Skip to main content

Uveal Melanoma: Metastases

  • Chapter
  • First Online:
Clinical Ophthalmic Oncology

Abstract

Although there are effective treatments for primary uveal melanoma, the prognosis for metastatic disease is poor. There is no curative therapy for metastatic uveal melanoma, but options include local interventions such as surgical resection, chemoembolization, radioembolization, radiofrequency ablation, or systemic therapy including chemotherapy, targeted therapy, and immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pons F, Plana M, Caminal JM, et al. Metastatic uveal melanoma: is there a role for conventional chemotherapy? – A single center study based on 58 patients. Melanoma Res. 2011;21(3):217–22. https://doi.org/10.1097/CMR.0b013e3283457726.

    Article  PubMed  Google Scholar 

  2. Gragoudas ES, Egan KM, Seddon JM, et al. Survival of patents with metastases from uveal melanoma. Ophthalmology. 1991;98(3):383–90. https://doi.org/10.1016/S0161-6420(91)32285-1.

    Article  CAS  PubMed  Google Scholar 

  3. Moser JC, Pulido JS, Dronca RS, et al. The Mayo Clinic experience with the use of kinase inhibitors, ipilimumab, bevacizumab, and local therapies in the treatment of metastatic uveal melanoma. Melanoma Res. 2015;25(1):59–63. https://doi.org/10.1097/CMR.0000000000000125.

    Article  CAS  PubMed  Google Scholar 

  4. Mariani P, Almubarak MM, Kollen M, et al. Radiofrequency ablation and surgical resection of liver metastases from uveal melanoma. Eur J Surg Oncol. 2016;42(5):706–12. https://doi.org/10.1016/j.ejso.2016.02.019.

    Article  CAS  PubMed  Google Scholar 

  5. Sisley K, Rennie IG, Parsons MA, et al. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer. 1997;19(1):22–8. http://www.ncbi.nlm.nih.gov/pubmed/9135991.

    Article  CAS  PubMed  Google Scholar 

  6. Tschentscher F, Prescher G, Horsman DE, et al. Partial deletions of the long and short arm of chromosome 3 point to two tumor suppressor genes in uveal melanoma. Cancer Res. 2001;61(8):3439–42. http://www.ncbi.nlm.nih.gov/pubmed/11309305.

    CAS  PubMed  Google Scholar 

  7. Onken MD, Worley LA, Ehlers JP, et al. Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res. 2004;64(20):7205–9. https://doi.org/10.1158/0008-5472.CAN-04-1750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jager MJ, Hurks HMH, Levitskaya J, et al. HLA expression in uveal melanoma: there is no rule without some exception. Hum Immunol. 2002;63(6):444–51. http://www.ncbi.nlm.nih.gov/pubmed/12039519.

    Article  CAS  PubMed  Google Scholar 

  9. Diener-West M, Reynolds SM, Agugliaro DJ, et al. Screening for metastasis from choroidal melanoma: The Collaborative Ocular Melanoma Study Group Report 23. J Clin Oncol. 2004;22(12):2438–44. https://doi.org/10.1200/JCO.2004.08.194.

    Article  PubMed  Google Scholar 

  10. Kujala E, Mäkitie T, Kivelä T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003;44(11):4651–9. http://www.ncbi.nlm.nih.gov/pubmed/14578381.

    Article  PubMed  Google Scholar 

  11. Singh AD. Uveal melanoma: implications of tumor doubling time. Ophthalmology. 2001;108(5):829–31. http://www.ncbi.nlm.nih.gov/pubmed/11319992.

    Article  CAS  PubMed  Google Scholar 

  12. Eskelin S, Pyrhönen S, Summanen P, et al. Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment. Ophthalmology. 2000;107(8):1443–9. http://www.ncbi.nlm.nih.gov/pubmed/10919885.

    Article  CAS  PubMed  Google Scholar 

  13. Albert DM, Ryan LM, Borden EC. Metastatic ocular and cutaneous melanoma: a comparison of patient characteristics and prognosis. Arch Ophthalmol (Chicago, Ill 1960). 1996;114(1):107–8. http://www.ncbi.nlm.nih.gov/pubmed/8540843.

