[Skip to Content]
[Skip to Content Landing]

Practical Considerations for the Use of Circulating Tumor DNA in the Treatment of Patients With CancerA Narrative Review

To identify the key insights or developments described in this article
1 Credit CME
Abstract

Importance  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.

Observations  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.

Conclusions and Relevance  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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: July 14, 2022.

Published Online: October 20, 2022. doi:10.1001/jamaoncol.2022.4457

Corresponding Author: Christian Rolfo, MD, PhD, MBA, Center for Thoracic Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, One Levy Pl, Box 1079, New York, NY 10029 (christian.rolfo@mssm.edu).

Author Contributions: All authors had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Krebs, Malapelle, Paz-Ares, Schuler, Vainer, Yoshino, Rolfo.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Krebs, Malapelle, Schuler, Thomas, Vainer, Yoshino, Rolfo.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Andre, Rolfo.

Administrative, technical, or material support: Malapelle, Paz-Ares.

Supervision: Paz-Ares, Schuler, Rolfo.

Conflict of Interest Disclosures: Dr Krebs reported nonfinancial support and grants from Roche during the conduct of the study; consulting and speaker fees from AstraZeneca, Bayer, Guardant, Janssen, Roche, and Seattle Genetics; travel expenses from BerGenBio, Immutep, and Janssen; institutional funding from AstraZeneca, Bayer, BerGenBio, Blueprint, Carrick, Chugai, Immutep, Janssen, Novartis, Nurix, Relay Therapeutics, Roche, Seattle Genetics, and Turning Point Therapeutics outside the submitted work. Dr Malapelle reported speaking and advisory fees from Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GlaxoSmithKline, Merck, AstraZeneca, Janssen, Diatech, Novartis, and Hedera, all outside the submitted work. Dr Andre reported grants from Novartis, Daiichi, Roche, Eli Lilly, AstraZeneca, and Pfizer compensated to the hospital, all outside the submitted work. Dr Paz-Ares reported speaking and/or scientific advisory fees from Amgen, AstraZeneca, Pfizer, Bristol Myers Squibb, Roche , Merck Sharp & Dohme, Mirarti, Bayer, Eli Lilly, PharmaMar, Ipsen, Guardant, Merck, and Novartis; grants from Pfizer, Bristol Myers Squibb, AstraZeneca, and PharmaMar; being a cofounder of Altum sequencing; and being a board member of Genómica, all outside the submitted work. Dr Schuler reported scientific consulting and presentation fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck, Serono, and Novartis; consulting fees from Roche and Sanofi; and grants to the institution from AstraZeneca and Bristol Myers Squibb, outside the submitted work; in addition, Dr Schuler reports a patent for a highly sensitive PCR method for mutation detection issued to the University Duisburg-Essen. Dr Thomas reported grants from Roche, AstraZeneca, Bayer, Amgen, Pfizer, BeiGene, Seattle Genetics, Sun Pharma, and Eisai; and being chief executive officer of Omico, during the conduct of the study. Dr Vainer reported personal fees from Roche, Pfizer, AbbVie, Takeda, Bayer, and AstraZeneca; and nonfinancial support from Bristol Myers Squibb, during the conduct of the study. Dr Yoshino reported personal fees from Chugai, Merck, Bayer, Ono, and Merck Sharp & Dohme; and grants from Merck Sharp & Dohme, Daiichi Sankyo, Ono, Taiho, Amgen, Sanofi, Pfizer, Genomedia, Sysmex, Nippon Boehringer Ingelheim, and Chugai, all outside the submitted work. Dr Rolfo reported advisory board, speaking fees, and nonfinancial medical writing support from Roche and nonfinancial support during the conduct of the study; advisory/committee fees from Bristol Myers Squibb, AstraZeneca, Merck Sharp & Dohme, Pfizer, Mirarti, COR2ED, Daiichi Sankyo, Sanofi, Genzyme-Regeneron, Bayer, and Eisai; grants from the US National Institutes of Health’s SeroNet, the Lung Cancer Research Foundation, and Pfizer; and being on data safety monitoring/advisory boards for EMD, Merck Serono, ISLB president, the International Association for the Study of Lung Cancer, European School of Oncology, European Society for Medical Oncology, editor-in-chief of Critical Reviews in Oncology/Hematology at Elsevier, and former associate editor of ESMO Open, all outside the submitted work. No other disclosures were reported.

