Yale Cancer Center Precision Medicine Tumor Board: one tumour, multiple targets

e14006 Background: Next generation sequencing (NGS) allows for reliable, comprehensive and cost-effective identification of clinically actionable genetic and genomic alterations. The increasing adoption of NGS in clinical oncology has increased our ability to identify germline alterations predisposing to cancer development as well as somatic changes enabling prescription of individualized cancer treatment and enhanced clinical trial participation. Here we summarize implementation of an NGS-based precision medicine initiative involving oncology patients from a single institution cancer center. Methods: IRB-approved NGS matched whole exome (WES) germline and solid tumor somatic tumor sequencing together with somatic tumor RNA sequencing (RNA-seq) were performed using germline DNA extracted from peripheral blood lymphocytes and nucleic acids for tumor DNA and RNA sequencing obtained from formalin-fixed, paraffin-embedded tumor specimens. Results of sequencing and analyses were presented to a multi-disciplinary tumor board to establish recommendations for management of germline pathogenic variation, therapeutic drug matching, clinical trials eligibility and molecularly informed patient prognosis. Results: A total of 1,005 patients completed sequencing. Germline and somatic WES exceeded 100X and 250X mean target coverage, respectively; somatic RNA-seq exceeded 200 million mean reads. Patients ranged in age from 17 to 90 years. The study cohort comprised comparable numbers of female (51%) and male (49%) patients. Ethnicities and races were broadly represented with 22% of participants identifying as Hispanic, 14% as Asian, 4% as Black, 55% as Non-Hispanic White and 5% as other. The most common solid tumor histological classification was colorectal (18%), followed by breast (16%), prostate (7%), head and neck (7%), sarcoma (7%), ovarian (5%), melanoma (4%) and lung (3%). Bioinformatic analyses and precision medicine tumor board review established that 12% of patients harbored a germline pathogenic variant and 43% carried clinically actionable genetic/genomic alterations; a majority of patients met molecular requirements for participation in a clinical trial. Conclusions: This study confirms the feasibility and utility of clinical NGS and precision medicine tumor board review in clinical oncology to identify germline genetic pathology, deliver personalized cancer therapeutics, increase clinical trial enrollment and clarify diagnosis and prognosis.

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Molecular tumor board (MTB): Development of clinical pathways for precision medicine. Experiences of center for breast cancer at national cancer center, Korea

Annals of Oncology ◽

10.1093/annonc/mdy428.013 ◽

2018 ◽

Vol 29 ◽

pp. ix18

Author(s):

I.H. Park ◽

C. Park ◽

W. Jang ◽

H. Yang ◽

K. An ◽

...

Keyword(s):

Breast Cancer ◽

Precision Medicine ◽

Clinical Pathways ◽

Tumor Board ◽

Cancer Center ◽

Molecular Tumor Board

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Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan

The Lancet Oncology ◽

10.1016/s1470-2045(20)30683-5 ◽

2021 ◽

Vol 22 (3) ◽

pp. 306-307

Author(s):

Joanna A Gibson ◽

Karin E Finberg ◽

ILKe Nalbantoglu ◽

Michael Cecchini ◽

Amanda Ganzak ◽

...

Keyword(s):

Precision Medicine ◽

Treatment Plan ◽

Diagnosis And Treatment ◽

Tumor Board ◽

Cancer Center

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The Value of a Second Opinion for Breast Cancer Patients Referred to a National Cancer Institute (NCI)-Designated Cancer Center with a Multidisciplinary Breast Tumor Board

Annals of Surgical Oncology ◽

10.1245/s10434-018-6599-y ◽

2018 ◽

Vol 25 (10) ◽

pp. 2953-2957 ◽

Cited By ~ 10

Author(s):

Denise Garcia ◽

Laura S. Spruill ◽

Abid Irshad ◽

Jennifer Wood ◽

Denise Kepecs ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

National Cancer Institute ◽

Breast Tumor ◽

Second Opinion ◽

Tumor Board ◽

Cancer Center ◽

Breast Cancer Patients

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

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.11035 ◽

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.

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Cancer Imaging at the Crossroads of Precision Medicine: Perspective From an Academic Imaging Department in a Comprehensive Cancer Center

Journal of the American College of Radiology ◽

10.1016/j.jacr.2015.11.002 ◽

2016 ◽

Vol 13 (4) ◽

pp. 365-371 ◽

Cited By ~ 5

Author(s):

Annick D. Van den Abbeele ◽

Katherine M. Krajewski ◽

Sree Harsha Tirumani ◽

Fiona M. Fennessy ◽

Pamela J. DiPiro ◽

...

