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The Changing Paradigm of Treatment for Non-Small Cell Lung Cancer Intracranial Metastases

  • Lung Cancer (R Mudad, Section Editor)
  • Published:
Current Pulmonology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Evaluate safety and efficacy of newer systemic therapies for intracranial metastases (IM) from non-small cell lung cancer (NSCLC) when given alone and with concurrent radiation therapy (RT) and determine which patients with IM may benefit from upfront systemic therapy while withholding RT.

Recent Findings

In NSCLC, chemotherapy regimens are associated with approximately 20% intracranial overall response rates (ORRs) and immunotherapies 30–50% intracranial ORRs. However, tyrosine kinase inhibitor (TKI) therapies for EGFR-mutated patients provide ORRs ranging from 50 to 90%. Prospective data suggest erlotinib, when combined with stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT), substantially increases grade 3–5 toxicities. For immunotherapy, retrospective studies suggest increased intracranial control rates with concurrent RT, though possibly with increased radiation necrosis rates.

Summary

Upfront TKIs may allow appropriately selected patients to avoid or delay RT and possible resultant RT side effects. However, delayed RT is counterbalanced by retrospective data that suggests upfront RT prolongs overall survival (OS) when performed before starting TKI therapy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.

    Article  Google Scholar 

  2. Patchell RA. The management of brain metastases. Cancer Treat Rev. 2003;29(6):533–40.

    Article  Google Scholar 

  3. Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neuro-Oncol. 2005;75(1):5–14.

    Article  Google Scholar 

  4. Goncalves PH, Peterson SL, Vigneau FD, Shore RD, Quarshie WO, Islam K, et al. Risk of brain metastases in patients with nonmetastatic lung cancer: analysis of the metropolitan Detroit surveillance, epidemiology, and end results (SEER) data. Cancer-Am Cancer Soc. 2016;122(12):1921–7.

    Google Scholar 

  5. Gaspar LE, Chansky K, Albain KS, Vallieres E, Rusch V, Crowley JJ, et al. Time from treatment to subsequent diagnosis of brain metastases in stage III non-small-cell lung cancer: a retrospective review by the Southwest Oncology Group. J Clin Oncol. 2005;23(13):2955–61.

    Article  Google Scholar 

  6. Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer. 2015;88(1):108–11.

    Article  Google Scholar 

  7. Gahr S, Stoehr R, Geissinger E, Ficker JH, Brueckl WM, Gschwendtner A, et al. EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice. Br J Cancer. 2013;109(7):1821–8.

    Article  CAS  Google Scholar 

  8. Sholl LM, Aisner DL, Varella-Garcia M, Berry LD, Dias-Santagata D, Wistuba II, et al. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: the lung cancer mutation consortium experience. J Thorac Oncol. 2015;10(5):768–77.

    Article  CAS  Google Scholar 

  9. Ren S, Zhang S, Jiang T, He Y, Ma Z, Cai H, et al. Early detection of lung cancer by using an autoantibody panel in Chinese population. Oncoimmunology. 2018;7(2):e1384108.

    Article  Google Scholar 

  10. Reynolds C, Masters E, Black-Shinn J, Mardekian J, Espirito J, Boyd M, et al. Real world utilization and outcomes of ALK-positive crizotinib treated metastatic NSCLC patients in US Community oncology practice. J Thorac Oncol. 2017;12(1):S1172–S3.

    Article  Google Scholar 

  11. Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745–51.

    Article  CAS  Google Scholar 

  12. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, 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(4):419–25.

    Article  Google Scholar 

  13. Nieder C, Hintz M, Oehlke O, Bilger A, Grosu AL. Validation of the graded prognostic assessment for lung cancer with brain metastases using molecular markers (lung-molGPA). Radiat Oncol. 2017;12.

  14. • Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, et al. Estimating survival in patients with lung cancer and brain metastases an update of the graded prognostic assessment for lung cancer using molecular markers (lung-molGPA). Jama Oncol. 2017;3(6):827–31 This study reports the graded prognostic assessment for lung cancer and is the first model to incorporate EGFR and ALK mutations.

    Article  Google Scholar 

  15. Weltman E, Salvajoli JV, Brandt RA, de Morais HR, Prisco FE, Cruz JC, et al. Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys. 2000;46(5):1155–61.

    Article  CAS  Google Scholar 

  16. Lorenzoni J, Devriendt D, Massager N, David P, Ruiz S, Vanderlinden B, et al. Radiosurgery for treatment of brain metastases: estimation of patient eligibility using three stratification systems. Int J Radiat Oncol Biol Phys. 2004;60(1):218–24.

    Article  Google Scholar 

  17. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008;70(2):510–4.

    Article  Google Scholar 

  18. Golden DW, Lamborn KR, McDermott MW, Kunwar S, Wara WM, Nakamura JL, et al. Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site. J Neurosurg. 2008;109(Suppl):77–86.