Additional Contributions: Research support in the form of third-party medical writing assistance and formatting for this narrative review—furnished by Blair Jarvis, MSc, on behalf of Health Interactions, and Islay Steele, PhD, Health Interactions—was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

References
1.
Rolfo  C , Mack  PC , Scagliotti  GV ,  et al.  Liquid biopsy for advanced non-small cell lung cancer (NSCLC): a statement paper from the IASLC.   J Thorac Oncol. 2018;13(9):1248-1268. doi:10.1016/j.jtho.2018.05.030 PubMedGoogle ScholarCrossref
2.
Rolfo  C , Mack  P , Scagliotti  GV ,  et al.  Liquid biopsy for advanced NSCLC: a consensus statement from the international association for the study of lung cancer.   J Thorac Oncol. 2021;16(10):1647-1662. doi:10.1016/j.jtho.2021.06.017 PubMedGoogle ScholarCrossref
3.
Guardant Health. Guardant Health CDx Technical Information. Accessed July 1, 2022. https://guardant360cdx.com/wp-content/uploads/guardant360-cdx-technical-information.pdf
4.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer, Version 4. 2022. Accessed July 1, 2022. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
5.
Foundation Medicine. FoundationOne Liquid CDx Technical Information. Accessed July 1, 2022. https://info.foundationmedicine.com/hubfs/FMI%20Labels/FoundationOne_Liquid_CDx_Label_Technical_Info.pdf
6.
Van Cutsem  E , Cervantes  A , Adam  R ,  et al.  ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.   Ann Oncol. 2016;27(8):1386-1422. doi:10.1093/annonc/mdw235 PubMedGoogle ScholarCrossref
7.
Metzenmacher  M , Váraljai  R , Hegedüs  B ,  et al.  Plasma next generation sequencing and droplet digital-qPCR-based quantification of circulating cell-free RNA for noninvasive early detection of cancer.   Cancers (Basel). 2020;12(2):353. doi:10.3390/cancers12020353 PubMedGoogle ScholarCrossref
8.
Stadler  ZK , Maio  A , Chakravarty  D ,  et al.  Therapeutic implications of germline testing in patients with advanced cancers.   J Clin Oncol. 2021;39(24):2698-2709. doi:10.1200/JCO.20.03661 PubMedGoogle ScholarCrossref
9.
Slavin  TP , Banks  KC , Chudova  D ,  et al.  Identification of incidental germline mutations in patients with advanced solid tumors who underwent cell-free circulating tumor DNA sequencing.   J Clin Oncol. 2018;36(35):JCO1800328. doi:10.1200/JCO.18.00328 PubMedGoogle ScholarCrossref
10.
Chang  C-M , Lin  K-C , Hsiao  N-E ,  et al.  Clinical application of liquid biopsy in cancer patients.   BMC Cancer. 2022;22(1):413. doi:10.1186/s12885-022-09525-0 PubMedGoogle ScholarCrossref
11.
Corcoran  RB , Chabner  BA .  Application of cell-free DNA analysis to cancer treatment.   N Engl J Med. 2018;379(18):1754-1765. doi:10.1056/NEJMra1706174 PubMedGoogle ScholarCrossref
12.
Rolfo  C , Castiglia  M , Hong  D ,  et al.  Liquid biopsies in lung cancer: the new ambrosia of researchers.   Biochim Biophys Acta. 2014;1846(2):539-546. doi:10.1016/j.bbcan.2014.10.001 PubMedGoogle ScholarCrossref
13.
Cristofanilli  M , Pierga  JY , Reuben  J ,  et al.  The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper.   Crit Rev Oncol Hematol. 2019;134:39-45. doi:10.1016/j.critrevonc.2018.12.004 PubMedGoogle ScholarCrossref
14.
Corcoran  RB .  Circulating tumor DNA: clinical monitoring and early detection.   Annu Rev Cancer Biol. 2019;3:187-201. doi:10.1146/annurev-cancerbio-030518-055719 Google ScholarCrossref
15.
