Mammalian Target of Rapamycin Inhibitor Induced Complete Remission of a Recurrent Subependymal Giant Cell Astrocytoma in a Patient Without Features of Tuberous Sclerosis Complex
Deepika Appalla MD
Division of Pediatric Hematology and Oncology, Department of Paediatrics, The Children's Hospital at Saint Peter's University Hospital, New Brunswick, New Jersey
Search for more papers by this authorAndres Depalma MD
University Radiology, Saint Peter's University Hospital, New Brunswick, New Jersey
Search for more papers by this authorCorresponding Author
Stanley Calderwood MD
Division of Pediatric Hematology and Oncology, Department of Paediatrics, The Children's Hospital at Saint Peter's University Hospital, New Brunswick, New Jersey
Correspondence to: Stanley Calderwood, Division of Pediatric Hematology and Oncology, Department of Paediatrics, The Children's Hospital at Saint Peter's University Hospital, 254 Easton Ave., New Brunswick, NJ 08901.
E-mail: [email protected]
Search for more papers by this authorDeepika Appalla MD
Division of Pediatric Hematology and Oncology, Department of Paediatrics, The Children's Hospital at Saint Peter's University Hospital, New Brunswick, New Jersey
Search for more papers by this authorAndres Depalma MD
University Radiology, Saint Peter's University Hospital, New Brunswick, New Jersey
Search for more papers by this authorCorresponding Author
Stanley Calderwood MD
Division of Pediatric Hematology and Oncology, Department of Paediatrics, The Children's Hospital at Saint Peter's University Hospital, New Brunswick, New Jersey
Correspondence to: Stanley Calderwood, Division of Pediatric Hematology and Oncology, Department of Paediatrics, The Children's Hospital at Saint Peter's University Hospital, 254 Easton Ave., New Brunswick, NJ 08901.
E-mail: [email protected]
Search for more papers by this authorConflict of interest: Nothing to declare.
Abstract
The majority of patients with subependymal giant cell astrocytoma (SEGA) have tuberous sclerosis complex (TSC). In such patients, the mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to induce responses. Isolated SEGA have been reported in patients without clinical or genetic features of TSC. The treatment of these patients with everolimus has not previously been reported. We treated a patient with a recurrent isolated SEGA with an mTOR inhibitor. The patient tolerated therapy well and had a sustained complete remission. MTOR inhibitors may be useful for the treatment of isolated SEGA. Further study is warranted.
Supporting Information
| Filename | Description |
|---|---|
| pbc25964-sup-0001-FigureS1.tif775 KB | Supplemental Figure 1: Immediate post-operative axial T1 post-contrast image following left frontal craniotomy for resection of the left ventricular mass. There is no evidence of abnormal nodular enhancement at the surgical bed to suggest residual tumor. |
| pbc25964-sup-0002-FigureS2.tif775 KB | Supplemental Figure 2: Axial T1 post-contrast image obtained 3 months post-operatively showing a new area of nodular enhancement measuring 1.3×1.1×1.8 cm in the region of the previously visualized mass in the left frontal horn at the left foramen of Monro and moderate ventriculomegaly, suggesting tumor recurrence. |
| pbc25964-sup-0003-FigureS3.tif736.3 KB | Supplement Figure 3: Axial T1 post-contrast image showing resolution of previously seen nodular areas of enhancement in the left frontal horn. There has been complete resolution of the patient's ventriculomegaly. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Roth J, Roach ES, Bartels U, Jozwiak S, Koenig MK, Weiner HL, Franz DN, Wang HZ. Subependymal giant cell strocytoma: Diagnosis, screening, and treatment. Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012. Pediatr Neurol 2013; 49: 439–444.
- 2Sinson G, Sutton LN, Yachnis AT, Duhaime AC, Schut L. Subependymal giant cell astrocytomas in children. Pediatr Neurosurg 1994; 20: 233–239.
- 3Beaumont TL, Godzik J, Dahiya S, Smyth MD. Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: Case report. J Neurosurg Pediatr 2015; 16: 134–137.
