherent in the development of peritoneal sclerosis, include cytokines that are induced by exposure of the peritoneal membrane to high concentrations of glucose, advanced glycation of the peritoneal membrane and oxidative stress. The cumulative exposure to bioincompatible dialysate is likely to have an etiological role as the duration of dialysis correlates with the likelihood of developing peritoneal sclerosis. Indeed peritoneal dialysis using more biocompatible fluids has been shown to reduce the development of peritoneal sclerosis. The individual contribution of the factors implicated in the development of peritoneal sclerosis will only be determined by large scale peritoneal biopsy registries, which will be able to prospectively incorporate clinical and histological data and support clinical decision making.

scholarly journals A164 UPTAKE OF FECAL CALPROTECTIN IN PRACTICE: PATTERNS IN A TERTIARY GI REFERRAL CENTRE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 28-30
Author(s):  
A Kundra ◽  
T Ritchie ◽  
M Ropeleski
Keyword(s):  
Medical Therapy ◽  
Bowel Disease ◽  
Large Scale ◽  
Clinical Decision Making ◽  
Practice Patterns ◽  
Clinical Decision ◽  
Fecal Calprotectin ◽  
Time Interval ◽  
Chart Audit ◽  
Frequency Pattern

Abstract Background Fecal Calprotectin (FC) is helpful in distinguishing functional from organic bowel disease. Also, it has proven useful in monitoring disease activity in inflammatory bowel disease (IBD). The uptake of its use in clinical practice has increased considerably, though access varies significantly. Studies exploring current practice patterns among GI specialists and how to optimize its use are limited. In 2017, Kingston Health Sciences Centre (KHSC) began funding FC testing at no cost to patients. Aims We aimed to better understand practice patterns of gastroenterologists in IBD patients where there is in house access to FC assays, and to generate hypotheses regarding its optimal use in IBD monitoring. We hypothesize that FC is not being used in a regular manner for monitoring of IBD patients. Methods A retrospective chart audit study was done on all KHSC patients who had FC testing completed from 2017–2018. Qualitative data was gathered from dictated reports using rigorous set definitions regarding indication for the test, change in clinical decision making, and frequency patterns of testing. Specifically, change in use for colonoscopy or in medical therapy was coded only if the dictated note was clear that a decision hinged largely on the FC result. Frequency of testing was based on test order date. Reactive testing was coded as tests ordered to confirm a clinical flare. Variable testing was coded where monitoring tests that varied in intervals greater than 3 months and crossed over the other set frequency codes. Quantitative data regarding FC test values, and dates were also collected. This data was then analyzed using descriptive statistics. Results Of the 834 patients in our study, 7 were under 18 years old and excluded. 562(67.34%) of these patients had a pre-existing diagnosis of IBD; 193 (34%) with Ulcerative Colitis (UC), 369 (66%) with Crohn’s Disease (CD). FC testing changed the clinician’s decision for medical therapy in 12.82% of cases and use for colonoscopy 13.06% of the time for all comers. Of the FC tests, 79.8% were sent in a variable frequency pattern and 2.68% with reactive intent. The remaining 17.5% were monitored with a regular pattern, with 8.57% patients having their FC monitored at regular intervals greater than 6 months, 7.68% every 6 months, and 1.25% less than 6 months. The average FC level of patients with UC was 356.2ug/ml and 330.6 ug/ml for CD. The mean time interval from 1st to 2nd test was 189.6 days. Conclusions FC testing changed clinical decisions regarding medical therapy and use for colonoscopy about 13% of the time. FC testing was done variably 79.8% of the time, where as 17.5% of patients had a regular FC monitoring schedule. An optimal monitoring interval for IBD flares using FC for maximal clinical benefit has yet to be determined. Large scale studies will be required to answer this question. Funding Agencies None

scholarly journals Implementing Precision Medicine in Community-Based Oncology Programs: Three Models

2019 ◽  
Vol 15 (6) ◽  
pp. 325-329 ◽  
Author(s):  
Laura A. Levit ◽  
Edward S. Kim ◽  
Barbara L. McAneny ◽  
Lincoln D. Nadauld ◽  
Kathryn Levit ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Cancer Care ◽  
Large Scale ◽  
Administrative Support ◽  
Clinical Pathways ◽  
Clinical Decision ◽  
Successful Implementation ◽  
Precision Oncology ◽  
Community Based ◽  
Tumor Boards

