J Pathol Transl Med.  2024 Jul;58(4):147-164. 10.4132/jptm.2023.11.01.

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP

• Kim M
• Shim HS
• Kim S
• Lee IH
• Kim J
• Yoon S
• Kim HD
• Park I
• Jeong JH
• Yoo C
• Cheon J
• Kim IH
• Lee J
• Hong SH
• Park S
• Jung HA
• Kim JW
• Kim HJ
• Cha Y
• Lim SM
• Kim HS
• Lee CK
• Kim JH
• Chun SH
• Yun J
• Park SY
• Lee HS
• Cho YM
• Nam SJ
• Na K
• Yoon SO
• Lee A
• Jang KT
• Yun H
• Lee S
• Kim JH
• Kim WS

• KMID: 2557755
• DOI: http://doi.org/10.4132/jptm.2023.11.01

Abstract

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Keyword

Next-generation sequencing; Solid cancer; Precision medicine; Korea

Reference

References

1. Yoon S, Kim M, Hong YS, et al. Recommendations for the use of next-generation sequencing and the molecular tumor board for patients with advanced cancer: a report from KSMO and KCSG Precision Medicine Networking Group. Cancer Res Treat. 2022; 54:1–9.

2. Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017; 23:703–13.

3. Tsimberidou AM, Hong DS, Ye Y, et al. Initiative for molecular profiling and advanced cancer therapy (IMPACT): an MD Anderson precision medicine study. JCO Precis Oncol. 2017; 2017:PO.17.00002.

4. Massard C, Michiels S, Ferte C, et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov. 2017; 7:586–95.

5. Cousin S, Grellety T, Toulmonde M, et al. Clinical impact of extensive molecular profiling in advanced cancer patients. J Hematol Oncol. 2017; 10:45.

6. Tsimberidou AM, Wen S, Hong DS, et al. Personalized medicine for patients with advanced cancer in the phase I program at MD Anderson: validation and landmark analyses. Clin Cancer Res. 2014; 20:4827–36.

7. Andre F, Filleron T, Kamal M, et al. Genomics to select treatment for patients with metastatic breast cancer. Nature. 2022; 610:343–8.

8. Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022; 20:497–530.

9. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020; 38:1–10.

10. 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; 21:1353–65.

11. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015; 372:30–9.

12. 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; 17:984–93.

13. Planchard D, Smit EF, Groen HJ, et al. Dabrafenib plus trametinib in patients with previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017; 18:1307–16.

14. Subbiah V, Lassen U, Elez E, et al. Dabrafenib plus trametinib in patients with BRAF(V600E)-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020; 21:1234–43.

15. Salama AK, Li S, Macrae ER, et al. Dabrafenib and trametinib in patients with tumors with BRAF(V600E) mutations: results of the NCI-MATCH trial subprotocol H. J Clin Oncol. 2020; 38:3895–904.

16. Wen PY, Stein A, van den Bent M, et al. Dabrafenib plus trametinib in patients with BRAF(V600E)-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol. 2022; 23:53–64.

17. Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Ann Oncol. 2022; 33:406–15.

18. Subbiah V, Wolf J, Konda B, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol. 2022; 23:1261–73.

19. 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; 378:731–9.

20. Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020; 21:271–82.

21. Chakravarty D, Gao J, Phillips SM, et al. OncoKB: a precision oncology knowledge base. JCO Precis Oncol. 2017; 2017:PO.17.00011.

22. McConnell L, Houghton O, Stewart P, et al. A novel next generation sequencing approach to improve sarcoma diagnosis. Mod Pathol. 2020; 33:1350–9.

23. Szurian K, Kashofer K, Liegl-Atzwanger B. Role of next-generation sequencing as a diagnostic tool for the evaluation of bone and soft-tissue tumors. Pathobiology. 2017; 84:323–38.

24. Gounder MM, Agaram NP, Trabucco SE, et al. Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma. Nat Commun. 2022; 13:3406.

25. Moch H, Amin MB, Berney DM, et al. The 2022 World Health Organization classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol. 2022; 82:458–68.

26. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016; 131:803–20.