Connors  D , Allen  J , Alvarez  JD ,  et al.  International liquid biopsy standardization alliance white paper.   Crit Rev Oncol Hematol. 2020;156:103112. doi:10.1016/j.critrevonc.2020.103112 PubMedGoogle ScholarCrossref
16.
Rolfo  C , Cardona  AF , Cristofanilli  M ,  et al; ISLB.  Challenges and opportunities of cfDNA analysis implementation in clinical practice: Perspective of the International Society of Liquid Biopsy (ISLB).   Crit Rev Oncol Hematol. 2020;151:102978. doi:10.1016/j.critrevonc.2020.102978 PubMedGoogle ScholarCrossref
17.
Bronkhorst  AJ , Ungerer  V , Holdenrieder  S .  The emerging role of cell-free DNA as a molecular marker for cancer management.   Biomol Detect Quantif. 2019;17:100087. doi:10.1016/j.bdq.2019.100087 PubMedGoogle ScholarCrossref
18.
Salvianti  F , Gelmini  S , Costanza  F ,  et al.  The pre-analytical phase of the liquid biopsy.   N Biotechnol. 2020;55:19-29. doi:10.1016/j.nbt.2019.09.006 PubMedGoogle ScholarCrossref
19.
Jenkins  S , Yang  JC , Ramalingam  SS ,  et al.  Plasma ctDNA analysis for detection of the EGFR T790M mutation in patients with advanced non-small cell lung cancer.   J Thorac Oncol. 2017;12(7):1061-1070. doi:10.1016/j.jtho.2017.04.003 PubMedGoogle ScholarCrossref
20.
Zugazagoitia  J , Gómez-Rueda  A , Jantus-Lewintre  E ,  et al.  Clinical utility of plasma-based digital next-generation sequencing in oncogene-driven non-small-cell lung cancer patients with tyrosine kinase inhibitor resistance.   Lung Cancer. 2019;134:72-78. doi:10.1016/j.lungcan.2019.05.032 PubMedGoogle ScholarCrossref
21.
Jin  P , Kang  Q , Wang  X ,  et al.  Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm.   J Gastroenterol Hepatol. 2015;30(5):830-833. doi:10.1111/jgh.12855 PubMedGoogle ScholarCrossref
22.
Cohen  JD , Li  L , Wang  Y ,  et al.  Detection and localization of surgically resectable cancers with a multi-analyte blood test.   Science. 2018;359(6378):926-930. doi:10.1126/science.aar3247 PubMedGoogle ScholarCrossref
23.
Blandin Knight  S , Crosbie  PA , Balata  H , Chudziak  J , Hussell  T , Dive  C .  Progress and prospects of early detection in lung cancer.   Open Biol. 2017;7(9):170070. doi:10.1098/rsob.170070 PubMedGoogle ScholarCrossref
24.
Phallen  J , Sausen  M , Adleff  V ,  et al.  Direct detection of early-stage cancers using circulating tumor DNA.   Sci Transl Med. 2017;9(403):eaan2415. doi:10.1126/scitranslmed.aan2415 PubMedGoogle ScholarCrossref
25.
Steensma  DP , Bejar  R , Jaiswal  S ,  et al.  Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes.   Blood. 2015;126(1):9-16. doi:10.1182/blood-2015-03-631747 PubMedGoogle ScholarCrossref
26.
Young  AL , Challen  GA , Birmann  BM , Druley  TE .  Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults.   Nat Commun. 2016;7:12484. doi:10.1038/ncomms12484 PubMedGoogle ScholarCrossref
27.
Genovese  G , Kähler  AK , Handsaker  RE ,  et al.  Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence.   N Engl J Med. 2014;371(26):2477-2487. doi:10.1056/NEJMoa1409405 PubMedGoogle ScholarCrossref
28.
Xie  M , Lu  C , Wang  J ,  et al.  Age-related mutations associated with clonal hematopoietic expansion and malignancies.   Nat Med. 2014;20(12):1472-1478. doi:10.1038/nm.3733 PubMedGoogle ScholarCrossref
29.
Severson  EA , Riedlinger  GM , Connelly  CF ,  et al.  Detection of clonal hematopoiesis of indeterminate potential in clinical sequencing of solid tumor specimens.   Blood. 2018;131(22):2501-2505. doi:10.1182/blood-2018-03-840629 PubMedGoogle ScholarCrossref
