Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Child's Nervous System
Published in: Child's Nervous System 10/2016

01-10-2016 | Special Annual Issue

Conventional chemotherapy and perspectives for molecular-based oncological treatment in pediatric hemispheric low-grade gliomas

Authors: María Baro Fernández, Vanesa Pérez Alonso

Published in: Child's Nervous System | Issue 10/2016

Login to get access

Abstract

Introduction

Pediatric low-grade gliomas (PLGG) are the most common primary central nervous system tumor in children. Patients in whom gross total resection can be achieved have an excellent overall (OS) and event-free survival (EFS) and do not require adjuvant therapy. However, children with unresectable tumors often experience multiple progressions and require additional treatment.

Conventional chemotherapy

Radiotherapy results in long-term tumor control, but it is associated with significant toxicity, making chemotherapy the preferred therapeutic option. Several chemotherapy combinations have been found to be successful in PLGG, but 5-year EFS has been below 60 % with most of them.

Molecular-based treatment

Recent molecular advances have led to a better understanding of the molecular pathways involved in the biology of LGG, allowing the development of promising tumor-specific, molecularly targeted therapies.
Literature
1.
Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Krucho C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 16(Suppl 4):iv1-63
2.
Garzón M, García-Fructuoso G, Suñol M, Mora J, Cruz O (2013) Low-grade gliomas in children: single institutional experience. Childs Nerv Syst 31:1321–1331CrossRef
3.
Bandopadhayay P, Bergthold G, London WB, Goumnerova LC, Morales La Madrid A, Marcus KJ, Guo D, Ullrich NJ, Robison NJ, Chi SN, Beroukhim R, Kieram MW, Manley PE (2014) Long-term outcome of 4040 children diagnosed with pediatric low-grade gliomas: an analysis of the Surveillance Epidemiology and End Results (SEER) database. Pediatr Blood Cancer 61:1173–1179CrossRefPubMedPubMedCentral
4.
Stokland T, Liu JF, Ironside JW, Ellison DW, Taylor R, Robinson KJ, Picton SV, Walker DA (2010) A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population based cohort study (CCLG CNS9702). Neuro Oncol 12:1257–1268PubMedPubMedCentral
5.
Youland RS, Khwaja SS, Schomas DA, Keating GS, Wetjen M, Laack NN (2013) Prognostic factors and survival patterns in pediatric low-grade gliomas over 4 decades. J Pediatr Hematol Oncol 35:197–205CrossRefPubMed
6.
7.
Chamdine O, Broniscer A, Wu S, Gajjar A, Qaddoumi I (2016) Metastatic low-grade gliomas in children: 20-years’ experience at St. Jude Children’s Research Hospital. Pediatr Blood Cancer 63:62–70CrossRefPubMed
8.
Wisoff JH, Sanford RA, Heier LA, Sposto R, Burger PC, Yates AJ, Holmes EJ, Kun LE (2011) Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children’s Oncology Group. Neurosurgery 68:1548–1555CrossRefPubMed
9.
Müller K, Gnekow A, Falkstein F, Scheiderbauer J, Zwiener I, Pietsch T, Warmuth-metz M, Voges J, Nikkhah G, Flentje M, Combs SE, Vordemark D, Kocher M, Kortmann RD (2013) Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH). Strahlenther Onkol 189:647–655CrossRefPubMed
10.
Raikar SS, Halloran DR, Elliot M, McHugh M, Patel S, Gauvain KM (2014) Outcomes of pediatric low-grade gliomas treated with radiation therapy: a single institution study. J Pediatr Hematol Oncol 36:e366–e370CrossRefPubMedPubMedCentral
11.
Williams NL, Rotondo RL, Bradley JA, Pincus DW, Fort JA, Wynn T, Morris CG, Mendenhall NP, Indelicato DJ (2016) Late effects after radiotherapy for childhood low-grade glioma. Am J Clin Oncol. doi:10.​1097/​COC.​0000000000000267​
12.
Nwachukwu CR, Youland RS, Chioreso C, Wetjen N, NageswaraRao A, Keating G, Laack NN (2015) Health related quality of life (HRQOL) in long term survivors of pediatric low grade gliomas (LGGs). J Neurooncol 121:599–607CrossRefPubMed
13.
Nageswara Rao AA, Packer RJ (2014) Advances in the management of low-grade gliomas. Curr Oncol Rep 16:398CrossRefPubMed
14.
Guerreiro Stucklin AS, Tabori U, Grotzer MA (2016) The changing landscape of pediatric low-grade gliomas: clinical challenges and emerging therapies. Neuropediatrics 47:70–83CrossRefPubMed
