The molecular tumor board: a tool for the governance of precision oncology in the real world

Clinical oncology is going through a period of profound change. Targeted therapy, and more recently immunotherapy, have revolutionized the natural history and outcomes of many solid tumors. Clinical oncology is now indissoluble from molecular oncology, a rapidly evolving field. This profound transformation is the rationale for molecular tumor board (MTB) implementation. MTBs represent a resource for the development of precision oncology and clinical practice implementation is a complex and important challenge for the future of clinical and molecular oncology. Economic sustainability of genomic tests, access to drugs or clinical trials according to the MTB recommendation, and expanded use of existing anticancer drugs are required for MTBs to become a useful tool for the governance of precision oncology in the real world. This is an ongoing process, with establishment of MTBs the first step. Continuing to work in collaboration with scientific societies, MTBs are poised to become a homogeneous and well-structured reality that can make the care pathway of the patient with cancer more efficient, with the ultimate goal to offer personalized therapy based on the most advanced scientific knowledge.

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Impact of Molecular Tumor Board (MTB) on precision oncology in a community setting

Gynecologic Oncology ◽

10.1016/s0090-8258(21)00987-2 ◽

2021 ◽

Vol 162 ◽

pp. S180

Author(s):

Adam ElNaggar ◽

Gregory Vidal ◽

Ari VanderWalde ◽

Lee Schwartzberg ◽

Axel Grothey ◽

...

Keyword(s):

Community Setting ◽

Tumor Board ◽

Precision Oncology ◽

Molecular Tumor Board

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The challenge of the Molecular Tumor Board empowerment in clinical oncology practice: A Position Paper on behalf of the AIOM- SIAPEC/IAP-SIBioC-SIC-SIF-SIGU-SIRM Italian Scientific Societies

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2021.103567 ◽

2021 ◽

pp. 103567

Author(s):

Antonio Russo ◽

Lorena Incorvaia ◽

Ettore Capoluongo ◽

Pierosandro Tagliaferri ◽

Antonio Galvano ◽

...

Keyword(s):

Clinical Oncology ◽

Position Paper ◽

Tumor Board ◽

Scientific Societies ◽

Molecular Tumor Board ◽

Oncology Practice

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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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Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study—An Asian Tertiary Cancer Center Experience

JCO Precision Oncology ◽

10.1200/po.20.00261 ◽

2021 ◽

pp. 859-875

Author(s):

Amanda O. L. Seet ◽

Aaron C. Tan ◽

Tira J. Tan ◽

Matthew C. H. Ng ◽

David W. M. Tai ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Tumor Tissue ◽

Molecular Profiling ◽

Tumor Board ◽

Cancer Center ◽

Precision Oncology ◽

Molecular Tumor Board ◽

Tumor Types ◽

Tertiary Cancer Center

PURPOSE Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.

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Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board

JCO Precision Oncology ◽

10.1200/po.16.00022 ◽

2017 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Mark E. Burkard ◽

Dustin A. Deming ◽

Benjamin M. Parsons ◽

Paraic A. Kenny ◽

Marissa R. Schuh ◽

...

Keyword(s):

Clinical Trials ◽

Precision Medicine ◽

Clinical Utility ◽

Journal Club ◽

Academic Community ◽

Tumor Board ◽

Observational Research ◽

Evidence Based ◽

Precision Oncology ◽

Molecular Tumor Board

Purpose Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region. Materials and Methods We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes. Results We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled. Conclusion The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology.

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A virtual molecular tumor board to improve efficiency and scalability of delivering precision oncology to physicians and their patients

JAMIA Open ◽

10.1093/jamiaopen/ooz045 ◽

2019 ◽

Vol 2 (4) ◽

pp. 505-515 ◽

Cited By ~ 11

Author(s):

Michael J Pishvaian ◽

Edik M Blais ◽

R Joseph Bender ◽

Shruti Rao ◽

Simina M Boca ◽

...

Keyword(s):

Treatment Plan ◽

Critical Role ◽

Tumor Board ◽

Care Process ◽

Molecular Profile ◽

Molecular Testing ◽

Precision Oncology ◽

Therapy Options ◽

Scoring Model ◽

Molecular Tumor Board

Abstract Objectives Scalable informatics solutions that provide molecularly tailored treatment recommendations to clinicians are needed to streamline precision oncology in care settings. Materials and Methods We developed a cloud-based virtual molecular tumor board (VMTB) platform that included a knowledgebase, scoring model, rules engine, an asynchronous virtual chat room and a reporting tool that generated a treatment plan for each of the 1725 patients based on their molecular profile, previous treatment history, structured trial eligibility criteria, clinically relevant cancer gene-variant assertions, biomarker-treatment associations, and current treatment guidelines. The VMTB systematically allows clinician users to combine expert-curated data and structured data from clinical charts along with molecular testing data to develop consensus on treatments, especially those that require off-label and clinical trial considerations. Results The VMTB was used as part of the cancer care process for a focused subset of 1725 patients referred by advocacy organizations wherein resultant personalized reports were successfully delivered to treating oncologists. Median turnaround time from data receipt to report delivery decreased from 14 days to 4 days over 4 years while the volume of cases increased nearly 2-fold each year. Using a novel scoring model for ranking therapy options, oncologists chose to implement the VMTB-derived therapies over others, except when pursuing immunotherapy options without molecular support. Discussion VMTBs will play an increasingly critical role in precision oncology as the compendium of biomarkers and associated therapy options available to a patient continues to expand. Conclusion Further development of such clinical augmentation tools that systematically combine patient-derived molecular data, real-world evidence from electronic health records and expert curated knowledgebases on biomarkers with computational tools for ranking best treatments can support care pathways at point of care.

