Fifteen years of precision medicine in the lung cancer management: Perspectives and Challenges

Main Article Content

Carlos Gil Ferreira Pedro De Marchi Gilson Gabriel Viana Veloso Marina Xavier Reis Isabella Favato Barcelos Tatiane Montella

Abstract

Precision medicine has revolutionized lung cancer management – particularly non-squamous cell carcinomas – with a broader genomic comprehension and the possibility of offering tailored treatments guided by oncogenic driver mutations – the basis of precision medicine. Since the publication of the IPASS trial in 2009 a new Era of molecular actionability began for lung cancer research and treatment. The remarkable past fifteen years were characterized by advances on genomic testing methodologies, the emergence of new biomarkers and targeted therapies, and the widespread of precision medicine in lung cancer care from advanced to earlier stages – specially for the adenocarcinoma histology, a heterogeneous disease with unprecedent improvements in outcomes. Nonetheless, several barriers need to be overcome with the adoption of cutting-edge technologies, such as the high cost of new diagnostic and therapeutical technologies and their discrepant accessibility, mainly in low- and middle-income countries. Moreover, there is still a lack of clear clinical actionability for squamous cell carcinoma and small cell lung cancer in which ideal biomarkers are yet to be discovered and validated. Herein, we aimed to discuss several aspects on how precision medicine positively impacted on lung cancer management and the lessons learned. Additionally, we scoped future perspectives on precision oncology in lung cancer as technology advances.

Keywords: lung cancer, precision medicine, thoracic oncology, next sequencing generation, health-care policies

Article Details

How to Cite
FERREIRA, Carlos Gil et al. Fifteen years of precision medicine in the lung cancer management: Perspectives and Challenges. Medical Research Archives, [S.l.], v. 12, n. 2, feb. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5169>. Date accessed: 28 apr. 2024. doi: https://doi.org/10.18103/mra.v12i2.5169.
Section
Research Articles

References

1. Ibodeng G-O, Uche IN, Mokua R, et al. A snapshot of lung cancer: where are we now?-a narrative review. Ann Transl Med. 2023;11(6):261. doi:10.21037/atm-22-4479
2. Debela DT, Muzazu SG, Heraro KD, et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE open Med. 2021;9:20503121211034370. doi:10.1177/20503121211034366
3. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
4. Bersani F, Morena D, Picca F, et al. Future perspectives from lung cancer pre-clinical models: new treatments are coming? Transl lung cancer Res. 2020;9(6):2629-2644. doi:10.21037/tlcr-20-189
5. Ru Zhao Y, Xie X, de Koning HJ, Mali WP, Vliegenthart R, Oudkerk M. NELSON lung cancer screening study. Cancer Imaging. 2011;11 Spec No(1A):S79-84. doi:10.1102/1470-7330.2011.9020
6. Gredner T, Mons U, Niedermaier T, Brenner H, Soerjomataram I. Impact of tobacco control policies implementation on future lung cancer incidence in Europe: An international, population-based modeling study. Lancet Reg Heal Eur. 2021;4:100074. doi:10.1016/j.lanepe.2021.100074
7. Passiglia F, Scagliotti G V. The evolving paradigm of precision medicine in lung cancer. Curr Opin Pulm Med. 2021;27(4):249-254. doi:10.1097/MCP.0000000000000778
8. Ferreira CG, Reis MX, Veloso GGV. Editorial: Molecular genetic testing and emerging targeted therapies for non-small cell lung cancer. Front Oncol. 2023;13:1308525. doi:10.3389/fonc.2023.1308525
9. Čerina D, Krpina K, Jakopović M, et al. The Challenges and Opportunities of the Implementation of Comprehensive Genomic Profiling in Everyday Clinical Practice with Non-Small Cell Lung Cancer: National Results from Croatia. Cancers (Basel). 2023;15(13):3395. doi:10.3390/cancers15133395
10. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92-98. doi:10.1056/NEJMoa011954