30.
Chabon  JJ , Hamilton  EG , Kurtz  DM ,  et al.  Integrating genomic features for non-invasive early lung cancer detection.   Nature. 2020;580(7802):245-251. doi:10.1038/s41586-020-2140-0 PubMedGoogle ScholarCrossref
31.
Razavi  P , Li  BT , Brown  DN ,  et al.  High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants.   Nat Med. 2019;25(12):1928-1937. doi:10.1038/s41591-019-0652-7 PubMedGoogle ScholarCrossref
32.
Bar-Sagi  D , Knelson  EH , Sequist  LV .  A bright future for KRAS inhibitors.   Nat Cancer. 2020;1(1):25-27. doi:10.1038/s43018-019-0016-8 PubMedGoogle ScholarCrossref
33.
Papaemmanuil  E , Gerstung  M , Malcovati  L ,  et al; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium.  Clinical and biological implications of driver mutations in myelodysplastic syndromes.   Blood. 2013;122(22):3616-3627. doi:10.1182/blood-2013-08-518886 PubMedGoogle ScholarCrossref
34.
Xiao  J , Li  W , Huang  Y ,  et al.  A next-generation sequencing-based strategy combining microsatellite instability and tumor mutation burden for comprehensive molecular diagnosis of advanced colorectal cancer.   BMC Cancer. 2021;21(1):282. doi:10.1186/s12885-021-07942-1 PubMedGoogle ScholarCrossref
35.
Büttner  R , Gosney  JR , Skov  BG ,  et al.  Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer.   J Clin Oncol. 2017;35(34):3867-3876. doi:10.1200/JCO.2017.74.7642 PubMedGoogle ScholarCrossref
36.
Yarchoan  M , Hopkins  A , Jaffee  EM .  Tumor mutational burden and response rate to PD-1 inhibition.   N Engl J Med. 2017;377(25):2500-2501. doi:10.1056/NEJMc1713444 PubMedGoogle ScholarCrossref
37.
Gandara  DR , Paul  SM , Kowanetz  M ,  et al.  Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab.   Nat Med. 2018;24(9):1441-1448. doi:10.1038/s41591-018-0134-3 PubMedGoogle ScholarCrossref
38.
Galldiks  N , Kocher  M , Ceccon  G ,  et al.  Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression.   Neuro Oncol. 2020;22(1):17-30. doi:10.1093/neuonc/noz147 PubMedGoogle ScholarCrossref
39.
Büttner  R , Longshore  JW , López-Ríos  F ,  et al.  Implementing TMB measurement in clinical practice: considerations on assay requirements.   ESMO Open. 2019;4(1):e000442. doi:10.1136/esmoopen-2018-000442 PubMedGoogle ScholarCrossref
40.
Peters  S , Cho  BC , Reinmuth  N ,  et al.  Tumor mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a phase III study of first-line durvalumab ± tremelimumab vs chemotherapy.   Cancer Res. 2019:79. doi:10.1158/1538-7445.AM2019-CT074 Google ScholarCrossref
41.
Socinski  M , Velcheti  V , Mekhail  T ,  et al.  Final efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC).   Ann Oncol. 2019;30(suppl 5):851-934. doi:10.1093/annonc/mdz394.081Google ScholarCrossref
42.
Mok  T , Gadgeel  S , Kim  E ,  et al.  Blood first line ready screening trial (B-F1RST) and blood first assay screening trial (BFAST) enable clinical development of novel blood-based biomarker assays for tumor mutational burden (TMB) and somatic mutations in 1L advanced or metastatic NSCLC.   Ann Oncol. 2017;28(suppl 5):460-496. doi:10.1093/annonc/mdx380.084Google ScholarCrossref
43.
Woodhouse  R , Li  M , Hughes  J ,  et al.  Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin.   PLoS One. 2020;15(9):e0237802. doi:10.1371/journal.pone.0237802 PubMedGoogle ScholarCrossref
44.
