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. 2021 Jan 11;11(1):103.
doi: 10.3390/diagnostics11010103.

Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late

Maarten J IJzerman  1   2   3 , Jasper de Boer  4 , Arun Azad  3 , Koen Degeling  1   2 , Joel Geoghegan  5 , Chelsee Hewitt  6 , Frédéric Hollande  1 , Belinda Lee  3   7   8 , Yat Ho To  3   7 , Richard W Tothill  1 , Gavin Wright  9 , Jeanne Tie  3   7   10 , Sarah-Jane Dawson  1   3
Affiliations

Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late

Maarten J IJzerman et al. Diagnostics (Basel). .

Abstract

Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. A multi-disciplinary workshop (n = 98 registrations) was organized to discuss routine implementation of liquid biopsies in cancer management. Real-time polls were used to engage with experts' about the current evidence of clinical utility and the barriers to implementation of liquid biopsies. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss applications. The workshop concluded that tumor-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays will most likely provide better clinical utility than tumor-agnostic assays, yet at a higher cost. For routine application, it will be essential to determine clinical utility, to define the minimum quality standards and performance of testing platforms and to ensure their use is integrated into current clinical workflows including how they complement tissue biopsies and imaging. Early health economic models may help identifying the most viable application of liquid biopsies. Alternative funding models for the translation of complex molecular diagnostics, such as liquid biopsies, may also be explored if clinical utility has been demonstrated and when their use is recommended in multi-disciplinary consensus guidelines.

Keywords: CTC; biomarkers; cancer; cancer surveillance; ctDNA; early detection; genomics; health economics; health services research; liquid biopsy; minimal residual disease.

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Conflict of interest statement

S.-J.D. has received research funding to her institution from Roche-Genentech and Cancer Therapeutics CRC. She has been a member of advisory boards for AstraZeneca and Inivata. M.J.I. has received research funding to his institution from Illumina and has been a member of advisory boards for Illumina and RTI Health Solutions. A.A. received research funding as an investigator and to his institution from Astellas, Merck Serono, Astra Zeneca, Bristol Myers Squibb, Aptevo Therapeutics, Glaxo Smith Kline, Pfizer, MedImmune, SYNthorx, Bionomics, Sanofi Aventis, Novartis and Ipsen. Other authors declare no conflicts of interest. None of the listed funders had a role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Example of an evidence slider with which the translational research phase was determined. Each workshop participant could vote once (green dots) following a discussion about this case in the break-out sessions. The individual votes are used to construct density plots.
Figure 2
Figure 2
Pre-workshop question asking which application will likely have the most impact and for which application the most scientific progress has been made.
Figure 3
Figure 3
Results of ranking 5 statements related to clinical use of ctDNA.
Figure 4
Figure 4
Ranking of statements relevant for health economic modeling of liquid biopsies.
Figure 5
Figure 5
Density plots presenting the translational stage of the 4 ctDNA applications.
See this image and copyright information in PMC

References

    1. Ashworth T.R. A Case of Cancer in Which Cells Similar to Those in the Tumors Were Seen in the Blood after Death. Australas. Med. J. 1869;14:146–149.
    1. Allard W.J., Matera J., Miller M.C., Repollet M., Connelly M.C., Rao C., Tibbe A.G.J., Uhr J.W., Terstappen L.W.M.M. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin. Cancer Res. Am. Assoc. Cancer Res. 2004;10:6897–6904. doi: 10.1158/1078-0432.CCR-04-0378. - DOI - PubMed
    1. De Bono J.S., Scher H.I., Montgomery R.B., Parker C., Miller M.C., Tissing H., Doyle G.V., Terstappen L.W.W.M., Pienta K.J., Raghavan D. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin. Cancer Res. Am. Assoc. Cancer Res. 2008;14:6302–6309. doi: 10.1158/1078-0432.CCR-08-0872. - DOI - PubMed
    1. Cristofanilli M., Hayes D.F., Budd G.T., Ellis M.J., Stopeck A., Reuben J.M., Doyle G.V., Matera J., Allard W.J., Miller M.C., et al. Circulating tumor cells: A novel prognostic factor for newly diagnosed metastatic breast cancer. J. Clin. Oncol. 2005;23:1420–1430. doi: 10.1200/JCO.2005.08.140. - DOI - PubMed
    1. Cohen S.J., Punt C.J.A., Iannotti N., Saidman B.H., Sabbath K.D., Gabrail N.Y., Picus J., Morse M., Mitchell E., Miller M.C., et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J. Clin. Oncol. 2008;26:3213–3221. doi: 10.1200/JCO.2007.15.8923. - DOI - PubMed

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