    Article  CAS  Google Scholar 

  14. Bedikian AY, Legha SS, Mavligit G, et al. Treatment of uveal melanoma metastatic to the liver. A review of the M. D. Anderson cancer center experience and prognostic factors. Cancer. 1995;76(9):1665–70. https://doi.org/10.1002/1097-0142(19951101)76:9<1665::AID-CNCR2820760925>3.0.CO;2-J.

    Article  CAS  PubMed  Google Scholar 

  15. Rajpal S, Moore R, Karakousis CP. Survival in metastatic ocular melanoma. Cancer. 1983;52(2):334–6. http://www.ncbi.nlm.nih.gov/pubmed/6190546.

    Article  CAS  PubMed  Google Scholar 

  16. Collaborative Ocular Melanoma Study Group. Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS): COMS report no. 15. Arch Ophthalmol (Chicago, Ill 1960). 2001;119(5):670–6. http://www.ncbi.nlm.nih.gov/pubmed/11346394

    Article  Google Scholar 

  17. Singh AD, Shields CL, Shields JA. Prognostic factors in uveal melanoma. Melanoma Res. 2001;11(3):255–63. http://www.ncbi.nlm.nih.gov/pubmed/11468514.

    Article  CAS  PubMed  Google Scholar 

  18. Eskelin S, Kivelä T. Imaging to detect metastases from malignant uveal melanoma. Arch Ophthalmol (Chicago, Ill 1960). 2002;120(5):676. http://www.ncbi.nlm.nih.gov/pubmed/12003636.

    Google Scholar 

  19. Gombos DS, Van Quill KR, Uusitalo M, et al. Geographic disparities in diagnostic screening for metastatic uveal melanoma. Ophthalmology. 2004;111(12):2254–8. https://doi.org/10.1016/j.ophtha.2004.06.022.

    Article  PubMed  Google Scholar 

  20. Group COMS. COMS Manual of Procedures: Accession No. PBS 179693. Springfield: National Technical Information Service; 1995.

    Google Scholar 

  21. Rietschel P, Panageas KS, Hanlon C, et al. Variates of survival in metastatic uveal melanoma. J Clin Oncol. 2005;23(31):8076–80. https://doi.org/10.1200/JCO.2005.02.6534.

    Article  PubMed  Google Scholar 

  22. Kim IK, Lane AM, Gragoudas ES. Survival in patients with presymptomatic diagnosis of metastatic uveal melanoma. Arch Ophthalmol (Chicago, Ill 1960). 2010;128(7):871–5. https://doi.org/10.1001/archophthalmol.2010.121.

    Article  Google Scholar 

  23. Choudhary MM, Gupta A, Bena J, et al. Hepatic ultrasonography for surveillance in patients with uveal melanoma. JAMA Ophthalmol. 2016;134(2):174–80. https://doi.org/10.1001/jamaophthalmol.2015.4810.

    Article  PubMed  Google Scholar 

  24. Marshall E, Romaniuk C, Ghaneh P, et al. MRI in the detection of hepatic metastases from high-risk uveal melanoma: a prospective study in 188 patients. Br J Ophthalmol. 2012;97:1–5. https://doi.org/10.1136/bjophthalmol-2012-302323.

    Article  Google Scholar 

  25. Triozzi PL, Singh AD. Blood biomarkers of uveal melanoma metastasis. Br J Ophthalmol. 2011;95(1):3–4. https://doi.org/10.1136/bjo.2010.193896.

    Article  PubMed  Google Scholar 

  26. Triozzi PL, Singh AD. Blood biomarkers for uveal melanoma. Future Oncol. 2012;8(2):205–15. https://doi.org/10.2217/fon.11.150.

    Article  PubMed  Google Scholar 

  27. Brasiuniene B, Sokolovas V, Brasiunas V, et al. Combined treatment of uveal melanoma liver metastases. Eur J Med Res. 2011;16(2):71–5. http://www.ncbi.nlm.nih.gov/pubmed/21463985.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Salmon RJ, Levy C, Plancher C, et al. Treatment of liver metastases from uveal melanoma by combined surgery-chemotherapy. Eur J Surg Oncol. 1998;24(2):127–30. http://www.ncbi.nlm.nih.gov/pubmed/9591028.

