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Review
. 2024 Feb;21(1):40-50.
doi: 10.1177/17407745231203330. Epub 2023 Oct 31.

Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials

R Taylor Sundby  1 , Steven D Rhodes  2 , Edina Komlodi-Pasztor  3 , Herb Sarnoff  4   5 , Vito Grasso  6   7 , Meena Upadhyaya  8 , AeRang Kim  9 , D Gareth Evans  10 , Jaishri O Blakeley  11 , C Oliver Hanemann  12 , Chetan Bettegowda  13
Affiliations
Review

Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials

R Taylor Sundby et al. Clin Trials. 2024 Feb.

Abstract

Introduction: Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation of a common data model would further enhance biomarker discovery by enabling effective concatenation of data from multiple studies.

Methods: The Response Evaluation in Neurofibromatosis and Schwannomatosis biomarker working group reviewed published data on emerging trends in neurofibromatosis 1 and schwannomatosis biomarker research and developed recommendations in a series of consensus meetings.

Results: Liquid biopsy has emerged as a promising assay for neurofibromatosis 1/schwannomatosis biomarker discovery and validation. In addition, we review recommendations for a range of biomarkers in clinical trials, neurofibromatosis 1/schwannomatosis-specific data annotations, and common data models for data integration.

Conclusion: These Response Evaluation in Neurofibromatosis and Schwannomatosis consensus guidelines are intended to provide best practices for the inclusion of biomarker studies in neurofibromatosis 1/schwannomatosis clinical trials, data, and sample annotation and to lay a framework for data harmonization and concatenation between trials.

Keywords: Biomarker; cell-free DNA; consensus guidelines; cytokines; liquid biopsy; neurofibromatosis; open science; schwannomatosis.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.T.S. has patent filings related to cancer biomarkers. C.B. is a consultant to Depuy-Synthes, Bionaut Labs, Haystack Oncology, Privo Technologies, and Galectin Therapeutics. C.B. is a co-founder of OrisDx and Belay Diagnostics. C.O.H. has received research support from BergenBio. J.O.B. serves on the advisory board of SpringWorks Therapeutics. HS is CEO of Infixion Bioscience. V.G. is Executive Vice President and CEO of the NYS Academy of Family Physicians and a member of the Board of Directors of the Neural Stem Cell Institute.

Figures

Figure 1.
Figure 1.
Incorporation of molecular biomarkers in NF1/SWN clinical trials. Exploratory correlatives with tissue and circulating biomarkers in interventional trials, windows of opportunity trials, and natural history studies hold promise for enhancing diagnosis, prognostication, and treatment stratification of patients with NF1/SWN.
Figure 2.
Figure 2.
Common data models and annotation ontology enables powered biomarker discovery and validation through the integration of multi-modal data from multiple studies and institutions. To power biomarker discovery in rare diseases like NF1 and SWN, standardized data collection, annotation, and processing must be widely adopted. This would enable data concatenation and harmonization. Importantly, resultant data, including raw molecular data, should be publicly available and disseminated through data repositories.
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References

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