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Child's Nervous System

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01-08-2011 | Review Paper

The management of subependymal giant cell tumors in tuberous sclerosis: a clinician's perspective

Authors: Romina Moavero, Mariangela Pinci, Roberta Bombardieri, Paolo Curatolo

Published in: Child's Nervous System | Issue 8/2011

Abstract

Background

Tuberous sclerosis (TSC) is a genetic multisystem disorder associated with hamartomas in several organs including subependymal giant cell tumors (SGCT). SGCT have the potential to grow and therefore to become symptomatic and are one of the main causes of death in TSC individuals. Surgical resection is the procedure of choice for SGCT. However, the discovery of mTOR pathway upregulation in TSC-associated tumors and recent evidence that mTOR inhibitors may induce regression of SGCT open up new treatment strategies. Based on a review of the currently available literature and on personal experience, current options for the management of TSC patients and appropriate indications, taking into account benefits and risks of surgery and pharmacotherapy, are discussed.

Discussion

An earlier diagnosis of SGCT in neurologically asymptomatic children may allow a precocious surgical removal of the tumor, thus minimizing surgery-related morbidity and mortality. Biologically targeted pharmacotherapy with mTOR inhibitors such as sirolimus and everolimus provides a safe and efficacious treatment option for patients with SGCT and has the potential to change the clinical management of these tumors. However, whether pharmacotherapy is sufficient to control growth or if it only delays the need for surgical removal of symptomatic SGCT remains unclear. Further studies are needed to determine the optimal levels of mTOR inhibitors that preserve maximal anti-tumor efficacy while minimizing side effects.

Curatolo P, Bombardieri R, Jozwiak S (2008) Tuberous sclerosis. Lancet 372:657–668PubMedCrossRef

DiMario FJ Jr (2004) Brain abnormalities in tuberous sclerosis complex. J Child Neurol 19:650–657PubMed

Luat AF, Makki M, Chugani HT (2007) Neuroimaging in tuberous sclerosis complex. Curr Opin Neurol 20:142–150PubMedCrossRef

Goh S, Butler W, Thiele EA (2004) Subependymal giant cell tumors in tuberous sclerosis complex. Neurology 63:1457–1461PubMed

Adriaensen ME, Schaefer-Prokop CM, Stijnen T, Duyndam DA, Zonnenberg BA, Prokop M (2009) Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol 16:691–696PubMedCrossRef

Shepherd CW, Gomez MR, Lie JT, Crowson CS (1991) Causes of death in patients with tuberous sclerosis. Mayo Clin Proc 66:792–796PubMed

Berhouma M (2010) Management of subependymal giant cell tumors in tuberous sclerosis complex: the neurosurgeon's perspective. World J Pediatr 6:103–110PubMedCrossRef

Jiang T, Jia G, Ma Z, Luo S, Zhang Y (2011) The diagnosis and treatment of subependymal giant cell astrocytoma combined with tuberous sclerosis. Childs Nerv Syst 27:55–62PubMedCrossRef

Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G, Dinopoulos A, Thomas G, Crone KR (2006) Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 59:490–498PubMedCrossRef

10.

Koenig MK, Butler IJ, Northrup H (2008) Regression of subependymal giant cell astrocytoma with rapamycin in tuberous sclerosis complex. J Child Neurol 23:1238–1239PubMedCrossRef

11.

Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 363:1801–1811PubMedCrossRef

12.

Sepp T, Yates JR, Green AJ (1996) Loss of heterozygosity in tuberous sclerosis hamartomas. J Med Genet 33:962–964PubMedCrossRef

13.

Chan JA, Zhang H, Roberts PS, Jozwiak S, Wieslawa G, Lewin-Kowalik J, Kotulska K, Kwiatkowski DJ (2004) Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol 63:1236–1242PubMed

14.

Ichikawa T, Wakisaka A, Daido S, Takao S, Tamiya T, Date I, Koizumi S, Niida Y (2005) A case of solitary subependymal giant cell astrocytoma: two somatic hits of TSC2 in the tumor, without evidence of somatic mosaicism. J Mol Diagn 7:544–549PubMedCrossRef

15.

Niida Y, Stemmer-Rachamimov AO, Logrip M, Tapon D, Perez R, Kwiatkowski DJ, Sims K, MacCollin M, Louis DN, Ramesh V (2001) Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions. Am J Hum Genet 69:493–503PubMedCrossRef

16.