27. Louis DN, Aldape K, Brat DJ, et al. Announcing cIMPACT-NOW: the consortium to inform molecular and practical approaches to CNS tumor taxonomy. Acta Neuropathol. 2017; 133:1–3.

28. WHO classification of tumours of the central nervous system tumours. 5th ed. Lyon: International Agency for Research on Cancer;2021.

29. Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017; 376:629–40.

30. Janne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015; 372:1689–99.

31. Westover D, Zugazagoitia J, Cho BC, Lovly CM, Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol. 2018; 29:i10–9.

32. Wang Z, Xing Y, Li B, Li X, Liu B, Wang Y. Molecular pathways, resistance mechanisms and targeted interventions in non-smallcell lung cancer. Mol Biomed. 2022; 3:42.

33. He J, Zhou Z, Sun X, et al. The new opportunities in medicinal chemistry of fourth-generation EGFR inhibitors to overcome C797S mutation. Eur J Med Chem. 2021; 210:112995.

34. Coleman N, Hong L, Zhang J, Heymach J, Hong D, Le X. Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven nonsmall-cell lung cancer. ESMO Open. 2021; 6:100319.

35. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007; 448:561–6.

36. 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; 377:829–38.

37. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018; 379:2027–39.

38. Shiba-Ishii A, Johnson TW, Dagogo-Jack I, et al. Analysis of lorlatinib analogs reveals a roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer. Nat Cancer. 2022; 3:710–22.

39. Yun MR, Kim DH, Kim SY, et al. Repotrectinib exhibits potent antitumor activity in treatment-naive and solvent-front-mutant ROS1-rearranged non-small cell lung cancer. Clin Cancer Res. 2020; 26:3287–95.

40. Le DT, Kim TW, Van Cutsem E, et al. Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instabilityhigh/mismatch repair-deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol. 2020; 38:11–9.

41. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361:947–57.

42. 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; 13:239–46.

43. Wu YL, 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, openlabel, phase 3 trial. Lancet Oncol. 2017; 18:1454–66.

44. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018; 378:113–25.

45. Cho BC, Han JY, Kim SW, et al. A phase 1/2 study of lazertinib 240 mg in patients with advanced EGFR T790M-positive NSCLC after previous EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2022; 17:558–67.

46. Yun CH, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A. 2008; 105:2070–5.

47. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014; 4:1046–61.

48. Zhou C, Ramalingam SS, Kim TM, et al. Treatment outcomes and safety of mobocertinib in platinum-pretreated patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer: a phase 1/2 open-label nonrandomized clinical trial. JAMA Oncol. 2021; 7:e214761.

49. 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; 39:3391–402.

50. Planchard D, Kim TM, Mazieres J, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016; 17:642–50.

51. Soria JC, Tan DS, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged nonsmall-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017; 389:917–29.

52. 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; 383:2018–29.

53. Janne PA, Riely GJ, Gadgeel SM, et al. Adagrasib in non-small-cell lung cancer harboring a KRAS(G12C) mutation. N Engl J Med. 2022; 387:120–31.

54. Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021; 384:2371–81.

55. 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; 383:931–43.

56. Wolf J, Seto T, Han JY, et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med. 2020; 383:944–57.

57. Drilon A, Oxnard GR, Tan DS, et al. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med. 2020; 383:813–24.

58. Gainor JF, Curigliano G, Kim DW, 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; 22:959–69.

59. Shaw AT, Riely GJ, Bang YJ, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019; 30:1121–6.

60. Drilon A, Siena S, Dziadziuszko R, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020; 21:261–70.

61. Mazieres J, Lafitte C, Ricordel C, et al. Combination of trastuzumab, pertuzumab, and docetaxel in patients with advanced nonsmall-cell lung cancer harboring HER2 mutations: results from the IFCT-1703 R2D2 trial. J Clin Oncol. 2022; 40:719–28.

62. Li BT, Smit EF, Goto Y, et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med. 2022; 386:241–51.

63. Le X, Cornelissen R, Garassino M, et al. Poziotinib in non-smallcell lung cancer harboring HER2 exon 20 insertion mutations after prior therapies: ZENITH20-2 trial. J Clin Oncol. 2022; 40:710–8.

