Abstract
Gliomas are the most common central nervous system neoplasms affecting children and can be both high- and low-grade. Paediatric low-grade glioma may be either World Health Organization grade I or grade II. Despite being classified as grade II diffuse astrocytoma, these neoplasms arising in children are distinct clinically and molecularly from their adult counterparts. They do not tend to progress to higher grade lesions and only rarely harbour an IDH mutation. Here, we review the clinical, histologic and molecular features of paediatric grade II diffuse glioma, highlighting their diagnostic criteria, prevalence across brain locations, their most common molecular features and how to test for them, and lastly the current status of therapeutic options available for their treatment.
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Kaatsch P (2010) Epidemiology of childhood cancer. Cancer Treat Rev 36(4):277–285
Arora RS, Alston RD, Eden TO, Estlin EJ, Moran A, Birch JM (2009) Age-incidence patterns of primary CNS tumors in children, adolescents, and adults in England. Neuro-oncology 13:223–234
Qaddoumi I, Sultan I, Gajjar A (2009) Outcome and prognostic feature in pediatric gliomas: a review of 6212 cases from the surveillance, epidemiology and end results (SEER) database. Cancer 115(24):5761–5770
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK et al (2016) The 2016 world health organization classification of tumor of the central nervous system: a summary. Acta Neuropathol 131:803–820
Van den Bent MJ (2010) Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician’s perspective. Acta Neuropathol 120(3):297–304
Bandopadhayay P, Bergthold G, London WB, Goumnerova LC, Morales La Madrid A, Marcus KJ et al (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(7):1173–1179
Stokland T, Liu JF, Ironside JW, Ellison DW, Taylor R, Robinson KJ et al (2010) A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study. Neuro-oncology 12(12): 1257–1268.
Claes A, Idema AJ, Wesseling P (2007) Diffuse glioma growth: a guerilla war. Acta Neuropathol 114(5):443–458
Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J et al (2015) Brain tumour cells interconnect to a functional and resistant network. Nature 528(7580):93–98
Peiffer J, Kleihues P (1999) Hans-Joachim Scherer (1906–1945), pioneer in glioma research. Brain Pathol 9:241–245
Perry A, Wesseling P (2016) Histologic classification of gliomas. Handb Clin Neurol 134:71–95
Wesseling P, van den Bent M, Perry A (2015) Oligodendroglioma: pathology, molecular mechanisms and markers. Acta Neuropathol 129:809–827
Freeman C, Farmer JP, Montes J (1998) Low-grade astrocytomas in children: evolving management strategies. Int J Radiat Oncol Biol Phys 41(5):979–987
Sievert A, Fisher M (2009) Pediatric low-grade gliomas. J Child Neurol 24(11):1397–1408
Zhang J, Wu G, Miller C, Tatevossian R, Dalton J, Tang B et al (2013) Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet 45(6):602–612
Bandopadhayay P, Ramkissoon L, Jain P, Bergthold G, Wala J, Zeid R et al (2016) MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat Genet 48(3):273–282
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321(5897):1807–1812
Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116(6):597–602
Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP et al (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30(1):7–11
Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A et al (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1010 diffuse gliomas. Acta Neuropathol 118(4):469–474
Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Seo SI et al (2009) Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 125(2):353–355
Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27(25):4150–4154
Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174(4):1149–1153
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–773
De Carli E, Wang X, Puget S (2009) IDH1 and IDH2 mutations in glioma. N Engl J Med 360(21):2248
Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Lyons-Weiler MA, LaFramboise WA et al (2011) IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children’s Oncology Group. Child’s Nerv Syst 27(1):87–94
Kannan K, Inagaki A, Silber J, Gorovets D, Zhang J, Kastenhuber ER et al (2012) Whole-exome sequencing identifies ATRX mutations as a key molecular determinant in lower-grade glioma. Oncotarget 3(10):1194–1203
Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA, Fontebasso AM et al (2012) Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumours carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol 124(5):615–625.