The use of precision medicine and the number of genomic-based treatments and immunotherapies is increasing. Nevertheless, oncology providers face challenges to implementing precision medicine, including in community practices, where most patients receive treatment. On January 31, 2018, ASCO hosted Precision Medicine: Expanding Opportunities, the inaugural event in ASCO’s new State of Cancer Care in America (SOCCA) event series. This article draws from the inaugural SOCCA event and the experiences of the SOCCA event participants to summarize the opportunities and challenges of precision medicine, and to highlight three successful models of implementing precision oncology in large, multisite community practices or networks: (1) Intermountain Healthcare, (2) Levine Cancer Institute, Atrium Health, and (3) National Cancer Care Alliance. The experience of these practices suggests that practice innovations that offer clinical decision support through molecular tumor boards and clinical pathways, and administrative support for prior authorization and clinical trial matching are key to successful implementation of large-scale, community-based precision medicine programs.

Princess Margaret Cancer Centre (PMCC) Integrated Molecular Profiling in Advanced Cancers Trial (IMPACT) using genotyping and targeted next-generation sequencing (NGS).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11002-11002 ◽  
Author(s):  
Philippe L. Bedard ◽  
Amit M. Oza ◽  
Ming-Sound Tsao ◽  
Natasha B. Leighl ◽  
Frances A. Shepherd ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Screening Program ◽  
Illumina Miseq ◽  
Response Assessment ◽  
Clinical Decision ◽  
Molecular Profiling ◽  
Routine Care ◽  
Targeted Next Generation Sequencing

11002 Background: IMPACT is an institution-wide screening program to identify patients (pts) treated at PMCC with somatic alterations that can be matched to targeted therapies. Methods: Pts with advanced breast, colorectal (CRC), non-small cell lung (NSCLC), ovarian cancers and selected other solid tumors treated at PMCC were eligible. Tumor DNA was isolated from a FFPE archived sample and genotyped using a customized Sequenom panel (23 genes, 280 mutations) in a CLIA-certified laboratory. Verified mutations were reported in pts electronic health records. Selected FFPE samples were further characterized by NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons, ≥500x coverage) for platform validation. Results: From Mar 1/12-Jan 10/13, 485 pts were enrolled with median 1 prior treatment for advanced disease (range 0-6). Of 33 (7%) screen failures, 5% were for insufficient tissue and 2% for clinical deterioration. Median DNA quantity from FFPE = 4250ng (range 15-32550ng). The median time from tissue receipt to reporting was 5 weeks (range 1-23). Mutations were identified by Sequenom in 137/349 (39%) pts, including 24/79 (30%) breast, 40/80 (50%) CRC, 54/88 (61%) NSCLC, 17/78 (22%) ovarian, and 2/24 (8%) other cancers. Mutations detected were: 76 KRAS, 35 PIK3CA, 22 EGFR, 5 NRAS, 5 ERBB2, 5 CTNNB1, 4 BRAF, and 1 AKT1. MiSeq was concordant with Sequenom in 112/113 (99%) pts, with mutations identified in 94/114 (82%). The average number of mutations detected by MiSeq was 1.72/pt (range 0-7) compared with 0.49/pt by Sequenom (range 0-2). After a median follow up of 5.0 months, 31/137 (23%) pts with mutations have been matched to targeted therapies, including 14 pts enrolled in clinical trials (15 trials) matched to their genotype. Of the 10 trial pts with at least one response assessment, 3 PR (1 confirmed) and 2 SD ≥ 24 weeks have been observed. Conclusions: Molecular profiling can be integrated into the routine care of advanced cancer pts. Genotyping and targeted NGS are feasible in a clinical laboratory using stored archival FFPE tumor samples. NGS identifies additional actionable mutations to inform clinical-decision making. Clinical trial information: NCT01505400.