15.
Khatua S, Wang J, Rajaram V (2015) Review of low-grade gliomas in children—evolving molecular era and therapeutics insights. Childs Nerv Systm 31-643-652
16.
Raabe E, Kieran MW, Cohen KJ (2013) New strategies in pediatric gliomas: molecular advances in pediatric low-grade gliomas as a model. Clin Cancer Res 19:4553–4558CrossRefPubMedPubMedCentral
17.
Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN (1993) Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11:850–856PubMed
18.
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 86:747–754CrossRefPubMed
19.
Gnekow AK, Falkenstein F, von Hornstein S, Zwiener I, Berkefeld S, Bison B, Warmuth-Metz M, Hernáiz driever P, Sorensen N, Kortmann RD, Pietsch T, Faldum A (2012) Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology. Neuro Oncol 14:1265–1284CrossRefPubMedPubMedCentral
20.
Gnekow AK, Kandels D, Walker DA, Perilongo G, Grill J, Stokland T, Sehested AM, van Schouten AYN, de Paoli A, de Salvo GL (2014) Abstracts from the sixteenth international symposium on pediatric neuro-oncology: a randomized trial of intensification of induction chemotherapy within an 18 months treatment-strategy on tumor response at 24 weeks and progression-free-survival in pediatric low grade glioma (LGG). Preliminary results of the SIOP-LGG-2004-Working Group. Neuro Oncol 16:i60–i70CrossRef
21.
Genc DB, Canpolat C, Berrak SG (2012) Clinical features and management of carboplatin-related hypersensitivity reactions in pediatric low-grade glioma. Support Care Cancer 20:385–393CrossRefPubMed
22.
Massimino M, Spreafico F, Cefalo G, Riccardi R, Tesoro-Tess JD, Gandola L, Riva D, Ruggiero A, Valentini L, Mazza E, Genitori L, di Rocco C, Navarria P, Casanova M, Ferrari A, Luksch R, Terenziani M, Balestrini MR, Colosimo C, Fossati-Bellani F (2002) High response rate to cisplatin/etoposide regimen in children with low-grade glioma. J Clin Oncol 20:4209–4216CrossRefPubMed
23.
Massimino M, Spreafico F, Riva D, Biassoni V, Poggi G, Solero C, Gandola L, Genitori L, Modena P, Simonetti F, Potepan P, Casanova M, Meazza C, Clerici CA, Catania S, Sardi I, Giangaspero F (2010) A lower dose, lower toxicity regimen for childhood progressive low-grade glioma. J Neurooncol 100:65–71CrossRefPubMed
24.
Prados ME, Edwards MSB, Rabbitt J, Lamborn K, Davies RL, Levin VA (1997) Treatment of pediatric low-grade gliomas with a nistrosurea-based multiagent chemotherapy regimen. J Neurooncol 32:235–241CrossRefPubMed
25.
Mishra KK, Squire S, Lamborn K, Banerjee A, Gupta N, Wara WM, Prados MD, Berger MS, Haas-Kogan DA (2010) Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15 year update. J Neurooncol 100:121–127CrossRefPubMedPubMedCentral
26.
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 30:2641–2647CrossRefPubMedPubMedCentral
27.
Singh G, Wei XC, Hader W, Chan JA, Bouffet E, Lafay-Cousin L (2013) Sustained response of weekly vinblastine in 2 children with pilomyxoid astrocytoma associated with diencephalic syndrome. J Pediatr Hematol Oncol 35:e53–e56CrossRefPubMed
28.
Bouffet E, Jakacki R, Goldman S, Hargrave D, Hawkins C, Shroff M, Hukim J, Bartels U, Foreman N, Kellie S, Hilden J, Etzl M, Wilson B, Stephens D, Tabori U, Baruchel S (2012) Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol 30:1358–1363CrossRefPubMed
29.
30.
Cappellano AM, Petrilli AS, da Silva NS, Silva FA, Paiva PM, Cavalheiro S, Bouffet E (2015) Single agent vinorelbine in pediatric patients with progressive optic pathway glioma. J Neurooncol 121:405–412CrossRefPubMed
31.
Lashkari HP, Saso S, Moreno L, Athanasiou T, Zacharoulis S (2011) Using different schedules of temozolomide to treat low grade gliomas: systematic review of their efficacy and toxicity. J Neurooncol 1055:135–147CrossRef
32.
Gururangan S, Fisher MJ, Allen JC, Herndon JE, Quinn JA, Reardon DA, Vredenburgh JJ, Desjardins A, Phillips PC, Watral MA, Krauser JM, Friedman AH, Friedman HS (2007) Temozolomide in children with progressive low-grade glioma. Neuro Oncol 9:161–168CrossRefPubMedPubMedCentral
33.
