1. Tsao AS, Scagliotti GV, Bunn PA, Jr., Carbone DP, Warren GW, Bai C, et al. Scientific Advances in Lung Cancer 2015. J Thorac Oncol. 2016;11(5):613-38. 10.1016/j.jtho.2016.03.012
2. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(2):123-35. 10.1056/NEJMoa1504627
3. Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2015;21(19):4286-93. 10.1158/1078-0432.CCR-14-2607
4. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015;372(26):2509-20. 10.1056/NEJMoa1500596
5. Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018;378(8):731-9. 10.1056/NEJMoa1714448
6. Food and Drug Administration. FDA/CEDR resources page [Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors.
7. Lin Z, Neiswender J, Fang B, Ma X, Zhang J, Hu X. Value of circulating cell-free DNA analysis as a diagnostic tool for breast cancer: a meta-analysis. Oncotarget. 2017;8(16):26625-36. 10.18632/oncotarget.15775
8. Gao Y, Zhang K, Xi H, Cai A, Wu X, Cui J, et al. Diagnostic and prognostic value of circulating tumor DNA in gastric cancer: a meta-analysis. Oncotarget. 2017;8(4):6330-40. 10.18632/oncotarget.14064
9. Jiang T, Zhai C, Su C, Ren S, Zhou C. The diagnostic value of circulating cell free DNA quantification in non-small cell lung cancer: A systematic review with meta-analysis. Lung Cancer. 2016;100:63-70. 10.1016/j.lungcan.2016.06.013
10. Spindler KG, Boysen AK, Pallisgard N, Johansen JS, Tabernero J, Sorensen MM, et al. Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2017;22(9):1049-55. 10.1634/theoncologist.2016-0178
11. Zhou Q, Li W, Leng B, Zheng W, He Z, Zuo M, et al. Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis. PLoS One. 2016;11(6):e0155495. 10.1371/journal.pone.0155495
12. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426-37. 10.1038/nrc3066
13. Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M. Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology. 1989;46(5):318-22. 10.1159/000226740
14. Nie K, Jia Y, Zhang X. Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer. Tumour Biol. 2015;36(1):7-19. 10.1007/s13277-014-2758-3
15. Rolfo C, Castiglia M, Hong D, Alessandro R, Mertens I, Baggerman G, et al. Liquid biopsies in lung cancer: the new ambrosia of researchers. Biochimica et biophysica acta. 2014;1846(2):539-46. 10.1016/j.bbcan.2014.10.001
16. Wu YL, Lee V, Liam CK, Lu S, Park K, Srimuninnimit V, 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. 10.1016/j.lungcan.2018.10.004
17. Marchetti A, Palma JF, Felicioni L, De Pas TM, Chiari R, Del Grammastro M, et al. Early Prediction of Response to Tyrosine Kinase Inhibitors by Quantification of EGFR Mutations in Plasma of NSCLC Patients. J Thorac Oncol. 2015;10(10):1437-43. 10.1097/JTO.0000000000000643
18. Douillard JY, Ostoros G, Cobo M, Ciuleanu T, Cole R, McWalter G, 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):1345-53. 10.1097/JTO.0000000000000263
19. Koeppel F, Blanchard S, Jovelet C, Genin B, Marcaillou C, Martin E, et al. Whole exome sequencing for determination of tumor mutation load in liquid biopsy from advanced cancer patients. PLoS One. 2017;12(11):e0188174. 10.1371/journal.pone.0188174
20. Gandara DR, Paul SM, Kowanetz M, Schleifman E, Zou W, Li Y, et al. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nature medicine. 2018;24(9):1441-8. 10.1038/s41591-018-0134-3
21. Andrew A. Davis YKC, Sarita Agte, Alan Pan, Nicholas I Simon, Timothy J. Taxter, ... Comparison of tumor mutational burden (TMB) across tumor tissue and circulating tumor DNA (ctDNA). J Clin Oncol. 2017;35. 10.1200/JCO.2017.35.15_suppl.e23028
22. Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The Eighth Edition Lung Cancer Stage Classification. Chest. 2017;151(1):193-203. 10.1016/j.chest.2016.10.010
23. William D. Travis EB, Harris HKM-HaCC. Tumours of the Lung, Pleura, Thymus and Heart. IARC Press WHO classification of tumors. 2004.
24. ThermoFisher Scientific. Oncomine Solid Tumour Kits [Available from: https://www.thermofisher.com/se/en/home/clinical/diagnostic-testing/condition-disease-diagnostics/oncology-diagnostics/oncomine-solid-tumour-kits.html.