Jozwiak J, Jozwiak S, Wlodarski P (2008) Possible mechanisms of disease development in tuberous sclerosis. Lancet Oncol 9:73–79PubMedCrossRef

17.

Lopes MB, Altermatt HJ, Scheithauer BW, Shepherd CW, VandenBerg SR (1996) Immunohistochemical characterization of subependymal giant cell astrocytomas. Acta Neuropathol 91:368–375PubMedCrossRef

18.

Raju GP, Urion DK, Sahin M (2007) Neonatal subependymal giant cell astrocytoma: new case and review of literature. Pediatr Neurol 36:128–131PubMedCrossRef

19.

Medhkour A, Traul D, Husain M (2002) Neonatal subependymal giant cell astrocytoma. Pediatr Neurosurg 36:271–274PubMedCrossRef

20.

Mirkin LD, Ey EH, Chaparro M (1999) Congenital subependymal giant-cell astrocytoma: case report with prenatal ultrasonogram. Pediatr Radiol 29:776–780PubMedCrossRef

21.

Oikawa S, Sakamoto K, Kobayashi N (1994) A neonatal huge subependymal giant cell astrocytoma: case report. Neurosurgery 35:748–750PubMedCrossRef

22.

Tien RD, Hesselink JR, Duberg A (1990) Rare subependymal giant-cell astrocytoma in a neonate with tuberous sclerosis. AJNR Am J Neuroradiol 11:1251–1252PubMed

23.

Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ (2001) Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet 68:64–80PubMedCrossRef

24.

Pascual-Castroviejo I, Pascual-Pascual SI, Velazquez-Fragua R, Viano J, Carceller F, Hernandez-Moneo JL, Gutierrez-Molina M, Morales C (2010) Subependymal giant cell astrocytoma in tuberous sclerosis complex. A presentation of eight paediatric patients. Neurologia 25:314–321PubMed

25.

Frerebeau P, Benezech J, Segnarbieux F, Harbi H, Desy A, Marty-Double C (1985) Intraventricular tumors in tuberous sclerosis. Childs Nerv Syst 1:45–48PubMedCrossRef

26.

Fujiwara S, Takaki T, Hikita T, Nishio S (1989) Subependymal giant-cell astrocytoma associated with tuberous sclerosis. Do subependymal nodules grow? Childs Nerv Syst 5:43–44PubMedCrossRef

27.

Altermatt HJ, Scheithauer BW (1992) Cytomorphology of subependymal giant cell astrocytoma. Acta Cytol 36:171–175PubMed

28.

Torres VE, King BF, McKusick MA, Bjornsson J, Zincke H (2001) Update on tuberous sclerosis complex. Contrib Nephrol 136:33–49PubMedCrossRef

29.

Nabbout R, Santos M, Rolland Y, Delalande O, Dulac O, Chiron C (1999) Early diagnosis of subependymal giant cell astrocytoma in children with tuberous sclerosis. J Neurol Neurosurg Psychiatry 66:370–375PubMedCrossRef

30.

de Ribaupierre S, Dorfmuller G, Bulteau C, Fohlen M, Pinard JM, Chiron C, Delalande O (2007) Subependymal giant-cell astrocytomas in pediatric tuberous sclerosis disease: when should we operate? Neurosurgery 60:83–89, Discussion, 89–90PubMed

31.

Cuccia V, Zuccaro G, Sosa F, Monges J, Lubienieky F, Taratuto AL (2003) Subependymal giant cell astrocytoma in children with tuberous sclerosis. Childs Nerv Syst 19:232–243PubMed

32.

Genitori L, Donati PA, Giordano F, Mussa F, Sanzo M, Sardo L, Spacca B, Di Pietro G, Shamsaldin M, Oliveri G (2006) Neurosurgical strategies in the management of subependymal giant cell tumors in tuberous sclerosis complex. In: Curatolo P, Riva D (eds) Neurocutaneous syndromes in children. John Libbey Eurotext, Montrouge, France, pp 117–138

33.

O'Callaghan FJ, Martyn CN, Renowden S, Noakes M, Presdee D, Osborne JP (2008) Subependymal nodules, giant cell astrocytomas and the tuberous sclerosis complex: a population-based study. Arch Dis Child 93:751–754PubMedCrossRef

34.

Di Rocco C, Iannelli A, Marchese E (1995) On the treatment of subependymal giant cell astrocytomas and associated hydrocephalus in tuberous sclerosis. Pediatr Neurosurg 23:115–121PubMedCrossRef

35.

