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Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer

  • Lung Cancer (H Borghaei, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC).

Recent Findings

Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1–4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5–15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy.

Summary

The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

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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, 2017. CA Cancer J Clin. 2017;67:7–30.

    Article  PubMed  Google Scholar 

  2. Davis FG, Dolecek TA, McCarthy BJ, Villano JL. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data. Neuro-Oncol. 2012;14:1171–7.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Chen AM, Jahan TM, Jablons DM, Garcia J, Larson DA. Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer: clinical implications for the subsequent management of the brain. Cancer. 2007;109:1668–75.

    Article  PubMed  Google Scholar 

  4. Mamon HJ, Yeap BY, Jänne PA, Reblando J, Shrager S, Jaklitsch MT, et al. High risk of brain metastases in surgically staged IIIA non–small-cell lung cancer patients treated with surgery, chemotherapy, and radiation. J Clin Oncol. 2005;23(7):1530–7.

    Article  PubMed  Google Scholar 

  5. Ceresoli GL, Reni M, Chiesa G, Carretta A, Schipani S, Passoni P, et al. Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment: risk factors analysis. Cancer. 2002;95:605–12.

    Article  PubMed  Google Scholar 

  6. 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;295:2483–91.

    Article  CAS  PubMed  Google Scholar 

  7. 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;10:1037–44.

    Article  PubMed  Google Scholar 

  8. Kocher M, Soffietti R, Abacioglu U, Villà 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 Off J Am Soc Clin Oncol. 2011;29:134–41.

    Article  Google Scholar 

  9. •• 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;316:401–9. This randomized controlled trial demonstrated improved cognitive function with SRS alone for limited brain metastases compared to SRS + WBRT.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Weissman DE. Glucocorticoid treatment for brain metastases and epidural spinal cord compression: a review. J Clin Oncol Off J Am Soc Clin Oncol. 1988;6:543–51.

    Article  CAS  Google Scholar 

  11. Phillips TL, Scott CB, Leibel SA, Rotman M, Weigensberg IJ. Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89-05. Int J Radiat Oncol Biol Phys. 1995;33:339–48.

    Article  CAS  PubMed  Google Scholar 

  12. Sause WT, Crowley JJ, Morantz R, Rotman M, Mowry PA, Bouzaglou A, et al. Solitary brain metastasis: results of an RTOG/SWOG protocol evaluation surgery + RT versus RT alone. Am J Clin Oncol. 1990;13:427–32.

    Article  CAS  PubMed  Google Scholar 

  13. Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, et al. The effect of gene alterations and tyrosine kinase inhibition on survival and cause of death in patients with adenocarcinoma of the lung and brain metastases. Int J Radiat Oncol Biol Phys. 2016;96:406–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. 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;37:745–51.

    Article  CAS  PubMed  Google Scholar 

  15. Agboola O, Benoit B, Cross P, Da Silva V, Esche B, Lesiuk H, et al. Prognostic factors derived from recursive partition analysis (RPA) of Radiation Therapy Oncology Group (RTOG) brain metastases trials applied to surgically resected and irradiated brain metastatic cases. Int J Radiat Oncol Biol Phys. 1998;42:155–9.

    Article  CAS  PubMed  Google Scholar 

  16. 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;70:510–4.

    Article  PubMed  Google Scholar 

  17. Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77:655–61.

    Article  PubMed  Google Scholar 

  18. 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 Off J Am Soc Clin Oncol. 2012;30:419–25.

    Article  Google Scholar 

  19. •• 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;3:827–31. This update to the graded prognostic assessment score utilizes molecular data ( EGFR , ALK mutational status) for patients with NSCLC. The most favorable patients exhibited median survival approaching 4 years which is dramatically increased compared to historic estimates of 6 months.

    Article  PubMed  Google Scholar 

  20. 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;322:494–500.

    Article  CAS  PubMed  Google Scholar 

  21. Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery. Ann Neurol. 1993;33:583–90.

