515
Views
4
CrossRef citations to date
0
Altmetric
REVIEW

Clinical Utility and Application of Liquid Biopsy Genotyping in Lung Cancer: A Comprehensive Review

, ORCID Icon, , ORCID Icon, , & show all
Pages 11-25 | Received 30 Aug 2022, Accepted 26 Jan 2023, Published online: 03 Feb 2023

References

  • 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
  • Gambardella V, Tarazona N, Cejalvo JM, et al. Personalized medicine: recent progress in cancer therapy. Cancers. 2020;12(4):1009. doi:10.3390/cancers12041009
  • Ferrara MG, Di Noia V, D’Argento E, et al. Oncogene-addicted non-small-cell lung cancer: treatment opportunities and future perspectives. Cancers. 2020;12(5):1196. doi:10.3390/cancers12051196
  • Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–1500. doi:10.1126/science.1099314
  • Kwak EL, Bang Y-J, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–1703. doi:10.1056/NEJMoa1006448
  • Shaw AT, Solomon BJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2015;372:683–684.
  • Wang R, Hu H, Pan Y, et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol. 2012;30(35):4352–4359. doi:10.1200/JCO.2012.44.1477
  • Farago AF, Taylor MS, Doebele RC, et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol. 2018;2018:253.
  • Planchard D, Besse B, Groen HJ, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17:984–993.
  • Ou SH, Kwak EL, Siwak-Tapp C, et al. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol. 2011;6:942–946. doi:10.1097/JTO.0b013e31821528d3
  • Awad MM, Oxnard GR, Jackman DM, et al. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol. 2016;34:721–773. doi:10.1200/JCO.2015.63.4600
  • Rossi A. New options for combination therapy for advanced non-squamous NSCLC. Expert Rev Respir Med. 2019;13(11):1095–1107. doi:10.1080/17476348.2019.1667233
  • Joyner MJ, Paneth N. Promises, promises, and precision medicine. J Clin Invest. 2019;129(3):946–948. doi:10.1172/JCI126119
  • Imyanitov EN, Iyevleva AG, Levchenko EV. Molecular testing and targeted therapy for non-small cell lung cancer: current status and perspectives. Crit Rev Oncol Hematol. 2021;157:103194. doi:10.1016/j.critrevonc.2020.103194
  • Mosele F, Remon J, Mateo J, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31:1491–1505. doi:10.1016/j.annonc.2020.07.014
  • Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic - implementation issues and future challenges. Nat Rev Clin Oncol. 2021;18(5):297–312. doi:10.1038/s41571-020-00457-x
  • Douillard JY, Ostoros G, Cobo M, et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol. 2014;9(9):1345–1353. doi:10.1097/JTO.0000000000000263
  • Mok T, Wu YL, Lee JS, et al. Detection and dynamic changes of EGFR mutations from circulating tumor DNA as a predictor of survival outcomes in NSCLC patients treated with first-line intercalated erlotinib and chemotherapy. Clin Cancer Res. 2015;21(14):3196–3203. doi:10.1158/1078-0432.CCR-14-2594
  • Diaz LA, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579–586. doi:10.1200/JCO.2012.45.2011
  • Chen M, Zhao H. Next-generation sequencing in liquid biopsy: cancer screening and early detection. Hum Genomics. 2019;13(1):34. doi:10.1186/s40246-019-0220-8
  • ESMO. Clinical practice living guidelines – metastatic non-small-cell lung cancer. Available from: https://www.esmo.org/guidelines/guidelines-by-topic/lung-and-chest-tumours/clinical-practice-living-guidelines-metastatic-non-small-cell-lung-cancer. Accessed July 12, 2022.
