Bibliographic Details
| Title: |
Combined multimodal ctDNA analysis and radiological imaging for tumor surveillance in Non-small cell lung cancer |
| Authors: |
Martin Metzenmacher, Balazs Hegedüs, Jan Forster, Alexander Schramm, Peter A. Horn, Christoph A. Klein, Nicola Bielefeld, Till Ploenes, Clemens Aigner, Dirk Theegarten, Hans-Ulrich Schildhaus, Jens T. Siveke, Martin Schuler, Smiths S. Lueong |
| Source: |
Translational Oncology, Vol 15, Iss 1, Pp 101279- (2022) |
| Publisher Information: |
Elsevier, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Lung cancer, ddPCR, NGS, cfDNA methylation, Surveillance, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Background: Radiology is the current standard for monitoring treatment responses in lung cancer. Limited sensitivity, exposure to ionizing radiations and related sequelae constitute some of its major limitation. Non-invasive and highly sensitive methods for early detection of treatment failures and resistance-associated disease progression would have additional clinical utility. Methods: We analyzed serially collected plasma and paired tumor samples from lung cancer patients (61 with stage IV, 48 with stages I-III disease) and 61 healthy samples by means of next-generation sequencing, radiological imaging and droplet digital polymerase chain reaction (ddPCR) mutation and methylation assays. Results: A 62% variant concordance between tumor-reported and circulating-free DNA (cfDNA) sequencing was observed between baseline liquid and tissue biopsies in stage IV patients. Interestingly, ctDNA sequencing allowed for the identification of resistance-mediating p.T790M mutations in baseline plasma samples for which no such mutation was observed in the corresponding tissue. Serial circulating tumor DNA (ctDNA) mutation analysis by means of ddPCR revealed a general decrease in ctDNA loads between baseline and first reassessment. Additionally, serial ctDNA analyses only recapitulated computed tomography (CT) -monitored tumor dynamics of some, but not all lesions within the same patient. To complement ctDNA variant analysis we devised a ctDNA methylation assay (methcfDNA) based on methylation-sensitive restriction enzymes. cfDNA methylation showed and area under the curve (AUC) of > 0.90 in early and late stage cases. A decrease in methcfDNA between baseline and first reassessment was reflected by a decrease in CT-derive tumor surface area, irrespective of tumor mutational status. Conclusion: Taken together, our data support the use of cfDNA sequencing for unbiased characterization of the molecular tumor architecture, highlights the impact of tumor architectural heterogeneity on ctDNA-based tumor surveillance and the added value of complementary approaches such as cfDNA methylation for early detection and monitoring |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1936-5233 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S1936523321002709; https://doaj.org/toc/1936-5233 |
| DOI: |
10.1016/j.tranon.2021.101279 |
| Access URL: |
https://doaj.org/article/d3b1076963f443d6a11522f1b04db4d4 |
| Accession Number: |
edsdoj.3b1076963f443d6a11522f1b04db4d4 |
| Database: |
Directory of Open Access Journals |
