References

1. IARC. Cancer Incidence, Mortality and Prevalence Worldwide GLOBOCAN 2012. http://gco.iarc.fr

2. Malvezzi M, Carioli G, Bertuccio P et al. European cancer mortality predictions for the year 2017, with focus on lung cancer. Ann Oncol 2017; 28: 1117–1123.

3. Jemal A, Ward EM, Johnson CJ et al. Annual Report to the Nation on the Status of Cancer, 1975-2014, Featuring Survival. J Natl Cancer Inst 2017; 109: djx 0130.

4. Jemal A, Bray F, Center MM et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69–90.

5. Forman D, Bray F, Brewster D. Cancer Incidence in Five Continents . Lyon: IARC Press 2013.

6. Ordonez-Mena JM, Schottker B, Mons U et al. Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium. BMC Med 2016; 14: 62.

7. Malvezzi M, Bertuccio P, Levi F et al. European cancer mortality predictions for the year 2013. Ann Oncol 2013; 24: 792–800.

8. Jemal A, Ma J, Rosenberg PS et al. Increasing lung cancer death rates among young women in southern and midwestern States. J Clin Oncol 2012; 30: 2739–2744.

9. Hashim D, Boffetta P, La Vecchia C et al. The global decrease in cancer mortality: trends and disparities. Ann Oncol 2016; 27: 926–933.

10. Malhotra J, Malvezzi M, Negri E et al. Risk factors for lung cancer worldwide. Eur Respir J 2016; 48: 889–902.

11. Novello S, Stabile L, Siegfried J. Gender-related Differences in Lung Cancer. The IASLC Multidisciplinary Approach to Thoracic Oncology . Aurora, CO: IASLC Press 2014.

12. McCarthy W, Meza R, Jeon J, Moolgavkar S. Chapter 6: Lung cancer in never smokers: epidemiology and risk prediction models. Risk Anal 2012; 32(Suppl 1): S69.

13. Toh CK, Gao F, Lim WT et al. Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity. J Clin Oncol 2006; 24: 2245–2251.

14. Couraud S, Souquet PJ, Paris C et al. BioCAST/IFCT-1002: epidemiological and molecular features of lung cancer in never-smokers. Eur Respir J 2015; 45: 1403–1414.

15. Malhotra J, Borron C, Freedman ND et al. Association between Cigar or pipe smoking and cancer risk in men: a pooled analysis of five Cohort studies. Cancer Prev Res (Phila) 2017; 10: 704–709.

16. Lorenzo Bermejo J, Hemminki K. Familial lung cancer and aggregation of smoking habits: a simulation of the effect of shared environmental factors on the familial risk of cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 1738–1740.

17. Mucci LA, Hjelmborg JB, Harris JR et al. Familial risk and heritability of cancer among twins in Nordic Countries. JAMA 2016; 315: 68–76.

18. Timofeeva MN, Hung RJ, Rafnar T et al. Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls. Hum Mol Genet 2012; 21: 4980–4995.

19. Wang Y, McKay JD, Rafnar T et al. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nat Genet 2014; 46: 736–741.

20. McKay JD, Hung RJ, Han Y et al. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. Nat Genet 2017; 49: 1126–1132.

21. Freeman RK, Van Woerkom JM, Vyverberg A, Ascioti AJ. The effect of a multidisciplinary thoracic malignancy conference on the treatment of patients with lung cancer. Eur J Cardiothorac Surg 2010; 38: 1–5.

22. Forrest LM, McMillan DC, McArdle CS, Dunlop DJ. An evaluation of the impact of a multidisciplinary team, in a single centre, on treatment and survival in patients with inoperable non-small-cell lung cancer. Br J Cancer 2005; 93: 977–978.

23. Schmidt HM, Roberts JM, Bodnar AM et al. Thoracic multidisciplinary tumor board routinely impacts therapeutic plans in patients with lung and esophageal cancer: a prospective cohort study. Ann Thorac Surg 2015; 99: 1719–1724.

24. Ost DE, Ernst A, Lei X et al. Diagnostic yield and complications of bronchoscopy for peripheral lung lesions. Results of the AQuIRE Registry. Am J Respir Crit Care Med 2016; 193: 68–77.

25. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143: e142S–e165S.

26. van der Drift MA, van der Wilt GJ, Thunnissen FB, Janssen JP. A prospective study of the timing and cost-effectiveness of bronchial washing during bronchoscopy for pulmonary malignant tumors. Chest 2005; 128: 394–400.

27. Herth F, Becker HD, Ernst A. Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration: a randomized trial. Chest 2004; 125: 322–325.

28. Paone G, Nicastri E, Lucantoni G et al. Endobronchial ultrasound-driven biopsy in the diagnosis of peripheral lung lesions. Chest 2005; 128: 3551–3557.

29. Adams K, Shah PL, Edmonds L, Lim E. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax 2009; 64: 757–762.

30. Nakajima T, Kimura H, Takeuchi K et al. Treatment of lung cancer with an ALK inhibitor after EML4-ALK fusion gene detection using endobronchial ultrasound-guided transbronchial needle aspiration. J Thorac Oncol 2010; 5: 2041–2043.

31. Nakajima T, Yasufuku K, Nakagawara A et al. Multigene mutation analysis of metastatic lymph nodes in non-small cell lung cancer diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. Chest 2011; 140: 1319–1324.

32. Rekhtman N, Brandt SM, Sigel CS et al. Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing. J Thorac Oncol 2011; 6: 451–458.

33. Sakairi Y, Nakajima T, Yasufuku K et al. EML4-ALK fusion gene assessment using metastatic lymph node samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration. Clin Cancer Res 2010; 16: 4938–4945.

34. Chan EY, Gaur P, Ge Y et al. Management of the solitary pulmonary nodule. Arch Pathol Lab Med 2017; 141: 927–931.

35. Choi SH, Chae EJ, Kim JE et al. Percutaneous CT-guided aspiration and core biopsy of pulmonary nodules smaller than 1 cm: analysis of outcomes of 305 procedures from a tertiary referral center. AJR Am J Roentgenol 2013; 201: 964–970.