  • Goswami RS, Luthra R, Singh RR, et al. Identification of factors affecting the success of next-generation sequencing testing in solid tumors. Am J Clin Pathol. 2016;145(2):222–237. doi:10.1093/ajcp/aqv023
  • Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non–small cell lung cancer. Clin Cancer Res. 2019;25(15):4691–4700. doi:10.1158/1078-0432.CCR-19-0624
  • Kapeleris J, Kulasinghe A, Warkiani ME, et al. The prognostic role of circulating tumor cells (CTCs) in lung cancer. Front Oncol. 2018;8:311. doi:10.3389/fonc.2018.00311
  • Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10(8):472–484. doi:10.1038/nrclinonc.2013.110
  • Russo A, De Miguel Perez D, Gunasekaran M, et al. Liquid biopsy tracking of lung tumor evolutions over time. Expert Rev Mol Diagn. 2019;19(12):1099–1108. doi:10.1080/14737159.2020.1680287
  • Wu YL, Lee V, Liam CK, et al. Clinical utility of a blood-based EGFR mutation test in patients receiving first-line erlotinib therapy in the ENSURE, FASTACT-2, and ASPIRATION studies. Lung Cancer. 2018;126:1–8. doi:10.1016/j.lungcan.2018.10.004
  • Oxnard GR, Thress KS, Alden RS, et al. Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non–small-cell lung cancer. JCO. 2016;34(28):3375–3382. doi:10.1200/JCO.2016.66.7162
  • Malapelle U, Buono M, Pisapia P, et al. Circulating tumor DNA in cancer: predictive molecular pathology meets mathematics. Crit Rev Oncol Hematol. 2021;163:103394. doi:10.1016/j.critrevonc.2021.103394
  • Zill OA, Banks KC, Fairclough SR, et al. The landscape of actionable genomic alterations in cell-free circulating tumor DNA from 21,807 advanced cancer patients. Clin Cancer Res. 2018;24(15):3528–3538. doi:10.1158/1078-0432.CCR-17-3837
  • Darbeheshti F, Yu F, Makrigiorgos GM. Pre-PCR mutation-enrichment methods for liquid biopsy applications. Cancers. 2022;14(13):3143. doi:10.3390/cancers14133143
  • Aggarwal C, Rolfo CD, Oxnard GR, Gray JE, Sholl LM, Gandara DR. Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice. Nat Rev Clin Oncol. 2021;18(1):56–62. doi:10.1038/s41571-020-0423-x
  • Keppens C, Palma JF, Das PM, et al. Detection of EGFR variants in plasma: a multilaboratory comparison of a real-time PCR EGFR mutation test in Europe. J Mol Diagn. 2018;20(4):483–494. doi:10.1016/j.jmoldx.2018.03.006
  • Remon J, Lacroix L, Jovelet C, et al. Real-world utility of an amplicon-based next-generation sequencing liquid biopsy for broad molecular profiling in patients with advanced non–small-cell lung cancer. JCO Precis Oncol. 2019;3:1–14.
  • Hu Y, Ulrich BC, Supplee J, et al. False-positive plasma genotyping due to clonal hematopoiesis. Clin Cancer Res. 2018;24(18):4437–4443. doi:10.1158/1078-0432.CCR-18-0143
  • Gray JE, Okamoto I, Sriuranpong V, et al. Tissue and plasma EGFR mutation analysis in the FLAURA trial: osimertinib versus comparator egfr tyrosine kinase inhibitor as first-line treatment in patients with EGFR-mutated advanced non–small cell lung cancer. Clin Cancer Res. 2019;25(22):6644–6652. doi:10.1158/1078-0432.CCR-19-1126
  • Zhang M, Feng Y, Qu C, et al. Comparison of the somatic mutations between circulating tumor DNA and tissue DNA in Chinese patients with non-small cell lung cancer. Int J Biol Markers. 2022;37(4):386–394.
  • Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39–51. doi:10.1016/j.jtho.2015.09.009
  • Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–3559. doi:10.1200/JCO.2007.13.9030
  • Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711–1723. doi:10.1056/NEJMoa2027071
  • Downey RJ, Martini N, Rusch VW, Bains MS, Korst RJ, Ginsberg RJ. Extent of chest wall invasion and survival in patients with lung cancer. Ann Thorac Surg. 1999;68(1):188–193. doi:10.1016/S0003-4975(99)00456-7
  • Guo N, Lou F, Ma Y, et al. Circulating tumor DNA detection in lung cancer patients before and after surgery. Sci Rep. 2016;6:33519. doi:10.1038/srep33519
  • Chen K, Zhang J, Guan T, et al. Comparison of plasma to tissue DNA mutations in surgical patients with non-small cell lung cancer. J Thorac Cardiovasc Surg. 2017;154(3):1123–1131. doi:10.1016/j.jtcvs.2017.04.073
  • Newman AM, Bratman SV, To J, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20:548–554. doi:10.1038/nm.3519
  • Wu F, Fan J, He Y, et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer. Nat Commun. 2021;12(1):2540. doi:10.1038/s41467-021-22801-0
  • Chaudhuri AA, Chabon JJ, Lovejoy AF, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov. 2017;7(12):1394–1403. doi:10.1158/2159-8290.CD-17-0716
  • Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017;545(7655):446–451. doi:10.1038/nature22364
  • Ulrich B, Pradines A, Mazières J, Guibert N. Detection of tumor recurrence via circulating tumor DNA profiling in patients with localized lung cancer: clinical considerations and challenges. Cancers. 2021;13(15):3759. doi:10.3390/cancers13153759
  • Jamal-Hanjani M, Wilson GA, Horswell S, et al. Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer. Ann Oncol. 2016;27(5):862–867. doi:10.1093/annonc/mdw037
  • Ulrich BC, Guibert N. Towards a comprehensive framework for cell-free DNA analysis: lessons from TRACERx. Ann Transl Med. 2017;5:428. doi:10.21037/atm.2017.08.12
  • 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
  • Guibert N, Pradines A, Favre G, Mazieres J. Current and future applications of liquid biopsy in nonsmall cell lung cancer from early to advanced stages. Eur Respir Rev. 2020;29(155):190052. doi:10.1183/16000617.0052-2019
  • Aberle DR, Adams AM; National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395–409.
  • de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382(6):503–513. doi:10.1056/NEJMoa1911793
  • Pastorino U, Sverzellati N, Sestini S, et al. Ten-year results of the Multicentric Italian Lung Detection trial demonstrate the safety and efficacy of biennial lung cancer screening. Eur J Cancer. 2019;118:142–148. doi:10.1016/j.ejca.2019.06.009
  • 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
  • Bohers E, Viailly PJ, Jardin F. cfDNA sequencing: technological approaches and bioinformatic issues. Pharmaceuticals. 2021;14(6):596. doi:10.3390/ph14060596
  • Pierga JY, Bidard FC, Mathiot C, et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a Phase II randomized trial. Clin Cancer Res. 2008;14(21):7004–7010. doi:10.1158/1078-0432.CCR-08-0030
  • van Dalum G, Stam G-J, Scholten LFA, et al. Importance of circulating tumor cells in newly diagnosed colorectal cancer. Int J Oncol. 2015;46:1361–1368. doi:10.3892/ijo.2015.2824
  • Ilie M, Hofman V, Long-Mira E, et al. ”Sentinel” circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS One. 2014;9:e111597. doi:10.1371/journal.pone.0111597
  • Leroy S, Benzaquen J, Mazzetta A, et al. Circulating tumour cells as a potential screening tool for lung cancer (the AIR study): protocol of a prospective multicentre cohort study in France. BMJ Open. 2017;7:e018884. doi:10.1136/bmjopen-2017-018884
  • Marquette CH, Boutros J, Benzaquen J, et al. Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study. Lancet Respir Med. 2020;8(7):709–716. doi:10.1016/S2213-2600(20)30081-3
