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Pathologists at the Forefront: Shaping the Future of Cancer Treatment with Molecular Tumor Boards

Molecular Tumor Boards

What is a mTB

The goal of personalized healthcare (PHC) is to customize treatment to the individual characteristics of each patient, maximizing efficacy and minimizing adverse effects. This paradigm considers genetic, environmental, and lifestyle factors. Central to PHC is embracing new validated technologies like circulating tumor DNA (ctDNA), digital health, and next-generation sequencing (NGS), while incorporating the evolution of existing ones – for example, multiplexed histology.1 NGS provides detailed genetic information, uncovering mutations and variations linked to diseases, leading to deeper more comprehensive understanding of pathogenesis and opportunities for novel targeted therapies. However, NGS results can be challenging to interpret in the context of technical quality, biologic relevance, and clinical impact, leading to the use of molecular tumor boards (mTBs) to support interpretation and align across functional expertise.2

mTBs are crucial to enable PHC, bringing together multidisciplinary experts to analyze complex tumor-specific genetic data. Commonly, mTBs consist of oncologists, pathologists, pharmacists, and molecular scientific experts at their core. A recent systematic literature review looking at 35 mTB publications shows more insights into mTB participation: oncologists (100%), pathologists (91%), geneticists (69%), bioinformatics (38%), clinical molecular biologists (25%), pharmacists (22%), and bioethicists (9%) (Figure 1).3 Classically, mTB participation is in person. However, with the community embracing virtual meetings, studies have shown a 46% increase in stakeholder participation and a 20% increase in overall cases presented. Usual tumor types presented at mTBs include sarcomas (21%), breast cancers (20%), brain tumors (15%), GYN tumors (14%), and unknown/other tumors (31%). This multidisciplinary and collaborative approach ensures the integration of the latest scientific discoveries into diagnosis and clinical care resulting in significant improvement in patient outcomes.4

Figure 1: Molecular tumor board workflow. Ultimately, the treating physician will make the final treatment decision.

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Table 1

Knowledgebase Variant annotation Drug availability Trial matching Literature citation Website
CGI Yes Yes No Yescancergenomeinterpreter.org
CIViCYesYesNoYescivicdb.org
DEPOYesYesNoYes**link does not work**
HemOnc.org

Yes

YesNoYeshemonc.org
JAX CKB+YesYesYes*Yesckb.genomenon.com
MCG

Yes

YesYesmycancergenome.org 
OncoKBYesYesNoYesoncokb.org
PCTYesYesYesYespct.mdanderson.org
PMKBYesYesNoYespmkb.weill.cornell.edu
Drug-associated knowledgebases
Genomics of drug sensitivity in cancerYesYesNoNocancerrxgene.org
PharmGKBYesYesNoNopharmgkb.org
Therapeutic target databasesYesYesNoYesdb.idrblab.net/ttd

*Available only with subscription to CKB BOOST. +Partially publicly available databases.

Table 1: Summary of publicly available precision oncology knowledgebases. Li X, Warner JL. A review of precision oncology knowledgebases for determining the clinical actionability of genetic variants. Front Cell Dev Biol. 2020;8:48. doi:10.3389/fcell.2020.00048 Licensed under Creative Commons Attribution License (CC BY).

References

  1. Jameson JL, Longo DL. Precision medicine - personalized, problematic, and promising. N Engl J Med. 2015;372:2229-2234. doi:10.1056/NEJMsb1503104
  2. Tsimberidou AM, Sireci A, Dumanois R, Pritchard D. Strategies to address the clinical practice gaps affecting the implementation of personalized medicine in cancer care. JCO Oncol Pract. 2024;20(6):761-766. doi:10.1200/OP.23.00601.
  3. Luchini C, Lawlor RT, Milella M, Scarpa A. Molecular tumor boards in clinical practice. Trends Cancer. 2020;6(9):738-744. doi:10.1016/j.trecan.2020.05.008.
  4. Tsimberidou A, et al. Molecular tumour boards - current and future considerations for precision oncology. Nat Rev Clin Oncol. 2023;20(12):843-863. doi:10.1038/s41571-023-00824-4.
  5. Larson KL, et al. Clinical outcomes of molecular tumor boards: A systematic review. JCO Precis Oncol. 2021;5:PO.20.00495. doi:10.1200/PO.20.00495.
  6. Kato S, et al. Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy. Nat Commun. 2020;11(1):4965. doi:10.1038/s41467-020-18613-3. PMID: 33009371; PMCID: PMC7532150.
  7. Helali A, et al. The impact of the multi-disciplinary molecular tumour board and integrative next generation sequencing on clinical outcomes in advanced solid tumours. Lancet Reg Health West Pac. 2023:36:100775. doi:10.1016/j.lanwpc.2023.100775.
  8. Southwest Oncology Group. Trial s2108cd. https://www.swog.org/clinical-trials/s2108cd
  9. Rieke D. et al. Comparison of treatment recommendations by molecular tumor boards worldwide. JCO Precis Oncol. 2018;2:1-14. doi:10.1200/PO.18.00098.
  10. Memorial Sloan Kettering Cancer Center. OncoKB. https://www.oncokb.org/
  11. The Jackson Laboratory. Clinical Knowledge Database. https://www.jax.org/clinical-genomics/ckb
  12. Tamborero D, et al. Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal. Nat Med. 2020;26(7):992-994. doi:10.1038/s41591-020-0969-2.
  13. Li MM, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: A joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4-23. doi:10.1016/j.jmoldx.2016.10.002.
  14. Johnson A, et al. The right drugs at the right time for the right patient: the MD Anderson precision oncology decision support platform. Drug Discov Today. 2015;20(12):1433-8. doi:10.1016/j.drudis.2015.05.013.
  15. O'Dwyer PJ, et al. The NCI-MATCH trial: lessons for precision oncology. Nat Med. 2023;29(6):1349-1357. doi:10.1038/s41591-023-02379-4.
  16. Mateo J, et al. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol. 2018;29(9):1895-1902. doi:10.1093/annonc/mdy263.
  17. Walters M, et al. Quantifying the value of the molecular tumor board: discordance recommendation rate and drug cost avoidance. JCO Precis Oncol. 2022;6:e2200132. doi:10.1200/PO.22.00132.
  18. Basse C, et al. Relevance of a molecular tumour board (MTB) for patients' enrolment in clinical trials: experience of the Institut Curie. ESMO Open. 2018;3(3):e000339. doi:10.1136/esmoopen-2018-000339.
  19. Sánchez NS, et al. Identification of actionable genomic alterations using circulating cell-free DNA. JCO Precis Oncol. 2019;3:PO.19.00017. doi:10.1200/PO.19.00017.
  20. Plotkin E, et al., Integration of pathology within the multidisciplinary cancer care team. J Clin Ocol. 37, 49-49(2019). doi:10.1200/JCO.2019.37.27_suppl.49
  21. Deverka P, et al. Clinical integration of next generation sequencing: coverage and reimbursement challenges. J Law Med Ethics. 2014;42:22-41. doi:10.1111/jlme.12160.
  22. Love T, et al. Development and validation of ACTE-MTB: A tool to systematically assess the maturity of molecular tumor boards. PLoS One. 2022;17(5):e0268477. doi:10.1371/journal.pone.0268477.
  23. Masood S, Siddiqi A. Cytopathology in focus: ROSE and telecytopathology: a point-of-care test. CAPOnlineToday. 2022.
  24. Li X, Warner JL. A review of precision oncology knowledgebases for determining the clinical actionability of genetic variants. Front Cell Dev Biol. 2020;8:48. doi:10.3389/fcell.2020.00048

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