25. Laurent-Puig P, Vaughn C, Lacroix L, M. L. Ion AmpliSeq Colon and Lung Cancer Research Panel v2 and Ion AmpliSeq RNA Fusion Lung Cancer Research Panel. Thermo Fisher Scientific,; 2016.
26. Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nature medicine. 2014;20(5):548-54. 10.1038/nm.3519
27. Newman AM, Lovejoy AF, Klass DM, Kurtz DM, Chabon JJ, Scherer F, et al. Integrated digital error suppression for improved detection of circulating tumor DNA. Nat Biotechnol. 2016;34(5):547-55. 10.1038/nbt.3520
28. Talevich E, Shain AH, Botton T, Bastian BC. CNVkit: Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing. PLoS Comput Biol. 2016;12(4):e1004873. 10.1371/journal.pcbi.1004873
29. Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A, et al. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer. 2004;91(2):355-8. 10.1038/sj.bjc.6601894
30. Yaung SJ, Krishna S, Xi L, Ju C, Palma JF, Schmid M. Assessment of a Highly Curated Somatic Oncology Database to Aid in the Interpretation of Clinically Important Variants in Next-Generation Sequencing Results. J Mol Diagn. 2020. 10.1016/j.jmoldx.2020.08.004
31. Hagemann IS, Devarakonda S, Lockwood CM, Spencer DH, Guebert K, Bredemeyer AJ, et al. Clinical next-generation sequencing in patients with non-small cell lung cancer. Cancer. 2015;121(4):631-9. 10.1002/cncr.29089
32. Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5(8):850-9. 10.1158/2159-8290.CD-15-0285
33. Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, et al. EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs. Clin Cancer Res. 2015;21(23):5305-13. 10.1158/1078-0432.CCR-15-1046
34. My Cancer Genome [Available from: https://www.mycancergenome.org/.
35. Chakravarty D, Gao J, Phillips SM, Kundra R, Zhang H, Wang J, et al. OncoKB: A Precision Oncology Knowledge Base. JCO Precis Oncol. 2017;2017. 10.1200/PO.17.00011
36. Wickham H. ggplot2: Elegant Graphics for Data Analysis: Springer-Verlag New York; 2016.
37. Skidmore Z, Wagner A, Lesurf R, Campbell K, Kunisaki J, Griffith O, et al. GenVisR: Genomic Visualizations in R. Bioinformatics. 2016;32:3012-4.
38. Gibbons DL, Byers LA, Kurie JM. Smoking, p53 mutation, and lung cancer. Mol Cancer Res. 2014;12(1):3-13. 10.1158/1541-7786.MCR-13-0539
39. Rekhtman N, Paik PK, Arcila ME, Tafe LJ, Oxnard GR, Moreira AL, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res. 2012;18(4):1167-76. 10.1158/1078-0432.CCR-11-2109
40. Muller JN, Falk M, Talwar J, Neemann N, Mariotti E, Bertrand M, et al. Concordance between Comprehensive Cancer Genome Profiling in Plasma and Tumor Specimens. J Thorac Oncol. 2017;12(10):1503-11. 10.1016/j.jtho.2017.07.014
41. Khagi Y, Goodman AM, Daniels GA, Patel SP, Sacco AG, Randall JM, et al. Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy. Clin Cancer Res. 2017;23(19):5729-36. 10.1158/1078-0432.CCR-17-1439
42. Kujala J, Hartikainen JM, Tengstrom M, Sironen R, Kosma VM, Mannermaa A. High mutation burden of circulating cell-free DNA in early-stage breast cancer patients is associated with a poor relapse-free survival. Cancer Med. 2020. 10.1002/cam4.3258
43. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488-98. 10.1056/NEJMoa1408617
44. Jiang J AH, Yao L, et al. Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Cell-Free DNA in Stage I-IV Non-Small Cell Lung Cancer. The Journal of molecular diagnostics : JMD. 2020;22(2):228-35. 10.1016/j.jmoldx.2019.10.013
45. Karlovich C GJ, 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):2386-95. 10.1158/1078-0432.CCR-15-1260
46. Lam VK, Zhang J, Wu CC, Tran HT, Li L, Diao L, et al. Genotype-Specific Differences in Circulating Tumor DNA Levels in Advanced NSCLC. J Thorac Oncol. 2020. 10.1016/j.jtho.2020.12.011
47. Cho MS, Park CH, Lee S, Park HS. Clinicopathological parameters for circulating tumor DNA shedding in surgically resected non-small cell lung cancer with EGFR or KRAS mutation. PLoS One. 2020;15(3):e0230622. 10.1371/journal.pone.0230622
48. Cancer. RCf. Swedish national care program for lung cancer [Available from: https://kunskapsbanken.cancercentrum.se/diagnoser/lungcancer/vardprogram/.