  • Brozos-Vázquez EM, Díaz-Peña R, García-González J, et al. Immunotherapy in nonsmall-cell lung cancer: current status and future prospects for liquid biopsy. Cancer Immunol Immunother. 2021;70(5):1177–1188. doi:10.1007/s00262-020-02752-z
  • Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–2454. doi:10.1056/NEJMoa1200690
  • Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833. doi:10.1056/NEJMoa1606774
  • De Giglio A, Di Federico A, Deiana C, et al. Advanced non-small-cell lung cancer: how to manage non-oncogene disease. Drugs Context. 2022;11:2–4. doi:10.7573/dic.2022-2-4
  • 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
  • Le DT, Uram JN, Wang H, et al. Blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–2520. doi:10.1056/NEJMoa1500596
  • Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–128. doi:10.1126/science.aaa1348
  • Vanderwalde A, Spetzler D, Xiao N, et al. Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients. Cancer Med. 2018;7(3):746–756. doi:10.1002/cam4.1372
  • Yu Y, Zeng D, Ou Q, et al. Association of survival and immune-related biomarkers with immunotherapy in patients with non-small cell lung cancer: a meta-analysis and individual patient-level analysis. JAMA Netw Open. 2019;2(7):e196879. doi:10.1001/jamanetworkopen.2019.6879
  • Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med. 2020;383(14):1328–1339. doi:10.1056/NEJMoa1917346
  • Kim ES, Velcheti V, Mekhail T, et al. Blood-based tumor mutational burden as a biomarker for atezolizumab in non-small cell lung cancer: the phase 2 B-F1RST trial. Nat Med. 2022;28(5):939–945. doi:10.1038/s41591-022-01754-x
  • Rizvi NA, Cho BC, Reinmuth N, et al. Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: the MYSTIC Phase 3 randomized clinical trial. JAMA Oncol. 2020;6(5):661–674. doi:10.1001/jamaoncol.2020.0237
  • Zhang Q, Luo J, Wu S, et al. Prognostic and predictive impact of circulating tumor DNA in patients with advanced cancers treated with immune checkpoint blockade. Cancer Discov. 2020;10(12):1842–1853. doi:10.1158/2159-8290.CD-20-0047
  • Gobbini E, Swalduz A, Levra MG, et al. Implementing ctDNA analysis in the clinic: challenges and opportunities in non-small cell lung cancer. Cancers. 2020;12(11):3112. doi:10.3390/cancers12113112
  • 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
  • Giroux Leprieur E, Herbretau G, Dumenil C, et al. Circulating tumor DNA evaluated by Next-Generation Sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer. Oncoimmunology. 2018;7(5):e1424675. doi:10.1080/2162402X.2018.1424675
  • Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14:985–990. doi:10.1038/nm.1789
  • Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24. doi:10.1126/scitranslmed.3007094
  • Goldberg SB, Narayan A, Kole AJ, et al. Early assessment of lung cancer immunotherapy response via circulating tumor DNA. Clin Cancer Res. 2018;24(8):1872–1880. doi:10.1158/1078-0432.CCR-17-1341
  • 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
  • Guibert N, Delaunay M, Lusque A, et al. PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. Lung Cancer. 2018;120:108–112. doi:10.1016/j.lungcan.2018.04.001
  • Nicolazzo C, Raimondi C, Mancini M, et al. Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. Sci Rep. 2016;6:31726. doi:10.1038/srep31726
  • Ulivi P. Non-invasive methods to monitor mechanisms of resistance to tyrosine kinase inhibitors in non-small-cell lung cancer: where do we stand? Int J Mol Sci. 2016;17(7):1186. doi:10.3390/ijms17071186
  • Lim M, Kim CJ, Sunkara V, Kim MH, Cho YK. Liquid biopsy in lung cancer: clinical applications of circulating biomarkers (CTCs and ctDNA). Micromachines. 2018;9(3):100. doi:10.3390/mi9030100
  • Aggarwal C, Thompson JC, Black TA, et al. Clinical Implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173–180. doi:10.1001/jamaoncol.2018.4305
