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. 2022 Aug;33(8):750-768.
doi: 10.1016/j.annonc.2022.05.520. Epub 2022 Jul 6.

ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group

J Pascual  1 , G Attard  2 , F-C Bidard  3 , G Curigliano  4 , L De Mattos-Arruda  5 , M Diehn  6 , A Italiano  7 , J Lindberg  8 , J D Merker  9 , C Montagut  10 , N Normanno  11 , K Pantel  12 , G Pentheroudakis  13 , S Popat  14 , J S Reis-Filho  15 , J Tie  16 , J Seoane  17 , N Tarazona  18 , T Yoshino  19 , N C Turner  20
Affiliations
Free article

ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group

J Pascual et al. Ann Oncol. 2022 Aug.
Free article

Abstract

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.

Keywords: circulating tumour DNA (ctDNA); liquid biopsy; precision medicine.

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Conflict of interest statement

Disclosure GA reports receipt of honoraria for participation in Advisory Board from Astellas, AstraZeneca, Bayer, Janssen, Novartis, Orion, Pfizer, Sanofi, Sapience, receipt of honoraria as invited speaker from Astellas, AstraZeneca, Janssen, receipt of royalties for licensing fees from Janssen, receipt of institutional research grants from Astellas and Janssen, non-remunerated activities as a PI in Astellas, Janssen, and non-remunerated advisory role in AstraZeneca and Janssen; FCB reports receipt of honoraria for participation in Advisory Board from Archer, BioNTech, Lilly, Novartis, Pfizer, receipt of honoraria to institution for participation in Advisory Board from AstraZeneca, receipt of honoraria as invited speaker from AstraZeneca, Novartis, Pfizer, Roche, Seagen, receipt of honoraria to institution as invited speaker from Pfizer, Sanofi, receipt of honoraria for expert testimony from Hikma, institutional non-financial interest for research as a coordinating PI from AstraZeneca, Pfizer, ProLynx, Saga and Seagen; GC reports receipt of honoraria for participation in Advisory Board from AstraZeneca, Bristol Myers Squibb (BMS), Daiichi Sankyo, Ellipsis, Exact Sciences, Lilly, Merck, Pfizer, Roche, Veracyte, receipt of honoraria as invited speaker from AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Roche, receipt of honoraria for writing engagement from Pfizer, institutional research grant for investigator initiated clinical trial from Merck, institutional funding for conduct of phase I studies from Astellas, AstraZeneca, Blueprint Medicine, BMS, Daiichi Sankyo, Kymab, Novartis, Philogen, Roche, Sanofi, non-remunerated activities as an officer of the Italian National Health Council—Advisor for Ministry of Health, non-remunerated advisory role as a member of the Scientific Council of Europa Donna, non-remunerated advisory role in Fondazione Beretta, and non-remunerated member of Board of Directors of the Lega Italiana Lotta ai Tumori; LDMA reports receipt of honoraria as invited speaker, participation in speaker bureau from Roche, institutional research collaboration grant from NanoString and receipt of education grant from BMS; MD reports receipt of honoraria for participation in Advisory Board from AstraZeneca, Boehringer Ingelheim, Genentech, Gritstone Oncology, Illumina, receipt of honoraria for consultancy from BioNTech, Novartis, RefleXion, Roche, has ownership interest with CiberMed, Foresight Diagnostics, receipt of royalties for licensing fees from Foresight Diagnostics, Roche Diagnostics, receipt of institutional financial interest as a coordinating PI from AstraZeneca, Varian, receipt of funding from Genentech, non-financial interest for receipt of reagents from Illumina, non-remunerated activities as a member of Board of Directors of Foresight Diagnostics; AI reports receipt of honoraria for participation in Advisory Board from Bayer, Chugai Pharmaceutical Co, GlaxoSmithKline, Philips, Roche, institutional non-financial interest as a coordinating PI from AstraZeneca, Bayer, Ipsen, Merck, Merck Sharp & Dohme (MSD) and Roche; JL reports receipt of honoraria to institution as invited speaker from Roche; JDM reports receipt of honoraria for participation in Advisory Board from Illumina, BMS, receipt of honoraria for consultancy from PierianDx, receipt of royalties for licensing fees administered by Stanford University from the United States Patent Office, non-remunerated activities as a member of Board of Directors of the Association for Molecular Pathology, non-remunerated leadership role as a Chair of the Informatics Subdivision of the Association for Molecular Pathology, non-remunerated leadership role as a Vice Chair of the CLSI MM23—Molecular Diagnostic Methods for Solid Tumors Committee of the Clinical and Laboratory Standards Institute (CLSI), non-remunerated activities in the US NIH/NCI as a PI for the NIH 1-UG1-CA233333-01, UNITS: The UNC/UT National Clinical Trials Network Group Integrated Translational Science Production and Consultation Center; CM reports receipt of honoraria for participation in Advisory Board from Biocartis, Merck Serono, receipt of honoraria as invited speaker from Amgen, Guardant Health, Merck Serono, and Pierre Fabre, Roche, receipt of royalties for licensing fees administered by Institut Investigació Hospital del Mar; NN reports receipt of honoraria for participation in Advisory Board from AstraZeneca, Bayer, Biocartis, Incyte, Novartis, Qiagen, Roche, receipt of honoraria as invited speaker from BMS, Eli Lilly, Illumina, Merck, MSD, Sanofi, Thermo Fisher, receipt of institutional research grants from AstraZeneca, Biocartis, Blueprint, Illumina, Incyte, Merck, Qiagen, Roche, Thermo Fisher, leadership non-remunerated role as a President of the International Quality Network for Pathology (IQN Path) and President of the Italian Cancer Society (SIC); KP reports receipt of honoraria for participation in Advisory Board from MSD, Menarini, Hello Healthcare, Sanofi, receipt of honoraria as invited speaker from Abcam, Ipsen Pharma, Medac, Agena, institutional financial interest from Angle plc, European Liquid Biopsy Society, Böhringer Ingelheim and for participation in IMI JT ID Cancer from EU/IMI Cancer-ID consortium; SP reports receipt of honoraria for participation in Advisory Board from Amgen, AstraZeneca, Bayer, BeiGene, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Guardant Health, Janssen, Eli Lilly, Merck KGaA, Novartis, Roche, Takeda, institutional financial interest for research as a coordinating PI from Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics, as a local PI from AstraZeneca, GlaxoSmithKline, Roche, Trizell, as a sub-investigator from Amgen, MSD, non-remunerated advisory role in ALK Positive UK, International Association for the Study of Lung Cancer, Lung Cancer Europe, Ruth Strauss Foundation, non-remunerated leadership role in the British Thoracic Oncology Group as a Chair of Steering Committee, European Thoracic Oncology Platform as a Foundation Council Member, non-remunerated member of Thoracic malignancy Faculty in the European Society for Medical Oncology, non-remunerated member of Board of Directors in the Mesothelioma Applied Research Foundation; JSRF reports consultancy fees from Goldman Sachs, Repare Therapeutics, Paige.AI and Eli-Lilly, membership of the Board of Directors Group Oncoclinicas, stock ownership of Repare Therapeutics, and honoraria for ad hoc participation in the Scientific Advisory Board of Repare Therapeutics, Paige.AI, Roche Tissue Diagnostics, Novartis, Roche/Genentech, Invicro and Personalis; JT reports consultancy fee from Haystack Oncology, receipt of honoraria for participation in Advisory Board from AstraZeneca, BMS, MSD, Inivata, Pierre Fabre, receipt of honoraria as invited speaker from Merck Serono, Amgen and Servier; JS reports ownership interest as a co-founder of Mosaic Biomedicals SL, member of Board of Directors of Northern Biologics Inc., receipt of institutional research grants from Roche Glycart AG, Mosaic Biomedicals SL, Hoffmann-La Roche Ltd, Northern Biologics Inc., Ridgeline Therapeutics, non-remunerated activities as a member of Board of Directors of Asociación Española Contra el Cáncer and a member of Board of Directors, Secretary General of the European Association for Cancer Research (AACR); TY reports receipt of honoraria as invited speaker from Bayer, Chugai, Eli Lilly, Merck Biopharma, Ono, Taiho, receipt of institutional research grants from Amgen, MSD, Ono, Taiho, receipt of institutional financial interest as a local PI from Chugai, Daiichi Sankyo, MSD, Ono, Parexel International, Sanofi and Sumitomo Dainippon; NT reports receipt of honoraria for participation in Advisory Board from Arvinas, AstraZeneca, BMS, GlaxoSmithKline, Lilly, MSD, Novartis, Pfizer, Repare Therapeutics, Roche/Genentech, Zentalis Pharmaceuticals, institutional funding for research from AstraZeneca, MSD, Pfizer, Roche/Genentech, institutional non-financial interest for provision of material for research from BioRad and for provision of assays from Guardant Health. JS is co-founder of Mosaic Biomedicals and has ownership interests from Mosaic Biomedicals and Northern Biologics and reports receipt of grant/research support from Mosaic Biomedicals, Northern Biologics, Roche/Glycart and Hoffmann la Roche. All other authors have declared no conflicts of interest.

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