64. Iwama E, Zenke Y, Sugawara S, et al. Trastuzumab emtansine for patients with non-small cell lung cancer positive for human epidermal growth factor receptor 2 exon-20 insertion mutations. Eur J Cancer. 2022; 162:99–106.

65. Peters S, Stahel R, Bubendorf L, et al. Trastuzumab emtansine (TDM1) in patients with previously treated HER2-overexpressing metastatic non-small cell lung cancer: efficacy, safety, and biomarkers. Clin Cancer Res. 2019; 25:64–72.

66. Yang G, Xu H, Yang Y, et al. Pyrotinib combined with apatinib for targeting metastatic non-small cell lung cancer with HER2 alterations: a prospective, open-label, single-arm phase 2 study (PATHER2). BMC Med. 2022; 20:277.

67. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344:783–92.

68. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012; 367:1783–91.

69. Krop IE, Kim SB, Gonzalez-Martin A, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2- positive advanced breast cancer (TH3RESA): a randomised, openlabel, phase 3 trial. Lancet Oncol. 2014; 15:689–99.

70. Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015; 372:724–34.

71. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020; 382:597–609.

72. Hyman DM, Piha-Paul SA, Won H, et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018; 554:189–94.

73. Smyth LM, Piha-Paul SA, Won HH, et al. Efficacy and determinants of response to HER kinase inhibition in HER2-mutant metastatic breast cancer. Cancer Discov. 2020; 10:198–213.

74. Andre F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019; 380:1929–40.

75. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021; 22:489–98.

76. Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017; 377:523–33.

77. Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018; 379:753–63.

78. Balasubramaniam S, Beaver JA, Horton S, et al. FDA approval summary: rucaparib for the treatment of patients with deleterious BRCA mutation-associated advanced ovarian cancer. Clin Cancer Res. 2017; 23:7165–70.

79. Tung NM, Robson ME, Ventz S, et al. TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol. 2020; 38:4274–82.

80. Gennari A, Andre F, Barrios CH, et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021; 32:1475–95.

81. Schmid P, Abraham J, Chan S, et al. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020; 38:423–33.

82. Howell SJ, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progressionfree survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol. 2022; 23:851–64.

83. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022; 40:3246–56.

84. Hyman DM, Smyth LM, Donoghue MT, et al. AKT inhibition in solid tumors with AKT1 mutations. J Clin Oncol. 2017; 35:2251–9.

85. Kuemmel S, Harrach H, Schmutzler RK, et al. Olaparib for metastatic breast cancer in a patient with a germline PALB2 variant. NPJ Breast Cancer. 2020; 6:31.

86. Janjigian YY, Maron SB, Chatila WK, et al. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020; 21:821–31.

87. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376:687–97.

88. Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020; 382:2419–30.

89. Chung HC, Bang YJ, Fuchs CS, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol. 2021; 17:491–501.

90. Wainberg ZA, Enzinger PC, Kang YK, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2022; 23:1430–40.

91. Lee J, Kim ST, Kim K, et al. Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: the VIKTORY Umbrella trial. Cancer Discov. 2019; 9:1388–405.

92. Maron SB, Moya S, Morano F, et al. Epidermal growth factor receptor inhibition in epidermal growth factor receptor-amplified gastroesophageal cancer: retrospective global experience. J Clin Oncol. 2022; 40:2458–67.

93. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359:1757–65.

94. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009; 360:1408–17.

95. Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013; 369:1023–34.

96. Van Cutsem E, Lenz HJ, Kohne CH, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015; 33:692–700.

97. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019; 381:1632–43.

98. Kopetz S, Guthrie KA, Morris VK, et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAFmutant metastatic colorectal cancer (SWOG S1406). J Clin Oncol. 2021; 39:285–94.

99. Overman MJ, Lonardi S, Wong KY, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018; 36:773–9.

100. Andre T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020; 383:2207–18.

101. Strickler JH, Cercek A, Siena S, et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023; 24:496–508.

102. Fakih MG, Kopetz S, Kuboki Y, et al. Sotorasib for previously treated colorectal cancers with KRAS(G12C) mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 2022; 23:115–24.

