Korean Journal of Radiology

  • 제22권4호
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  • Pages.584-595
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  • 2021
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  • 1229-6929(pISSN)
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  • 2005-8330(eISSN)
대한영상의학회 (The Korean Society of Radiology)
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Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis

  • Pyeong Hwa Kim (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Chong Hyun Suh (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Ho Sung Kim (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kyung Won Kim (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Dong Yeong Kim (Department of Quarantine, Incheon Airport National Quarantine Station) ;
  • Eudocia Q. Lee (Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School) ;
  • Ayal A. Aizer (Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School) ;
  • Jeffrey P. Guenette (Department of Radiology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School) ;
  • Raymond Y. Huang (Department of Radiology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School)
  • 투고 : 2020.05.08
  • 심사 : 2020.07.16
  • 발행 : 2021.04.01
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초록

Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion: ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

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참고문헌

  1. Sampson JH, Carter JH Jr, Friedman AH, Seigler HF. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 1998;88:11-20
  2. Amer MH, Al-Sarraf M, Vaitkevicius VK. Clinical presentation, natural history and prognostic factors in advanced malignant melanoma. Surg Gynecol Obstet 1979;149:687-692
  3. Budman DR, Camacho E, Wittes RE. The current causes of death in patients with malignant melanoma. Eur J Cancer 1978;14:327-330
  4. Davies MA, Liu P, McIntyre S, Kim KB, Papadopoulos N, Hwu WJ, et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer 2011;117:1687-1696
  5. Fife KM, Colman MH, Stevens GN, Firth IC, Moon D, Shannon KF, et al. Determinants of outcome in melanoma patients with cerebral metastases. J Clin Oncol 2004;22:1293-1300
  6. Goyal S, Silk AW, Tian S, Mehnert J, Danish S, Ranjan S, et al. Clinical management of multiple melanoma brain metastases: a systematic review. JAMA Oncol 2015;1:668-676
  7. Braschi-Amirfarzan M, Tirumani SH, Hodi FS Jr, Nishino M. Immune-checkpoint inhibitors in the era of precision medicine: what radiologists should know. Korean J Radiol 2017;18:42-53
  8. Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 2018;50:1-11
  9. Nabors LB, Portnow J, Ammirati M, Baehring J, Brem H, Butowski N, et al. NCCN guidelines insights: central nervous system cancers, version 1.2017. J Natl Compr Canc Netw 2017;15:1331-1345
  10. Robert C, Ribas A, Schachter J, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol 2019;20:1239-1251
  11. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521-2532
  12. Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015;16:375-384
  13. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-723
  14. Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol 2013;31:616-622
  15. Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 2018;19:672-681
  16. Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med 2018;379:722-730
  17. Tawbi HAH, Forsyth PA, Hodi FS, Lao CD, Moschos SJ, Hamid O, et al. Efficacy and safety of the combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma brain metastases (CheckMate 204). J Clin Oncol 2019;37:9501
  18. Anderson ES, Postow MA, Wolchok JD, Young RJ, Ballangrud A, Chan TA, et al. Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. J Immunother Cancer 2017;5:76
  19. Nardin C, Mateus C, Texier M, Lanoy E, Hibat-Allah S, Ammari S, et al. Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases. Melanoma Res 2018;28:111-119
  20. Trommer-Nestler M, Marnitz S, Kocher M, Ruess D, Schlaak M, Theurich S, et al. Robotic stereotactic radiosurgery in melanoma patients with brain metastases under simultaneous anti-PD-1 treatment. Int J Mol Sci 2018;19:2653
  21. Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med 2013;2:899-906
  22. Rulli E, Legramandi L, Salvati L, Mandala M. The impact of targeted therapies and immunotherapy in melanoma brain metastases: a systematic review and meta-analysis. Cancer 2019;125:3776-3789
  23. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009;151:W65-W94