    Article  CAS  PubMed  Google Scholar 

  29. Augsburger JJ, Corrêa ZM, Shaikh AH. Effectiveness of treatments for metastatic uveal melanoma. Am J Ophthalmol. 2009;148(1):119–27. https://doi.org/10.1016/j.ajo.2009.01.023.

    Article  PubMed  Google Scholar 

  30. Augsburger JJ, Corrêa ZM, Shaikh AH. Quality of evidence about effectiveness of treatments for metastatic uveal melanoma. Trans Am Ophthalmol Soc. 2008;106:128–35; discussion 135-7. http://www.ncbi.nlm.nih.gov/pubmed/19277228

    PubMed  PubMed Central  Google Scholar 

  31. 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(2):228–47. https://doi.org/10.1016/j.ejca.2008.10.026.

    Article  CAS  PubMed  Google Scholar 

  32. Pyrhönen S. The treatment of metastatic uveal melanoma. Eur J Cancer. 1998;34(Suppl 3):S27–30. http://www.ncbi.nlm.nih.gov/pubmed/9849406.

    Article  PubMed  Google Scholar 

  33. Kivelä T, Suciu S, Hansson J, et al. Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer. 2003;39(8):1115–20. http://www.ncbi.nlm.nih.gov/pubmed/12736111.

    Article  PubMed  Google Scholar 

  34. Pföhler C, Cree IA, Ugurel S, et al. Treosulfan and gemcitabine in metastatic uveal melanoma patients: results of a multicenter feasibility study. Anti-Cancer Drugs. 2003;14(5):337–40. https://doi.org/10.1097/01.cad.0000070764.25457.ce.

    Article  CAS  PubMed  Google Scholar 

  35. Singh AD, Borden EC. Metastatic uveal melanoma. Ophthalmol Clin N Am. 2005;18(1):143–50, ix. https://doi.org/10.1016/j.ohc.2004.07.003.

    Article  Google Scholar 

  36. Keilholz U, Scheibenbogen C, Brado M, et al. Regional adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells for liver metastases. Eur J Cancer. 1994;30A(1):103–5. http://www.ncbi.nlm.nih.gov/pubmed/8142149.

    Article  CAS  PubMed  Google Scholar 

  37. Heppt MV, Steeb T, Gabriel J, et al. Immune checkpoint blockade for unresectable or metastatic uveal melanoma: a systematic review. Cancer Treat Rev. 2018;60(2017):44–52. https://doi.org/10.1016/j.ctrv.2017.08.009.

    Article  Google Scholar 

  38. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. https://doi.org/10.1056/NEJMoa1003466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kottschade LA, McWilliams RR, Markovic SN, et al. The use of pembrolizumab for the treatment of metastatic uveal melanoma. Melanoma Res. 2016;26(3):300–3. https://doi.org/10.1097/CMR.0000000000000242.

    Article  CAS  PubMed  Google Scholar 

  40. Heppt MV, Heinzerling L, Kähler KC, et al. Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. Eur J Cancer. 2017;82:56–65. https://doi.org/10.1016/j.ejca.2017.05.038.

    Article  CAS  PubMed  Google Scholar 

  41. Kirchberger MC, Moreira A, Erdmann M, et al. Real world experience in low-dose ipilimumab in combination with PD-1 blockade in advanced melanoma patients. Oncotarget. 2018;9(48):28903–9. https://doi.org/10.18632/oncotarget.25627.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Tarhini AA, Cherian J, Moschos SJ, et al. Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma. J Clin Oncol. 2012;30(3):322–8. https://doi.org/10.1200/JCO.2011.37.5394.

    Article  CAS  PubMed  Google Scholar 

  43. Bosch JJ, Iheagwara UK, Reid S, et al. Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells. Cancer Immunol Immunother. 2010;59(1):103–12. https://doi.org/10.1007/s00262-009-0729-0.