Dziadziuszko  R , Peters  S , Gadgeel  SM ,  et al.  Atezolizumab (Atezo) vs platinum-based chemo in blood-based tumour mutational burden-positive (bTMB+) patients (pts) with first-line (1L) advanced/metastatic (m)NSCLC: Results of the Blood First Assay Screening Trial (BFAST) phase III cohort C.   Ann Oncol. 2021;32(suppl 5):950-951. doi:10.1016/j.annonc.2021.08.1883 Google ScholarCrossref
45.
Willis  J , Lefterova  MI , Artyomenko  A ,  et al.  Validation of microsatellite instability detection using a comprehensive plasma-based genotyping panel.   Clin Cancer Res. 2019;25(23):7035-7045. doi:10.1158/1078-0432.CCR-19-1324 PubMedGoogle ScholarCrossref
46.
Passiglia  F , Rizzo  S , Rolfo  C ,  et al.  Metastatic site location influences the diagnostic accuracy of ctDNA EGFR- mutation testing in NSCLC patients: a pooled analysis.   Curr Cancer Drug Targets. 2018;18(7):697-705. doi:10.2174/1568009618666180308125110 PubMedGoogle ScholarCrossref
47.
Zito Marino  F , Liguori  G , Aquino  G ,  et al.  Intratumor heterogeneity of ALK-rearrangements and homogeneity of EGFR-mutations in mixed lung adenocarcinoma.   PLoS One. 2015;10(9):e0139264. doi:10.1371/journal.pone.0139264 PubMedGoogle ScholarCrossref
48.
De Mattia  E , Roncato  R , Palazzari  E , Toffoli  G , Cecchin  E .  Germline and somatic pharmacogenomics to refine rectal cancer patients selection for neo-adjuvant chemoradiotherapy.   Front Pharmacol. 2020;11:897. doi:10.3389/fphar.2020.00897 PubMedGoogle ScholarCrossref
49.
Rolfo  C , Russo  A .  Liquid biopsy for early stage lung cancer moves ever closer.   Nat Rev Clin Oncol. 2020;17(9):523-524. doi:10.1038/s41571-020-0393-z PubMedGoogle ScholarCrossref
50.
Klein  EA , Richards  D , Cohn  A ,  et al.  Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set.   Ann Oncol. 2021;32(9):1167-1177. doi:10.1016/j.annonc.2021.05.806 PubMedGoogle ScholarCrossref
51.
Liu  MC , Oxnard  GR , Klein  EA , Swanton  C , Seiden  MV ; CCGA Consortium.  Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA.   Ann Oncol. 2020;31(6):745-759. doi:10.1016/j.annonc.2020.02.011 PubMedGoogle ScholarCrossref
52.
Ali  N , Lifford  KJ , Carter  B ,  et al.  Barriers to uptake among high-risk individuals declining participation in lung cancer screening: a mixed methods analysis of the UK Lung Cancer Screening (UKLS) trial.   BMJ Open. 2015;5(7):e008254. doi:10.1136/bmjopen-2015-008254 PubMedGoogle ScholarCrossref
53.
Lecomte  T , Berger  A , Zinzindohoué  F ,  et al.  Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis.   Int J Cancer. 2002;100(5):542-548. doi:10.1002/ijc.10526 PubMedGoogle ScholarCrossref
54.
Wang  S , An  T , Wang  J ,  et al.  Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer.   Clin Cancer Res. 2010;16(4):1324-1330. doi:10.1158/1078-0432.CCR-09-2672 PubMedGoogle ScholarCrossref
55.
Santiago-Walker  A , Gagnon  R , Mazumdar  J ,  et al.  Correlation of BRAF mutation status in circulating-free DNA and tumor and association with clinical outcome across four BRAFi and MEKi clinical trials.   Clin Cancer Res. 2016;22(3):567-574. doi:10.1158/1078-0432.CCR-15-0321 PubMedGoogle ScholarCrossref
56.
Scherer  F , Kurtz  DM , Newman  AM ,  et al.  Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA.   Sci Transl Med. 2016;8(364):364ra155. doi:10.1126/scitranslmed.aai8545 PubMedGoogle ScholarCrossref
57.
Zhuang  R , Li  S , Li  Q ,  et al.  The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis.   PLoS One. 2017;12(8):e0182562. doi:10.1371/journal.pone.0182562 PubMedGoogle ScholarCrossref
