Wanyuan Cui1, Charlotte Milner-Watts1, Terri P McVeigh2, Anna Minchom1, Jaishree Bholse1, Michael Davidson1, Nadia Yousaf3, Suzanne MacMahon4, Hood Mugalaasi5, Ranga Gunapala1, Richard Lee6, Angela George7, Sanjay Popat8, Mary O'Brien9. 1. Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom. 2. Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom. 3. Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; Thoracic Oncology, Institute of Cancer Research, London, United Kingdom. 4. Centre for Molecular Pathology, Royal Marsden NHS Foundation Trust, London, United Kingdom; Cancer Genomics, North Thames Genomic Laboratory Hub, London, United Kingdom. 5. Centre for Molecular Pathology, Royal Marsden NHS Foundation Trust, London, United Kingdom; Division of Molecular Pathology, Institute of Cancer Research, London, United Kingdom. 6. Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Early Diagnosis and Detection, NIHR Royal Marsden and ICR Biomedical Research Centre, United Kingdom. 7. Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; Gynaecology Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom. 8. Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; Thoracic Oncology, Institute of Cancer Research, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom. 9. Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address: Mary.obrien@rmh.nhs.uk.
Abstract
INTRODUCTION: The diagnostic pathway for lung cancer can be long. Availability of front-line targeted therapies for NSCLC demands access to good quality tissue for genomic sequencing and rapid reporting of results. Diagnosis of lung cancer and availability of tissue was delayed during the COVID-19 pandemic. METHODS: A pilot study assessing Guardant360™ cfDNA-NGS in patients with radiological-suspected advanced-stage lung cancer was performed at an academic cancer centre during COVID-19. Variants were tiered using AMP/ASCO/CAP guidelines and discussed at a tumour molecular board. The primary endpoint was the proportion of patients who commenced targeted treatment based on cfDNA-NGS results without tissue molecular results, predicted to be ≥ 10%. RESULTS: Between April 2020-May 2021, 51 patients were enrolled; 49 were evaluable. The median age was 71 years, 43% were never-smokers, 86% had stage IV disease. 80% of evaluable cfDNA-NGS were informative (tumour-derived cfDNA detected). cfDNA-NGS detected 30 (61%) AMP/ASCO/CAP tier 1 variants, including 20 additional tier 1 variants compared to tissue testing. Three patients with non-informative cfDNA-NGS had tier 1 variants identified on tissue testing. Eleven (22%; 95%CI 12%-27%) patients commenced targeted therapy based on cfDNA-NGS results without tissue molecular results, meeting the primary endpoint. Median time to results was shorter for cfDNA-NGS compared to standard-of-care tissue tests (9 versus 25 days, P < 0.0001). CONCLUSION: Blood-first cfDNA-NGS in NSCLC patients increased the breadth and rapidity of detection of actionable variants with high tissue concordance and led to timely treatment decisions. A blood-first approach should be considered to improve the speed and accuracy of therapeutic decision-making. Crown
INTRODUCTION: The diagnostic pathway for lung cancer can be long. Availability of front-line targeted therapies for NSCLC demands access to good quality tissue for genomic sequencing and rapid reporting of results. Diagnosis of lung cancer and availability of tissue was delayed during the COVID-19 pandemic. METHODS: A pilot study assessing Guardant360™ cfDNA-NGS in patients with radiological-suspected advanced-stage lung cancer was performed at an academic cancer centre during COVID-19. Variants were tiered using AMP/ASCO/CAP guidelines and discussed at a tumour molecular board. The primary endpoint was the proportion of patients who commenced targeted treatment based on cfDNA-NGS results without tissue molecular results, predicted to be ≥ 10%. RESULTS: Between April 2020-May 2021, 51 patients were enrolled; 49 were evaluable. The median age was 71 years, 43% were never-smokers, 86% had stage IV disease. 80% of evaluable cfDNA-NGS were informative (tumour-derived cfDNA detected). cfDNA-NGS detected 30 (61%) AMP/ASCO/CAP tier 1 variants, including 20 additional tier 1 variants compared to tissue testing. Three patients with non-informative cfDNA-NGS had tier 1 variants identified on tissue testing. Eleven (22%; 95%CI 12%-27%) patients commenced targeted therapy based on cfDNA-NGS results without tissue molecular results, meeting the primary endpoint. Median time to results was shorter for cfDNA-NGS compared to standard-of-care tissue tests (9 versus 25 days, P < 0.0001). CONCLUSION: Blood-first cfDNA-NGS in NSCLC patients increased the breadth and rapidity of detection of actionable variants with high tissue concordance and led to timely treatment decisions. A blood-first approach should be considered to improve the speed and accuracy of therapeutic decision-making. Crown
Authors: Doreen A Ezeife; Eldon Spackman; Rosalyn A Juergens; Janessa J Laskin; Jason S Agulnik; Desiree Hao; Scott A Laurie; Jennifer H Law; Lisa W Le; Lesli A Kiedrowski; Barbara Melosky; Frances A Shepherd; Victor Cohen; Paul Wheatley-Price; Rachel Vandermeer; Janice J Li; Roxanne Fernandes; Aria Shokoohi; Richard B Lanman; Natasha B Leighl Journal: Ther Adv Med Oncol Date: 2022-07-26 Impact factor: 5.485
Authors: Miguel Garcia-Pardo; Kasia Czarnecka; Jennifer H Law; Alexandra Salvarrey; Roxanne Fernandes; Jason Fan; Lucy Corke; Thomas K Waddell; Kazuhiro Yasufuku; Laura L Donahoe; Andrew Pierre; Lisa W Le; Noor Ghumman; Geoffrey Liu; Frances A Shepherd; Penelope Bradbury; Adrian Sacher; Tracy Stockley; Prodipto Pal; Patrik Rogalla; Ming Sound Tsao; Natasha B Leighl Journal: Ther Adv Med Oncol Date: 2022-09-20 Impact factor: 5.485