36. Fontaine-Delaruelle C, Souquet PJ, Gamondes D et al. Negative predictive value of transthoracic core-needle biopsy: a multicenter study. Chest 2015; 148: 472–480.

37. Lee SM, Park CM, Lee KH et al. C-arm cone-beam CT-guided percutaneous transthoracic needle biopsy of lung nodules: clinical experience in 1108 patients. Radiology 2014; 271: 291–300.

38. Takeshita J, Masago K, Kato R et al. CT-guided fine-needle aspiration and core needle biopsies of pulmonary lesions: a single-center experience with 750 biopsies in Japan. AJR Am J Roentgenol 2015; 204: 29–34.

39. Travis WD, Brambilla E, Burke AP et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart , 4th edition. Lyon, France: IARC Press 2015.

40. Travis WD, Brambilla E, Noguchi M et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 2013; 137: 668–684.

41. Travis WD, Brambilla E, Noguchi M et al. International Association for the Study of Lung cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol 2011; 6: 244–285.

42. Dietel M, Bubendorf L, Dingemans AM et al. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group. Thorax 2016; 71: 177–184.

43. 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 Pathology. J Thorac Oncol 2013; 8: 823–859.

44. Kerr KM, Bubendorf L, Edelman MJ et al. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Ann Oncol 2014; 25: 1681–1690.

45. Lindeman N, Cagle P, Aisner D et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med 2018; 142: 321–346.

46. Kalemkerian GP, Narula N, Kennedy EB et al. Molecular testing guideline for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol 2018; 36: 911–919.

47. Mok T, Carbone D, Hirsch F. IASLC Atlas of EGFR testing in Lung cancer. IASLC 2017. wclc2017.iaslc.org.

48. Oxnard GR, Miller VA, Robson ME et al. Screening for germline EGFR T790M mutations through lung cancer genotyping. J Thorac Oncol 2012; 7: 1049–1052.

49. Mok T, Wu YL, Lee JS et al. Detection and dynamic changes of EGFR mutations from circulating tumor DNA as a predictor of survival outcomes in NSCLC patients treated with first-line intercalated erlotinib and chemotherapy. Clin Cancer Res 2015; 21: 3196–3203.

50. Tsao M, Hirsch F, Yatabe Y. IASLC Atlas of ALK and ROS1 Testing in Lung Cancer, Second Edition. Aurora, CO: International Association for the Study of Lung Cancer 2016.

51. Kerr KM, Lopez RF. Precision medicine in NSCLC and pathology: how does ALK fit in the pathway? Ann Oncol 2016; 27(Suppl 3): iii16–iii24.

52. van der Wekken AJ, Pelgrim R, t Hart N et al. Dichotomous ALK-IHC Is a better predictor for ALK inhibition outcome than traditional ALK-FISH in advanced non-small cell lung cancer. Clin Cancer Res 2017; 23: 4251–4258.

53. 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: 829–838.

54. Lindeman NI, Cagle PT, Aisner DL et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the college of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Thorac Oncol 2018; 13: 323–358.

55. Gainor JF, Dardaei L, Yoda S et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov 2016; 6: 1118–1133.

56. Deeb KK, Hohman CM, Risch NF et al. Routine clinical mutation profiling of non-small cell lung cancer using next-generation sequencing. Arch Pathol Lab Med 2015; 139: 913–921.

57. Kerr KM, Hirsch FR. Programmed death ligand-1 immunohistochemistry: friend or foe? Arch Pathol Lab Med 2016; 140: 326–331.

58. Hirsch FR, McElhinny A, Stanforth D et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 2017; 12: 208–222.

59. Ratcliffe MJ, Sharpe A, Midha A et al. Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res 2017; 23: 3585–3591.

60. Rimm DL, Han G, Taube JM et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol 2017; 3: 1051–1058.

61. Adam J, Le Stang N, Rouquette I et al. Multicenter French harmonization study for PD-L1 IHC testing in non-small cell lung cancer. Ann Oncol 2018; 29: 953–958.

62. Reck M, Rodriguez-Abreu D, Robinson AG et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375: 1823–1833.

63. Herbst RS, Baas P, Kim DW et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016; 387: 1540–1550.

63a. Herbst RS, Garon EB, Kim D-W et al. Long-term follow-up in the KEYNOTE-010 study of pembrolizumab (pembro) for advanced NSCLC, including in patients (pts) who completed 2 years of pembro and pts who received a second course of pembro. Ann Oncol 2018; 29(Suppl 10); LBA4.

64. Hellmann MD, Ciuleanu T-E, Pluzanski A et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 2018; 378: 2093–2104.

65. Rizvi NA, Hellmann MD, Snyder A et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348: 124–128.

66. Carbone DP, Reck M, Paz-Ares L et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med 2017; 376: 2415–2426.

67. Rizvi H, Sanchez-Vega F, La K et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand (PD-L)-ligand 1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol 2018; 36: 633–641.

68. Rolfo C, Mack PC, Scagliotti GV et al. ASLC statement paper: liquid biopsy for advanced non-small cell lung cancer (NSCLC). J Thorac Oncol 2018; 13: 1248–1268.

69. 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: 1441–1448.

70. Velcheti V, Kim ES, Mekhail T et al. Prospective clinical evaluation of blood-based tumor mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC): interim B-F1RST results. J Clin Oncol 2018; 36: 12001–12001.

70a. Peters S, Chul Cho B, Reinmuth N et al. Abstract CT074: Tumor mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a phase III study of first-line durvalumab ± tremelimumab vs chemotherapy. Cancer Res 2019; 79 (Suppl 13): abstr CT074.

71. Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer 2012; 76: 138–143.

72. Ferrucci PF, Ascierto PA, Pigozzo J et al. Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab. Ann Oncol 2016; 27: 732–738.