    Article  CAS  PubMed  Google Scholar 

  22. 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. 1996;78:1470–6.

    Article  CAS  PubMed  Google Scholar 

  23. 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;29:711–7.

    Article  CAS  PubMed  Google Scholar 

  24. 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;280:1485–9.

    Article  CAS  PubMed  Google Scholar 

  25. • 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;18:1040–8. This randomized controlled trial confirmed the superiority of post-operative SRS to brain metastasis resection cavities compared to observation with regard to local recurrence.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Churilla TM, Chowdhury I, Handorf E, Collette L, Collette S, Dong Y, et al. Comparison of local control of brain metastasis with stereotactic radiosurgery versus surgical resection: a secondary analysis of EORTC 22952-26001. Int. J. Radiat Oncol. 2017;99:S158–9.

    Google Scholar 

  27. Roos DE, Wirth A, Burmeister BH, Spry NA, Drummond KJ, Beresford JA, et al. Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05). Radiother Oncol J Eur Soc Ther Radiol Oncol. 2006;80:318–22.

    Article  Google Scholar 

  28. Soltys SG, Adler JR, Lipani JD, Jackson PS, Choi CYH, Puataweepong P, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2008;70:187–93.

    Article  PubMed  Google Scholar 

  29. Brennan C, Yang TJ, Hilden P, Zhang Z, Chan K, Yamada Y, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88:130–6.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Keller A, Doré M, Cebula H, Thillays F, Proust F, Darié I, et al. Hypofractionated stereotactic radiation therapy to the resection bed for intracranial metastases. Int J Radiat Oncol Biol Phys. 2017;99:1179–89.

    Article  PubMed  Google Scholar 

  31. •• 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;18:1049–60. This randomized controlled trial established the role of post-operative SRS to brain metastasis resection cavities compared to the current standard of care, WBRT. Patients receiving post-operative SRS exhibited less cognitive deterioration than WBRT.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Johnson MD, Avkshtol V, Baschnagel AM, Meyer K, Ye H, Grills IS, et al. Surgical resection of brain metastases and the risk of leptomeningeal recurrence in patients treated with stereotactic radiosurgery. Int J Radiat Oncol. 2016;94:537–43.

    Article  Google Scholar 

  33. Soliman H, Ruschin M, Angelov L, Brown PD, Chiang VLS, Kirkpatrick JP, et al. Consensus contouring guidelines for postoperative completely resected cavity stereotactic radiosurgery for brain metastases. Int. J. Radiat. Oncol. [Internet]. 2017 [cited 2017 Dec 22]; Available from: http://www.sciencedirect.com/science/article/pii/S0360301617339536

  34. Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47:291–8.

    Article  CAS  PubMed  Google Scholar 

  35. Tsao MN, Rades D, Wirth A, Lo SS, Danielson BL, Gaspar LE, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2012;2:210–25.

    Article  PubMed Central  PubMed  Google Scholar 

  36. • 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;15:387–95. This prospective registry study demonstrated the feasibility of SRS for patients with greater than 4 brain metastases.

    Article  PubMed  Google Scholar 

  37. Yamamoto M, Serizawa T, Higuchi Y, Sato Y, Kawagishi J, Yamanaka K, et al. A multi-institutional prospective observational study of stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901 study update): irradiation-related complications and long-term maintenance of mini-mental state examination scores. Int J Radiat Oncol Biol Phys. 2017;99:31–40.

    Article  PubMed  Google Scholar 

  38. Roberge D, Brown P, Mason W, O’Callaghan C, Ding K, Whitton A, et al. CMET-48. 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-Oncol. 2017;19:vi49.

    Article  PubMed Central  Google Scholar 

  39. Muacevic A, Wowra B, Siefert A, Tonn J-C, Steiger H-J, Kreth FW. Microsurgery plus whole brain irradiation versus gamma knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre phase III trial. J Neuro-Oncol. 2008;87:299–307.

