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Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients

Stage II–IIIA nonsmall cell lung cancer (NSCLC) patients receive adjuvant chemotherapy after surgery as standard‐of‐care treatment, even though only approximately 5.8% of patients will benefit. Identifying patients with minimal residual disease (MRD) after surgery using tissue‐informed testing of po...

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Autores principales: Vessies, Daan C. L., Schuurbiers, Milou M. F., van der Noort, Vincent, Schouten, Irene, Linders, Theodora C., Lanfermeijer, Mirthe, Ramkisoensing, Kalpana L., Hartemink, Koen J., Monkhorst, Kim, van den Heuvel, Michel M., van den Broek, Daan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297781/
https://www.ncbi.nlm.nih.gov/pubmed/35674097
http://dx.doi.org/10.1002/1878-0261.13267
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author Vessies, Daan C. L.
Schuurbiers, Milou M. F.
van der Noort, Vincent
Schouten, Irene
Linders, Theodora C.
Lanfermeijer, Mirthe
Ramkisoensing, Kalpana L.
Hartemink, Koen J.
Monkhorst, Kim
van den Heuvel, Michel M.
van den Broek, Daan
author_facet Vessies, Daan C. L.
Schuurbiers, Milou M. F.
van der Noort, Vincent
Schouten, Irene
Linders, Theodora C.
Lanfermeijer, Mirthe
Ramkisoensing, Kalpana L.
Hartemink, Koen J.
Monkhorst, Kim
van den Heuvel, Michel M.
van den Broek, Daan
author_sort Vessies, Daan C. L.
collection PubMed
description Stage II–IIIA nonsmall cell lung cancer (NSCLC) patients receive adjuvant chemotherapy after surgery as standard‐of‐care treatment, even though only approximately 5.8% of patients will benefit. Identifying patients with minimal residual disease (MRD) after surgery using tissue‐informed testing of postoperative plasma circulating cell‐free tumour DNA (ctDNA) may allow adjuvant therapy to be withheld from patients without MRD. However, the detection of MRD in the postoperative setting is challenging, and more sensitive methods are urgently needed. We developed a method that combines variant calling and a novel ctDNA fragment length analysis using hybrid capture sequencing data. Among 36 stage II–IIIA NSCLC patients, this method distinguished patients with and without recurrence of disease in a 20 times repeated 10‐fold cross validation with 75% accuracy (P = 0.0029). In contrast, using only variant calling or only fragment length analysis, no signification distinction between patients was shown (P = 0.24 and P = 0.074 respectively). In addition, a variant‐level fragmentation score was developed that was able to classify variants detected in plasma cfDNA into tumour‐derived or white‐blood‐cell‐derived variants with 84% accuracy. The findings in this study may help drive the integration of various types of information from the same data, eventually leading to cheaper and more sensitive techniques to be used in this challenging clinical setting.
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spelling pubmed-92977812022-07-22 Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients Vessies, Daan C. L. Schuurbiers, Milou M. F. van der Noort, Vincent Schouten, Irene Linders, Theodora C. Lanfermeijer, Mirthe Ramkisoensing, Kalpana L. Hartemink, Koen J. Monkhorst, Kim van den Heuvel, Michel M. van den Broek, Daan Mol Oncol Research Articles Stage II–IIIA nonsmall cell lung cancer (NSCLC) patients receive adjuvant chemotherapy after surgery as standard‐of‐care treatment, even though only approximately 5.8% of patients will benefit. Identifying patients with minimal residual disease (MRD) after surgery using tissue‐informed testing of postoperative plasma circulating cell‐free tumour DNA (ctDNA) may allow adjuvant therapy to be withheld from patients without MRD. However, the detection of MRD in the postoperative setting is challenging, and more sensitive methods are urgently needed. We developed a method that combines variant calling and a novel ctDNA fragment length analysis using hybrid capture sequencing data. Among 36 stage II–IIIA NSCLC patients, this method distinguished patients with and without recurrence of disease in a 20 times repeated 10‐fold cross validation with 75% accuracy (P = 0.0029). In contrast, using only variant calling or only fragment length analysis, no signification distinction between patients was shown (P = 0.24 and P = 0.074 respectively). In addition, a variant‐level fragmentation score was developed that was able to classify variants detected in plasma cfDNA into tumour‐derived or white‐blood‐cell‐derived variants with 84% accuracy. The findings in this study may help drive the integration of various types of information from the same data, eventually leading to cheaper and more sensitive techniques to be used in this challenging clinical setting. John Wiley and Sons Inc. 2022-06-27 2022-07 /pmc/articles/PMC9297781/ /pubmed/35674097 http://dx.doi.org/10.1002/1878-0261.13267 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Vessies, Daan C. L.
Schuurbiers, Milou M. F.
van der Noort, Vincent
Schouten, Irene
Linders, Theodora C.
Lanfermeijer, Mirthe
Ramkisoensing, Kalpana L.
Hartemink, Koen J.
Monkhorst, Kim
van den Heuvel, Michel M.
van den Broek, Daan
Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients
title Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients
title_full Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients
title_fullStr Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients
title_full_unstemmed Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients
title_short Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II–IIIA NSCLC patients
title_sort combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour dna of stage ii–iiia nsclc patients
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297781/
https://www.ncbi.nlm.nih.gov/pubmed/35674097
http://dx.doi.org/10.1002/1878-0261.13267
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