Khaw SL, Coleman LT, Downie PA, Heath JA, Ashley DM (2007) Temozolomide in pediatric low grade glioma. Pediatr Blood Cancer 49:808–811CrossRefPubMed
34.
Nicholson HS, Kretschmar CS, Krailo M, Berstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH (2007) Phase II study of temozolomide in children and adolescents with recurrent central nervous system tumors. A report from the Children Oncology Group. Cancer 110:1542–1550CrossRefPubMed
35.
Kuo DJ, Weiner HL, Wissoff J, Miller DC, Knopp EA, Finlay JL (2003) Temozolomide is active in childhood, progressive, unresectable, low grade gliomas. J Pediatr Hematol Oncol 25:372–378CrossRefPubMed
36.
Packer RJ, Jakacki RI, Horn M, Rood B, Vezina G, MacDonald T, Fisher MJ, Cohen B (2009) Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan. Pediatr Blood Cancer 52:791–795CrossRefPubMed
37.
Hwang EI, Jakacki RI, Fisher MJ, Kilburn LB, Horn M, Vezina G, Rood BR, Packer RJ (2013) Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas. Pediatr Blood Cancer 60:776–782CrossRefPubMed
38.
Gururangan S, Fangusaro J, Young Poussaint T, McLendon RE, Onar-Thomas A, Wu S, Packer RJ, Banerjee A, Gilbertson RJ, Fahey F, Vajapeyam S, Jakacki R, Gajjar A, Goldman S, Pollack IF, Friedman HS, Boyett JM, Fouladi M, Kun LE (2014) Efficacy of bevacizumab plus irinotecan in children with recurrent low grade gliomas—a Pediatric Brain Tumor Consortium study. Neuro Oncol 16:310–317CrossRefPubMed
39.
Mirow C, Pietsch T, Berkefeld S, Kwiecien R, Warmuth-Metz M, Falkenstein F, Diehl B, von Hornstein S, Gnekow AK (2014) Children < 1 year show an inferior outcome when treated according to the traditional LGG treatment strategy: a report from the German multicenter trial HIT-LGG 1996 for children with low grade glioma (LGG). Pediatr Blood Cancer 61:457–463CrossRefPubMed
40.
von Hornstein S, Kortmann RD, Pietsch T, Emser A, Warmuth-Metz M, Soerensen N, Straeter R, Graf N, Thieme B, Gnekow AK (2011) Impact of chemotherapy on disseminated low-grade glioma in children and adolescents: report from the HIT-LGG 1996 trial. Pediatr Blood Cancer 56:1046–1054CrossRef
41.
Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A, Aldape K, Brat D, Collins VP, Eberhart C, Figarella-Branger D, Fuller GN, Giangaspero F, Giannini C, Hawkins C, Kleihues P, Korsunov A, Kros JM, Beatriz Lopes M, Ng HK, Ohgaki H, Paulus W, Pietsch T, Rosemblum M, Rushing E, Soylemezoglu F, Wiestler O, Wesseling P (2014) International Society of Neuropathology-Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24(5):429–435CrossRefPubMed
42.
Hernáiz Driever P, von Hornstein S, Pietsch T, Kortmann R, Warmuth-Metz M, Emser A, Gnekow AK (2010) Natural history and management of low-grade glioma in NF-1 children. J Neurooncol 100(2):199–207CrossRefPubMed
43.
Penman CL, Faulkner C, Lowis SP, Murian KM (2015) Current understanding of BRAF alterations in diagnosis, prognosis, and therapeutic targeting in pediatric low-grade gliomas. Front Oncol 5:Art 54. doi:10.​3389/​fonc.​2015.​00054
44.
Bar EE, Lin A, Tihan T, Burger PC, Eberhart CG (2008) Frequent gains al chromosome 7q34 involving BRAF in pilocytic astrocytoma. J Neuropathol Exp Neurol 67:878–887CrossRefPubMed
45.
Lin A, Rodriguez FJ, Karajjanis MA, Williams SC, Legault G, Zaqzaq D, Burger PC, Allen JC, Eberhart CG, Bar EE (2012) BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of two novel KIAA1549-BRAF fusion variants. J Neuropathol Exp Neurol 71:66–72CrossRefPubMedPubMedCentral
46.
Hawkins C, Walker E, Mohamed N, Zhang C, Jacob K, Shirinian M, Alon N, Khan D, Fried I, Scheinemann K, Tsangaris E, Dirks P, Tressler R, Bouffet E, Jabado N, Tabori U (2011) BRAF-KIAA1549 fusion predicts better clinical outcome in pediatric low-grade astrocytoma. Clin Can Res 17:4790–4798CrossRef
47.
Jacob K, Albrecht S, Sollier C, Faury D, Sader E, Montpetit A, Serre D, Hauser P, Garami M, Bognar L, Hanzely Z, Montes JL, Atkinson J, Farmer JP, Bouffet E, Hawkins C, Tabori U, Jabado N (2009) Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumors. Br J Can 101:722–733CrossRef
48.
