Implementation of Up-front ctDNA Into Lung Cancer Care and Development of Liquid Biopsy-based Decision Support Models - LM² Study

Despite scientific evidence, use of liquid biopsy (LB) in diagnosis and monitoring of lung cancer (LC) is limited since it requires major changes in diagnostic and care pathways. Analyzing tumor markers (TMs), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in blood (LB) can inform about the nature of the tumor, the most appropriate therapy, therapy response and resistance. Lungmarker2 is a multicenter, prospective, implementation and diagnostic cohort study. This study aims to implement up-front ctDNA analysis ('plasma first approach') into routine diagnostic work-up of all advanced stage LC patients in the Southeast of the Netherlands (the participating hospitals in the OncoZON region). Thereby, additional information about the molecular make-up of the tumor becomes available, the number of tissue Next-Generation Sequencing (NGS) analyses will decrease and time to therapeutic decision making is shortened. Next, using ctDNA, TM and other information, multi-parametric decision support models are built and validated that may support diagnosis, predict the outcome of the next imaging procedure and progression-free survival during follow-up. The final goal is to develop a super-resolution microscopy test that can detect PD-L1 expression on CTCs.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Aged 18 or above and suspected of having lung cancer

Exclusion Criteria:

* Presence of another malignant tumor, i.e. diagnosed with a tumor in the past 5 years

• BACKGROUNDIgnatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic - implementation issues and future challenges. Nat Rev Clin Oncol. 2021 May;18(5):297-312. doi: 10.1038/s41571-020-00457-x. Epub 2021 Jan 20. PMID 33473219
• BACKGROUNDIJzerman MJ, de Boer J, Azad A, Degeling K, Geoghegan J, Hewitt C, Hollande F, Lee B, To YH, Tothill RW, Wright G, Tie J, Dawson SJ. Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late. Diagnostics (Basel). 2021 Jan 11;11(1):103. doi: 10.3390/diagnostics11010103. PMID 33440749
• BACKGROUNDRolfo C, Mack P, Scagliotti GV, Aggarwal C, Arcila ME, Barlesi F, Bivona T, Diehn M, Dive C, Dziadziuszko R, Leighl N, Malapelle U, Mok T, Peled N, Raez LE, Sequist L, Sholl L, Swanton C, Abbosh C, Tan D, Wakelee H, Wistuba I, Bunn R, Freeman-Daily J, Wynes M, Belani C, Mitsudomi T, Gandara D. Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer. J Thorac Oncol. 2021 Oct;16(10):1647-1662. doi: 10.1016/j.jtho.2021.06.017. Epub 2021 Jul 8. PMID 34246791
• BACKGROUNDde Kock R, Deiman B, Kraaijvanger R, Scharnhorst V. Optimized (Pre) Analytical Conditions and Workflow for Droplet Digital PCR Analysis of Cell-Free DNA from Patients with Suspected Lung Carcinoma. J Mol Diagn. 2019 Sep;21(5):895-902. doi: 10.1016/j.jmoldx.2019.05.003. Epub 2019 Jun 21. PMID 31229652
• BACKGROUNDGenet SAAM, Visser E, van den Borne BEEM, Soud MY, Belderbos HNA, Stege G, de Saegher MEA, Eduati F, Broeren MAC, van Dongen J, Brunsveld L, van de Kerkhof D, Scharnhorst V. Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer. Oncotarget. 2020 Jul 7;11(27):2660-2668. doi: 10.18632/oncotarget.27664. eCollection 2020 Jul 7. PMID 32676167
• BACKGROUNDde Kock R, van den Borne B, Youssef-El Soud M, Belderbos H, Brunsveld L, Scharnhorst V, Deiman B. Therapy Monitoring of EGFR-Positive Non-Small-Cell Lung Cancer Patients Using ddPCR Multiplex Assays. J Mol Diagn. 2021 Apr;23(4):495-505. doi: 10.1016/j.jmoldx.2021.01.003. Epub 2021 Jan 22.