Shepherd CW, Gomez MR (1991) Mortality in the Mayo Clinic Tuberous Sclerosis Complex Study. Ann NY Acad Sci 615:375–377PubMedCrossRef

36.

Hyman MH, Whittemore VH (2000) National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol 57:662–665PubMedCrossRef

37.

Roach ES, DiMario FJ, Kandt RS, Northrup H (1999) Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol 14:401–407PubMedCrossRef

38.

Torres OA, Roach ES, Delgado MR, Sparagana SP, Sheffield E, Swift D, Bruce D (1998) Early diagnosis of subependymal giant cell astrocytoma in patients with tuberous sclerosis. J Child Neurol 13:173–177PubMedCrossRef

39.

Sinson G, Sutton LN, Yachnis AT, Duhaime AC, Schut L (1994) Subependymal giant cell astrocytomas in children. Pediatr Neurosurg 20:233–239PubMedCrossRef

40.

Kim SK, Wang KC, Cho BK, Jung HW, Lee YJ, Chung YS, Lee JY, Park SH, Kim YM, Choe G, Chi JG (2001) Biological behavior and tumorigenesis of subependymal giant cell astrocytomas. J Neurooncol 52:217–225PubMedCrossRef

41.

Franz DN, de Vries PJ, Crino PB (2009) Giant cell astrocytomas in tuberous sclerosis complex. Arch Dis Child 94:75–76PubMed

42.

Sharma MC, Ralte AM, Gaekwad S, Santosh V, Shankar SK, Sarkar C (2004) Subependymal giant cell astrocytoma–a clinicopathological study of 23 cases with special emphasis on histogenesis. Pathol Oncol Res 10:219–224PubMedCrossRef

43.

Pollizzi K, Malinowska-Kolodziej I, Stumm M, Lane H, Kwiatkowski D (2009) Equivalent benefit of mTORC1 blockade and combined PI3K-mTOR blockade in a mouse model of tuberous sclerosis. Mol Cancer 8:38PubMedCrossRef

44.

Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, Kwiatkowski DJ (2008) Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci 28:5422–5432PubMedCrossRef

45.

Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, Salisbury S, Franz DN (2008) Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358:140–151PubMedCrossRef

46.

Lam C, Bouffet E, Tabori U, Mabbott D, Taylor M, Bartels U (2010) Rapamycin (sirolimus) in tuberous sclerosis associated pediatric central nervous system tumors. Pediatr Blood Cancer 54:476–479PubMedCrossRef

47.

Birca A, Mercier C, Major P (2010) Rapamycin as an alternative to surgical treatment of subependymal giant cell astrocytomas in a patient with tuberous sclerosis complex. J Neurosurg Pediatr 6:381–384PubMedCrossRef

48.

Davies DM, Johnson SR, Tattersfield AE, Kingswood JC, Cox JA, McCartney DL, Doyle T, Elmslie F, Saggar A, de Vries PJ, Sampson JR (2008) Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med 358:200–203PubMedCrossRef

49.

Yalon M, Ben-Sira L, Constantini S, Toren A (2011) Regression of subependymal giant cell astrocytomas with RAD001 (Everolimus) in tuberous sclerosis complex. Childs Nerv Syst 27:179–181PubMedCrossRef

50.

Woodrum C, Nobil A, Dabora SL (2010) Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors. J Transl Med 8:14PubMedCrossRef

51.

Lee N, Woodrum CL, Nobil AM, Rauktys AE, Messina MP, Dabora SL (2009) Rapamycin weekly maintenance dosing and the potential efficacy of combination sorafenib plus rapamycin but not atorvastatin or doxycycline in tuberous sclerosis preclinical models. BMC Pharmacol 9:8PubMedCrossRef

52.

Moavero R, Cerminara C, Curatolo P (2010) Epilepsy secondary to tuberous sclerosis: lessons learned and current challenges. Childs Nerv Syst 26:1495–1504PubMedCrossRef

Title: The management of subependymal giant cell tumors in tuberous sclerosis: a clinician's perspective
Authors: Romina Moavero
Mariangela Pinci
Roberta Bombardieri
Paolo Curatolo
Publication date: 01-08-2011
Publisher: Springer-Verlag
Published in: Child's Nervous System / Issue 8/2011
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-011-1406-0

2024 ASCO Annual Meeting

Springer Medicine

The management of subependymal giant cell tumors in tuberous sclerosis: a clinician's perspective

Abstract

Background

Discussion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Discussion

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