    Article  Google Scholar 

  40. Prabhu RS, Press RH, Patel KR, Boselli DM, Symanowski JT, Lankford SP, et al. Single-fraction stereotactic radiosurgery (SRS) alone versus surgical resection and SRS for large brain metastases: a multi-institutional analysis. Int J Radiat Oncol Biol Phys. 2017;99:459–67.

    Article  PubMed  Google Scholar 

  41. Jimenez RB, Alexander BM, Mahadevan A, Niemierko A, Rajakesari S, Arvold ND, et al. The impact of different stereotactic radiation therapy regimens for brain metastases on local control and toxicity. Adv Radiat Oncol. 2017;2:391–7.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Kondziolka D, Parry PV, Lunsford LD, Kano H, Flickinger JC, Rakfal S, et al. The accuracy of predicting survival in individual patients with cancer. J Neurosurg. 2014;120:24–30.

    Article  PubMed  Google Scholar 

  43. Lin NU, Claus E, Sohl J, Razzak AR, Arnaout A, Winer EP. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer. 2008;113:2638–45.

    Article  PubMed  Google Scholar 

  44. Churilla TM, Handorf E, Collette S, Collette L, Dong Y, Aizer AA, et al. Whole brain radiotherapy after stereotactic radiosurgery or surgical resection among patients with 1–3 brain metastases and favorable prognoses: a secondary analysis of EORTC 22952–26001. Ann. Oncol. [Internet]. [cited 2017 Jul 14]; Available from: doi: https://doi.org/10.1093/annonc/mdx332/3894530/Whole-Brain-Radiotherapy-after-Stereotactic

  45. 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 Biol Phys. 2017;99:1173–8.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5:2892–911.

    PubMed Central  PubMed  Google Scholar 

  47. Shi Y, JS-K A, Thongprasert S, Srinivasan S, Tsai C-M, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. 2014;9:154–62.

    CAS  Google Scholar 

  48. Lockman PR, Mittapalli RK, Taskar KS, Rudraraju V, Gril B, Bohn KA, et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2010;16:5664–78.

    Article  CAS  Google Scholar 

  49. Dagogo-Jack I, Gill CM, Cahill DP, Santagata S, Brastianos PK. Treatment of brain metastases in the modern genomic era. Pharmacol Ther. 2017;170:64–72.

    Article  CAS  PubMed  Google Scholar 

  50. Wong A. The emerging role of targeted therapy and immunotherapy in the management of brain metastases in non-small cell lung cancer. Front Oncol. 2017;7:33.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Chamberlain MC, Baik CS, Gadi VK, Bhatia S, Chow LQM. Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma. Neuro-Oncol. 2017;19:i1–24.

    Article  PubMed  Google Scholar 

  52. Sekine A, Satoh H. Paradigm shift of therapeutic management of brain metastases in EGFR-mutant non-small cell lung cancer in the era of targeted therapy. Med Oncol Northwood Lond Engl. 2017;34:121.

    Article  Google Scholar 

  53. Martínez P, Mak RH, Oxnard GR. Targeted therapy as an alternative to whole-brain radiotherapy in EGFR-mutant or ALK-positive non-small-cell lung Cancer with brain metastases. JAMA Oncol. 2017;3:1274–5.

    Article  PubMed  Google Scholar 

  54. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–46.

    Article  CAS  PubMed  Google Scholar 

  55. Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.

    Article  CAS  PubMed  Google Scholar 

  56. Park SJ, Kim HT, Lee DH, Kim KP, Kim S-W, Suh C, et al. Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation. Lung Cancer Amst Neth. 2012;77:556–60.

    Article  CAS  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 Amst Neth. 2013;82:282–7.

    Article  CAS  Google Scholar 

  58. Wu Y-L, Zhou C, Cheng Y, Lu S, Chen G-Y, Huang C, et al. Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases: a phase II study (CTONG-0803). Ann Oncol Off J Eur Soc Med Oncol. 2013;24:993–9.

    Article  Google Scholar 

  59. Schuler M, Wu Y-L, 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 Off Publ Int Assoc Study Lung Cancer. 2016;11:380–90.