    Article  Google Scholar 

  19. Zindler JD, Jochems A, Lagerwaard FJ, Beumer R, Troost EGC, Eekers DBP, et al. Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer: two externally validated nomograms. Radiother Oncol. 2017;123(2):189–94.

    Article  Google Scholar 

  20. Chao JH, Phillips R, Nickson JJ. Roentgen-ray therapy of cerebral metastases. Cancer Am Cancer Soc. 1954;7(4):682–9.

    CAS  Google Scholar 

  21. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494–500.

    Article  CAS  Google Scholar 

  22. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665–72.

    Article  Google Scholar 

  23. Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, et al. The palliation of brain metastases: final results of the first two studies by the radiation therapy oncology group. Int J Radiat Oncol Biol Phys. 1980;6(1):1–9.

    Article  CAS  Google Scholar 

  24. Noordijk EM, Vecht CJ, Haaxma-Reiche H, Padberg GW, Voormolen JH, Hoekstra FH, et al. The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age. Int J Radiat Oncol Biol Phys. 1994;29(4):711–7.

    Article  CAS  Google Scholar 

  25. Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer Am Cancer Soc. 1996;78(7):1470–6.

    CAS  Google Scholar 

  26. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):1485–9.

    Article  CAS  Google Scholar 

  27. Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, 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(10055):2004–14.

    Article  CAS  Google Scholar 

  28. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–44.

    Article  Google Scholar 

  29. Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):1049–60.

    Article  Google Scholar 

  30. •• Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, et al. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA. 2016;316(4):401–9 Phase III evidence that the addition of WBRT to SRS leads to measurable cognitive decline in comparison to SRS alone.

    Article  Google Scholar 

  31. Churilla TM, Ballman KV, Brown PD, Twohy EL, Jaeckle K, Farace E, et al. Stereotactic radiosurgery with or without whole-brain radiation therapy for limited brain metastases: a secondary analysis of the North Central Cancer Treatment Group N0574 (Alliance) randomized controlled trial. Int J Radiat Oncol. 2017;99(5):1173–8.

    Article  Google Scholar 

  32. •• Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387–95 Prospective data that indicates patients with 2–5 IM have overall survival rates no different from patients with 6–10 IM.

    Article  Google Scholar 

  33. Ali MA, Hirshman BR, Wilson B, Carroll KT, Proudfoot JA, Goetsch SJ, et al. Survival patterns of 5750 stereotactic radiosurgery-treated patients with brain metastasis as a function of the number of lesions. World Neurosurg. 2017;107:944.

    Article  Google Scholar 

  34. Routman DM, Bian SX, Diao K, Liu JL, Yu C, Ye J, et al. The growing importance of lesion volume as a prognostic factor in patients with multiple brain metastases treated with stereotactic radiosurgery. Cancer Med. 2018.

  35. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, 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(21):2483–91.

    Article  CAS  Google Scholar 

  36. Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, 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(2):134–41.

    Article  Google Scholar 

  37. Mahajan A, Ahmed S, McAleer MF, Weinberg JS, Li J, Brown P, 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(8):1040–8.

    Article  Google Scholar 

  38. Trifiletti DM, Sheehan JP, Grover S, Dutta SW, Rusthoven CG, Kavanagh BD, et al. National trends in radiotherapy for brain metastases at time of diagnosis of non-small cell lung cancer. J Clin Neurosci. 2017;45:48–53.

    Article  Google Scholar 

  39. Brown PD, Shook S, Laack NN, Wefel JS, Choucair A, Suh JH, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiation therapy (WBRT): first report of RTOG 0614, a placebo-controlled, double-blind. Randomized Trial Int J Radiat Oncol. 2012;84(3):S1–2.

    Article  Google Scholar 

  40. Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, 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(34):3810–6.

    Article  Google Scholar 

  41. Slade AN, Stanic S. The impact of RTOG 0614 and RTOG 0933 trials in routine clinical practice: the US Survey of Utilization of Memantine and IMRT planning for hippocampus sparing in patients receiving whole brain radiotherapy for brain metastases. Contemp Clin Trials. 2016;47:74–7.

    Article  Google Scholar 

  42. Jeene PM, de Vries KC, van Nes JGH, Kwakman JJM, Wester G, Rozema T, et al. Survival after whole brain radiotherapy for brain metastases from lung cancer and breast cancer is poor in 6325 Dutch patients treated between 2000 and 2014. Acta Oncol 2017:1–7.

  43. Grommes C, Oxnard GR, Kris MG, Miller VA, Pao W, Holodny AI, et al. “Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro-Oncology. 2011;13(12):1364–9.