73. Mezquita L, Auclin E, Ferrara R et al. Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non-small cell lung cancer. JAMA Oncol 2018; 4: 351–357.

74. Kuhn MJ, Hammer GM, Swenson LC et al. MRI evaluation of “solitary” brain metastases with triple-dose gadoteridol: comparison with contrast-enhanced CT and conventional-dose gadopentetate dimeglumine MRI studies in the same patients. Comput Med Imaging Graph 1994; 18: 391–399.

75. Wu Y, Li P, Zhang H et al. Diagnostic value of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for the detection of metastases in non-small-cell lung cancer patients. Int J Cancer 2013; 132: E37–E47.

76. Chang MC, Chen JH, Liang JA et al. Meta-analysis: comparison of F-18 fluorodeoxyglucose-positron emission tomography and bone scintigraphy in the detection of bone metastasis in patients with lung cancer. Acad Radiol 2012; 19: 349–357.

77. Grootjans W, de Geus-Oei LF, Troost EG et al. PET in the management of locally advanced and metastatic NSCLC. Nat Rev Clin Oncol 2015; 12: 395–407.

78. Amin MB, Edge S, Greene F et al. AJCC Cancer Staging Manual , 8th edition. New York: Springer International Publishing 2017.

79. Brierley J, Gospodarowicz MK, Wittekind C, Union for International Cancer Control. TNM Classification of Malignant Tumours 8th edition, 1–241.

80. Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228–247.

81. Wolchok JD, Hoos A, O’Day S et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15: 7412–7420.

82. Bohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol 2014; 25(Suppl 4): iv369.

83. Seymour L, Bogaerts J, Perrone A et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 2017; 18: e143–e152.

84. Hodi FS, Ballinger M, Lyons B et al. Immune-modified response evaluation criteria in solid tumors (imRECIST): refining guidelines to assess the clinical benefit of cancer immunotherapy. J Clin Oncol 2018; 36: 850–858.

85. Gandara DR, Pawel JV, Sullivan RN et al. Impact of atezolizumab (atezo) treatment beyond disease progression (TBP) in advanced NSCLC: results from the randomized phase III OAK study. J Clin Oncol 2017; 35: 9001.

86. Tazdait M, Mezquita L, Lahmar J et al. Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: comparison of RECIST 1.1, irRECIST and iRECIST criteria. Eur J Cancer 2018; 88: 38–47.

87. Mazieres J, Fehrenbacher L, Rittmeyer A et al.  Non-classical response measured by immune-modified RECIST and post-progression treatment effects of atezolizumab in 2L/3L NSCLC: Results from the randomized phase II study POPLAR. J Clin Oncol 2016; 34: 9032.

88. Kazandjian D, Keegan P, Suzman DL et al. Characterization of patients treated with a programmed cell death protein 1 inhibitor (anti-PD-1) past RECIST progression from a metastatic non-small cell lung cancer (mNSCLC) trial. J Clin Oncol 2017; 44: 3.

89. Ung KA, Campbell BA, Duplan D et al. Impact of the lung oncology multidisciplinary team meetings on the management of patients with cancer. Asia Pac J Clin Oncol 2016; 12: e298–e304.

90. Baser S, Shannon VR, Eapen GA et al. Smoking cessation after diagnosis of lung cancer is associated with a beneficial effect on performance status. Chest 2006; 130: 1784–1790.

91. Hughes AN, O’Brien ME, Petty WJ et al. Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers. J Clin Oncol 2009; 27: 1220–1226.

92. Rowland C, Danson SJ, Rowe R et al. Quality of life, support and smoking in advanced lung cancer patients: a qualitative study. BMJ Support Palliat Care 2016; 6: 35–42.

93. Brahmer JR, Rodriguez-Abreu D, Robinson AG et al. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol 2017; 18: 1600–1609.

95a. Mok TSK, Wu YL, Kudaba I et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019; 393: 1819–1830.

96. Gandhi L, Rodriguez-Abreu D, Gadgeel S et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378: 2078–2092.

97. Socinski MA, Jotte RM, Cappuzzo F et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 2018; 378: 2288–2301.

97a. Reck M, Mok TSK, Nishio M et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med 2019; 7: 387–401.

98. Papadimitrakopoulou V, Cobo M, Bordon R et al. IMPOWER132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC. IASLC 19th World Conference on Lung Cancer 2018; abstr. OA05.07.

98a. West H, McCleod M, Hussein M et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2019; 20: 924–937.

99. Paz-Ares LG, Luft A, Vicente D et al. Pembrolizumab plus chemotherapy for squamous non–small-cell lung cancer. N Engl J Med 2018; 379: 2040–2051.

100. Jotte RM, Cappuzzo F, Vynnychenko I et al. IMpower131: primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. J Clin Oncol 2018; 36(18 Suppl): LBA9000.

101. Brahmer JR, Rodriguez-Abreu D, Robinson AG et al. Progression after the next line of therapy (PFS2) and updated OS among patients (pts) with advanced NSCLC and PD-L1 tumor proportion score (TPS) ?50% enrolled in KEYNOTE-024. J Clin Oncol 2017; 35: 9000.

102. Ramalingam SS, Hellmann MD, Awad MM et al. Abstract CT078: tumor mutational burden (TMB) as a biomarker for clinical benefit from dual immune checkpoint blockade with nivolumab (nivo) + ipilimumab (ipi) in first-line (1L) non-small cell lung cancer (NSCLC): identification of TMB cutoff from CheckMate 568. Cancer Res 2018; 78: CT078.

103. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ 1995; 311: 899–909.

104. NSCLC Meta-Analyses Collaborative Group. Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol 2008; 26: 4617–4625.

105. Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy and supportive care versus supportive care alone for advanced non-small cell lung cancer. Cochrane Database Syst Rev 2010; CD007309.