103. Yaeger R, Weiss J, Pelster MS, et al. Adagrasib with or without cetuximab in colorectal cancer with mutated KRAS G12C. N Engl J Med. 2023; 388:44–54.

104. Garmezy B, Gheeya J, Lin HY, et al. Clinical and molecular characterization of POLE mutations as predictive biomarkers of response to immune checkpoint inhibitors in advanced cancers. JCO Precis Oncol. 2022; 6:e2100267.

105. Rousseau B, Bieche I, Pasmant E, et al. PD-1 blockade in solid tumors with defects in polymerase epsilon. Cancer Discov. 2022; 12:1435–48.

106. Wang F, Zhao Q, Wang YN, et al. Evaluation of POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. JAMA Oncol. 2019; 5:1504–6.

107. Ferrarotto R, Eckhardt G, Patnaik A, et al. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Ann Oncol. 2018; 29:1561–8.

108. Ferrarotto R, Mitani Y, Diao L, et al. Activating NOTCH1 mutations define a distinct subgroup of patients with adenoid cystic carcinoma who have poor prognosis, propensity to bone and liver metastasis, and potential responsiveness to Notch1 inhibitors. J Clin Oncol. 2017; 35:352–60.

109. Jhaveri KL, Wang XV, Makker V, et al. Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: results from the NCI-MATCH trial (EAY131) subprotocol Q. Ann Oncol. 2019; 30:1821–30.

110. Kurzrock R, Bowles DW, Kang H, et al. Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study. Ann Oncol. 2020; 31:412–21.

111. Takahashi H, Tada Y, Saotome T, et al. Phase II trial of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2-positive salivary duct carcinoma. J Clin Oncol. 2019; 37:125–34.

112. Tabernero J, Bahleda R, Dienstmann R, et al. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2015; 33:3401–8.

113. Nogova L, Sequist LV, Perez Garcia JM, et al. Evaluation of BGJ398, a fibroblast growth factor receptor 1-3 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: results of a global phase I, dose-escalation and dose-expansion study. J Clin Oncol. 2017; 35:157–65.

114. Goke F, Franzen A, Hinz TK, et al. FGFR1 expression levels predict BGJ398 sensitivity of FGFR1-dependent head and neck squamous cell cancers. Clin Cancer Res. 2015; 21:4356–64.

115. Kochanny SE, Worden FP, Adkins DR, et al. A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Cancer. 2020; 126:2146–52.

116. Rothenberger NJ, Stabile LP. Hepatocyte growth factor/c-Met signaling in head and neck cancer and implications for treatment. Cancers (Basel). 2017; 9:39.

117. Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019; 381:317–27.

118. Reiss KA, Mick R, O’Hara MH, et al. Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2. J Clin Oncol. 2021; 39:2497–505.

119. Strickler JH, Satake H, George TJ, et al. Sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer. N Engl J Med. 2023; 388:33–43.

120. Bekaii-Saab TS, Yaeger R, Spira AI, et al. Adagrasib in advanced solid tumors harboring a KRAS(G12C) mutation. J Clin Oncol. 2023; 41:4097–106.

121. Payne SN, Maher ME, Tran NH, et al. PIK3CA mutations can initiate pancreatic tumorigenesis and are targetable with PI3K inhibitors. Oncogenesis. 2015; 4:e169.

122. Harder J, Ihorst G, Heinemann V, et al. Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer. Br J Cancer. 2012; 106:1033–8.

123. Singhi AD, Ali SM, Lacy J, et al. Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma. J Natl Compr Canc Netw. 2017; 15:555–62.

124. Schram AM, O’Reilly EM, O’Kane GM, et al. Efficacy and safety of zenocutuzumab in advanced pancreas cancer and other solid tumors harboring NRG1 fusions. J Clin Oncol. 2021; 39(15 Suppl):3003.