    Article  Google Scholar 

  44. Kawamura T, Hata A, Takeshita J, Fujita S, Hayashi M, Tomii K, et al. High-dose erlotinib for refractory leptomeningeal metastases after failure of standard-dose EGFR-TKIs. Cancer Chemother Pharmacol. 2015;75(6):1261–6.

    Article  CAS  Google Scholar 

  45. Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629–40.

    Article  CAS  Google Scholar 

  46. •• Yang JCH, Cho BC, Kim DW, Kim SW, Lee JS, Su WC, et al. Osimertinib for patients (pts) with leptomeningeal metastases (LM) from EGFR-mutant non-small cell lung cancer (NSCLC): updated results from the BLOOM study. J Clin Oncol. 2017:35 Abstract reporting measured CSF penetration and efficacy of Osimertinib using neurological assessment and brain imaging in patients with leptomeningeal metastases from EGFR mutation positive NSCLC.

  47. Vansteenkiste J, Reungwetwattana T, Nakagawa K, Cho BC, Dols MAC, Cho EK, et al. CNS response to osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFR-TKI sensitising mutation (EGFRm)-positive advanced non-small cell lung cancer (NSCLC): Data from the FLAURA study. Ann Oncol. 2017;28:189.

    Google Scholar 

  48. Crino L, Ahn MJ, De Marinis F, Groen HJ, Wakelee H, Hida T, et al. Multicenter phase II study of whole-body and intracranial activity with ceritinib in patients with ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib: results from ASCEND-2. J Clin Oncol. 2016;34(24):2866–73.

    Article  CAS  Google Scholar 

  49. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829–38.

    Article  CAS  Google Scholar 

  50. Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, 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(22):2490–8.

    Article  CAS  Google Scholar 

  51. Gauvain C, Vauleon E, Chouaid C, Lerhun E, Jabot L, Scherpereel A, et al. Intracerebral efficacy and tolerance of nivolumab in non-small-cell lung cancer patients with brain metastases. Lung Cancer. 2018;116:62–6.

    Article  Google Scholar 

  52. Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, 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(7):976–83.

    Article  CAS  Google Scholar 

  53. Takamori S, Toyokawa G, Okamoto I, Takada K, Kozuma Y, Matsubara T, et al. Discrepancy in programmed cell death-ligand 1 between primary and metastatic non-small cell lung cancer. Anticancer Res. 2017;37(8):4223–8.

    PubMed  Google Scholar 

  54. •• Arbour KC, Kris MG, Riely GJ, Ni A, Beal K, Daras M, et al. Twice weekly pulse and daily continuous-dose erlotinib as initial treatment for patients with epidermal growth factor receptor-mutant lung cancers and brain metastases. Cancer Am Cancer Soc. 2018;124(1):105–9 Phase III evidence that EGFR inhibition, albeit with erlotinib a first generation TKI, may lead to increased toxicity when combined with radiation therapy. This study highlights the importance of ongoing research that reports toxicity after combined TKI/radiation therapy.

    CAS  Google Scholar 

  55. Sperduto PW, Wang M, Robins HI, Schell MC, Werner-Wasik M, Komaki R, et al. A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320. Int J Radiat Oncol Biol Phys. 2013;85(5):1312–8.

    Article  CAS  Google Scholar 

  56. Schuler M, Wu YL, Hirsh V, O’Byrne K, Yamamoto N, Mok T, et al. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016;11(3):380–90.

    Article  Google Scholar 

  57. Iuchi T, Shingyoji M, Sakaida T, Hatano K, Nagano O, Itakura M, et al. Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma. Lung Cancer. 2013;82(2):282–7.

    Article  CAS  Google Scholar 

  58. Pesce GA, Klingbiel D, Ribi K, Zouhair A, von Moos R, Schlaeppi M, et al. Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03). Eur J Cancer. 2012;48(3):377–84.

    Article  Google Scholar 

  59. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113–25.

    Article  Google Scholar 

  60. Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, et al. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from PROFILE 1014. J Clin Oncol. 2016;34(24):2858–65.

    Article  CAS  Google Scholar 

  61. Weickhardt AJ, Scheier B, Burke JM, Gan G, Lu X, Bunn PA Jr, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012;7(12):1807–14.

    Article  CAS  Google Scholar 

  62. Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, 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(10072):917–29.

    Article  CAS  Google Scholar 

  63. •• Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829–38 Analysis shows efficacy of Brigatinib and durable responses when treating IM in patients with ALK rearrangement positive NSCLC.

    Article  CAS  Google Scholar 

  64. Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, et al. Exploratory analysis of brigatinib activity in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer and brain metastases in two clinical trials. J Clin Oncol. 2018:JCO2017775841.

  65. Patil T, Smith DE, Bunn PA, Aisner DL, Le AT, Hancock M, et al. The incidence of brain metastases in stage IV ROS1-rearranged non-small cell lung cancer and rate of central nervous system progression on crizotinib. J Thorac Oncol. 2018.