- 4Ichikawa T, Wakisaka A, Daido S, Takao S, Tamiya T, Date I, Koizumi S, Niida Y. A case of solitary subependymal giant cell astrocytoma: Two somatic hits of TSC2 in the tumor, without evidence of somatic mosaicism. J Mol Diagn 2005; 7: 544–549.
- 5Curran MP. Everolimus: In patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex. Paediatr Drugs 2012; 14: 51–60.
- 6Jozwiak S, Stein K, Kotulska K. Everolimus (RAD001): First systemic treatment for subependymal giant cell astrocytoma associated with tuberous sclerosis complex. Future Oncol 2012; 8: 1515–1523.
- 7Yalon M, Ben-Sira L, Constantini S, Toren A. Regression of subependymal giant cell astrocytomas with RAD001 (Everolimus) in tuberous sclerosis complex. Child's Nerv Syst 2011; 27: 179–181.
- 8Hoogeveen-Westerveld M, Wentink M, van den Heuvel D, Mozaffari M, Ekong R, Povey S, den Dunnen JT, Metcalfe K, Vallee S, Krueger S, Bergoffen J, Shashi V, Elmslie F, Kwiatkowski D, Sampson J, Vidales C, Dzarir J, Garcia-Planells J, Dies K, Maat-Kievit A et al. Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with tuberous sclerosis complex. Hum Mutat 2011; 32: 424–435.
- 9Xu K, Liu P, Wei W. mTOR signaling in tumorigenesis. Biochim Biophys Acta 2014; 1846: 638–654.
- 10Curatolo P, Moavero R. mTOR inhibitors in tuberous sclerosis complex. Curr Neuropharmacol 2012; 10: 404–415.
- 11Chan JA, Zhang H, Roberts PS, Jozwiak S, Wieslawa G, Lewin-Kowalik J, Kotulska K, Kwiatkowski DJ. Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: Biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol 2004; 63: 1236–1242.
- 12Jozwiak J, Jozwiak S, Wlodarski P. Possible mechanisms of disease development in tuberous sclerosis. Lancet Oncol 2008; 9: 73–79.
- 13Parry L, Maynard JH, Patel A, Hodges AK, von Deimling A, Sampson JR, Cheadle JP. Molecular analysis of the TSC1 and TSC2 tumour suppressor genes in sporadic glial and glioneuronal tumours. Hum Genet 2000; 107: 350–356.
- 14Campen CJ, Porter BE. Subependymal giant cell astrocytoma (SEGA) treatment update. Curr Treat Options Neurol 2011; 13: 380–385.
- 15Matsumura H, Takimoto H, Shimada N, Hirata M, Ohnishi T, Hayakawa T. Glioblastoma following radiotherapy in a patient with tuberous sclerosis. Neurol Med Chiru 1998; 38: 287–291.
- 16Kortmann RD, Timmermann B, Taylor RE, Scarzello G, Plasswilm L, Paulsen F, Jeremic B, Gnekow AK, Dieckmann K, Kay S, Bamberg M. Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II: Treatment-related late toxicity. Strahlenther Onkol 2003; 179: 585–597.
- 17Li J, Kim SG, Blenis J. Rapamycin: One drug, many effects. Cell Metab 2014; 19: 373–379.
- 18Tyburczy ME, Kotulska K, Pokarowski P, Mieczkowski J, Kucharska J, Grajkowska W, Roszkowski M, Jozwiak S, Kaminska B. Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex and new therapeutic implications. Am J Pathol 2010; 176: 1878–1890.
- 19Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Whittemore VH, Thiele EA, Ford JP, Shah G, Cauwel H, Lebwohl D, Sahmoud T, Jozwiak S. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): A multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2013; 381: 125–132.
- 20Grunwald V, Weikert S, Pavel ME, Horsch D, Luftner D, Janni W, Geberth M, Weber MM. Practical management of everolimus-related toxicities in patients with advanced solid tumors. Onkologie 2013; 36: 295–302.