106. Delbaldo C, Michiels S, Syz N et al. Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA 2004; 29: 2470–484.

107. Pujol JL, Barlesi F, Daures JP. Should chemotherapy combinations for advanced non-small cell lung cancer be platinum-based? A meta-analysis of phase III randomized trials. Lung Cancer 2006; 51: 335–345.

108. Park JO, Kim SW, Ahn JS et al. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol 2007; 25: 5233–5239.

109. Rossi A, Chiodini P, Sun JM et al. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data. Lancet Oncol 2014; 15: 1254–1262.

110. 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: 92–98.

111. Grossi F, Aita M, Defferrari C et al. Impact of third-generation drugs on the activity of first-line chemotherapy in advanced non-small cell lung cancer: a meta-analytical approach. Oncologist 2009; 14: 497–510.

112. de Castria TB, da Silva EM, Gois AF, Riera R. Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer. Cochrane Database Syst Rev 2013; CD009256.

113. Socinski MA, Bondarenko I, Karaseva NA et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012; 30: 2055–2062.

114. Paz-Ares L, Mezger J, Ciuleanu TE et al. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. Lancet Oncol 2015; 16: 328–337.

115. Thatcher N, Hirsch FR, Luft AV et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol 2015; 16: 763–774.

116. Paz-Ares L, Socinski MA, Shahidi J et al. Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer. Ann Oncol 2016; 27: 1573–1579.

117. Li M, Zhang Q, Fu P et al. Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials. PLoS One 2012; 7: e37229.

118. Scagliotti GV, Parikh P, von Pawel J et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26: 3543–3551.

119. 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: 253–263.

120. Ciuleanu T, Brodowicz T, Zielinski C et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009; 374: 1432–1440.

121. Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542–2550.

122. Zhou C, Wu YL, Chen G et al. BEYOND: a randomized, double-blind, placebo-controlled, multicenter, phase III study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer. J Clin Oncol 2015; 33: 2197–2204.

123. Reck M, von Pawel J, Zatloukal P et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: aVAil. J Clin Oncol 2009; 27: 1227–1234.

124. Lima AB, Macedo LT, Sasse AD. Addition of bevacizumab to chemotherapy in advanced non-small cell lung cancer: a systematic review and meta-analysis. PLoS One 2011; 6: e22681.

125. Soria JC, Mauguen A, Reck M et al. Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol 2013; 24: 20–30.

126. Besse B, Le Moulec S, Mazieres J et al. Bevacizumab in patients with nonsquamous non-small cell lung cancer and asymptomatic, untreated brain metastases (BRAIN): a nonrandomized, phase II study. Clin Cancer Res 2015; 21: 1896–1903.

127. Cappuzzo F, Ciuleanu T, Stelmakh L et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010; 11: 521–529.

128. Cicenas S, Geater SL, Petrov P et al. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer 2016; 102: 30–37.

129. Paz-Ares LG, de Marinis F, Dediu M et al. PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2013; 31: 2895–2902.

130. Paz-Ares L, de Marinis F, Dediu M et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 2012; 13: 247–255.

131. Barlesi F, Scherpereel A, Rittmeyer A et al. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: aVAPERL (MO22089). J Clin Oncol 2013; 31: 3004–3011.

132. Barlesi F, Scherpereel A, Gorbunova V et al. Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial. Ann Oncol 2014; 25: 1044–1052.

133. Patel JD, Socinski MA, Garon EB et al. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol 2013; 31: 4349–4357.

134. Perol M, Chouaid C, Perol D et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2012; 30: 3516–3524.

135. Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009; 373: 1525–1531.

136. Gridelli C, Ardizzoni A, Le Chevalier T et al. Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel. Ann Oncol 2004; 15: 419–426.

137. Quoix E, Zalcman G, Oster JP et al. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: iFCT-0501 randomised, phase 3 trial. Lancet 2011; 378: 1079–1088.

138. Bronte G, Rolfo C, Passiglia F et al. What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis. Crit Rev Oncol Hematol 2015; 95: 306–317.

139. Zukin M, Barrios CH, Pereira JR et al. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol 2013; 31: 2849–2853.

140. Gridelli C, Perrone F, Gallo C et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003; 95: 362–372.

141. Spigel D, Schwartzberg L, Waterhouse D et al. P3.02c-026 is nivolumab safe and effective in elderly and PS2 patients with Non-Small Cell Lung Cancer (NSCLC)? Results of CheckMate 153. J Thorac Oncol 12: S1287–S1288.

142. Popat S, Ardizzoni A, Ciuleanu T et al. 1303PD Nivolumab in previously treated patients with metastatic squamous NSCLC: results of a European single-arm, phase 2 trial (CheckMate 171) including patients aged ?70 years and with poor performance status. Ann Oncol 2017; 28(Suppl 5): v460-v496.

143. Kudoh S, Takeda K, Nakagawa K et al. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904).  J Clin Oncol  2006; 24: 3657–3663.

144. Santos FN, de Castria TB, Cruz MR, Riera R. Chemotherapy for advanced non-small cell lung cancer in the elderly population. Cochrane Database Syst Rev 2015; CD010463.

145. Fiteni F, Anota A, Bonnetain F et al. Health-related quality of life in elderly patients with advanced non-small cell lung cancer comparing carboplatin and weekly paclitaxel doublet chemotherapy with monotherapy. Eur Respir J 2016; 48: 861–872.

146. Corre R, Greillier L, Le Caer H et al. Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the phase III randomized ESOGIA-GFPC-GECP 08-02 study. J Clin Oncol 2016; 34: 1476–1483.

147. Brahmer J, Reckamp KL, Baas P et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373: 123–135.

148. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373: 1627–1639.

149. Rittmeyer A, Barlesi F, Waterkamp D et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 2017; 389: 255–265.

149a. Fehrenbacher L, von Pawel J, Park K et al. Updated efficacy analysis including secondary population results for OAK: a randomized phase III study of atezolizumab versus docetaxel in patients with previously treated advanced non-small cell lung cancer. J Thorac Oncol 2018; 13: 1156–1170.