125. Pishvaian MJ, Garrido-Laguna I, Liu SV, Multani PS, Chow-Maneval E, Rolfo C. Entrectinib in TRK and ROS1 fusion-positive metastatic pancreatic cancer. JCO Precis Oncol. 2018; 2:1–7.

126. Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1- mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020; 21:796–807.

127. Zhu AX, Macarulla T, Javle MM, et al. Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. 2021; 7:1669–77.

128. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020; 21:671–84.

129. Javle M, Roychowdhury S, Kelley RK, et al. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021; 6:803–15.

130. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med. 2023; 388:228–39.

131. Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021; 22:1290–300.

132. Lee CK, Chon HJ, Cheon J, et al. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19-14). Lancet Gastroenterol Hepatol. 2023; 8:56–65.

133. Ohba A, Morizane C, Ueno M, et al. Multicenter phase II trial of trastuzumab deruxtecan for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial. Future Oncol. 2022; 18:2351–60.

134. Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol. 2018; 36:2044–51.

135. Oaknin A, Bosse TJ, Creutzberg CL, et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022; 33:860–77.

136. Leon-Castillo A, Britton H, McConechy MK, et al. Interpretation of somatic POLE mutations in endometrial carcinoma. J Pathol. 2020; 250:323–35.

137. Rios-Doria E, Momeni-Boroujeni A, Friedman CF, et al. Integration of clinical sequencing and immunohistochemistry for the molecular classification of endometrial carcinoma. Gynecol Oncol. 2023; 174:262–72.

138. Talhouk A, McConechy MK, Leung S, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015; 113:299–310.

139. Leon-Castillo A, de Boer SM, Powell ME, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol. 2020; 38:3388–97.

140. Kommoss S, McConechy MK, Kommoss F, et al. Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Ann Oncol. 2018; 29:1180–8.

141. van den Heerik A, Horeweg N, Nout RA, et al. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020; 30:2002–7.

142. Gonzalez-Martin A, Pothuri B, Vergote I, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019; 381:2391–402.

143. Coleman RL, Fleming GF, Brady MF, et al. Veliparib with firstline chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019; 381:2403–15.

144. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016; 375:2154–64.

145. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018; 379:2495–505.

146. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019; 381:2416–28.

147. Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014; 15:852–61.

148. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 390:1949–61.

149. Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017; 18:1274–84.

150. Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019; 381:338–48.

151. Van Allen EM, Mouw KW, Kim P, et al. Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov. 2014; 4:1140–53.

152. Liu D, Plimack ER, Hoffman-Censits J, et al. Clinical validation of chemotherapy response biomarker ERCC2 in muscle-invasive urothelial bladder carcinoma. JAMA Oncol. 2016; 2:1094–6.

153. de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020; 382:2091–102.

154. Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med. 2020; 383:2345–57.

155. Jonasch E, Donskov F, Iliopoulos O, et al. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N Engl J Med. 2021; 385:2036–46.

156. Choi Y, Keam B, Kim M, et al. Bevacizumab plus erlotinib combination therapy for advanced hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma: a multicenter retrospective analysis in Korean patients. Cancer Res Treat. 2019; 51:1549–56.

157. Srinivasan R, Gurram S, Harthy MA, et al. Results from a phase II study of bevacizumab and erlotinib in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) or sporadic papillary renal cell cancer. J Clin Oncol. 2020; 38(15 Suppl):5004.

158. Iannantuono GM, Riondino S, Sganga S, Roselli M, Torino F. Activity of ALK inhibitors in renal cancer with ALK alterations: a systematic review. Int J Mol Sci. 2022; 23:3995.

159. Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018; 19:603–15.

160. Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014; 371:1867–76.

161. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017; 377:1813–23.

162. Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014; 371:1877–88.

163. Gutzmer R, Stroyakovskiy D, Gogas H, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF(V600) mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020; 395:1835–44.

164. Carvajal RD, Antonescu CR, Wolchok JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011; 305:2327–34.

165. Hodi FS, Corless CL, Giobbie-Hurder A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013; 31:3182–90.

166. Dummer R, Schadendorf D, Ascierto PA, et al. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017; 18:435–45.

167. Shin SJ, Lee J, Kim TM, et al. A phase Ib trial of belvarafenib in combination with cobimetinib in patients with advanced solid tumors: interim results of dose-escalation and patients with NRASmutant melanoma of dose-expansion. J Clin Oncol. 2021; 39(15 Suppl):3007.