A community-based program for personalized cancer care using next-generation sequencing (NGS).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11102-11102
Author(s):  
Shile Liang ◽  
Pranil Chandra ◽  
Zeqiang Ma ◽  
Debbie Haynes ◽  
James Prescott ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Molecular Profiling ◽  
Targeted Agents ◽  
Community Based ◽  
Off Label ◽  
Molecular Abnormalities ◽  
Tumor Types

11102 Background: Despite growing interest and need, molecular profiling of tumor samples is largely unavailable in community cancer centers, where nearly 80% of cancer patients (pts) are treated. In 10/12, Sarah Cannon Research Institute (SCRI) launched a community-based molecular profiling program to: 1) better understand the molecular constituency of cancer patients, 2) identify appropriate pts for phase I and II clinical trials of targeted agents, and 3) identify pts with molecular abnormalities responsive to FDA-approved agents. Methods: Eligible pts consented to testing of available biospecimens, which were interrogated for alterations in 35 cancer-related genes using NGS (1000X average coverage) in a CLIA/CAP laboratory. Results were reported to the treating physician within 14 days and stored in a database to enable correlation with clinical outcomes. Results: As of 1/13, 209 pts had been enrolled with 84% having sufficient material for assay. At least 1 mutation was detected in 46% of tumors. Results in the 3 most commonly assayed tumor types are summarized (Table). Mutations for which there are FDA-approved targeted agents were found in 14 off-label tumors (EGFR 4, KIT 3, SMO 3, BRAF 2, HER2 2). 40 pts (27%) were subsequently enrolled in clinical trials; in 19 of these, assay results influenced clinical trial selection. Conclusions: This program provides molecular profiling data to community oncologists for clinical decision making. Experience to date indicates this information can be provided in a timely manner for incorporation into clinical practice. Profiling results will enable: 1) selection of pts with appropriate tumor targets for investigational targeted agents, 2) enhanced study enrollment, 3) evaluation of FDA approved targeted agents in off-label tumor types, and 4) correlation of treatment outcomes with patterns of tumor molecular abnormalities. [Table: see text]

A comparison of patients' and physicians' expectations regarding precision oncology tests.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1568-1568
Author(s):  
Navdeep Dehar ◽  
Tasnima Abedin ◽  
Patricia A. Tang ◽  
D. Gwyn Bebb ◽  
Winson Y. Cheung
Keyword(s):  
Decision Making ◽  
Genetic Testing ◽  
Cancer Biology ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Survey Study ◽  
Precision Oncology ◽  
Diagnosis And Prognosis ◽  
Genetic Test Results ◽  
Survey Responses

1568 Background: With the increasing number and frequency of biomarker and genetic tests that are offered to patients with cancer, it is important to ensure that they fully understand the implications of these tests. In this survey study, we aimed to compare the attitudes and expectations of patients and cancer physicians about the role of biomarker and genetic testing in clinical decision-making. Methods: Two separate, complimentary, self-administered questionnaires for cancer patients and their physicians, respectively, were collected in Calgary, Alberta, Canada. Survey responses from patients were subsequently matched with those of their corresponding oncologists to form patient–oncologist dyads. We determined the concordance rates between responses of patients and those of their oncologists. Results: A total of 113 patients and 15 physicians participated in the study from July to September 2019. Patients demonstrated good understanding of general cancer biology (79%) and diagnostic processes (91%) associated with precision oncology. About 70% patients were willing to undergo minor procedures, and participate in research involving biomarker or genetic testing; however, this was over-estimated by their physicians in 82% of cases. Many patients felt that their tumor should be tested to guide treatment (70%) and were not bothered by potential delays in treatment due to testing (23%). These views from patients were largely shared by their oncologists (concordance 64%). While only 28% patients thought that they had enough knowledge to make informed decisions, majority (68%) said that they needed more information. Importantly, knowledge and expectations regarding the applications of biomarker or genetic test results on actual diagnosis and prognosis were grossly discrepant between patients and their oncologists (concordance 26% and 36%, respectively). Conclusions: Patients and cancer physicians tend to be aware of the advances in precision oncology and are willing to participate in biomarker and genetic testing and research. However, they do not consistently agree about the roles and applications of these tests, which may result in misplaced expectations. Strategies to improve education and communication are needed to align these expectations and improve the quality of clinical decision-making.

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