150. Ferrara R, Mezquita L, Auclin E et al. Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: does age really matter? Cancer Treat Rev 2017; 60: 60–68.

151. Herbst R, Garon E, Kim D-W et al. OA03.07 KEYNOTE-010: durable clinical benefit in patients with previously treated, PD-L1-expressing NSCLC who completed pembrolizumab. J Thoracic Oncol 2017; 12: S254–S255.

152. Shepherd FA, Dancey J, Ramlau R et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000; 18: 2095–2103.

153. Fossella FV, DeVore R, Kerr RN et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000; 18: 2354–2362.

154. Gridelli C, Gallo C, Di Maio M et al. A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the second-line treatment of non-small-cell lung cancer. The DISTAL 01 study. Br J Cancer 2004; 91: 1996.

155. Schuette W, Nagel S, Blankenburg T et al. Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel. J Clin Oncol 2005; 23: 8389–8395.

156. Hanna N, Shepherd FA, Fossella FV et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004; 22: 1589–1597.

157. Garon EB, Ciuleanu TE, Arrieta O et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014; 384: 665–673.

158. Reck M, Paz-Ares L, Bidoli P et al. Outcomes in patients with aggressive or refractory disease from REVEL: a randomized phase III study of docetaxel with ramucirumab or placebo for second-line treatment of stage IV non-small-cell lung cancer. Lung Cancer 2017; 112: 181–187.

159. Reck M, Kaiser R, Mellemgaard A et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 2014; 15: 143–155.

160. Novello S, Kaiser R, Mellemgaard A et al. Analysis of patient-reported outcomes from the LUME-Lung 1 trial: a randomised, double-blind, placebo-controlled, Phase III study of second-line nintedanib in patients with advanced non-small cell lung cancer. Eur J Cancer 2015; 51: 317–326.

161. Cortot AB, Audigier-Valette C, Molinier O et al. Weekly paclitaxel plus bevacizumab versus docetaxel as second or third-line treatment in advanced non-squamous non-small cell lung cancer (NSCLC): Results from the phase III study IFCT-1103 ULTIMATE. J Clin Oncol 2016; 34: 9005.

162. Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123–132.

163. Ciuleanu T, Stelmakh L, Cicenas S et al. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol 2012; 13: 300–308.

164. Karampeazis A, Voutsina A, Souglakos J et al. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer 2013; 119: 2754–2764.

165. Garassino MC, Martelli O, Broggini M et al. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol 2013; 14: 981–988.

166. Zhao N, Zhang XC, Yan HH et al. Efficacy of epidermal growth factor receptor inhibitors versus chemotherapy as second-line treatment in advanced non-small-cell lung cancer with wild-type EGFR: a meta-analysis of randomized controlled clinical trials. Lung Cancer 2014; 85: 66–73.

167. Tomasini P, Brosseau S, Mazieres J et al. EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR wild-type pre-treated advanced nonsmall cell lung cancer in daily practice. Eur Respir J 2017; 50: 1700514.

168. Soria JC, Felip E, Cobo M et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol 2015; 16: 897–907.

169. Felip E, Hirsh V, Popat S et al. Symptom and quality of life improvement in LUX-Lung 8, an open-label phase III study of second-line afatinib versus erlotinib in patients with advanced squamous cell carcinoma of the lung after first-line platinum-based chemotherapy. Clin Lung Cancer 2018; 19: 74–83.

170. 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: 2129–2139.

171. Paez JG, Janne PA, Lee JC et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497–1500.

172. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957.

173. Han JY, Park K, Kim SW et al. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol 2012; 30: 1122–1128.

174. 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: 2380–2388.

175. 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: 239–246.

176. Sequist LV, Yang JC, 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: 3327–3334.

177. Wu YL, Zhou C, Hu CP et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014; 15: 213–222.

178. Inoue A, Kobayashi K, Usui K et al. First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol 2009; 27: 1394–1400.

179. Park K, Yu CJ, Kim SW et al. First-line erlotinib therapy until and beyond response evaluation criteria in solid tumors progression in Asian patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer: the ASPIRATION Study. JAMA Oncol 2016; 2: 305–312.

180. Mok TSK, Kim S-W, Wu Y-L et al. Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation-positive non-small-cell lung cancer resistant to first-line gefitinib (IMPRESS): overall survival and biomarker analyses. J Clin Oncol 2017; 35: 4027–4034.

181. Park K, Tan EH, O’Byrne K et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol 2016; 17: 577–589.

182. Paz-Ares L, Tan EH, O’Byrne K et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol 2017; 28: 270–277.

183. Yang JC, Wu YL, Schuler M et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015; 16: 141–151.

184. 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, open-label, phase 3 trial. Lancet Oncol 2017; 18: 1454–1466.

185. Mok TS, Cheng Y, Zhou X et al. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol 2018; 36: 2244–2250.

186. 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: 1046–1061.

187. 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: 113–125.

187a. Planchard D, Boyer MJ, Lee JS et al. Postprogression outcomes for osimertinib versus standard-of-care EGFR-TKI in patients with previously untreated EGFR-mutated advanced non-small cell lung cancer. Clin Cancer Res 2019; 25: 2058–2063.

188. Soria JC, Wu YL, Nakagawa K et al. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol 2015; 16: 990–998.

189. Nakamura A, Morita S, Hosomi Y et al.  Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009). J Clin Oncol 2018; 36(Suppl): abstr 9005.

189a. Noronha V, Joshi A, Patil VM et al. Phase III randomized trial comparing gefitinib to gefitinib with pemetrexed-carboplatin chemotherapy in patients with advanced untreated EGFR mutant non-small cell lung cancer (gef vs gef+C). J Clin Oncol 2019; 37(Suppl): abstr 9001.

190. Seto T, Kato T, Nishio M et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 2014; 15: 1236–1244.

191. Yamamoto N, Seto T, Nishio M et al. Erlotinib plus bevacizumab (EB) versus erlotinib alone (E) as first-line treatment for advanced EGFR mutation-positive non-squamous non-small-cell lung cancer (NSCLC): survival follow-up results of JO25567. J Clin Oncol 2018; 36(Suppl): abstr 9007.