49. Aggarwal C, Thompson JC, Black TA, Katz SI, Fan R, Yee SS, 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):173-80. 10.1001/jamaoncol.2018.4305
50. Meric-Bernstam F, Brusco L, Shaw K, Horombe C, Kopetz S, Davies MA, et al. Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials. J Clin Oncol. 2015;33(25):2753-62. 10.1200/JCO.2014.60.4165
51. Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018;378(22):2093-104. 10.1056/NEJMoa1801946
52. Thompson JC YS, Troxel AB, et al. Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA. Clin Cancer Res. 2016;22(23):5772-82. 10.1158/1078-0432.CCR-16-1231
53. Liu J, Chen X, Wang J, Zhou S, Wang CL, Ye MZ, et al. Biological background of the genomic variations of cf-DNA in healthy individuals. Ann Oncol. 2019;30(3):464-70. 10.1093/annonc/mdy513
54. Coombs CC, Zehir A, Devlin SM, Kishtagari A, Syed A, Jonsson P, et al. Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes. Cell Stem Cell. 2017;21(3):374-82 e4. 10.1016/j.stem.2017.07.010
55. Hu Y, Ulrich BC, Supplee J, Kuang Y, Lizotte PH, Feeney NB, et al. False-Positive Plasma Genotyping Due to Clonal Hematopoiesis. Clin Cancer Res. 2018;24(18):4437-43. 10.1158/1078-0432.CCR-18-0143
56. Fernandez-Cuesta L, Perdomo S, Avogbe PH, Leblay N, Delhomme TM, Gaborieau V, et al. Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer. EBioMedicine. 2016;10:117-23. 10.1016/j.ebiom.2016.06.032
57. Kadouri L, Rottenberg Y, Zick A, Hamburger T, Lipson D, Peretz T, et al. Homologous recombination in lung cancer, germline and somatic mutations, clinical and phenotype characterization. Lung Cancer. 2019;137:48-51. 10.1016/j.lungcan.2019.09.008
58. Zojer N, Dekan G, Ackermann J, Fiegl M, Kaufmann H, Drach J, et al. Aneuploidy of chromosome 7 can be detected in invasive lung cancer and associated premalignant lesions of the lung by fluorescence in situ hybridisation. Lung Cancer. 2000;28(3):225-35. 10.1016/s0169-5002(00)00097-0
59. Cerny T, Barnes DM, Hasleton P, Barber PV, Healy K, Gullick W, et al. Expression of epidermal growth factor receptor (EGF-R) in human lung tumours. Br J Cancer. 1986;54(2):265-9. 10.1038/bjc.1986.172
60. Sobol RE, Astarita RW, Hofeditz C, Masui H, Fairshter R, Royston I, et al. Epidermal growth factor receptor expression in human lung carcinomas defined by a monoclonal antibody. J Natl Cancer Inst. 1987;79(3):403-7.
61. Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, et al. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun. 2015;6:6377. 10.1038/ncomms7377
62. Shi X, Duan H, Liu X, Zhou L, Liang Z. Genetic alterations and protein expression in combined small cell lung cancers and small cell lung cancers arising from lung adenocarcinomas after therapy with tyrosine kinase inhibitors. Oncotarget. 2016;7(23):34240-9. 10.18632/oncotarget.9083
63. Babakoohi S, Fu P, Yang M, Linden PA, Dowlati A. Combined SCLC clinical and pathologic characteristics. Clin Lung Cancer. 2013;14(2):113-9. 10.1016/j.cllc.2012.07.002
64. Lei Y, Feng H, Qiang H, Shang Z, Chang Q, Qian J, et al. Clinical characteristics and prognostic factors of surgically resected combined small cell lung cancer: a retrospective study. Lung Cancer. 2020;146:244-51. 10.1016/j.lungcan.2020.06.021
65. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Jr., Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546-58. 10.1126/science.1235122
66. Chabon JJ, Hamilton EG, Kurtz DM, Esfahani MS, Moding EJ, Stehr H, et al. Integrating genomic features for non-invasive early lung cancer detection. Nature. 2020;580(7802):245-51. 10.1038/s41586-020-2140-0