11. Travis WD, Rekhtman N, Riley GJ, et al. Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. J Thorac Oncol. 2010;5(4):411-414. doi:10.1097/JTO.0b013e3181d57f6e
12. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004;22(11):2184-2191. doi:10.1200/JCO.2004.11.022
13. Scagliotti G, Hanna N, Fossella F, et al. The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. Oncologist. 2009;14(3):253-263. doi:10.1634/theoncologist.2008-0232
14. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. doi:10.1001/jama.2014.3741
15. Howlader N, Forjaz G, Mooradian MJ, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020;383(7):640-649. doi:10.1056/NEJMoa1916623
16. Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC. N Engl J Med. 2020;382(1):41-50. doi:10.1056/NEJMoa1913662
17. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol Off J Eur Soc Med Oncol. 2020;31(8):1056-1064. doi:10.1016/j.annonc.2020.04.478
18. Camidge DR, Kim HR, Ahn M-J, et al. Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. J Thorac Oncol. 2021;16(12):2091-2108. doi:10.1016/j.jtho.2021.07.035
19. Solomon BJ, Bauer TM, Mok TSK, et al. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023;11(4):354-366. doi:10.1016/S2213-2600(22)00437-4
20. Lynch TJ, Bell DW, Sordella R, et al. Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib. N Engl J Med. 2004;350(21):2129-2139. doi:10.1056/NEJMoa040938
21. Paez JG, Jänne PA, Lee JC, et al. EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy. Science (80- ). 2004;304(5676):1497-1500. doi:10.1126/science.1099314
22. Rudin CM, Avila-Tang E, Harris CC, et al. Lung cancer in never smokers: molecular profiles and therapeutic implications. Clin Cancer Res. 2009;15(18):5646-5661. doi:10.1158/1078-0432.CCR-09-0377
23. Cohen MH, Williams GA, Sridhara R, et al. United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res. 2004;10(4):1212-1218. doi:10.1158/1078-0432.ccr-03-0564
24. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet (London, England). 366(9496):1527-1537. doi:10.1016/S0140-6736(05)67625-8
25. Dziadziuszko R, Hirsch FR, Varella-Garcia M, Bunn PA. Selecting lung cancer patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors by immunohistochemistry and fluorescence in situ hybridization--why, when, and how? Clin Cancer Res. 2006;12(14 Pt 2):4409s-4415s. doi:10.1158/1078-0432.CCR-06-0087
26. Bunn PA, Dziadziuszko R, Varella-Garcia M, et al. Biological markers for non-small cell lung cancer patient selection for epidermal growth factor receptor tyrosine kinase inhibitor therapy. Clin Cancer Res. 2006;12(12):3652-3656. doi:10.1158/1078-0432.CCR-06-0261
27. Shigematsu H, Gazdar AF. Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer. 2006;118(2):257-262. doi:10.1002/ijc.21496
28. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004;101(36):13306-13311. doi:10.1073/pnas.0405220101
29. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139. doi:10.1056/NEJMoa040938
30. 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
31. Hirsch FR, Varella-Garcia M, Bunn PA, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol. 2006;24(31):5034-5042. doi:10.1200/JCO.2006.06.3958
32. Tsao M-S, Sakurada A, Cutz J-C, et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med. 2005;353(2):133-144. doi:10.1056/NEJMoa050736
33. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma. N Engl J Med. 2009;361(10):947-957. doi:10.1056/NEJMoa0810699
34. Hirsch FR, Bunn PA. EGFR testing in lung cancer is ready for prime time. Lancet Oncol. 2009;10(5):432-433. doi:10.1016/S1470-2045(09)70110-X
35. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR. N Engl J Med. 2010;362(25):2380-2388. doi:10.1056/NEJMoa0909530
36. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239-246. doi:10.1016/S1470-2045(11)70393-X
37. Sequist L V, Yang JC-H, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327-3334. doi:10.1200/JCO.2012.44.2806
38. Hosomi Y, Morita S, Sugawara S, et al. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020;38(2):115-123. doi:10.1200/JCO.19.01488