Okita Y, Narita Y, Miyakita Y, Ohno M, Matsushita Y, Fukushima S et al (2012) IDH1/2 mutation is a prognostic marker for survival and predicts response to chemotherapy for grade II gliomas concomitantly treated with radiation therapy. Int J Oncol 41:1325–1336
Hartmann C, Hentschel B, Tatagiba M, Schramm J, Schnell O, Seidel C et al (2011) Molecular markers in low-grade gliomas: predictive or prognostic? Clin Cancer Res 17:4588–4599
Houillier C, Wang X, Kaloshi G, Mokhtari K, Guillevin R, Laffaire J et al (2010) IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology 75:1560–1566
Metellus P, Coulibaly B, Colin C, de Paula AM, Vasiljevic A, Taieb D et al (2010) Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis. Acta Neuropathol 120:719–729
Mukasa A, Takayanagi S, Saito K, Shibahara J, Tabei Y, Furuya K et al (2012) Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients. Cancer Sci 103:587–592
Kim YH, Nobusawa S, Mittelbronn M, Paulus W, Brokinkel B, Keyvani K et al (2010) Molecular classification of low-grade diffuse gliomas. Am J Pathol 177:2708–2714
Jaeckle KA, Decker PA, Ballman KV, Flynn PJ, Giannini C, Scheithauer BW et al (2011) Transformation of low grade glioma and correlation with outcome: an NCCTG database analysis. J Neurooncol 104(1):253–259
Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601
Kato Y, Jin G, Kuan CT, McLendon RE, Yan H, Bigner DD (2009) A monoclonal antibody IMab-1 specifically recognizes IDH1R132H, the most common glioma-derived mutation. Biochem Biophys Res Commun 390:547–551
Arita H, Narita Y, Yoshida A et al (2015) Brain Tumor Pathol (2015). IDH1/2 mutation detection in gliomas. Brain Tumor Pathol. 32(2): 78–89
Okamoto Y, Di Patre PL, Burkhard C, Horstmann S, Jourde B, Fahey M et al (2004) Population-based study on the incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol 108(1):49–56
Watanabe T, Nakamura M, Kros JM, Burkhard C, Yonekawa Y, Kleihues P et al (2002) Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytoma. Acta Neuropathol 103(3):267–275
Dougherty MJ, Santi M, Brose MS, Ma C, Resnick AC, Sievert AJ et al (2010) Activating mutations in BRAF characterize a spectrum of pediatric low-grade gliomas. Neuro-oncology 12(7):621–630
Horbinski C, Nikiforova MN, Hagenkord JM, Hamilton RL, Pollack IF (2012) Interplay among BRAF, p16, p53, and MIB1 in pediatric low-grade gliomas. Neuro-oncology 14(6):777–789
Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioma. Nature 482(7384):226–231
Wu G, Diaz AK, Paugh BS, Ranklin SL, Ju B, Li Y et al (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46(5):444–450
Cheng Y, Ng HK, Zhang SF, Ding M, Pang JC, Zheng J et al (1999) Genetic alterations in pediatric high-grade astrocytomas. Hum Pathol 30(11):1284–1290
Antonelli M, Buttarelli FR, Arcella A, Nobusawa S, Donofrio V, Oghaki H et al (2010) Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high grade glioma. J Neurooncol 99(2):209–215
Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H (1996) Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6:217–224
Ichimura K, Bolin MB, Goike HM, Schmidt EE, Moshref A, Collins VP (2000) Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res 60:417–424
Vojtesek B, Bartek J, Midgley CA, Lane DP (1992) An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods 151(1–2):237–244
Maurer G, Tarkowski B, Baccarini M (2011) Raf kinases in cancer-roles and therapeutic opportunities. Oncogene 30:3477–3488
Bar EE, Lin A, Tihan T, Burger PC, Eberhart CG (2008) Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma. J Neuropathol Exp Neurol 67:878–887
Pfister S, Janzarik WG, Remke M, Ernst A, Werft W, Becker N et al (2008) BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 118:1739–1749