    Article  CAS  PubMed  Google Scholar 

  44. Bosch JJ, Thompson JA, Srivastava MK, et al. MHC class II-transduced tumor cells originating in the immune-privileged eye prime and boost CD4(+) T lymphocytes that cross-react with primary and metastatic uveal melanoma cells. Cancer Res. 2007;67(9):4499–506. https://doi.org/10.1158/0008-5472.CAN-06-3770.

    Article  CAS  PubMed  Google Scholar 

  45. Brovkina AF, Keshelava VV, Sologub VK, et al. Live xenogenic vaccine in the prevention of metastases of uveal melanoma. Vestn Oftalmol. 125(5):46–50. http://www.ncbi.nlm.nih.gov/pubmed/19916336

  46. Ma J, Usui Y, Takeuchi M, et al. Human uveal melanoma cells inhibit the immunostimulatory function of dendritic cells. Exp Eye Res. 2010;91(4):491–9. https://doi.org/10.1016/j.exer.2010.06.025.

    Article  CAS  PubMed  Google Scholar 

  47. Triozzi PL, Eng C, Singh AD. Targeted therapy for uveal melanoma. Cancer Treat Rev. 2008;34(3):247–58. https://doi.org/10.1016/j.ctrv.2007.12.002.

    Article  CAS  PubMed  Google Scholar 

  48. Onken MD, Worley LA, Long MD, et al. Oncogenic mutations in GNAQ occur early in uveal melanoma. Invest Ophthalmol Vis Sci. 2008;49(12):5230–4. https://doi.org/10.1167/iovs.08-2145.

    Article  PubMed  Google Scholar 

  49. Van Raamsdonk CD, Griewank KG, Crosby MB, et al. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010;363(23):2191–9. https://doi.org/10.1056/NEJMoa1000584.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Mariani P, Servois V, Piperno-Neumann S. Therapeutic options in metastatic uveal melanoma. Dev Ophthalmol. 2012;49:166–81. https://doi.org/10.1159/000328333.

    Article  PubMed  Google Scholar 

  51. Hsueh EC, Essner R, Foshag LJ, et al. Prolonged survival after complete resection of metastases from intraocular melanoma. Cancer. 2004;100(1):122–9. https://doi.org/10.1002/cncr.11872.

    Article  PubMed  Google Scholar 

  52. Frenkel S, Nir I, Hendler K, et al. Long-term survival of uveal melanoma patients after surgery for liver metastases. Br J Ophthalmol. 2009;93(8):1042–6. https://doi.org/10.1136/bjo.2008.153684.

    Article  CAS  PubMed  Google Scholar 

  53. Fournier GA, Albert DM, Arrigg CA, et al. Resection of solitary metastasis. Approach to palliative treatment of hepatic involvement with choroidal melanoma. Arch Ophthalmol (Chicago, Ill 1960). 1984;102(1):80–2. http://www.ncbi.nlm.nih.gov/pubmed/6200095

    Article  CAS  Google Scholar 

  54. Aoyama T, Mastrangelo MJ, Berd D, et al. Protracted survival after resection of metastatic uveal melanoma. Cancer. 2000;89(7):1561–8. http://www.ncbi.nlm.nih.gov/pubmed/11013372.

    Article  CAS  PubMed  Google Scholar 

  55. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg. 1999;230(1):1–8. http://www.ncbi.nlm.nih.gov/pubmed/10400029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lieberman S, Goldin E, Lotem M, et al. Irrigation of the bile ducts with chilled saline during percutaneous radiofrequency ablation of a hepatic ocular melanoma metastasis. AJR Am J Roentgenol. 2004;183(3):596–8. https://doi.org/10.2214/ajr.183.3.1830596.

    Article  PubMed  Google Scholar 

  57. Valpione S, Aliberti C, Parrozzani R, et al. A retrospective analysis of 141 patients with liver metastases from uveal melanoma: a two-cohort study comparing transarterial chemoembolization with CPT-11 charged microbeads and historical treatments. Melanoma Res Melanoma Res. 2015;25(25):164–8. https://doi.org/10.1097/CMR.0000000000000129.

    Article  CAS  PubMed  Google Scholar 

  58. Sato T. Lack of effect from chemoembolization for liver metastases from uveal melanoma. In: Proc Am Soc Clin Oncol; 1995.