39. Noronha V, Patil VM, Joshi A, et al. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020;38(2):124-136. doi:10.1200/JCO.19.01154
40. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
41. Cho BC, Felip E, Spira AI, et al. LBA14 Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Ann Oncol. 2023;34:S1306. doi:10.1016/j.annonc.2023.10.062
42. 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(18):1693-1703. doi:10.1056/NEJMoa1006448
43. Kazandjian D, Blumenthal GM, Chen H-Y, et al. FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. Oncologist. 2014;19(10):e5-11. doi:10.1634/theoncologist.2014-0241
44. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Patho. J Thorac Oncol. 2013;8(7):823-859. doi:10.1097/JTO.0b013e318290868f
45. Leighl NB, Rekhtman N, Biermann WA, et al. Molecular Testing for Selection of Patients With Lung Cancer for Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/Internat. J Clin Oncol. 2014;32(32):3673-3679. doi:10.1200/JCO.2014.57.3055
46. Solomon BJ, Mok T, Kim D-W, et al. First-Line Crizotinib versus Chemotherapy in ALK -Positive Lung Cancer. N Engl J Med. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440
47. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056-1064. doi:10.1016/j.annonc.2020.04.478
48. Solomon BJ, Bauer TM, Mok TSK, et al. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023;11(4):354-366. doi:10.1016/S2213-2600(22)00437-4
49. Elsayed M, Christopoulos P. Therapeutic Sequencing in ALK+ NSCLC. Pharmaceuticals. 2021;14(2):80. doi:10.3390/ph14020080
50. Gainor JF, Shaw AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist. 2013;18(7):865-875. doi:10.1634/theoncologist.2013-0095
51. U.S. Food and Drug Administrarion. FDA Approves Crizotinib Capsules. Published 2016. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizotinib-capsules
52. Shaw AT, Ou S-HI, Bang Y-J, et al. Crizotinib in ROS1 -Rearranged Non–Small-Cell Lung Cancer. N Engl J Med. 2014;371(21):1963-1971. doi:10.1056/NEJMoa1406766
53. U.S. Food and Drug Administrarion. FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation. Published 2017. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-dabrafenib-and-trametinib-combination-metastatic-nsclc-braf-v600e
54. Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17(7):984-993. doi:10.1016/S1470-2045(16)30146-2
55. Planchard D, Smit EF, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18(10):1307-1316. doi:10.1016/S1470-2045(17)30679-4
56. U.S. Food and Drug Administrarion. FDA approves larotrectinib for solid tumors with NTRK gene fusions. Published 2018. https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions
57. U.S. Food and Drug Administrarion. FDA Approves First Targeted Therapy to Treat Aggressive Form of Lung Cancer. Published 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer
58. U.S. Food and Drug Administrarion. FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC. Published online 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sotorasib-kras-g12c-mutated-nsclc
59. U.S. Food and Drug Administrarion. FDA D.I.S.C.O. Burst Edition: FDA approvals of Retevmo (selpercatinib) for adult patients with locally advanced or metastatic RET fusion-positive solid tumors, and Retevmo (selpercatinib) for adult patients with locally advanced or metastatic RET fusion-p. Published 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approvals-retevmo-selpercatinib-adult-patients-locally-advanced-or
60. U.S. Food and Drug Administrarion. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. Published 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung
61. Rosner S, Valdivia A, Hoe HJ, et al. Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress. Am Soc Clin Oncol Educ book Am Soc Clin Oncol Annu Meet. 2023;43:e389968. doi:10.1200/EDBK_389968
62. Sadik H, Pritchard D, Keeling D-M, et al. Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non-Small-Cell Lung Cancer. JCO Precis Oncol. 2022;6:e2200246. doi:10.1200/PO.22.00246