  24. Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S, et al. Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv Res 2004;4:38
  25. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64:383-394
  26. Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol 2012;13:459-465
  27. Hamza TH, van Houwelingen HC, Stijnen T. The binomial distribution of meta-analysis was preferred to model within-study variability. J Clin Epidemiol 2008;61:41-51
  28. Stijnen T, Hamza TH, Ozdemir P. Random effects meta-analysis of event outcome in the framework of the generalized linear mixed model with applications in sparse data. Stat Med 2010;29:3046-3067
  29. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560
  30. Kim KW, Lee J, Choi SH, Huh J, Park SH. Systematic review and meta-analysis of studies evaluating diagnostic test accuracy: a practical review for clinical researchers-part I. general guidance and tips. Korean J Radiol 2015;16:1175-1187
  31. Lee J, Kim KW, Choi SH, Huh J, Park SH. Systematic review and meta-analysis of studies evaluating diagnostic test accuracy: a practical review for clinical researchers-part II. Statistical methods of meta-analysis. Korean J Radiol 2015;16:1188-1196
  32. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-634
  33. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ 2001;323:101-105
  34. Higgins JP, Thompson SG. Controlling the risk of spurious findings from meta-regression. Stat Med 2004;23:1663-1682
  35. Knapp G, Hartung J. Improved tests for a random effects meta-regression with a single covariate. Stat Med 2003;22:2693-2710
  36. Kluger HM, Chiang V, Mahajan A, Zito CR, Sznol M, Tran T, et al. Long-term survival of patients with melanoma with active brain metastases treated with pembrolizumab on a phase II trial. J Clin Oncol 2019;37:52-60
  37. Queirolo P, Spagnolo F, Ascierto PA, Simeone E, Marchetti P, Scoppola A, et al. Efficacy and safety of ipilimumab in patients with advanced melanoma and brain metastases. J Neurooncol 2014;118:109-116
  38. Weber JS, Amin A, Minor D, Siegel J, Berman D, O'Day SJ. Safety and clinical activity of ipilimumab in melanoma patients with brain metastases: retrospective analysis of data from a phase 2 trial. Melanoma Res 2011;21:530-534
  39. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23-34
  40. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015;372:2006-2017
  41. Cao Y, Tsien CI, Shen Z, Tatro DS, Ten Haken R, Kessler ML, et al. Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy. J Clin Oncol 2005;23:4127-4136
  42. Quail DF, Joyce JA. The microenvironmental landscape of brain tumors. Cancer Cell 2017;31:326-341
  43. Walle T, Martinez Monge R, Cerwenka A, Ajona D, Melero I, Lecanda F. Radiation effects on antitumor immune responses: current perspectives and challenges. Ther Adv Med Oncol 2018 Jan [Epub]. https://doi.org/10.1177/1758834017742575
  44. Colaco RJ, Martin P, Kluger HM, Yu JB, Chiang VL. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? J Neurosurg 2016;125:17-23
  45. Patel KR, Shoukat S, Oliver DE, Chowdhary M, Rizzo M, Lawson DH, et al. Ipilimumab and stereotactic radiosurgery versus stereotactic radiosurgery alone for newly diagnosed melanoma brain metastases. Am J Clin Oncol 2017;40:444-450
  46. Kaidar-Person O, Zagar TM, Deal A, Moschos SJ, Ewend MG, Sasaki-Adams D, et al. The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy. Anticancer Drugs 2017;28:669-675
  47. Diao K, Bian SX, Routman DM, Yu C, Ye JC, Wagle NA, et al. Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity. J Neurooncol 2018;139:421-429
  48. Skrepnik T, Sundararajan S, Cui H, Stea B. Improved time to disease progression in the brain in patients with melanoma brain metastases treated with concurrent delivery of radiosurgery and ipilimumab. Oncoimmunology 2017;6:e1283461
  49. Lehrer EJ, Peterson J, Brown PD, Sheehan JP, Quinones-Hinojosa A, Zaorsky NG, et al. Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: an international meta-analysis of individual patient data. Radiother Oncol 2019;130:104-112
  50. Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009;15:7412-7420
  51. Nishino M, Giobbie-Hurder A, Manos MP, Bailey N, Buchbinder EI, Ott PA, et al. Immune-related tumor response dynamics in melanoma patients treated with pembrolizumab: identifying markers for clinical outcome and treatment decisions. Clin Cancer Res 2017;23:4671-4679
  52. Hodi FS, Hwu WJ, Kefford R, Weber JS, Daud A, Hamid O, et al. Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab. J Clin Oncol 2016;34:1510-1517