Sievert AJ, Jackson EM, Gai X, Hakonarson H, Judkins AR, Resnick AC et al (2009) Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene. Brain Pathol 19:449–458
Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K et al (2008) Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–8677
Schiffman JD, Hodgson JG, VandenBerg SR, Flaherty P, Polley MY, Yu M et al (2010) Oncogenic BRAF mutation with CDKN2A inactivation is characteristic of a subset of pediatric malignant astrocytomas. Cancer Res 70:512–519
Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Harold-Mende C et al (2011) Analysis of BRAFV600E in 1320 nervous system tumours reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma, and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121:397–405
Tatevossian RD, Lawson AR, Forshew T, Hindley GF, Ellison DW, Sheer D (2010) MAPK pathway activation and the origins of pediatric low-grade astrocytomas. J Cell Physiol 222(3):509–514
Lassaletta A, Mistry M, Arnoldo A, Ryall S, Guereirro Strucklin A, Krishnatry R et al (2016) Relationship of BRAF V600E and associated secondary mutations on survival rate and response to conventional therapies in childhood low-grade glioma. J Clin Oncol 34:suppl; abstr 10509
Hawkins C, Walker E, Mohamed N, Zhang C, Jacob K, Shirinian M et al (2011) BRAF-KIAA1549 fusion predicts better clinical outcome in pediatric low-grade astrocytoma. Clin Cancer Res 17(14):4790–4798
Ida CM, Lambert SR, Rodriguez FJ, Voss JS, McCann BE, Seys AR et al (2012) BRAF alterations are frequent in cerebellar low-grade astrocytomas with diffuse growth pattern. J Neuropathol Exp Neurol 71:631–639
Forshew T, Tatevossian RG, Lawson AR, Ma J, Neale G, Ogunkolade BW et al (2009) Activation of the ERK/MAPK pathway: a signature genetic defect in posterior fossa pilocytic astrocytomas. J Pathol 218:172–181
Basto D, Trovisco V, Lopes JM, Martins A, Pardal F, Soares P et al (2005) Mutation analysis of B-RAF gene in human gliomas. Acta Neuropathol 109:207–210
Knobbe CB, Reifenberger J, Reifenberger G (2004) Mutation analysis of the Ras pathway genes NRAS, HRAS, KRAS and BRAF in glioblastomas. Acta Neuropathol 108:467–470
Dias-Santagata D, Lam Q, Vernovsky K, Vena N, Lennerz JK, Borger DR et al (2011) BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. PLoS ONE 6:17948
Lin A, Rodriguez FJ, Karajannis MA, Williams SC, Legault G, Zagzag D et al (2012) BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants. J Neuropathol Exp Neurol 71:66–72
Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H et al (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405
Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M et al (2012) Dabrafenib in BRAF mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. The Lancet 380(9839):358–365
Kiernan MW (2014) Targeting BRAF in pediatric brain tumors. Am Soc Clin Oncol Educ Book 2014:E436–E340
Karajannis MA, Legault G, Fisher MJ, Milla SS, Cohen KJ, Wisoff JH et al (2014) Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytoma. Neuro-oncology 16(10):1408–1416
Capper D, Preusser M, Habel A, Sahm F, Ackermann U, Schindler G et al (2011) Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol 122:11–19
Tian Y, Rich BE, Vena N, Craig JM, Macconaill LE, Rajaram V et al (2011) Detection of KIAA1549-BRAF fusion transcripts in formalin-fixed paraffin-embedded pediatric low-grade gliomas. J Mol Diagn 13(6): 669–677
Ryall S, Krishnatry R, Arnoldo A, Buczkowicz P, Mistry M, Siddaway R (2016) Targeted detection of genetic alternations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in pediatric thalamic glioma. Acta Neuropathol Commun 4(1):93
Liggett W, Sidransky D (1998) Role of the p16 tumor suppressor gene in cancer. J Clin Oncol 16(3):1197–1206
Ruas M, Peter G. (1998) The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta. 1378(2):115–177