63. Yang JC-H, Schuler MH, Yamamoto N, et al. LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol. 2012;30(18_suppl):LBA7500-LBA7500. doi:10.1200/jco.2012.30.18_suppl.lba7500
64. Wu Y-L, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454-1466. doi:10.1016/S1470-2045(17)30608-3
65. Soria J-C, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137
66. Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017;376(7):629-640. doi:10.1056/NEJMoa1612674
67. Wu Y-L, 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
68. Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021;39(30):3391-3402. doi:10.1200/JCO.21.00662
69. Solomon BJ, Mok T, Kim D-W, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440
70. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795
71. Camidge DR, Kim HR, Ahn M-J, et al. Brigatinib versus Crizotinib in ALK -Positive Non–Small-Cell Lung Cancer. N Engl J Med. 2018;379(21):2027-2039. doi:10.1056/NEJMoa1810171
72. Soria J-C, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet (London, England). 2017;389(10072):917-929. doi:10.1016/S0140-6736(17)30123-X
73. Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187
74. Shaw AT, Riely GJ, Bang Y-J, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol Off J Eur Soc Med Oncol. 2019;30(7):1121-1126. doi:10.1093/annonc/mdz131
75. Solomon BJ, Drilon A, Lin JJ, et al. 1372P Repotrectinib in patients (pts) with NTRK fusion-positive (NTRK+) advanced solid tumors, including NSCLC: Update from the phase I/II TRIDENT-1 trial. Ann Oncol. 2023;34:S787-S788. doi:10.1016/j.annonc.2023.09.2405
76. Patel MR, Bauer TM, Liu S V., et al. STARTRK-1: Phase 1/2a study of entrectinib, an oral Pan-Trk, ROS1, and ALK inhibitor, in patients with advanced solid tumors with relevant molecular alterations. J Clin Oncol. 2015;33(15_suppl): 2596-2596. doi:10.1200/jco.2015.33.15_suppl.2596
77. Drilon A, Siena S, Ou S-HI, et al. Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017;7(4):400-409. doi:10.1158/2159-8290.CD-16-1237
78. Skoulidis F, Li BT, Dy GK, et al. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021;384(25):2371-2381. doi:10.1056/NEJMoa2103695
79. Jänne PA, Riely GJ, Gadgeel SM, et al. Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRAS G12C Mutation. N Engl J Med. 2022;387(2):120-131. doi:10.1056/NEJMoa2204619
80. Gainor JF, Curigliano G, Kim D-W, et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021;22(7):959-969. doi:10.1016/S1470-2045(21)00247-3
81. Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of Selpercatinib in RET Fusion–Positive Non–Small-Cell Lung Cancer. N Engl J Med. 2020;383(9):813-824. doi:10.1056/NEJMoa2005653
82. Riely GJ, Smit EF, Ahn M-J, et al. Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAF V600 -Mutant Metastatic Non–Small-Cell Lung Cancer. J Clin Oncol. 2023;41(21):3700-3711. doi:10.1200/JCO.23.00774
83. Drilon AE, Camidge DR, Ou S-HI, et al. Efficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC). J Clin Oncol. 2016;34(15_suppl):108-108. doi:10.1200/JCO.2016.34.15_suppl.108
84. Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N Engl J Med. 2020;383(10):944-957. doi:10.1056/NEJMoa2002787
85. Paik PK, Felip E, Veillon R, et al. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020;383(10):931-943. doi:10.1056/NEJMoa2004407
86. Paz-Ares L, Doebele RC, Farago AF, et al. Entrectinib in NTRK fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of patients (pts) enrolled in STARTRK-2, STARTRK-1 and ALKA-372-001. Ann Oncol. 2019;30:ii48-ii49. doi:10.1093/annonc/mdz063.011
87. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children. N Engl J Med. 2018;378(8):731-739. doi:10.1056/NEJMoa1714448
88. Li BT, Smit EF, Goto Y, et al. Trastuzumab Deruxtecan in HER2 -Mutant Non–Small-Cell Lung Cancer. N Engl J Med. 2022;386(3):241-251. doi:10.1056/NEJMoa2112431