  • Mack PC, Banks KC, Espenschied CR, et al. Spectrum of driver mutations and clinical impact of circulating tumor DNA analysis in non-small cell lung cancer: analysis of over 8000 cases. Cancer. 2020;126(14):3219–3228. doi:10.1002/cncr.32876
  • Ramalingam SS, Gray JE, Ohe Y, et al. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): final overall survival analysis. Ann Oncol. 2019;30(suppl 5):v914–v915. doi:10.1093/annonc/mdz394.076
  • Douillard JY, Ostoros G, Cobo M, et al. First‐line gefitinib in Caucasian EGFR mutation‐positive NSCLC patients: a phase‐IV, open‐label, single‐arm study. Br J Cancer. 2014;110(1):55–62. doi:10.1038/bjc.2013.721
  • Reck M, Hagiwara K, Han B, et al. ctDNA determination of EGFR mutation status in European and Japanese patients with advanced NSCLC: the ASSESS study. J Thorac Oncol. 2016;11(10):1682–1689. doi:10.1016/j.jtho.2016.05.036
  • Wu YL, Sequist LV, Hu CP, et al. EGFR mutation detection in circulating cell‐free DNA of lung adenocarcinoma patients: analysis of LUX‐Lung 3 and 6. Br J Cancer. 2017;116(2):175–185. doi:10.1038/bjc.2016.420
  • Han B, Tjulandin S, Hagiwara K, et al. EGFR mutation prevalence in Asia‐Pacific and Russian patients with advanced NSCLC of adenocarcinoma and non‐adenocarcinoma histology: the IGNITE study. Lung Cancer. 2017;113:37–44. doi:10.1016/j.lungcan.2017.08.021
  • Papadimitrakopoulou VA, Wu YL, Han JY, et al. Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study. Ann Oncol. 2018;29:Viii741. doi:10.1093/annonc/mdy424.064
  • Karlovich C, Goldman JW, Sun JM, et al. Assessment of EGFR mutation status in matched plasma and tumor tissue of NSCLC patients from a Phase I study of rociletinib (CO‐1686). Clin Cancer Res. 2016;22(10):2386–2395. doi:10.1158/1078-0432.CCR-15-1260
  • Sacher AG, Paweletz C, Dahlberg SE, et al. Prospective validation of rapid plasma genotyping for the detection of EGFR and KRAS mutations in advanced lung cancer. JAMA Oncol. 2016;2(8):1014–1022. doi:10.1001/jamaoncol.2016.0173
  • Zheng D, Ye X, Zhang MZ, et al. Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR‐TKI resistance. Sci Rep. 2016;6(1):20913. doi:10.1038/srep20913
  • Qian X, Liu J, Sun Y, et al. Circulating cell‐free DNA has a high degree of specificity to detect exon 19 deletions and the single‐point substitution mutation L858R in non‐small cell lung cancer. Oncotarget. 2016;7(20):29154–29165. doi:10.18632/oncotarget.8684
  • Luo J, Shen L, Zheng D. Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta‐analysis. Sci Rep. 2014;4:6269. doi:10.1038/srep06269
  • Qiu M, Wang J, Xu Y. Circulating tumor DNA is effective for the detection of EGFR mutation in non‐small cell lung cancer: a meta‐analysis. Cancer Epidemiol Biomarkers Prev. 2015;24(1):206–212. doi:10.1158/1055-9965.EPI-14-0895
  • Mao C, Yuan JQ, Yang ZY, Fu XH, Wu XY, Tang JL. Blood as a substitute for tumor tissue in detecting EGFR mutations for guiding EGFR TKIs treatment of nonsmall cell lung cancer: a systematic review and meta‐ analysis. Medicine. 2015;94(21):e775. doi:10.1097/MD.0000000000000775
  • Zhou S, Huang R, Cao Y. Detection of epidermal growth factor receptor mutations in peripheral blood circulating tumor DNA in patients with advanced non‐small cell lung cancer: a PRISMA‐compliant meta‐analy‐ sis and systematic review. Medicine. 2020;99(40):e21965. doi:10.1097/MD.0000000000021965
  • Passiglia F, Rizzo S, Di Maio M, et al. The diagnostic accuracy of circulating tumor DNA for the detection of EGFR‐T790M mutation in NSCLC: a systematic review and meta‐analysis. Sci Rep. 2018;8(1):13379. doi:10.1038/s41598-018-30780-4
  • Piper-Vallillo AJ, Sequist LV, Piotrowska Z. Emerging treatment paradigms for EGFR-mutant lung cancers progressing on osimertinib: a review. J Clin Oncol. 2020;38:2926–2936. doi:10.1200/JCO.19.03123
  • Zhou C, Imamura F, Cheng Y, et al. Early clearance of plasma EGFR mutations as a predictor of response to osimertinib and comparator EGFR-TKIs in the FLAURA trial. J Clin Oncol. 2019;37(suppl 15):9020. doi:10.1200/JCO.2019.37.15_suppl.9020