  66. Lim SM, Kim HR, Lee JS, Lee KH, Lee YG, JooMin Y, 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(23):2613.

    Article  CAS  Google Scholar 

  67. Drilon A, Rekhtman N, Arcila M, Wang L, Ni A, Albano M, et al. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol. 2016;17(12):1653–60.

    Article  CAS  Google Scholar 

  68. Chen L, Douglass J, Kleinberg L, Ye X, Marciscano AE, Forde PM, et al. Concurrent immune checkpoint inhibitors and stereotactic radiosurgery for brain metastases in non-small cell lung cancer, melanoma, and renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2018;100(4):916–25.

    Article  Google Scholar 

  69. Schapira E, Hubbeling H, Yeap BY, Mehan WA Jr, Shaw AT, Oh K, et al. Improved overall survival and locoregional disease control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for lung cancer patients with brain metastases. Int J Radiat Oncol Biol Phys. 2018;101(3):624–9.

    Article  Google Scholar 

  70. Besse B, Le Moulec S, Mazieres J, Senellart H, Barlesi F, Chouaid C, 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(8):1896–903.

    Article  CAS  Google Scholar 

  71. Levy C, Allouache D, Lacroix J, Dugue AE, Supiot S, Campone M, et al. REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours. Ann Oncol. 2014;25(12):2351–6.

    Article  CAS  Google Scholar 

  72. Lou E, Sperduto PW. Integrating bevacizumab and radiation treatment of brain metastasis: is there sense and sensibility in this approach? Ann Transl Med. 2016;4(2):36.

    PubMed  PubMed Central  Google Scholar 

  73. Cagney DN, Martin AM, Catalano PJ, Reitman ZJ, Mezochow GA, Lee EQ, et al. Impact of pemetrexed on intracranial disease control and radiation necrosis in patients with brain metastases from non-small cell lung cancer receiving stereotactic radiation. Radiother Oncol. 2018;126(3):511–8.

    Article  CAS  Google Scholar 

  74. • Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, et al. Management of brain metastases in tyrosine kinase inhibitor-naive epidermal growth factor receptor-mutant non-small-cell lung cancer: a retrospective multi-institutional analysis. J Clin Oncol. 2017;35(10):1070 Although retrospective and subject to selection bias, this study by Magnuson suggests that both SRS and WBRT prior to starting EGFR inhibition lead to significantly enhanced survival in patients with IM from NSCLC.

    Article  CAS  Google Scholar 

  75. Roberge D, Brown P, Mason W, O’Callaghan C, Ding KY, Whitton A, et al. Ce7 Canadian Clinical Trials Group / Alliance for Clinical Trials in Oncology. A phase III trial of stereotactic radiosurgery compared with whole brain radiotherapy (WBRT) for 5–15 brain metastases. Neuro-Oncology. 2017;19:49.

    Article  Google Scholar 

  76. Robin TP, Camidge DR, Stuhr K, Nath SK, Breeze RE, Pacheco JM, et al. Excellent outcomes with radiosurgery for multiple brain metastases in ALK and EGFR driven non-small cell lung cancer. J Thorac Oncol. 2017.

  77. Pike LRG, Bang A, Ott P, Balboni T, Taylor A, Catalano P, et al. Radiation and PD-1 inhibition: favorable outcomes after brain-directed radiation. Radiother Oncol. 2017;124(1):98–103.

    Article  CAS  Google Scholar 

  78. Ahmed KA, Kim S, Arrington J, Naghavi AO, Dilling TJ, Creelan BC, et al. Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases. J Neuro-Oncol. 2017;133(2):331–8.

    Article  CAS  Google Scholar 

  79. Hubbeling HG, Schapira EF, Horick NK, Goodwin KEH, Lin JJ, Oh KS, et al. Safety of combined PD-1 pathway inhibition and intracranial radiation therapy in non-small cell lung cancer. J Thorac Oncol. 2018;13:550–8.

    Article  Google Scholar 

  80. Martin AM, Cagney DN, Catalano PJ, Alexander BM, Redig AJ, Schoenfeld JD, et al. Immunotherapy and symptomatic radiation necrosis in patients with brain metastases treated with stereotactic radiation. Jama Oncol. 2018.

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  1. University of Miami, Miami, FL, USA

    Gregory A. Azzam, Eric A. Mellon, Stuart E. Samuels & Raphael L. Yechieli

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Azzam, G.A., Mellon, E.A., Samuels, S.E. et al. The Changing Paradigm of Treatment for Non-Small Cell Lung Cancer Intracranial Metastases. Curr Pulmonol Rep 7, 203–213 (2018). https://doi.org/10.1007/s13665-018-0215-2

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