Keyword(s):

Precision Medicine ◽

Cancer Imaging ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Imaging Department

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Comparative Analysis of Public Knowledge Bases for Precision Oncology

JCO Precision Oncology ◽

10.1200/po.18.00371 ◽

2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Steffen Pallarz ◽

Manuela Benary ◽

Mario Lamping ◽

Damian Rieke ◽

Johannes Starlinger ◽

...

Keyword(s):

Genetic Alterations ◽

Knowledge Bases ◽

Tumor Board ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Accurate Information ◽

Precision Oncology ◽

Cancer Genes ◽

Qualitative Comparison ◽

Data Set

PURPOSE Precision oncology depends on the availability of up-to-date, comprehensive, and accurate information about associations between genetic variants and therapeutic options. Recently, a number of knowledge bases (KBs) have been developed that gather such information on the basis of expert curation of the scientific literature. We performed a quantitative and qualitative comparison of Clinical Interpretations of Variants in Cancer, OncoKB, Cancer Gene Census, Database of Curated Mutations, CGI Biomarkers (the cancer genome interpreter biomarker database), Tumor Alterations Relevant for Genomics-Driven Therapy, and the Precision Medicine Knowledge Base. METHODS We downloaded each KB and restructured their content to describe variants, genes, drugs, and gene-drug associations in a common format. We normalized gene names to Entrez Gene IDs and drug names to ChEMBL and DrugBank IDs. For the analysis of clinically relevant gene-drug associations, we obtained lists of genes affected by genetic alterations and putative drug therapies for 113 patients with cancer whose cases were presented at the Molecular Tumor Board (MTB) of the Charité Comprehensive Cancer Center. RESULTS Our analysis revealed that the KBs are largely overlapping but also that each source harbors a notable amount of unique information. Although some KBs cover more genes, others contain more data about gene-drug associations. Retrospective comparisons with findings of the Charitè MTB at the gene level showed that use of multiple KBs may considerably improve retrieval results. The relative importance of a KB in terms of cancer genes was assessed in more detail by logistic regression, which revealed that all but one source had a notable impact on result quality. We confirmed these findings using a second data set obtained from an independent MTB. CONCLUSION To date, none of the existing publicly available KBs on gene-drug associations in precision oncology fully subsumes the others, but all of them exhibit specific strengths and weaknesses. Consideration of multiple KBs, therefore, is essential to obtain comprehensive results.

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Utility of a multidisciplinary tumor board in the management of pancreatic diseases.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.319 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 319-319

Author(s):

David G. Brauer ◽

Matthew S. Strand ◽

Dominic E. Sanford ◽

Maria Majella Doyle ◽

Faris Murad ◽

...

Keyword(s):

Treatment Plan ◽

Diagnostic Testing ◽

Retrospective Chart Review ◽

Multidisciplinary Care ◽

Tumor Board ◽

Cancer Center ◽

Common Diagnosis ◽

Tumor Boards ◽

Cancer Network ◽

The Impact

319 Background: Multidisciplinary Tumor Boards (MTBs) are a requirement for comprehensive cancer centers and are routinely used to coordinate multidisciplinary care in oncology. Despite their widespread use, the impact of MTBs is not well characterized. We studied the outcomes of all patients presented at our pancreas MTB, with the goal of evaluating our current practices and resource utilization. Methods: Data were prospectively collected for all patients presented at a weekly pancreas-specific MTB over the 12-month period at a single-institution NCI-designated cancer center. The conference is attended by surgical, medical, and radiation oncologists, interventional gastroenterologists, pathologists, and radiologists (diagnostic and interventional). Retrospective chart review was performed at the end of the 12-month period under an IRB-approved protocol. Results: A total of 470 patient presentations were made over a 12-month period. Average age at time of presentation was 61.5 years (range 17 – 89) with 51% males. 61.7% of cases were presented by surgical oncologists and 26% by medical oncologists. 174 cases were the result of new diagnoses or referrals. 78 patients were presented more than once (average of 2.3 times). Pancreatic adenocarcinoma was the most common diagnosis (37%), followed by uncharacterized pancreatic mass (16%), and pancreatic cyst (7%). The treatment plan proposed by the presenting clinician was known or could be evaluated prior to conference in 402 cases. Presentation of a case at MTB changed the plan of management 25% (n = 100) of the time, including MTB recommendation against a planned resection in 46 cases. When the initial plan changed as a result of MTB discussion, the most common new plan was to obtain further diagnostic testing such as biopsy and/or endoscopy (n = 24). Conclusions: MTBs are required and resource-intensive but offer the opportunity to discuss a wide array of pathologies and influence management decisions in a sizable proportion of cases. Additional investigations evaluating adherence rates to MTB decisions and to published guidelines (i.e. National Comprehensive Cancer Network) will further enhance the assessment and utility of MTBs.

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