    Google Scholar 

  59. Sato T, Eschelman DJ, Gonsalves CF, et al. Immunoembolization of malignant liver tumors, including uveal melanoma, using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2008;26(33):5436–42. https://doi.org/10.1200/JCO.2008.16.0705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Valsecchi ME, Terai M, Eschelman DJ, et al. Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases. J Vasc Interv Radiol. 2015;26(4):523–32.e2. https://doi.org/10.1016/j.jvir.2014.11.037.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Varghese S, Xu H, Bartlett D, et al. Isolated hepatic perfusion with high-dose melphalan results in immediate alterations in tumor gene expression in patients with metastatic ocular melanoma. Ann Surg Oncol. 2010;17(7):1870–7. https://doi.org/10.1245/s10434-010-0998-z.

    Article  PubMed  Google Scholar 

  62. van Iersel LBJ, Hoekman EJ, Gelderblom H, et al. Isolated hepatic perfusion with 200 mg melphalan for advanced noncolorectal liver metastases. Ann Surg Oncol. 2008;15(7):1891–8. https://doi.org/10.1245/s10434-008-9881-6.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Alexander HR, Libutti SK, Pingpank JF, et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003;9(17):6343–9. http://www.ncbi.nlm.nih.gov/pubmed/14695133.

    CAS  PubMed  Google Scholar 

  64. Karydis I, Gangi A, Wheater MJ, et al. Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease. J Surg Oncol. 2017;117:1170. https://doi.org/10.1002/jso.24956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ben-Shabat I, Belgrano V, Ny L, et al. Long-Term Follow-Up Evaluation of 68 Patients with Uveal Melanoma Liver Metastases Treated with Isolated Hepatic Perfusion. Ann Surg Oncol. 2016;23(4):1327–34. https://doi.org/10.1245/s10434-015-4982-5.

    Article  PubMed  Google Scholar 

  66. Leyvraz S, Piperno-Neumann S, Suciu S, et al. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol. 2014;25:742. https://doi.org/10.1093/annonc/mdt585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Sato T. Locoregional management of hepatic metastasis from primary uveal melanoma. Semin Oncol. 2010;37(2):127–38. https://doi.org/10.1053/j.seminoncol.2010.03.014.

    Article  PubMed  Google Scholar 

  68. Eldredge-Hindy H, Ohri N, Anne PR, et al. Yttrium-90 microsphere brachytherapy for liver metastases from uveal melanoma: clinical outcomes and the predictive value of fluorodeoxyglucose positron emission tomography. Am J Clin Oncol. 2016;39(2):189–95. https://doi.org/10.1097/COC.0000000000000033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tran E, Turcotte S, Gros A, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344(6184):641–5. https://doi.org/10.1126/science.1251102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chandran SS, Somerville RPT, Yang JC, et al. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study. Lancet Oncol. 2017;18(6):792–802. https://doi.org/10.1016/S1470-2045(17)30251-6.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Singh AD, Topham A. Survival rates with uveal melanoma in the United States: 1973-1997. Ophthalmology. 2003;110(5):962–5. https://doi.org/10.1016/S0161-6420(03)00077-0.

    Article  PubMed  Google Scholar 

  72. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9):1881–5. https://doi.org/10.1016/j.ophtha.2011.01.040.

    Article  PubMed  Google Scholar 

  73. Harbour JW. Molecular prognostic testing in uveal melanoma: has it finally come of age? Arch Ophthalmol (Chicago, Ill 1960). 2007;125(8):1122–3. https://doi.org/10.1001/archopht.125.8.1122.

    Article  CAS  Google Scholar 

  74. Choudhary MM, Triozzi PL, Singh AD. Uveal melanoma: evidence for adjuvant therapy. Int Ophthalmol Clin. 2015;55(1):45–51. https://doi.org/10.1097/IIO.0000000000000057.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arun D. Singh .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Xu, L.T., Funchain, P., Tarhini, A.A., Singh, A.D. (2019). Uveal Melanoma: Metastases. In: Damato, B., Singh, A. (eds) Clinical Ophthalmic Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-17879-6_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-17879-6_22

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-17878-9

  • Online ISBN: 978-3-030-17879-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics