Skip to main content

Advertisement

SpringerLink
Log in

The role of surgery for optic pathway gliomas in the era of precision medicine

  • Research
  • Published:
Child's Nervous System Aims and scope Submit manuscript

  • 1 Altmetric

Abstract

Optic pathway gliomas (OPGs) represent a unique subset of brain tumours that primarily affect the paediatric population. Traditionally, these tumours are managed conservatively due to their location to and association with vital structures. This article explores the evolving role of surgery in the management of OPGs, particularly in the context of advancements in precision medicine. The advent of targeted therapy, especially for tumours with specific genetic alterations, such as BRAF V600E mutations, has revolutionized the treatment landscape, offering new avenues for patient-specific therapy. However, surgery still plays a crucial role, especially for debulking in cases of hydrocephalus or when standard therapies are ineffective. Advances in surgical techniques, including neuronavigation, endoscopic approaches, and intraoperative neurophysiological monitoring, have enhanced the safety and efficacy of operative interventions. Despite these developments, the complexity of OPGs necessitates a multidisciplinary approach, focusing on long-term outcomes and quality of life. Future research is needed to further elucidate the role of surgery in an era increasingly dominated by molecular genetics and targeted therapies.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

  1. Cushing H, Eisenhardt L (1929) Meningiomas arising from the tuberculum sellae: with the syndrome of primary optic atrophy and bitemporal field defects combined with a normal sella turcica in a middle-aged person. Arch Ophthalmol 1:168–206

    Article  Google Scholar 

  2. Sawamura Y, Kamada K, Kamoshima Y, Yamaguchi S, Tajima T, Tsubaki J, Fujimaki T (2008) Role of surgery for optic pathway/hypothalamic astrocytomas in children. Neurooncology 10:725–733

    Google Scholar 

  3. Hill CS, Khan M, Phipps K, Green K, Hargrave D, Aquilina K (2021) Neurosurgical experience of managing optic pathway gliomas. Childs Nerv Syst 37:1917–1929

    Article  PubMed  PubMed Central  Google Scholar 

  4. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW (2021) The 2021 WHO classification of tumours of the central nervous system: a summary. Neurooncology 23:1231–1251

    CAS  Google Scholar 

  5. Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS (2023) CBTRUS Statistical Report: primary brain and other central nervous system tumours diagnosed in the United States in 2016–2020. Neurooncology 25:iv1–iv99

    Google Scholar 

  6. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS (2019) CBTRUS Statistical Report: primary brain and other central nervous system tumours diagnosed in the United States in 2012–2016. Neurooncology 21:v1–v100

    Google Scholar 

  7. Kim JW, Phi JH, Kim SK, Lee JH, Park SH, Won JK, Choi JY, Kang HJ, Park CK (2023) Comparison of the clinical features and treatment outcomes of pilocytic astrocytoma in paediatric and adult patients. Childs Nerv Syst 39:583–591

    Article  PubMed  Google Scholar 

  8. Binning MJ, Liu JK, Kestle JRW, Brockmeyer DL, Walker ML (2007) Optic pathway gliomas: a review. Neurosurgical Focus FOC 23:E2

    Article  Google Scholar 

  9. Listernick R, Louis DN, Packer RJ, Gutmann DH (1997) Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 Optic Pathway Glioma Task Force. Ann Neurol 41:143–149

    Article  CAS  PubMed  Google Scholar 

  10. Singhal S, Birch JM, Kerr B, Lashford L, Evans DG (2002) Neurofibromatosis type 1 and sporadic optic gliomas. Arch Dis Child 87:65–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Housepian EM, Linda Chi T (1993) Neurofibromatosis and optic pathways gliomas. J Neurooncol 15:51–55

    Article  CAS  PubMed  Google Scholar 

  12. Tow SL, Chandela S, Miller NR, Avellino AM (2003) Long-term outcome in children with gliomas of the anterior visual pathway. Pediatr Neurol 28:262–270

    Article  PubMed  Google Scholar 

  13. Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ, Fouladi M (2019) Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol 20:1011–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN et al (1993) Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11:850–856

    Article  CAS  PubMed  Google Scholar 

  15. Packer RJ, Ater J, Allen J, Phillips P, Geyer R, Nicholson HS, Jakacki R, Kurczynski E, Needle M, Finlay J, Reaman G, Boyett JM (1997) Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg 86:747–754

    Article  CAS  PubMed  Google Scholar 

  16. Mahoney DH Jr., Cohen ME, Friedman HS, Kepner JL, Gemer L, Langston JW, James HE, Duffner PK, Kun LE (2000) Carboplatin is effective therapy for young children with progressive optic pathway tumours: a Paediatric Oncology Group phase II study. Neuro Oncol 2:213–220

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, Lazarus KH, Packer RJ, Prados M, Sposto R, Vezina G, Wisoff JH, Pollack IF (2012) Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children’s Oncology Group. J Clin Oncol 30:2641–2647

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tsang DS, Murphy ES, Merchant TE (2017) Radiation therapy for optic pathway and hypothalamic low-grade gliomas in children. Int J Radiat Oncol Biol Phys 99:642–651

    Article  PubMed  Google Scholar 

  19. Gillett GR, Symon L (1987) Hypothalamic glioma. Surg Neurol 28:291–300

    Article  CAS  PubMed  Google Scholar 

  20. Wisoff JH, Abbott R, Epstein F (1990) Surgical management of exophytic chiasmatic-hypothalamic tumours of childhood. J Neurosurg 73:661–667

    Article  CAS  PubMed  Google Scholar 

  21. Konovalov A, Gorelyshev S, Serova N (1994) Surgery of giant gliomas of chiasma and IIIrd ventricle. Acta Neurochir (Wien) 130:71–79

    Article  CAS  PubMed  Google Scholar 

  22. Ahn Y, Cho BK, Kim SK, Chung YN, Lee CS, Kim IH, Yang SW, Kim HS, Kim HJ, Jung HW, Wang KC (2006) Optic pathway glioma: outcome and prognostic factors in a surgical series. Childs Nerv Syst 22:1136–1142

    Article  PubMed  Google Scholar 

  23. Sutton LN, Molloy PT, Sernyak H, Goldwein J, Phillips PL, Rorke LB, Moshang T, Lange B, Packer RJ (1995) Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery. J Neurosurg 83:583–589

    Article  CAS  PubMed  Google Scholar 

  24. Komotar RJ, Burger PC, Carson BS, Brem H, Olivi A, Goldthwaite PT, Tihan T (2004) Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurgery 54:72–80

    Article  PubMed  Google Scholar 

  25. Opocher E, Kremer LC, Da Dalt L, van de Wetering MD, Viscardi E, Caron HN, Perilongo G (2006) Prognostic factors for progression of childhood optic pathway glioma: a systematic review. Eur J Cancer 42:1807–1816

    Article  PubMed  Google Scholar 

  26. Rutka JT, Kuo JS (2004) Paediatric surgical neuro-oncology: current best care practices and strategies. J Neurooncol 69:139–150

    Article  PubMed  Google Scholar 

  27. Walker DA, Liu J, Kieran M, Jabado N, Picton S, Packer R, St Rose C (2013) A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro Oncol 15:462–468

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kim JW, Phi JH, Lee JY, Koh EJ, Kim KH, Kang HJ, Choi JY, Park SH, Wang KC, Kim SK (2022) Clinical outcome of optic pathway and hypothalamic gliomas: a 20-year single-institution retrospective study. World Neurosurg 166:e451–e459

    Article  PubMed  Google Scholar 

  29. Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW (2013) Whole-genome sequencing identifies genetic alterations in paediatric low-grade gliomas. Nat Genet 45:602–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tan JY, Wijesinghe IVS, Alfarizal Kamarudin MN, Parhar I (2021) Paediatric gliomas: BRAF and histone H3 as biomarkers, therapy and perspective of liquid biopsies. Cancers 13:607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ryall S, Tabori U, Hawkins C (2020) Paediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun 8:30

    Article  PubMed  PubMed Central  Google Scholar 

  32. Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, Schmieder K, Wesseling P, Mawrin C, Hasselblatt M, Louis DN, Korshunov A, Pfister S, Hartmann C, Paulus W, Reifenberger G, von Deimling A (2011) Analysis of BRAF V600E mutation in 1,320 nervous system tumours reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121:397–405

    Article  CAS  PubMed  Google Scholar 

  33. Lassaletta A, Zapotocky M, Mistry M, Ramaswamy V, Honnorat M, Krishnatry R, Guerreiro Stucklin A, Zhukova N, Arnoldo A, Ryall S, Ling C, McKeown T, Loukides J, Cruz O, de Torres C, Ho CY, Packer RJ, Tatevossian R, Qaddoumi I, Harreld JH, Dalton JD, Mulcahy-Levy J, Foreman N, Karajannis MA, Wang S, Snuderl M, Nageswara Rao A, Giannini C, Kieran M, Ligon KL, Garre ML, Nozza P, Mascelli S, Raso A, Mueller S, Nicolaides T, Silva K, Perbet R, Vasiljevic A, Faure Conter C, Frappaz D, Leary S, Crane C, Chan A, Ng HK, Shi ZF, Mao Y, Finch E, Eisenstat D, Wilson B, Carret AS, Hauser P, Sumerauer D, Krskova L, Larouche V, Fleming A, Zelcer S, Jabado N, Rutka JT, Dirks P, Taylor MD, Chen S, Bartels U, Huang A, Ellison DW, Bouffet E, Hawkins C, Tabori U (2017) Therapeutic and prognostic implications of BRAF V600E in paediatric low-grade gliomas. J Clin Oncol 35:2934–2941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hill CS, Devesa SC, Ince W, Borg A, Aquilina K (2020) A systematic review of ongoing clinical trials in optic pathway gliomas. Childs Nerv Syst 36:1869–1886

    Article  PubMed  PubMed Central  Google Scholar 

  35. Andrews LJ, Thornton ZA, Saincher SS, Yao IY, Dawson S, McGuinness LA, Jones HE, Jefferies S, Short SC, Cheng H-Y, McAleenan A, Higgins JPT, Kurian KM (2021) Prevalence of BRAFV600 in glioma and use of BRAF inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review. Neurooncology 24:528–540

    Google Scholar 

  36. Hargrave DR, Bouffet E, Tabori U, Broniscer A, Cohen KJ, Hansford JR, Geoerger B, Hingorani P, Dunkel IJ, Russo MW, Tseng L, Dasgupta K, Gasal E, Whitlock JA, Kieran MW (2019) Efficacy and safety of dabrafenib in paediatric patients with BRAF V600 mutation-positive relapsed or refractory low-grade glioma: results from a phase I/IIa study. Clin Cancer Res 25:7303–7311

    Article  CAS  PubMed  Google Scholar 

  37. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion-Sileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Swann S, Legos JJ, Jin F, Mookerjee B, Flaherty K (2015) Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet 386:444–451

    Article  CAS  PubMed  Google Scholar 

  38. Wen PY, Stein A, van den Bent M, De Greve J, Wick A, de Vos FYFL, von Bubnoff N, van Linde ME, Lai A, Prager GW, Campone M, Fasolo A, Lopez-Martin JA, Kim TM, Mason WP, Hofheinz R-D, Blay J-Y, Cho DC, Gazzah A, Pouessel D, Yachnin J, Boran A, Burgess P, Ilankumaran P, Gasal E, Subbiah V (2022) Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol 23:53–64

    Article  CAS  PubMed  Google Scholar 

  39. Bouffet E, Hansford JR, Garrè ML, Hara J, Plant-Fox A, Aerts I, Locatelli F, van der Lugt J, Papusha L, Sahm F, Tabori U, Cohen KJ, Packer RJ, Witt O, Sandalic L, Pereira Bento, da, Silva A, Russo M, Hargrave DR, (2023) Dabrafenib plus trametinib in paediatric glioma with BRAF V600 mutations. N Engl J Med 389:1108–1120

    Article  CAS  PubMed  Google Scholar 

  40. Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC (2016) Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med 375:2550–2560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kilburn LB, Khuong-Quang DA, Hansford JR, Landi D, van der Lugt J, Leary SES, Driever PH, Bailey S, Perreault S, McCowage G, Waanders AJ, Ziegler DS, Witt O, Baxter PA, Kang HJ, Hassall TE, Han JW, Hargrave D, Franson AT, Yalon Oren M, Toledano H, Larouche V, Kline C, Abdelbaki MS, Jabado N, Gottardo NG, Gerber NU, Whipple NS, Segal D, Chi SN, Oren L, Tan EEK, Mueller S, Cornelio I, McLeod L, Zhao X, Walter A, Da Costa D, Manley P, Blackman SC, Packer RJ, Nysom K (2024) The type II RAF inhibitor tovorafenib in relapsed/refractory paediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med 30:207–217

    Article  CAS  PubMed  Google Scholar 

  42. Ramaswamy V, Bartels U (2021) Selumetinib for optic pathway glioma: seeing through the fog, (not yet) the end of the tunnel? Neuro Oncol 23:1627–1628

    Article  PubMed  PubMed Central  Google Scholar 

  43. Samples DC, Mulcahy Levy JM, Hankinson TC (2022) Neurosurgery for optic pathway glioma: optimizing multidisciplinary management. Front Surg 9:884250

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ge M, Li S, Wang L, Li C, Zhang J (2015) The role of diffusion tensor tractography in the surgical treatment of paediatric optic chiasmatic gliomas. J Neurooncol 122:357–366

    Article  PubMed  Google Scholar 

  45. Birski M, Furtak J, Krystkiewicz K, Birska J, Zielinska K, Sokal P, Rusinek M, Paczkowski D, Szylberg L, Harat M (2021) Endoscopic versus stereotactic biopsies of intracranial lesions involving the ventricles. Neurosurg Rev 44:1721–1727

    Article  PubMed  Google Scholar 

  46. Goodden J, Pizer B, Pettorini B, Williams D, Blair J, Didi M, Thorp N, Mallucci C (2014) The role of surgery in optic pathway/hypothalamic gliomas in children. J Neurosurg Pediatr 13:1–12

    Article  PubMed  Google Scholar 

  47. Roth J, Constantini S, Cinalli G (2020) Neurofibromatosis type 1–related hydrocephalus: causes and treatment considerations. Child’s Nerv Syst 36:2385–2390

    Article  Google Scholar 

  48. Kang H, Kim KM, Kim MS, Kim JH, Park CK, Kim YH (2022) Safety of endoscopic endonasal biopsy for the pituitary stalk-hypothalamic lesions. Pituitary 25:143–151

    Article  CAS  PubMed  Google Scholar 

  49. Kim Y-H, Kang H, Dho Y-S, Hwang K, Joo J-D, Kim YH (2021) Multi-layer onlay graft using hydroxyapatite cement placement without cerebrospinal fluid diversion for endoscopic skull base reconstruction. J Korean Neurosurg Soc 64:619–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yang J, Kim YH, Phi JH, Kim SK, Wang KC (2022) Complications of endoscopic skull base surgery for sellar and parasellar tumours in pediatric population; neurosurgical perspectives. Front Oncol 12:769576

    Article  PubMed  PubMed Central  Google Scholar 

  51. Cho WS, Kim JE, Kang HS, Son YJ, Bang JS, Oh CW (2017) Keyhole approach and neuroendoscopy for cerebral aneurysms. J Korean Neurosurg Soc 60:275–281

    Article  PubMed  PubMed Central  Google Scholar 

  52. El Beltagy MA, Reda M, Enayet A, Zaghloul MS, Awad M, Zekri W, Taha H, El-Khateeb N (2016) Treatment and outcome in 65 children with optic pathway gliomas. World Neurosurg 89:525–534

    Article  PubMed  Google Scholar 

  53. Liu Y, Hao X, Liu W, Li C, Gong J, Ma Z, Tian Y (2018) Analysis of survival prognosis for children with symptomatic optic pathway gliomas who received surgery. World Neurosurg 109:e1–e15

    Article  PubMed  Google Scholar 

  54. Lober RM, Guzman R, Cheshier SH, Fredrick DR, Edwards MS, Yeom KW (2012) Application of diffusion tensor tractography in paediatric optic pathway glioma. J Neurosurg Pediatr 10:273–280

    Article  PubMed  Google Scholar 

  55. Kim K, Cho C, Bang MS, Shin HI, Phi JH, Kim SK (2018) Intraoperative neurophysiological monitoring: a review of techniques used for brain tumour surgery in children. J Korean Neurosurg Soc 61:363–375

    Article  PubMed  PubMed Central  Google Scholar 

  56. Gil Z, Beni-Adani L, Siomin V, Nagar H, Dvir R, Constantini S (2001) Ascites following ventriculoperitoneal shunting in children with chiasmatic-hypothalamic glioma. Childs Nerv Syst 17:395–398

    Article  CAS  PubMed  Google Scholar 

  57. West A, Berger MS, Geyer R (2008) Childhood optic pathway tumours associated with ascites following ventriculoperitoneal shunt placement. Pediatr Neurosurg 21:254–259

    Article  Google Scholar 

  58. Fangusaro J, Jones DT, Packer RJ, Gutmann DH, Milde T, Witt O, Mueller S, Fisher MJ, Hansford JR, Tabori U, Hargrave D, Bandopadhayay P (2024) Paediatric low-grade glioma: state-of-the-art and ongoing challenges. Neuro Oncol 26:25–37

    Article  PubMed  Google Scholar 

Download references

Funding

This research was supported and funded by the SNUH Kun-hee Lee Child Cancer & Rare Disease Project, Republic of Korea (grant number: 22 A-017-0100).

Author information

Authors and Affiliations

  1. Division of Paediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, 03080, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea

    Joo Whan Kim & Seung-Ki Kim

Authors
  1. Joo Whan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seung-Ki Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.-K.K. designed the study. J.W.K. and S.-K.K. collected the data. J.W.K. analysed the data and drafted the manuscript. S.-K.K. read and approved the final version for publication. All the authors significantly contributed to the content of the manuscript.

Corresponding author

Correspondence to Seung-Ki Kim.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, J.W., Kim, SK. The role of surgery for optic pathway gliomas in the era of precision medicine. Childs Nerv Syst (2024). https://doi.org/10.1007/s00381-024-06450-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00381-024-06450-4

Keywords

Search

Navigation