58.
Li  S , Lai  H , Liu  J ,  et al  Circulating tumor DNA predicts the response and prognosis in patients with early breast cancer receiving neoadjuvant chemotherapy.   JCO Precis Oncol. 2020:4:PO.19.00292. doi:10.1200/PO.19.00292Google ScholarCrossref
59.
Xu  RH , Wei  W , Krawczyk  M ,  et al.  Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma.   Nat Mater. 2017;16(11):1155-1161. doi:10.1038/nmat4997 PubMedGoogle ScholarCrossref
60.
Pazdirek  F , Minarik  M , Benesova  L ,  et al.  Monitoring of early changes of circulating tumor DNA in the plasma of rectal cancer patients receiving neoadjuvant concomitant chemoradiotherapy: evaluation for prognosis and prediction of therapeutic response.   Front Oncol. 2020;10:1028. doi:10.3389/fonc.2020.01028 PubMedGoogle ScholarCrossref
61.
Cavallone  L , Aguilar-Mahecha  A , Lafleur  J ,  et al.  Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.   Sci Rep. 2020;10(1):14704. doi:10.1038/s41598-020-71236-y PubMedGoogle ScholarCrossref
62.
Radovich  M , Jiang  G , Hancock  BA ,  et al.  Association of circulating tumor DNA and circulating tumor cells after neoadjuvant chemotherapy with disease recurrence in patients with triple-negative breast cancer: Preplanned secondary analysis of the BRE12-158 randomized clinical trial.   JAMA Oncol. 2020;6(9):1410-1415. doi:10.1001/jamaoncol.2020.2295 PubMedGoogle ScholarCrossref
63.
Tie  J , Cohen  JD , Lahouel  K ,  et al; DYNAMIC Investigators.  Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer.   N Engl J Med. 2022;386(24):2261-2272. doi:10.1056/NEJMoa2200075 PubMedGoogle ScholarCrossref
64.
Bettegowda  C , Sausen  M , Leary  RJ ,  et al.  Detection of circulating tumor DNA in early- and late-stage human malignancies.   Sci Transl Med. 2014;6(224):224ra24. doi:10.1126/scitranslmed.3007094 PubMedGoogle ScholarCrossref
65.
Merck Sharp & Dohme. KEYTRUDA (pembrolizumab). Prescribing Information. Accessed July 1, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125514s131lbl.pdf
66.
Wang  Q-X , Qu  C-H , Gao  Y-H ,  et al.  The degree of microsatellite instability predicts response to PD-1 blockade immunotherapy in mismatch repair-deficient/microsatellite instability-high colorectal cancers.   Exp Hematol Oncol. 2021;10(1):2. doi:10.1186/s40164-020-00193-z PubMedGoogle ScholarCrossref
67.
Rosenberg  JE , Gajate  P , Morales-Barrera  R ,  et al.  Safety and efficacy of rogaratinib in combination with atezolizumab in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (UC) and FGFR mRNA overexpression in the phase Ib/II FORT-2 study.   J Clin Oncol. 2021;39(15)(suppl). Abstract 4521. doi:10.1200/JCO.2021.39.15_suppl.4521 Google ScholarCrossref
68.
Cabel  L , Riva  F , Servois  V ,  et al.  Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study.   Ann Oncol. 2017;28(8):1996-2001. doi:10.1093/annonc/mdx212 PubMedGoogle ScholarCrossref
69.
Anagnostou  V , Forde  PM , White  JR ,  et al.  Dynamics of tumor and immune responses during immune checkpoint blockade in non–small cell lung cancer.   Cancer Res. 2019;79(6):1214-1225. doi:10.1158/0008-5472.CAN-18-1127 PubMedGoogle ScholarCrossref
70.
Hua  G , Zhang  X , Zhang  M ,  et al.  Real-world circulating tumor DNA analysis depicts resistance mechanism and clonal evolution in ALK inhibitor-treated lung adenocarcinoma patients.   ESMO Open. 2022;7(1):100337. doi:10.1016/j.esmoop.2021.100337 PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close