{"doi":"10.1001/jamaoncol.2022.4457","title":"Practical Considerations for the Use of Circulating Tumor DNA in the Treatment of Patients With Cancer","abstract":"<jats:sec id=\"ab-crv220006-1\"><jats:title>Importance</jats:title><jats:p>Personalized medicine based on tumor profiling and identification of actionable genomic alterations is pivotal in cancer management. Although tissue biopsy is still preferred for diagnosis, liquid biopsy of blood-based tumor analytes, such as circulating tumor DNA, is a rapidly emerging technology for tumor profiling.</jats:p></jats:sec><jats:sec id=\"ab-crv220006-2\"><jats:title>Observations</jats:title><jats:p>This review presents a practical overview for clinicians and allied health care professionals for selection of the most appropriate liquid biopsy assay, specifically focusing on circulating tumor DNA and how it may affect patient treatment and case management across multiple tumor types. Multiple factors influence the analytical validity, clinical validity, and clinical utility of testing. This review provides recommendations and practical guidance for best practice. Current methodologies include polymerase chain reaction-based approaches and those that use next-generation sequencing (eg, capture-based profiling, whole exome, or genome sequencing). Factors that may influence utility include sensitivity and specificity, quantity of circulating tumor DNA, detection of a small vs a large panel of genes, and clonal hematopoiesis of indeterminate potential. Currently, liquid biopsy appears useful in patients unable to undergo biopsy or where mutations detected may be more representative of the predominant tumor burden than for tissue-based assays. Other potential applications may include screening, primary diagnosis, residual disease, local recurrence, therapy selection, or early therapy response and resistance monitoring.</jats:p></jats:sec><jats:sec id=\"ab-crv220006-3\"><jats:title>Conclusions and Relevance</jats:title><jats:p>This review found that liquid biopsy is increasingly being used clinically in advanced lung cancer, and ongoing research is identifying applications of circulating tumor DNA-based testing that complement tissue analysis across a broad range of clinical settings. Circulating tumor DNA technologies are advancing quickly and are demonstrating potential benefits for patients, health care practitioners, health care systems, and researchers, at many stages of the patient oncologic journey.</jats:p></jats:sec>","journal":"JAMA Oncology","year":2022,"id":47060,"datarank":3.704407100518676,"base_score":4.795790545596741,"endowment":4.795790545596741,"self_citation_contribution":0.7193685818395114,"citation_network_contribution":2.9850385186791644,"self_endowment_contribution":0.7193685818395114,"citer_contribution":2.9850385186791644,"corpus_percentile":null,"corpus_rank":null,"citation_count":120,"citer_count":106,"citers_with_citation_signal":87,"citers_with_endowment":87,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":217350,"name":"Umberto Malapelle","orcid":null,"position":1,"is_corresponding":false},{"id":217351,"name":"Fabrice André","orcid":null,"position":2,"is_corresponding":false},{"id":1537,"name":"Luis Paz-Ares","orcid":null,"position":3,"is_corresponding":false},{"id":95441,"name":"Martin Schuler","orcid":null,"position":4,"is_corresponding":false},{"id":217352,"name":"David M. Thomas","orcid":null,"position":5,"is_corresponding":false},{"id":217353,"name":"Gilad Vainer","orcid":null,"position":6,"is_corresponding":false},{"id":217354,"name":"Takayuki Yoshino","orcid":null,"position":7,"is_corresponding":false},{"id":217355,"name":"Christian Rolfo","orcid":null,"position":8,"is_corresponding":false},{"id":217349,"name":"Matthew G. Krebs","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Practical Considerations for the Use of Circulating Tumor DNA in the Treatment of Patients With Cancer","abstract":"<jats:sec id=\"ab-crv220006-1\"><jats:title>Importance</jats:title><jats:p>Personalized medicine based on tumor profiling and identification of actionable genomic alterations is pivotal in cancer management. Although tissue biopsy is still preferred for diagnosis, liquid biopsy of blood-based tumor analytes, such as circulating tumor DNA, is a rapidly emerging technology for tumor profiling.</jats:p></jats:sec><jats:sec id=\"ab-crv220006-2\"><jats:title>Observations</jats:title><jats:p>This review presents a practical overview for clinicians and allied health care professionals for selection of the most appropriate liquid biopsy assay, specifically focusing on circulating tumor DNA and how it may affect patient treatment and case management across multiple tumor types. Multiple factors influence the analytical validity, clinical validity, and clinical utility of testing. This review provides recommendations and practical guidance for best practice. Current methodologies include polymerase chain reaction-based approaches and those that use next-generation sequencing (eg, capture-based profiling, whole exome, or genome sequencing). Factors that may influence utility include sensitivity and specificity, quantity of circulating tumor DNA, detection of a small vs a large panel of genes, and clonal hematopoiesis of indeterminate potential. Currently, liquid biopsy appears useful in patients unable to undergo biopsy or where mutations detected may be more representative of the predominant tumor burden than for tissue-based assays. Other potential applications may include screening, primary diagnosis, residual disease, local recurrence, therapy selection, or early therapy response and resistance monitoring.</jats:p></jats:sec><jats:sec id=\"ab-crv220006-3\"><jats:title>Conclusions and Relevance</jats:title><jats:p>This review found that liquid biopsy is increasingly being used clinically in advanced lung cancer, and ongoing research is identifying applications of circulating tumor DNA-based testing that complement tissue analysis across a broad range of clinical settings. 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