Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma
Autor: | Azam Ghafoor, Fang Wei, Udayan Guha, Wei Liao, Trinh Hoc Tran Pham, Mark Raffeld, Liqiang Xi, Seth M. Steinberg, Hadi Bagheri, Clive Morris, Nina Monkash, Gregory D. Jones, Jordan Cheng, Michael Tu, David Chia, Ahmad Shafiei, Constance M. Cultraro, Charles M. Strom, Vikram Misra, Elizabeth Akoth, Chul Kim, Nitin Roper, David T.W. Wong |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Saliva EGFR Mutant Oncology and Carcinogenesis medicine.disease_cause NSCLC Article 03 medical and health sciences 0302 clinical medicine Clinical Research Internal medicine medicine PTEN Osimertinib Liquid biopsy RC254-282 Cancer Lung biology business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens ctDNA medicine.disease 030104 developmental biology medicine.anatomical_structure Good Health and Well Being 030220 oncology & carcinogenesis osimertinib biology.protein Adenocarcinoma KRAS business |
Zdroj: | Cancers Cancers, vol 13, iss 13 Volume 13 Issue 13 Cancers, Vol 13, Iss 3342, p 3342 (2021) |
ISSN: | 2072-6694 |
Popis: | Simple Summary ctDNA assay is a promising non-invasive method to detect genomic alterations associated with lung cancer. In this prospective study of 25 patients with EGFR-mutant lung adenocarcinoma receiving osimertinib, ctDNA progression predated radiographic progression by 118 days in 11 of 20 patients with disease progression. Saliva-based ctDNA analysis and plasma NGS detected additional patients with ctDNA progression preceding clinical progression, suggesting the potential complementary roles of different ctDNA detection methodologies. Baseline mutant ctDNA level predicted progression-free survival while tumor volume measurements by volumetric CT did not. Serial ctDNA analysis of plasma and saliva is a clinically useful tool to monitor response and resistance to osimertinib. Abstract Background: We assessed whether serial ctDNA monitoring of plasma and saliva predicts response and resistance to osimertinib in EGFR-mutant lung adenocarcinoma. Three ctDNA technologies—blood-based droplet-digital PCR (ddPCR), next-generation sequencing (NGS), and saliva-based EFIRM liquid biopsy (eLB)—were employed to investigate their complementary roles. Methods: Plasma and saliva samples were collected from patients enrolled in a prospective clinical trial of osimertinib and local ablative therapy upon progression (NCT02759835). Plasma was analyzed by ddPCR and NGS. Saliva was analyzed by eLB. Results: A total of 25 patients were included. We analyzed 534 samples by ddPCR (n = 25), 256 samples by NGS (n = 24) and 371 samples by eLB (n = 22). Among 20 patients who progressed, ctDNA progression predated RECIST 1.1 progression by a median of 118 days (range: 61–272 days) in 11 (55%) patients. Of nine patients without ctDNA progression by ddPCR, two patients had an increase in mutant EGFR by eLB and two patients were found to have ctDNA progression by NGS. Levels of ctDNA measured by ddPCR and NGS at early time points, but not volumetric tumor burden, were associated with PFS. EGFR/ERBB2/MET/KRAS amplifications, EGFR C797S, PIK3CA E545K, PTEN V9del, and CTNNB1 S45P were key resistance mechanisms identified by NGS. Conclusion: Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles. |
Databáze: | OpenAIRE |
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