Quelle DE, Zindy F, Ashmun RA, Sherr CJ (1995) Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83:993–1000
Ivanchuk SM, Mondal S, Dirks PB, Rutka JT (2001) The INK4A/ARF locus: role in cell cycle control and apoptosis and implications for glioma growth. J Neurooncol 51:219–229
Bax DA, Mackay A, Little SE, Carvalho D, Viana-Pereira M, Tamber N et al (2010) A distinct spectrum of copy number aberrations in pediatric high-grade gliomas. Clin Cancer Res 16(13):3368–3377
Paugh BS, Broniscer A, Qu C, Miller CP, Zhang J, Tatevossian RG et al (2011) Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29(30):3999–4006
Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J et al (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28(18):3061–3068
Rodriguez EF, Scheithauer BW, Giannini C, Rynearson A, Cen L, Hoesley B et al (2011) PI3K/AKT pathway alterations are associated with clinically aggressive and histologically anaplastic subsets of pilocytic astrocytoma. Acta Neuropathol 121(3):407–420
Horbinski C, Hamilton RL, Nikiforov Y, Pollack IF (2010) Association of molecular alterations, including BRAF, with biology and outcome in pilocytic astrocytomas. Acta Neuropathol 119:641–649
Broniscer A, Baker SJ, West AN, Fraser MM, Proko E, Kocak M et al (2007) Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. J Clin Oncol 25:682–689
Mistry M, Zhukova N, Merico D, Rakopoulos P, Krishnatry R, Shago M et al (2015) BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high grade glioma. J Clin Oncol 33(9):1015–1022
Raabe EH, Lim KS, Kim JM, Meeker A, Mao XG, Nikkhah G et al (2011) BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model. Clin Cancer Res 17(11):3590–3599
Perry A, Nobori T, Ru N, Anderl K, Borell TJ, Mohapatra G et al (1997) Detection of p16gene deletions in gliomas: a comparison of fluorescence in situ hybridization (FISH) versus quantitative PCR. J Neuropathol Exp Neurol 56(9):999–1008
Chung CT, Santos Gda C, Hwang DM, Ludkovski O, Pintilie M, Squire JA et al (2010) FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma. J Clin Pathol 63(7):630–634
Purkait S, Jha P, Sharma M, Suri V, Sharma M, Kale S et al (2013) CDKN2A deletion in pediatric versus adult glioblastomas and predictive value of p16 immunohistochemistry. Neuropathology 33(4):405–412
Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C et al (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22(4):425–437
Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253
Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffett E et al (2012) K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124(3):439–447
Orillac C, Thomas C, Dastagirzada Y, Hildago ET, Golfinos JG, Zagzag D. (2016) Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation. Acta Neuropathol Commun 4(1):84
Gessi M, Capper D, Sahm F, Huang K, von Deimling A, Tippelt S et al (2016) Evidence of H3 K27M mutations in posterior fossa ependymomas. Acta Neuropathol 132(4):635–637
Gessi M, Gielen GH, Dreschmann V, Waha A, Pietsch T (2015) High frequency of H3F3A (K27M) mutations characterizes pediatric and adult high-grade gliomas of the spinal cord. Acta Neuropathol 130(3):435–437
Buczkowicz P, Bartels U, Bouffett E, Becher O, Hawkins C (2014) Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications. Acta Neuropathol 128(4):573–581
Bechet D, Gielen GG, Korshunov A, Pfister SM, Rousso C, Faury D et al (2014) Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas. Acta Neuropathol 128(5):733–741
Venneti S, Santi M, Felicella MM, Yarilin D, Phillips JJ, Sullivan LM et al. A sensitive and specific histopathologic prognostic marker for H3F3A K27M mutant pediatric glioblastomas. Acta Neuropathol 128(5):743–753
Tatevossian RG, Tang B, Dalton J, Forshew T, Lawson A, Ma J et al (2010) MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas. Acta Neuropathol 120(6):731–743