192. Rosell R, Dafni U, Felip E et al. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. Lancet Respir Med 2017; 5: 435–444.

193. Furuya N, Saito H, Watanabe K et al. Phase III study comparing bevacizumab plus erlotinib to erlotinib in patients with untreated NSCLC harboring activating EGFR mutations: NEJ026. J Clin Oncol 2018; 36(Suppl): abstr 9006.

194. Yu HA, Arcila ME, Rekhtman N et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19: 2240–2247.

195. Mok TS, Wu YL, Ahn MJ et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 2017; 376: 629–640.

196. Mok T, Ahn M-J, Han J-Y et al. CNS response to osimertinib in patients (pts) with T790M-positive advanced NSCLC: data from a randomized phase III trial (AURA3). J Clin Oncol 2017; 35: 9005.

196a. Mazières J, Drilon A, Lusque A et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 2019; 30: 1321–1328.

197. Camidge DR, Bang YJ, Kwak EL et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 2012; 13: 1011–1019.

198. Shaw AT, Yeap BY, Solomon BJ et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 2011; 12: 1004–1012.

199. Solomon BJ, Mok T, Kim DW et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371: 2167–2177.

200. Soria JC, 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 2017; 389: 917–929.

201. Cho BC, Kim DW, Bearz A et al. ASCEND-8: a randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol 2017; 12: 1357–1367.

202. Hida T, Nokihara H, Kondo M et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet 2017; 390: 29–39.

203a. Camidge DR, Dziadziuszko R, Peters S et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol 2019; 14: 1233-1243.

204. Shaw AT, Kim DW, Nakagawa K et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368: 2385–2394.

205. Costa DB, Kobayashi S, Pandya SS et al. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol 2011; 29: e443–e445.

206. Shaw AT, Kim TM, Crino L et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2017; 18: 874–886.

207. Novello S, Mazières J, Oh IJ et al. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol 2018; 29: 1409–1416.

208. de Castro J, Novello S, Mazieres J et al. 1346 PCNS efficacy results from the phase III ALUR study of alectinib vs chemotherapy in previously treated ALK+ NSCLC. Ann Oncol 2017; 28(Suppl 5): v460–v496.

209a. Kim DW, Tiseo M, Ahn MJ et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol 2017; 35: 2490–2498.

210. Shaw AT, Felip E, Bauer TM et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol 2017; 18: 1590–1599.

212. Felip E, Bauer T, Solomon B et al. MA07.11 safety and efficacy of lorlatinib (PF-06463922) in patients with advanced ALK+ or ROS1+ non-small-cell lung cancer (NSCLC). J Thorac Oncol 2017; 12: S383–S384.

212a. Shaw AT, Solomon BJ, Besse B et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol 2019; 37:1370–1379.

213. Shaw AT, Bauer TM, Takahashi T et al. 1380TiP A randomized, open-label comparison of lorlatinib versus crizotinib as first-line treatment for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. Ann Oncol 2017; 28(Suppl 5): v460–v496.

215. 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; 29: 2027–2039.

216. Shaw AT, Ou SH, Bang YJ et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 2014; 371: 1963–1971.

217. Moro-Sibilot D, Faivre L, Zalcman G et al. Crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC). Preliminary results of the ACSE phase II trial. J Clin Oncol 2015; 33: 8065.

218. Mazieres J, Zalcman G, Crino L et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort. J Clin Oncol 2015; 33: 992–999.

219. Goto K, Yang JC-H, Kim D-W et al. Phase II study of crizotinib in east Asian patients (pts) with ROS1-positive advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2016; 34: 9022.

220. Lim SM, Kim HR, Lee JS et al. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol 2017; 35: 2613–2618.

221. Davare MA, Vellore NA, Wagner JP et al. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci USA 2015; 112: E5381–E5390.

221a. Drilon A, Ou SI, Cho BC et al. Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent- front mutations. Cancer Discov 2018; 8: 1227–1236.

222. Barlesi F, Mazieres J, Merlio JP et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 2016; 387: 1415–1426.

223. Kris MG, Johnson BE, Berry LD et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 2014; 311: 1998–2006.

224. Paik PK, Arcila ME, Fara M et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29: 2046–2051.

225. Gautschi O, Milia J, Cabarrou B et al. Targeted therapy for patients with BRAF-mutant lung cancer: results from the European EURAF Cohort. J Thorac Oncol 2015; 10: 1451–1457.

226. Hyman DM, Puzanov I, Subbiah V et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 2015; 373: 726–736.

227. 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: 642–650.

228. Planchard D, Besse B, Groen HJM et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol 2016; 17: 984–993.

229. Planchard D, Smit EF, Groen HJM et al. Updated survival of patients (pts) with previously treated BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC) who received dabrafenib (D) or D + trametinib (T) in the phase II BRF113928 study. J Clin Oncol 2017; 28(Suppl 5): 9075.

230. Planchard D, Smit EF, Groen HJM 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: 1307–1316.

231. Lipson D, Capelletti M, Yelensky R et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 2012; 18: 382–384.

232. Michels S, Scheel AH, Scheffler M et al. Clinicopathological characteristics of RET rearranged lung cancer in European Patients. J Thorac Oncol 2016; 11: 122–127.

233. Gautschi O, Milia J, Filleron T et al. Targeting RET in patients with RET-rearranged lung cancers: results from the global, multicenter RET registry. J Clin Oncol 2017; 35: 1403–1410.

234. Drilon A, Bergagnini I, Delasos L et al. Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers. Ann Oncol 2016; 27: 1286–1291.

235. Lee SH, Lee JK, Ahn MJ et al. Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial. Ann Oncol 2017; 28: 292–297.

236. Yoh K, Seto T, Satouchi M et al. Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial. Lancet Respir Med 2017; 5: 42–50.

238. Spigel DR, Edelman MJ, O’Byrne K et al. Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: mETLung. J Clin Oncol 2017; 35: 412–420.

239. Yoshioka H, Azuma K, Yamamoto N et al. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol 2015; 26: 2066–2072.

240. Frampton GM, Ali SM, Rosenzweig M 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): 850–859.

241. 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: 108.

242. Awad MM, Leonardi GC, Kravets S et al. Impact of MET inhibitors on survival among patients (pts) with MET exon 14 mutant (METdel14) non-small cell lung cancer (NSCLC). J Clin Oncol 2017; 35: 8511.

243. Arcila ME, Chaft JE, Nafa K et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res 2012; 18: 4910–4918.

244. Mazieres J, Barlesi F, Filleron T et al. Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort. Ann Oncol 2016; 27(2): 281–286.

245. Hyman D, Piha-Paul SA, Won H et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018; 554: 189–194.

246. Kosaka T, Tanizaki J, Paranal RM et al. Response heterogeneity of EGFR and HER2 exon 20 insertions to covalent EGFR and HER2 inhibitors. Cancer Res 2017; 77: 2712.

247. Smit EF, Peters S, Dziadziuszko R et al. A single-arm phase II trial of afatinib in pretreated patients with advanced NSCLC harboring a HER2 mutation: the ETOP NICHE trial. J Clin Oncol 2017; 35: 9070.

248. Robichaux JP, Elamin YY, Tan Z et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non-small cell lung cancer. Nat Med 2018; 24(5): 638–646.

249. Li BT, Shen R, Buonocore D et al. Ado-trastuzumab emtansine for patients with HER2 mutant lung cancers: results from a phase II basket trial. J Clin Oncol 2018; 36: 2532–2537.

250. Stinchcombe T, Stahel RA, Bubendorf L et al. Efficacy, safety, and biomarker results of trastuzumab emtansine (T-DM1) in patients (pts) with previously treated HER2-overexpressing locally advanced or metastatic non-small cell lung cancer (mNSCLC). J Clin Oncol 2017; 35: 8509.

251. Ou SI, Schrock AB, Bocharov EV et al. HER2 transmembrane domain (TMD) mutations (V659/G660) that stabilize homo- and heterodimerization are rare oncogenic drivers in lung adenocarcinoma that respond to afatinib. J Thorac Oncol 2017; 12: 446–457.

252. Stransky N, Cerami E, Schalm S et al. The landscape of kinase fusions in cancer. Nat Commun 2014; 5: 4846.

252a. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731–747.

253. Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open 2016; 1: e000023.

254. Drilon A, Siena S, Ou SI 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: 400–409.

255. Hyman DM, Laetsch TW, Kummar S et al. The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers. J Clin Oncol 2017; 35(18 Suppl): LBA2501.

256. 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: 731–739.

257. Stevens R, Macbeth F, Toy E et al. Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer. Cochrane Database Syst Rev 2015; 1: CD002143.

258. Reveiz L, Rueda JR, Cardona AF. Palliative endobronchial brachytherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2012; 12: CD004284.

259. George R, Jeba J, Ramkumar G et al. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev 2015; CD006716.

260. Nayar G, Ejikeme T, Chongsathidkiet P et al. Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget 2017; 8: 73312–73328.

261. Chamberlain MC, Sandy AD, Press GA. Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain. Neurology 1990; 40: 435–438.

262. Collie DA, Brush JP, Lammie GA et al. Imaging features of leptomeningeal metastases. Clin Radiol 1999; 54: 765–771.

263. Sperduto PW, Kased N, Roberge D et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 2012; 30: 419–425.

264. Mulvenna P, Nankivell M, Barton R et al.  Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet 2016; 388: 2004–2014.

265. Tsao MN, Lloyd N, Wong RK et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev 2012; CD003869.

266. Vecht CJ, Hovestadt A, Verbiest HB et al. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology 1994; 44: 675–680.

267. Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol 2007; 25: 1260–1266.

268. Brown PD, Pugh S, Laack NN et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol 2013; 15: 1429–1437.

269. Gondi V, Pugh SL, Tome WA et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 2014; 32: 3810–3816.

270. Mahajan A, Ahmed S, McAleer MF et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18: 1040–1048.

271. Patchell RA, Tibbs PA, Walsh JW et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990; 322: 494–500.

272. Vecht CJ, Haaxma-Reiche H, Noordijk EM et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 1993; 33: 583–590.

273. Mintz AH, Kestle J, Rathbone MP et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996; 78: 1470–1476.

274. Patchell RA, Tibbs PA, Regine WF et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998; 280: 1485–1489.

275. Aoyama H, Shirato H, Tago M et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 2006; 295: 2483–2491.

276. Kocher M, Soffietti R, Abacioglu U et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 2011; 29: 134–141.

277. Sahgal A, Aoyama H, Kocher M et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 2015; 91: 710–717.

278. Ernst-Stecken A, Ganslandt O, Lambrecht U et al. Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Radiother Oncol 2006; 81: 18–24.

279. Patil CG, Pricola K, Sarmiento JM et al. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev 2012; CD006121.

280. Soon YY, Tham IW, Lim KH et al. Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases. Cochrane Database Syst Rev 2014; CD009454.

281. Robinet G, Thomas P, Breton JL et al. Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Francais de Pneumo-Cancerologie (GFPC) Protocol 95-1. Ann Oncol 2001; 12: 59–67.

282. Lim SH, Lee JY, Lee MY et al. A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer. Ann Oncol 2015; 26: 762–768.

283. Goldberg SB, Gettinger SN, Mahajan A et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol 2016; 17: 976–983.

284. Rangachari D, Yamaguchi N, VanderLaan PA et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer 2015; 88: 108–111.

285. Baik CS, Chamberlain MC, Chow LQ. Targeted therapy for brain metastases in EGFR-mutated and ALK-rearranged non-small-cell lung cancer. J Thorac Oncol 2015; 10: 1268–1278.