89. Slatko BE, Gardner AF, Ausubel FM. Overview of Next-Generation Sequencing Technologies. Curr Protoc Mol Biol. 2018;122(1):e59. doi:10.1002/cpmb.59
90. Magi A, Benelli M, Gozzini A, Girolami F, Torricelli F, Brandi ML. Bioinformatics for Next Generation Sequencing Data. Genes (Basel). 2010;1(2):294-307. doi:10.3390/genes1020294
91. Yu T, Morrison C, Gold E, Tradonsky A, Layton A. MA 11.06 Retrospective Analysis of NSCLC Testing in Low Tumor Content Samples: Single-Gene Tests, NGS, & the OncomineTM Dx Target Test. J Thorac Oncol. 2017;12(11):S1845. doi:10.1016/j.jtho.2017.09.546
92. Sholl LM, Aisner DL, Varella-Garcia M, et al. Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience. J Thorac Oncol. 2015;10(5):768-777. doi:10.1097/JTO.0000000000000516
93. Anaparthy N, Ho Y-J, Martelotto L, Hammell M, Hicks J. Single-Cell Applications of Next-Generation Sequencing. Cold Spring Harb Perspect Med. 2019;9(10). doi:10.1101/cshperspect.a026898
94. Hwang B, Lee JH, Bang D. Single-cell RNA sequencing technologies and bioinformatics pipelines. Exp Mol Med. 2018;50(8):1-14. doi:10.1038/s12276-018-0071-8
95. Zou D, Ye W, Hess LM, et al. Diagnostic Value and Cost-Effectiveness of Next-Generation Sequencing-Based Testing for Treatment of Patients with Advanced/Metastatic Non-Squamous Non-Small-Cell Lung Cancer in the United States. J Mol Diagn. 2022;24(8):901-914. doi:10.1016/j.jmoldx.2022.04.010
96. Arriola E, Bernabé R, Campelo RG, et al. Cost-Effectiveness of Next-Generation Sequencing Versus Single-Gene Testing for the Molecular Diagnosis of Patients With Metastatic Non-Small-Cell Lung Cancer From the Perspective of Spanish Reference Centers. JCO Precis Oncol. 2023;7:e2200546. doi:10.1200/PO.22.00546
97. Ferreira CG. Lung cancer in developing countries: access to molecular testing. Am Soc Clin Oncol Educ book Am Soc Clin Oncol Annu Meet. Published online 2013:327-331. doi:10.14694/EdBook_AM.2013.33.327
98. 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
99. U.S. Food and Drug Administrarion. FDA Approves First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic Test. Published 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test
100. Di Capua D, Bracken-Clarke D, Ronan K, Baird A-M, Finn S. The Liquid Biopsy for Lung Cancer: State of the Art, Limitations and Future Developments. Cancers (Basel). 2021;13(16):3923. doi:10.3390/cancers13163923
101. Rolfo C, Mack P, Scagliotti G V., 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
102. Scheffler M, Wiesweg M, Michels S, et al. Rebiopsy in advanced non-small cell lung cancer, clinical relevance and prognostic implications. Lung Cancer. 2022;168:10-20. doi:10.1016/j.lungcan.2022.04.006
103. Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer. N Engl J Med. 2017;376(7):629-640. doi:10.1056/NEJMoa1612674
104. Russano M, Napolitano A, Ribelli G, et al. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. J Exp Clin Cancer Res. 2020;39(1):95. doi:10.1186/s13046-020-01601-2
105. Chan HT, Chin YM, Nakamura Y, Low S-K. Clonal Hematopoiesis in Liquid Biopsy: From Biological Noise to Valuable Clinical Implications. Cancers (Basel). 2020;12(8):2277. doi:10.3390/cancers12082277
106. Hofman P. Matched tissue and liquid biopsies for advanced non-small cell lung cancer patients A potentially indispensable complementary approach. Transl Oncol. 2023;35:101735. doi:10.1016/j.tranon.2023.101735
107. de Scordilli M, Michelotti A, Bertoli E, De Carlo E, Del Conte A, Bearz A. Targeted Therapy and Immunotherapy in Early-Stage Non-Small Cell Lung Cancer: Current Evidence and Ongoing Trials. Int J Mol Sci. 2022;23(13). doi:10.3390/ijms23137222
108. Tsuboi M, Herbst RS, John T, et al. Overall Survival with Osimertinib in Resected EGFR -Mutated NSCLC. N Engl J Med. 2023;389(2):137-147. doi:10.1056/NEJMoa2304594
109. U.S. Food and Drug Administrarion. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. Published 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations
110. Solomon BJ, Ahn JS, Dziadziuszko R, et al. LBA2 ALINA: Efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC). Ann Oncol. 2023;34:S1295-S1296. doi:10.1016/j.annonc.2023.10.051
111. Sposito M, Belluomini L, Pontolillo L, et al. Adjuvant Targeted Therapy in Solid Cancers: Pioneers and New Glories. J Pers Med. 2023;13(10):1427. doi:10.3390/jpm13101427
112. Tsuboi M, Goldman JW, Wu Y-L, et al. LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive non-small-cell lung cancer. Future Oncol. 2022;18(28):3133-3141. doi:10.2217/fon-2022-0656
113. Zhou C, Solomon B, Loong HH, et al. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion–Positive NSCLC. N Engl J Med. 2023;389(20):1839-1850. doi:10.1056/NEJMoa2309457
114. Herbst RS, Wu Y-L, John T, et al. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. J Clin Oncol. 2023;41(10):1830-1840. doi:10.1200/JCO.22.02186
115. Vellekoop H, Versteegh M, Huygens S, et al. The Net Benefit of Personalized Medicine: A Systematic Literature Review and Regression Analysis. Value Health. 2022;25(8):1428-1438. doi:10.1016/j.jval.2022.01.006
116. Lu CY, Terry V, Thomas DM. Precision medicine: affording the successes of science. npj Precis Oncol. 2023;7(1):3. doi:10.1038/s41698-022-00343-y
117. Schluckebier L, Caetano R, Garay OU, et al. Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients. BMC Cancer. 2020;20(1):875. doi:10.1186/s12885-020-07240-2
118. Amaral Duarte F, Aguiar Junior PN, Dienstmann R, Ferreira CG. Precision medicine in Thoracic Oncology: understanding disparities to tackle inequities in access. Expert Rev Pharmacoecon Outcomes Res. 2023;23(9):981-987. doi:10.1080/14737167.2023.2260563
119. Aguiar PN, Haaland B, Park W, San Tan P, del Giglio A, de Lima Lopes G. Cost-effectiveness of Osimertinib in the First-Line Treatment of Patients With EGFR -Mutated Advanced Non–Small Cell Lung Cancer. JAMA Oncol. 2018;4(8):1080. doi:10.1001/jamaoncol.2018.1395
120. Carlson JJ, Suh K, Orfanos P, Wong W. Cost Effectiveness of Alectinib vs. Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer. Pharmacoeconomics. 2018;36(4):495-504. doi:10.1007/s40273-018-0625-6
121. Sivignon M, Monnier R, Tehard B, Roze S. Cost-effectiveness of alectinib compared to crizotinib for the treatment of first-line ALK+ advanced non-small-cell lung cancer in France. PLoS One. 2020;15(1):e0226196. doi:10.1371/journal.pone.0226196
122. Chen W, Wong NCB, Wang Y, et al. Mapping the value for money of precision medicine: a systematic literature review and meta-analysis. Front public Heal. 2023;11:1151504. doi:10.3389/fpubh.2023.1151504
123. Ocran Mattila P, Ahmad R, Hasan SS, Babar Z-U-D. Availability, Affordability, Access, and Pricing of Anti-cancer Medicines in Low- and Middle-Income Countries: A Systematic Review of Literature. Front public Heal. 2021;9:628744. doi:10.3389/fpubh.2021.628744
124. Kelner M, Carvalho da Silva B, Montella T, et al. Discrepancies Between the Cost of Advanced Lung Cancer Treatment and How Much Is Reimbursed by the Brazilian Public Healthcare System. Value Heal Reg issues. 2023;33:1-6. doi:10.1016/j.vhri.2022.08.004
125. Cutler DM. Early Returns From the Era of Precision Medicine. JAMA. 2020;323(2):109. doi:10.1001/jama.2019.20659
126. Aguiar PN, Matsas S, Dienstmann R, Ferreira CG. Challenges and opportunities in building a health economic framework for personalized medicine in oncology. Per Med. 2023;20(5):453-460. doi:10.2217/pme-2022-0008
127. Specchia ML, Frisicale EM, Carini E, et al. The impact of tumor board on cancer care: evidence from an umbrella review. BMC Health Serv Res. 2020;20(1):73. doi:10.1186/s12913-020-4930-3
128. Mano MS, Çitaku FT, Barach P. Implementing multidisciplinary tumor boards in oncology: a narrative review. Future Oncol. 2022;18(3):375-384. doi:10.2217/fon-2021-0471
129. Yopp AC, Mansour JC, Beg MS, et al. Establishment of a multidisciplinary hepatocellular carcinoma clinic is associated with improved clinical outcome. Ann Surg Oncol. 2014;21(4):1287-1295. doi:10.1245/s10434-013-3413-8