168. Menzies AM, Yeh I, Botton T, Bastian BC, Scolyer RA, Long GV. Clinical activity of the MEK inhibitor trametinib in metastatic melanoma containing BRAF kinase fusion. Pigment Cell Melanoma Res. 2015; 28:607–10.

169. Hutchinson KE, Lipson D, Stephens PJ, et al. BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition. Clin Cancer Res. 2013; 19:6696–702.

170. Bowyer SE, Rao AD, Lyle M, et al. Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma. Melanoma Res. 2014; 24:504–8.

171. Dankner M, Lajoie M, Moldoveanu D, et al. Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanomas. Clin Cancer Res. 2018; 24:6483–94.

172. Kim KB, Kefford R, Pavlick AC, et al. Phase II study of the MEK1/MEK2 inhibitor trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol. 2013; 31:482–9.

173. Marconcini R, Galli L, Antonuzzo A, et al. Metastatic BRAF K601E-mutated melanoma reaches complete response to MEK inhibitor trametinib administered for over 36 months. Exp Hematol Oncol. 2017; 6:6.

174. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006; 368:1329–38.

175. Heinrich MC, Rankin C, Blanke CD, et al. Correlation of long-term results of imatinib in advanced gastrointestinal stromal tumors with next-generation sequencing results: analysis of phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017; 3:944–52.

176. Cassier PA, Fumagalli E, Rutkowski P, et al. Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Clin Cancer Res. 2012; 18:4458–64.

177. Heinrich MC, Jones RL, von Mehren M, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020; 21:935–46.

178. McArthur GA, Demetri GD, van Oosterom A, et al. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol. 2005; 23:866–73.

179. Navarrete-Dechent C, Mori S, Barker CA, Dickson MA, Nehal KS. Imatinib treatment for locally advanced or metastatic dermatofibrosarcoma protuberans: a systematic review. JAMA Dermatol. 2019; 155:361–9.

180. Butrynski JE, D’Adamo DR, Hornick JL, et al. Crizotinib in ALKrearranged inflammatory myofibroblastic tumor. N Engl J Med. 2010; 363:1727–33.

181. Nishio M, Murakami H, Horiike A, et al. Phase I study of ceritinib (LDK378) in Japanese patients with advanced, anaplastic lymphoma kinase-rearranged non-small-cell lung cancer or other tumors. J Thorac Oncol. 2015; 10:1058–66.

182. Gettinger SN, Bazhenova LA, Langer CJ, et al. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial. Lancet Oncol. 2016; 17:1683–96.

183. Gounder M, Schoffski P, Jones RL, et al. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol. 2020; 21:1423–32.

184. Tap WD, Villalobos VM, Cote GM, et al. Phase I study of the mutant IDH1 inhibitor ivosidenib: safety and clinical activity in patients with advanced chondrosarcoma. J Clin Oncol. 2020; 38:1693–701.

185. Akumalla S, Madison R, Lin DI, et al. Characterization of clinical cases of malignant PEComa via comprehensive genomic profiling of DNA and RNA. Oncology. 2020; 98:905–12.

186. Wagner AJ, Ravi V, Riedel RF, et al. nab-Sirolimus for patients with malignant perivascular epithelioid cell tumors. J Clin Oncol. 2021; 39:3660–70.

187. Abdul Razak AR, Bauer S, Suarez C, et al. Co-targeting of MDM2 and CDK4/6 with siremadlin and ribociclib for the treatment of patients with well-differentiated or dedifferentiated liposarcoma: results from a proof-of-concept, phase Ib study. Clin Cancer Res. 2022; 28:1087–97.

188. LoRusso P, Yamamoto N, Patel MR, et al. The MDM2-p53 antagonist brigimadlin (BI 907828) in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study. Cancer Discov. 2023; 13:1802–13.

189. Dickson MA, Schwartz GK, Keohan ML, et al. Progression-free survival among patients with well-differentiated or dedifferentiated liposarcoma treated with CDK4 inhibitor palbociclib: a phase 2 clinical trial. JAMA Oncol. 2016; 2:937–40.

190. Schoffski P, Wozniak A, Stacchiotti S, et al. Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 ‘CREATE’. Ann Oncol. 2017; 28:3000–8.

191. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability: an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010; 11:220–8.

192. Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012; 481:287–94.

193. Yamamoto H, Hirasawa A. Homologous recombination deficiencies and hereditary tumors. Int J Mol Sci. 2021; 23:348.

194. Toh M, Ngeow J. Homologous recombination deficiency: cancer predispositions and treatment implications. Oncologist. 2021; 26:e1526–37.

195. Robson ME, Tung N, Conte P, et al. OlympiAD final overall survival and tolerability results: olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019; 30:558–66.

196. Norquist BM, Brady MF, Harrell MI, et al. Mutations in homologous recombination genes and outcomes in ovarian carcinoma patients in GOG 218: an NRG Oncology/Gynecologic Oncology Group Study. Clin Cancer Res. 2018; 24:777–83.

197. Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014; 20:764–75.

198. Geyer CE Jr, Garber JE, Gelber RD, et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022; 33:1250–68.

199. Telli ML, Timms KM, Reid J, et al. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin Cancer Res. 2016; 22:3764–73.

200. Watkins JA, Irshad S, Grigoriadis A, Tutt AN. Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers. Breast Cancer Res. 2014; 16:211.

201. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011; 474:609–15.

202. Lotan TL, Tomlins SA, Bismar TA, et al. Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers. I. Molecular Biomarkers in Prostate Cancer. Am J Surg Pathol. 2020; 44:e15–29.

203. Sztupinszki Z, Diossy M, Krzystanek M, et al. Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer. NPJ Breast Cancer. 2018; 4:16.

204. Wang X, Xu Y, Zhang Y, et al. HRD-MILN: accurately estimate tumor homologous recombination deficiency status from targeted panel sequencing data. Front Genet. 2022; 13:990244.

205. Lemery S, Keegan P, Pazdur R. First FDA approval agnostic of cancer site: when a biomarker defines the indication. N Engl J Med. 2017; 377:1409–12.

206. Bonneville R, Krook MA, Chen HZ, et al. Detection of microsatellite instability biomarkers via next-generation sequencing. Methods Mol Biol. 2020; 2055:119–32.

207. Haraldsdottir S. Microsatellite instability testing using next-generation sequencing data and therapy implications. JCO Precis Oncol. 2017; 1:1–4.

208. Salipante SJ, Scroggins SM, Hampel HL, Turner EH, Pritchard CC. Microsatellite instability detection by next generation sequencing. Clin Chem. 2014; 60:1192–9.

209. Niu B, Ye K, Zhang Q, et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data. Bioinformatics. 2014; 30:1015–6.

210. Kautto EA, Bonneville R, Miya J, et al. Performance evaluation for rapid detection of pan-cancer microsatellite instability with MANTIS. Oncotarget. 2017; 8:7452–63.

211. Hause RJ, Pritchard CC, Shendure J, Salipante SJ. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med. 2016; 22:1342–50.

212. Kim JE, Chun SM, Hong YS, et al. Mutation burden and I index for detection of microsatellite instability in colorectal cancer by targeted next-generation sequencing. J Mol Diagn. 2019; 21:241–50.

213. Middha S, Zhang L, Nafa K, et al. Reliable Pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precis Oncol. 2017; 2017:PO.17.00084.

214. Sharma P, Siddiqui BA, Anandhan S, et al. The next decade of immune checkpoint therapy. Cancer Discov. 2021; 11:838–57.

215. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015; 14:847–56.

216. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357:409–13.

217. Sha D, Jin Z, Budczies J, Kluck K, Stenzinger A, Sinicrope FA. Tumor mutational burden as a predictive biomarker in solid tumors. Cancer Discov. 2020; 10:1808–25.

218. Samstein RM, Lee CH, Shoushtari AN, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019; 51:202–6.

219. Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock R. The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell. 2021; 39:154–73.

220. 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; 27:4685–9.

221. Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017; 9:34.

222. Buchhalter I, Rempel E, Endris V, et al. Size matters: dissecting key parameters for panel-based tumor mutational burden analysis. Int J Cancer. 2019; 144:848–58.

223. Fumet JD, Truntzer C, Yarchoan M, Ghiringhelli F. Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts. Eur J Cancer. 2020; 131:40–50.

224. Luchini C, Bibeau F, Ligtenberg MJL, et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019; 30:1232–43.

225. Gambardella V, Tarazona N, Cejalvo JM, et al. Personalized medicine: recent progress in cancer therapy. Cancers (Basel). 2020; 12:1009.

226. Cescon DW, Bratman SV, Chan SM, Siu LL. Circulating tumor DNA and liquid biopsy in oncology. Nat Cancer. 2020; 1:276–90.

227. Sugimoto A, Matsumoto S, Udagawa H, et al. A large-scale prospective concordance study of plasma- and tissue-based next-generation targeted sequencing for advanced non-small cell lung cancer (LC-SCRUM-Liquid). Clin Cancer Res. 2023; 29:1506–14.

228. Benayed R, Offin M, Mullaney K, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res. 2019; 25:4712–22.

229. Heydt C, Wolwer CB, Velazquez Camacho O, et al. Detection of gene fusions using targeted next-generation sequencing: a comparative evaluation. BMC Med Genomics. 2021; 14:62.

230. Wyatt AW, Annala M, Aggarwal R, et al. Concordance of circulating tumor DNA and matched metastatic tissue biopsy in prostate cancer. J Natl Cancer Inst. 2017; 109:djx118.

231. Kingston B, Cutts RJ, Bye H, et al. Genomic profile of advanced breast cancer in circulating tumour DNA. Nat Commun. 2021; 12:2423.

232. Pascual J, Attard G, Bidard FC, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2022; 33:750–68.

233. Pisapia P, Malapelle U, Troncone G. Liquid biopsy and lung cancer. Acta Cytol. 2019; 63:489–96.

234. Kim H, Park KU. Clinical circulating tumor DNA testing for precision oncology. Cancer Res Treat. 2023; 55:351–66.

235. Cha Y, Kim S, Han SW. Utilizing plasma circulating tumor DNA sequencing for precision medicine in the management of solid cancers. Cancer Res Treat. 2023; 55:367–84.

236. 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; 126:3219–28.

237. 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; 25:4691–700.

238. Viller Tuxen I, Barlebo Ahlborn L, Mau-Soerensen M, et al. Plasma total cell-free DNA is a prognostic biomarker of overall survival in metastatic solid tumour patients. Br J Cancer. 2019; 121:125–30.

239. Mirtavoos-Mahyari H, Ghafouri-Fard S, Khosravi A, et al. Circulating free DNA concentration as a marker of disease recurrence and metastatic potential in lung cancer. Clin Transl Med. 2019; 8:14.

240. Zhang Y, Yao Y, Xu Y, et al. Pan-cancer circulating tumor DNA detection in over 10,000 Chinese patients. Nat Commun. 2021; 12:11.

241. Kim S, Lim Y, Kang JK, et al. Dynamic changes in longitudinal circulating tumour DNA profile during metastatic colorectal cancer treatment. Br J Cancer. 2022; 127:898–907.

242. Cai Z, Wang Z, Liu C, et al. Detection of microsatellite instability from circulating tumor DNA by targeted deep sequencing. J Mol Diagn. 2020; 22:860–70.

243. Fridland S, Choi J, Nam M, et al. Assessing tumor heterogeneity: integrating tissue and circulating tumor DNA (ctDNA) analysis in the era of immuno-oncology - blood TMB is not the same as tissue TMB. J Immunother Cancer. 2021; 9:e002551.

244. Gilson P, Merlin JL, Harle A. Detection of microsatellite instability: state of the art and future applications in circulating tumour DNA (ctDNA). Cancers (Basel). 2021; 13:1491.