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Precision oncology experience at a tertiary care center.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18118 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18118-e18118

Author(s):

Meena Sadaps ◽

Pauline Funchain ◽

Petros Grivas ◽

Bassam N. Estfan ◽

Jame Abraham ◽

...

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Real World ◽

Care Center ◽

Tertiary Care ◽

Cleveland Clinic ◽

Tumor Board ◽

Genomic Testing ◽

Precision Oncology ◽

Genomic Profiling

e18118 Background: Precision oncology – use of tumor genomic profiling to guide therapies – is widely discussed but with limited real-world data. We have previously reported our prospective study on feasibility and clinical utility of routine somatic genomic testing of solid tumors [ J Natl Cancer Inst. 2015; 108(3)], and here we report our longitudinal experience, focusing on therapeutic impact. Methods: Records were reviewed for consecutive adult patients seen at Cleveland Clinic for a solid tumor malignancy without known curative options where tumor genomic profiling was ordered using FoundationOne™ (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board, and therapeutic recommendations were conveyed to the primary oncologist. Data for this cohort study approved by the Cleveland Clinic IRB included subsequent therapies and clinical outcomes. Results: From 2013 to 2016, 330 patients had tumor genomic testing ordered. Median age was 61 years (range, 24-94); 170 (51.5%) were female; 289 (87.6%) were Caucasian. Colorectal (21.5%), breast (17%), lung (16.1%), and pancreatobiliary (11.5%) cancers were the most common diagnoses. In 300 resulted cases, a median of 4 (0-20) alterations per specimen were noted; the most commonly altered genes were TP53 (n = 174), KRAS (n = 75), APC (n = 65), CDKN2A/B (n = 49), and PIK3CA/ PIK3R (n = 46). A specific therapy targeting an actionable alteration was recommended in 51% (153/300) of patients, and 11.7% (n = 35) received such therapy: 14 on clinical trials, 5 on-label, and 16 off-label. Most common targets for therapy were PIK3CA/PIK3R/PTEN (n = 7), HER2 (6), BRAF (3), EGFR (3), and ALK, FLT3, NTRK1 and RET (2 each). At last follow-up, of 35 patients receiving targeted therapy, best responses were: complete response (n = 1, 2.9%), partial response (n = 5, 14.3%), stable disease (n = 14, 40%), progressive disease (n = 11, 31.4%); data not available for 4 patients. Non-availability of clinical trials was a common reason for non-receipt of targeted therapy. Conclusions: Tumor genomic profiling influenced treatment in 11.7% of patients in this cohort, and 57% of those receiving targeted therapy experienced clinical benefit. These data can help guide real-world discussions of precision oncology.

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Visualizing real-world outcomes through the lens of a molecular tumor board: Persona-typing pancreatic cancers for clinical decision support.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18100 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18100-e18100

Author(s):

Emanuel Petricoin ◽

Daniel Barg ◽

Patricia Miren de Arbeloa ◽

Michael J. Pishvaian ◽

Edik Matthew Blais

Keyword(s):

Cell Cycle ◽

Dna Damage Response ◽

Real World ◽

Clinical Decision ◽

Parp Inhibitors ◽

Tumor Board ◽

Brca Mutations ◽

Pancreatic Cancers ◽

Damage Response ◽

Molecular Tumor Board

e18100 Background: Despite the molecular diversity of pancreatic adenocarcinoma, standard therapy options remain largely molecularly-untailored except in the context of DNA damage response alterations such as BRCA mutations, NTRK fusions, or microsatellite instability. Methods: To broaden the utility of molecular profiling, we analyzed real-world outcomes and established 12 molecularly-driven clusters, or “persona types” (PTs), across a cohort of 1280 pancreatic cancers with CLIA-grade genomic/proteomic data (commercially available NGS/IHC panels). Patients were consented into Perthera’s precision oncology platform via referrals from advocacy programs and hospital partnerships for case review by a molecular tumor board (MTB). Persona types were generated using unsupervised k-means clustering of molecularly-tailored therapy recommendations formulated by the MTB. Progression-free survival was documented across all lines of therapy. Results: Personas based on multi-omic profiles and expert-driven recommendations were representative of molecular phenotypes reported in previous studies (e.g. DNA damage response deficiencies, BRAF mutations, other non-KRAS-drivers, SWI/SNF alterations, squamous-associated genes, cell cycle regulators, etc.). To streamline the exploration of real-world outcomes, we developed an interactive dashboard that enables users to compare PFS survival curves across Personas for various therapies such as gemcitabine/nab-paclitaxel, FOLFIRINOX, other standard regimens, immunotherapy, PARP inhibitors, RAF/MEK/ERK inhibitors, and more. Persona types associated with increased/decreased sensitivity to several classes of agents were identified (e.g. PD-1/L1 inhibitors in a persona enriched for cell cycle dysregulation, PARP inhibitors in a persona enriched for BRCA mutations). Conclusions: Empowering oncologists with personalized insights into real-world outcomes may promote investigator-initiated trials and augment clinical decision support, particularly when choosing between standard of care regimens or when exploring potential clinical trial options.

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