Ramkissoon L, Horowitz P, Craig J, Ramkissoon S, Rich B, Schumacher S et al (2013) Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1. Proc Natl Acad Sci 110(20):8188–8193
Rand V, Huang J, Stockwell T, Ferriera S, Buzko O, Levy S et al (2005) Sequence survey of receptor tyrosine kinases reveals mutations in glioblastoma. Proc Natl Acad Sci 102(40):14344–14349
Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R, Castano A et al (2012) Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337(6099):1231–1235
Jones D, Hutter B, Jager N, Korshunov A, Kool M, Warnatz HJ et al (2013) Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat Genet 45(8):927–932
Becker A, Scapulatempo-Neto C, Carloni A, Paulino A, Sheren J, Aisner D et al (2015) KIAA1549:BRAF gene fusion and FGFR1 hotspot mutations are prognostic factors in pilocytic astrocytomas. J Neuropathol Exp Neurol 74(7):743–754
Merchant TE, Conklin HM, Wu S, Lustig RH, Xiong X (2009) Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits. J Clin Oncol 27:3691–3697
Krishnatry R, Zhukova N, Guerreiro Strucklin A, Pole J, Mistry M, Fried I et al (2016) Clinical and treatment factor determining long-term outcomes for adult survivors of childhood low-grade glioma: a population-based study. Cancer 122(8):1261–1269
Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR et al (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(21):2641–2647
Gnekow AK, Falkenstein F, von Hornstein S, Zwiener I, Berkefeld S, Bison B et al (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-oncology 14(10):1265–1284
Chintagumpala M, Eckel SP, Krailo M, Morris M, Adesina A, Packer R et al (2015) A pilot study using carboplatin, vincristine, and temozolomide in children with progressive/symptomatic low-grade glioma: a Children’s Oncology Group study. Neuro-oncology 17(8):1132–1138
Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D et al (2007) Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer 110(7):1542–1550
Bouffett E, Jakacki R, Goldman S, Hargrave D, Hawkins C, Shroff M, et.al (2012) Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol 30(12):1358–1363
Lassaletta A, Scheinemann K, Zelcer SM, Hukin J, Wilson BA, Jabado N. (2016) Phase II weekly vinblastine for chemotherapy-naïve children with progressive low-grade glioma: a Canadian pediatric brain tumor consortium study. J Clin Oncol 34 3537–3543
Warren KE, Goldman S, Pollack IF, Fangusaro J, Schaiguevich P, Stewart CF et al (2011) Phase I trial of lenalidomide in pediatric patients with recurrent, refractory, or progressive primary CNS tumors: pediatric brain tumor consortium study PBTC-018. J Clin Oncol 29(3):324–329
Gururangan S, Fangusaro J, Poussaint TY, McLendon RE, Onar-Thomas A, Wu S et al (2014) Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas–a pediatric brain tumor consortium study. Neuro-oncology 16(2):310–317
Lutz M, Kapp M, Einsele H, Grigoleit GU, Mielke S (2014) Improvement of quality of life in patients with steroid-refractory chronic graft-versus-host disease treated with the mTOR inhibitor everolimus. Clin Transplant 28(12):1410–1415
Kieran MW, Yao X, Macy M, Leary S, Cohen K, MacDonald T et al (2014) A prospective multi-institutional phase II study of everolimus (RAD001), an mTor inhibitor, in pediatric patients with recurrent or progressive low-grade glioma. A POETIC consortium trial. Pediatr Blood Cancer 60:19–20
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Ryall, S., Tabori, U. & Hawkins, C. A comprehensive review of paediatric low-grade diffuse glioma: pathology, molecular genetics and treatment. Brain Tumor Pathol 34, 51–61 (2017). https://doi.org/10.1007/s10014-017-0282-z
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DOI: https://doi.org/10.1007/s10014-017-0282-z