    Google Scholar 

  60. • Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, et al. Management of brain metastases in tyrosine kinase inhibitor-naïve epidermal growth factor receptor-mutant non-small-cell lung cancer: a retrospective multi-institutional analysis. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35:1070–7. This multi-institutional retrospective analysis of patients with EGFR mutated NSCLC and brain metastases demonstrated a survival detriment to deferral of local therapy (WBRT or SRS) for up-front TKI therapy underscoring the need for a clinical trial.

    Article  CAS  Google Scholar 

  61. Kwak EL, Bang Y-J, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. N Engl J Med. 2010;363:1693–703.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Gainor JF, Varghese AM, S-HI O, Kabraji S, Awad MM, Katayama R, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2013;19:4273–81.

    Article  CAS  Google Scholar 

  63. Shaw AT, Kim D-W, Nakagawa K, Seto T, Crinó L, Ahn M-J, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–94.

    Article  CAS  PubMed  Google Scholar 

  64. Solomon BJ, Mok T, Kim D-W, Wu Y-L, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–77.

    Article  CAS  PubMed  Google Scholar 

  65. Gainor JF, Tan DSW, De Pas T, Solomon BJ, Ahmad A, Lazzari C, et al. Progression-free and overall survival in ALK-positive NSCLC patients treated with sequential crizotinib and ceritinib. Clin Cancer Res Off J Am Assoc Cancer Res. 2015;21:2745–52.

    Article  CAS  Google Scholar 

  66. Gainor JF, Sherman CA, Willoughby K, Logan J, Kennedy E, Brastianos PK, et al. Alectinib salvages CNS relapses in ALK-positive lung cancer patients previously treated with crizotinib and ceritinib. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. 2015;10:232–6.

    CAS  Google Scholar 

  67. • Shaw AT, Kim D-W, Mehra R, Tan DSW, Felip E, Chow LQM, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370:1189–97. This phase II trial of alectinib demonstrated an impressive 75% response rate highlighting the improved CNS activity of second generation TKIs.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Costa DB, Shaw AT, S-HI O, Solomon BJ, Riely GJ, Ahn M-J, et al. Clinical experience with crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33:1881–8.

    Article  CAS  Google Scholar 

  69. Costa DB, Kobayashi S, Pandya SS, Yeo W-L, Shen Z, Tan W, et al. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:e443–5.

    Article  Google Scholar 

  70. Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016;17:234–42.

    Article  CAS  PubMed  Google Scholar 

  71. Asher AL, Burri SH, Wiggins WF, Kelly RP, Boltes MO, Mehrlich M, et al. A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys. 2014;88:899–906.

    Article  PubMed  Google Scholar 

  72. Patel KR, Burri SH, Asher AL, Crocker IR, Fraser RW, Zhang C, et al. Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: a multi-institutional analysis. Neurosurgery. 2016;79:279–85.

    Article  PubMed  Google Scholar 

  73. Patel KR, Burri SH, Boselli D, Symanowski JT, Asher AL, Sumrall A, et al. Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis. J Neuro-Oncol. 2017;131:611–8.

    Article  CAS  Google Scholar 

  74. NRG Oncology Semiannual Meeting 2016 [Internet]. Available from: https://www.nrgoncology.org/LinkClick.aspx?fileticket=TTkEMgz9_7U%3D&portalid=0

  75. Gondi V, Tomé WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2010;97:370–6.

    Article  Google Scholar 

  76. 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 Off J Am Soc Clin Oncol. 2014;32:3810–6.

    Article  Google Scholar 

  77. National Comprehensive Cancer Network. Non-small cell lung cancer (version 2.2018). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf Accessed 1/5/2018.

  78. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. 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;17:976–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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  1. Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

    Thomas M. Churilla & Stephanie E. Weiss

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Churilla, T.M., Weiss, S.E. Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer. Curr Oncol Rep 20, 54 (2018). https://doi.org/10.1007/s11912-018-0695-9

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