130. Huang B, Chen Q, Allison D, et al. Molecular Tumor Board Review and Improved Overall Survival in Non-Small-Cell Lung Cancer. JCO Precis Oncol. 2021;5. doi:10.1200/PO.21.00210
131. Behel V, Noronha V, Choughule A, et al. Impact of Molecular Tumor Board on the Clinical Management of Patients With Cancer. JCO Glob Oncol. 2022;8:e2200030. doi:10.1200/GO.22.00030
132. De Marchi P, Leal LF, Duval da Silva V, da Silva ECA, Cordeiro de Lima VC, Reis RM. PD-L1 expression by Tumor Proportion Score (TPS) and Combined Positive Score (CPS) are similar in non-small cell lung cancer (NSCLC). J Clin Pathol. 2021;74(11):735-740. doi:10.1136/jclinpath-2020-206832
133. 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
134. Marcus L, Fashoyin-Aje LA, Donoghue M, et al. FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden-High Solid Tumors. Clin Cancer Res. 2021;27(17):4685-4689. doi:10.1158/1078-0432.CCR-21-0327
135. Ghiringhelli F, Bibeau F, Greillier L, et al. Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer. eBioMedicine. 2023;92:104633. doi:10.1016/j.ebiom.2023.104633
136. Doroshow DB, Wei W, Gupta S, et al. Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC. J Thorac Oncol. 2021;16(12):2139-2143. doi:10.1016/j.jtho.2021.07.032
137. Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1353-1365. doi:10.1016/S1470-2045(20)30445-9
138. Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 2016;17(12):e542-e551. doi:10.1016/S1470-2045(16)30406-5
139. Mino-Kenudson M, Schalper K, Cooper W, et al. Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee. J Thorac Oncol. 2022;17(12):1335-1354. doi:10.1016/j.jtho.2022.09.109
140. Ye L, Creaney J, Redwood A, Robinson B. The Current Lung Cancer Neoantigen Landscape and Implications for Therapy. J Thorac Oncol. 2021;16(6):922-932. doi:10.1016/j.jtho.2021.01.1624
141. Anagnostou V, Smith KN, Forde PM, et al. Evolution of Neoantigen Landscape during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer. Cancer Discov. 2017;7(3):264-276. doi:10.1158/2159-8290.CD-16-0828
142. Kovács SA, Fekete JT, Győrffy B. Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors. Acta Pharmacol Sin. 2023;44(9):1879-1889. doi:10.1038/s41401-023-01079-6
143. Liu M, Wu J, Wang N, et al. The value of artificial intelligence in the diagnosis of lung cancer: A systematic review and meta-analysis. PLoS One. 2023;18(3):e0273445. doi:10.1371/journal.pone.0273445
144. Gandhi Z, Gurram P, Amgai B, et al. Artificial Intelligence and Lung Cancer: Impact on Improving Patient Outcomes. Cancers (Basel). 2023;15(21). doi:10.3390/cancers15215236
145. Seegobin K, Majeed U, Wiest N, Manochakian R, Lou Y, Zhao Y. Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR. Front Oncol. 2021;11. doi:10.3389/fonc.2021.750657
146. Calles A, Riess JW, Brahmer JR. Checkpoint Blockade in Lung Cancer With Driver Mutation: Choose the Road Wisely. Am Soc Clin Oncol Educ B. 2020;(40):372-384. doi:10.1200/EDBK_280795
147. Man J, Zhang X, Dong H, et al. Screening and identification of key biomarkers in lung squamous cell carcinoma by bioinformatics analysis. Oncol Lett. 2019;18(5):5185-5196. doi:10.3892/ol.2019.10873
148. Lau SCM, Pan Y, Velcheti V, Wong KK. Squamous cell lung cancer: Current landscape and future therapeutic options. Cancer Cell. 2022;40(11):1279-1293. doi:10.1016/j.ccell.2022.09.018
149. Niu Z, Jin R, Zhang Y, Li H. Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials. Signal Transduct Target Ther. 2022;7(1):353. doi:10.1038/s41392-022-01200-x
150. Jin R, Peng L, Shou J, et al. EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes. Front Oncol. 2021;11. doi:10.3389/fonc.2021.680804
151. Meng Q, Dong Y, Tao H, et al. ALK ‐rearranged squamous cell carcinoma of the lung. Thorac Cancer. 2021;12(7):1106-1114. doi:10.1111/1759-7714.13818
152. Sun N, Zhuang Y, Zhang J, Chen S, Dai Y, Guo R. ALK Rearrangement in Small-Cell Lung Cancer and Durable Response to Alectinib: A Case Report. Onco Targets Ther. 2021;Volume 14:5161-5166. doi:10.2147/OTT.S323700