Cin H, Meyer C, Janzarik WG, Lambert S, Jones DT, Jacob K, Benner A, Witt H, Remke M, Bender S, Falkenstein F, Van Anh TN, Olbrich H, von Deimling A, Pekrun A, Kulozik AE, Gnekow A, Scheurlen W, Witt O, Omran H, Jabado N, Collins VP, Brummer T, Marschalek R, Lichter P, Korshunov A, Pfister (2011) Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol 121:763–774CrossRefPubMed
49.
Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddaoumi 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 D, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW (2013) Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet 45(6):602–612CrossRefPubMedPubMedCentral
50.
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 BRAFV600E mutation in 1320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, gsnglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121:397–405CrossRefPubMed
51.
Dahiya S, Haydon DH, Alvarado D, Gurnett CA, Gutmann DH, Leonard JR (2013) BRAF(V600E) mutation is a negative prognosticator in pediatric ganglioglioma. Acta Neuropathol 125(6):901–910CrossRefPubMed
52.
Hassan B, Akcakanat A, Holder AM, Meric-Bernstam F (2013) Targeting the PI3 kinase (Akt/m-TOR signaling pathway. Surg Oncol Clin N Am 22(4):641–664CrossRefPubMed
53.
Rush S, Foreman N, Liu A (2013) Brainstem ganglioglioma successfully treated with vemurafenib. J Clin Oncol 31(e1):59–60
54.
55.
del Bufalo F, Carai A, Figà-Talamanca L, Pettorini B, Mallucci C, Giangaspero F, Antonelli M, Badiali M, Moi L, Bianco G, Cacchione A, Locatelli F, Ferretti E, Mastronuzzi A (2014) Response of recurrent BRAFV600E mutated ganglioglioma to Vemurafenib as single agent. J Transl Med 12:356CrossRefPubMedPubMedCentral
56.
Skrypek M, Foreman N, Guillaume D, Moertel C (2014) Pylomixoid astrocytoma treated successfully with vemurafenib. Ped Blood Can 61(11):2099CrossRef
57.
García MA, Solomon DA, Haas-Kogan DA (2016) Exploiting molecular biology for diagnosis and targeted management of pediatric low grade gliomas. Future Oncol 12(12):1493–1506
58.
Karajannis MA, Fisher MJ, Milla SS, Cohen KJ, Wissoff JH, Harter DH, Goldberg JD, Hochman T, Merkelson A, Bloom MC, Sievert AJ, Resnick AC, Dhall G, Jones DT, Korshunov A, Pfister SM, Eberhart CG, Zagzag D, Allen JC (2014) Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas. Neuro Oncol 16(10):1408–1416CrossRefPubMedPubMedCentral
59.
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 59:490–498CrossRefPubMed
60.
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 363:1801–1811CrossRefPubMed
61.
Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Khhrman 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 (2013) 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 381:125–132CrossRefPubMed
62.
Yalon M, Rood B, MacDonald TJ, McCowage G, Kane R, Constantini S, Packer RJ (2013) A feasibility and efficacy study of rapamycin and erlotinib for recurrent pediatric low-grade glioma (LGG). Ped Blood Can 60:71–76CrossRef
63.
Dubois SG, Shusterman S, Ingle AM, Ahern CH, Reid JM, Wu B, Baruchel S, Glade-Bender J, Ivy P, Grier HE, Adamson PC, Blaney SM (2011) Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors; a Children’s Oncology Group Study. Clin Cancer Res 17:5113–5122CrossRefPubMedPubMedCentral
Metadata
Title
Conventional chemotherapy and perspectives for molecular-based oncological treatment in pediatric hemispheric low-grade gliomas
Authors
María Baro Fernández
Vanesa Pérez Alonso
Publication date
01-10-2016
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 10/2016
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-016-3132-0

Other articles of this Issue 10/2016

Child's Nervous System 10/2016 Go to the issue

Special Annual Issue

Advanced MR imaging in hemispheric low-grade gliomas before surgery; the indications and limits in the pediatric age

Special Annual Issue

An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update

Special Annual Issue

Epilepsy surgery for pediatric low-grade gliomas of the cerebral hemispheres: neurosurgical considerations and outcomes

Special Annual Issue

Neurosurgical tools to extend tumor resection in pediatric hemispheric low-grade gliomas: iMRI

Special Annual Issue

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions

A.J. Raimondi ISPN Award

The relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children.