  • Mack PC, Redman MW, Moon J, et al. Residual circulating tumor DNA (ctDNA) after two months of therapy to predict progression-free and overall survival in patients treated on S1403 with Afatinib ± cetuximab. J Clin Oncol. 2020;38(suppl 15):9532. doi:10.1200/JCO.2020.38.15_suppl.9532
  • Hofman P. Detecting resistance to therapeutic ALK inhibitors in tumor tissue and liquid biopsy markers: an update to a clinical routine practice. Cells. 2021;10(1):168. doi:10.3390/cells10010168
  • Kunimasa K, Kato K, Imamura F, et al. Quantitative detection of ALK fusion breakpoints in plasma cell‐free DNA from patients with non‐small cell lung cancer using PCR‐based target sequencing with a tiling primer set and two‐step mapping/alignment. PLoS One. 2019;14(9):e0222233. doi:10.1371/journal.pone.0222233
  • Dagogo-Jack I, Brannon AR, Ferris LA, et al. Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors through Longitudinal Analysis of Circulating Tumor DNA. JCO Precis Oncol. 2018;2018:PO.17.00160. doi:10.1200/PO.17.00160
  • McCoach CE, Blakely CM, Banks KC, et al. Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non-small cell lung cancer. Clin Cancer Res. 2018;24(12):2758–2770. doi:10.1158/1078-0432.CCR-17-2588
  • Shaw AT, Solomon BJ, Besse B, et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol. 2019;37(16):1370–1379. doi:10.1200/JCO.18.02236
  • Dagogo-Jack I, Rooney M, Lin JJ, et al. Treatment with next-generation ALK inhibitors fuels plasma ALK mutation diversity. Clin Cancer Res. 2019;25(22):6662–6670. doi:10.1158/1078-0432.CCR-19-1436
  • Lin JJ, Shaw AT. Recent advances in targeting ROS1 in lung cancer. J Thorac Oncol. 2017;12(11):1611–1625. doi:10.1016/j.jtho.2017.08.002
  • Davies KD, Le AT, Sheren J, et al. Comparison of molecular testing modalities for detection of ros1 rearrangements in a cohort of positive patient samples. J Thorac Oncol. 2018;13(10):1474–1482. doi:10.1016/j.jtho.2018.05.041
  • Paweletz CP, Sacher AG, Raymond CK, et al. Bias-corrected targeted next-generation sequencing for rapid, multiplexed detection of actionable alterations in cell-free DNA from advanced lung cancer patients. Clin Cancer Res. 2016;22(4):915–922. doi:10.1158/1078-0432.CCR-15-1627-T
  • Dagogo-Jack I, Rooney M, Nagy RJ, et al. Molecular analysis of plasma from patients with ROS1-positive NSCLC. J Thorac Oncol. 2019;14(5):816–824. doi:10.1016/j.jtho.2019.01.009
  • Ortiz-Cuaran S, Mezquita L, Swalduz A, et al. Circulating tumor DNA genomics reveal potential mechanisms of resistance to BRAF-targeted therapies in patients with braf-mutant metastatic non-small cell lung cancer. Clin Cancer Res. 2020;26(23):6242–6253. doi:10.1158/1078-0432.CCR-20-1037
  • Garlan F, Laurent-Puig P, Sefrioui D, et al. Early evaluation of circulating tumor DNA as marker of therapeutic efficacy in metastatic colorectal cancer patients (PLACOL Study). Clin Cancer Res. 2017;23:5416–25.17. doi:10.1158/1078-0432.CCR-16-3155
  • Guibert N, Jones G, Beeler JF, et al. Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer. Lung Cancer. 2019;137:1–6. doi:10.1016/j.lungcan.2019.09.005
  • Guo R, Offin M, Brannon AR, et al. MET exon 14-altered lung cancers and MET inhibitor resistance. Clin Cancer Res. 2021;27:799–806. doi:10.1158/1078-0432.CCR-20-2861
  • Lin JJ, Liu SV, McCoach CE, et al. Mechanisms of resistance to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer. Ann Oncol. 2020;31:1725–1733. doi:10.1016/j.annonc.2020.09.015
  • Schwartzberg LS, Horinouchi H, Chan D, et al. Liquid biopsy mutation panel for non-small cell lung cancer: analytical validation and clinical concordance. NPJ Precis Oncol. 2020;4:15. doi:10.1038/s41698-020-0118-x
  • Nacchio M, Sgariglia R, Gristina V, et al. KRAS mutations testing in non-small cell lung cancer: the role of liquid biopsy in the basal setting. J Thorac Dis. 2020;12:3836–3843. doi:10.21037/jtd.2020.01.19