153. Marcoux N, Gettinger SN, O’Kane G, et al. EGFR -Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. J Clin Oncol. 2019;37(4):278-285. doi:10.1200/JCO.18.01585
154. Cani M, Napoli VM, Garbo E, et al. Targeted Therapies in Small Cell Lung Cancer: From Old Failures to Novel Therapeutic Strategies. Int J Mol Sci. 2023;24(10):8883. doi:10.3390/ijms24108883
155. Ding X-L, Su Y-G, Yu L, et al. Clinical characteristics and patient outcomes of molecular subtypes of small cell lung cancer (SCLC). World J Surg Oncol. 2022;20(1):54. doi:10.1186/s12957-022-02528-y
156. Caliman E, Fancelli S, Petroni G, et al. Challenges in the treatment of small cell lung cancer in the era of immunotherapy and molecular classification. Lung Cancer. 2023;175:88-100. doi:10.1016/j.lungcan.2022.11.014
157. Ahn M-J, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023;389(22):2063-2075. doi:10.1056/NEJMoa2307980
158. Paz-Ares L, Champiat S, Lai WV, et al. Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. J Clin Oncol. 2023;41(16):2893-2903. doi:10.1200/JCO.22.02823
159. Lathyris DN, Patsopoulos NA, Salanti G, Ioannidis JPA. Industry sponsorship and selection of comparators in randomized clinical trials. Eur J Clin Invest. 2010;40(2):172-182. doi:10.1111/j.1365-2362.2009.02240.x
160. Peyrin-Biroulet L, Lopez A, Sandborn W. Head-to-head comparative studies: Challenges & opportunities? J Crohn’s Colitis. Published online September 22, 2016:jjw167. doi:10.1093/ecco-jcc/jjw167
161. Siringo M, Baena J, Bote de Cabo H, et al. Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer. Cancers (Basel). 2023;15(23):5505. doi:10.3390/cancers15235505
162. Pozza DH, Andrade de Mello RB. Treatment Sequencing Strategies in Lung Cancer. Zhongguo Fei Ai Za Zhi. 2022;25(5):323-336. doi:10.3779/j.issn.1009-3419.2022.104.01
163. Jiang W, Cai G, Hu PC, Wang Y. Personalized medicine in non-small cell lung cancer: a review from a pharmacogenomics perspective. Acta Pharm Sin B. 2018;8(4):530-538. doi:10.1016/j.apsb.2018.04.005
164. Goulet DR, Atkins WM. Considerations for the Design of Antibody-Based Therapeutics. J Pharm Sci. 2020;109(1):74-103. doi:10.1016/j.xphs.2019.05.031
165. Passaro A, Jänne PA, Peters S. Antibody-Drug Conjugates in Lung Cancer: Recent Advances and Implementing Strategies. J Clin Oncol. 2023;41(21):3747-3761. doi:10.1200/JCO.23.00013
166. Liao J, Li X, Gan Y, et al. Artificial intelligence assists precision medicine in cancer treatment. Front Oncol. 2023;12. doi:10.3389/fonc.2022.998222
167. Prelaj A, Ganzinelli M, Provenzano L, et al. APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research. Clin Lung Cancer. Published online December 2023. doi:10.1016/j.cllc.2023.12.012
168. Zhang Y-P, Zhang X-Y, Cheng Y-T, et al. Artificial intelligence-driven radiomics study in cancer: the role of feature engineering and modeling. Mil Med Res. 2023;10(1):22. doi:10.1186/s40779-023-00458-8
169. Rossi A, Pilotto S, Carbognin L, et al. Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer. J Mol Pathol. 2021;2(3):207-222. doi:10.3390/jmp2030018
170. Spreafico A, Hansen AR, Abdul Razak AR, Bedard PL, Siu LL. The Future of Clinical Trial Design in Oncology. Cancer Discov. 2021;11(4):822-837. doi:10.1158/2159-8290.CD-20-1301
171. Le-Rademacher J, Dahlberg S, Lee JJ, Adjei AA, Mandrekar SJ. Biomarker Clinical Trials in Lung Cancer: Design, Logistics, Challenges, and Practical Considerations. J Thorac Oncol. 2018;13(11):1625-1637. doi:10.1016/j.jtho.2018.08.2019
172. Palermos D, Sergentanis TN, Gavriatopoulou M, et al. Lung Cancer Clinical Trials with a Seamless Phase II/III Design: Systematic Review. J Clin Med. 2022;11(23). doi:10.3390/jcm11237176
173. Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-238. doi:10.1038/nrc.2017.7
174. Beaver JA, Jelovac D, Balukrishna S, et al. Detection of cancer DNA in plasma of patients with early-stage breast cancer. Clin Cancer Res. 2014;20(10):2643-2650. doi:10.1158/1078-0432.CCR-13-2933