286. Zimmermann S, Dziadziuszko R, Peters S. Indications and limitations of chemotherapy and targeted agents in non-small cell lung cancer brain metastases. Cancer Treat Rev 2014; 40: 716–722.

287. Lanuti M. Surgical management of oligometastatic non-small cell lung cancer. Thorac Surg Clin 2016; 26: 287–294.

288. Novoa NM, Varela G, Jimenez MF. Surgical management of oligometastatic non-small cell lung cancer. J Thorac Dis 2016; 8(Suppl 11): S895–S900.

289. Eberhardt WE, Mitchell A, Crowley J et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the M descriptors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 2015; 10: 1515–1522.

290. Downey RJ, Ng KK, Kris MG et al. A phase II trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis. Lung Cancer 2002; 38: 193–197.

291. De Ruysscher D, Wanders R, van Baardwijk A et al. Radical treatment of non-small-cell lung cancer patients with synchronous oligometastases: long-term results of a prospective phase II trial (Nct01282450). J Thorac Oncol 2012; 7: 1547–1555.

292. Gomez DR, Blumenschein GRJr, Lee JJ et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol 2016; 17: 1672–1682.

293. David EA, Clark JM, Cooke DT et al. The role of thoracic surgery in the therapeutic management of metastatic non-small cell lung cancer. J Thorac Oncol 2017; 12: 1636–1645.

294. Kimura M, Tojo T, Naito H et al. Effects of a simple intraoperative intrathoracic hyperthermotherapy for lung cancer with malignant pleural effusion or dissemination. Interact Cardiovasc Thorac Surg 2010; 10: 568–571.

295. Wolf AS, Flores RM. Extrapleural pneumonectomy for pleural malignancies. Thorac Surg Clin 2014; 24: 471–475.

296. Shaw P, Agarwal R. Pleurodesis for malignant pleural effusions. Cochrane Database Syst Rev 2004; CD002916.

297. Dresler CM, Olak J, Herndon JEII et al. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest 2005; 127: 909–915.

298. Davies HE, Mishra EK, Kahan BC et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA 2012; 307: 2383–2389.

299. Pilling JE, Dusmet ME, Ladas G, Goldstraw P. Prognostic factors for survival after surgical palliation of malignant pleural effusion. J Thorac Oncol 2010; 5: 1544–1550.

300. Van Breussegem A, Hendriks JM, Lauwers P, Van Schil PE. Salvage surgery after high-dose radiotherapy. J Thorac Dis 2017; 9(Suppl 3): S193–S200.

301. Duchateau N, Van Bouwel E, Van Schil PE. Salvage operation in case of oligometastatic disease. Ann Thorac Surg 2017; 103: e409–e411.

302. David EA, Andersen SW, Beckett LA et al. A model to predict the use of surgical resection for advanced-stage non-small cell lung cancer patients. Ann Thorac Surg 2017; 104: 1665–1672.

303. Ashworth AB, Senan S, Palma DA et al. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer 2014; 15: 346–355.

304. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol 1995; 13: 8–10.

305. Palma DA, Salama JK, Lo SS et al. The oligometastatic state - separating truth from wishful thinking. Nat Rev Clin Oncol 2014; 11: 549–557.

306. Detterbeck FC, Franklin WA, Nicholson AG et al. The IASLC lung cancer staging project: background data and proposed criteria to distinguish separate primary lung cancers from metastatic foci in patients with two lung tumors in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol 2016; 11: 651–665.

307. Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143(5 Suppl): e369S–e399S.

308. Tonnies M, Pfannschmidt J, Bauer TT et al. Metastasectomy for synchronous solitary non-small cell lung cancer metastases. Ann Thorac Surg 2014; 98: 249–256.

309. Griffioen GH, Lagerwaard FJ, Haasbeek CJ et al. Treatment of multiple primary lung cancers using stereotactic radiotherapy, either with or without surgery. Radiother Oncol 2013; 107: 403–408.

310. Chang JY, Liu YH, Zhu Z et al. Stereotactic ablative radiotherapy: a potentially curable approach to early stage multiple primary lung cancer. Cancer 2013; 119: 3402–3410.

311. Collen C, Christian N, Schallier D et al. Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. Ann Oncol 2014; 25: 1954–1959.

312. Iyengar P, Wardak Z, Gerber DE et al. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol 2018; 4: e173501.

313. deSouza NM, Liu Y, Chiti A et al. Strategies and technical challenges for imaging oligometastatic disease: recommendations from the European Organisation for Research and Treatment of Cancer imaging group. Eur J Cancer 2018; 91: 153–163.

314. Chow E, Zeng L, Salvo N et al. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol) 2012; 24: 112–124.

315. Sze WM, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy—a systematic review of the randomised trials. Cochrane Database Syst Rev 2004; CD004721.

316. Rosen LS, Gordon D, Tchekmedyian NS et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer 2004; 100: 2613–2621.

317. Henry DH, Costa L, Goldwasser F et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011; 29: 1125–1132.

318. Scagliotti GV, Hirsh V, Siena S et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol 2012; 7: 1823–1829.

319. Henry D, Vadhan-Raj S, Hirsh V et al. Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer 2014; 22: 679–687.

320. Temel JS, Greer JA, El-Jawahri A et al. Effects of early integrated palliative care in patients with lung and GI cancer: a randomized clinical trial. J Clin Oncol 2017; 35: 834–841.

321. Temel JS, Greer JA, Muzikansky A et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010; 363: 733–742.

322. Cherny NI, Dafni U, Bogaerts J et al. ESMO-Magnitude of Clinical Benefit Scale version 1.1. Ann Oncol 2017; 28: 2340–2366.

323. Horn L, Spigel DR, Vokes EE et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol 2017; 35: 3924–3933.

324. Dykewicz CA. Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Clin Infect Dis 2001; 33: 139–144.