nach oben

Current Oncology Reports

Erschienen in:

01.08.2014 | Pediatric Oncology (S Epelman, Section Editor)

Advances in the Management of Low-Grade Gliomas

verfasst von: Amulya A. Nageswara Rao, Roger J. Packer

Erschienen in: Current Oncology Reports | Ausgabe 8/2014

Einloggen, um Zugang zu erhalten

Abstract

Low-grade gliomas (LGGs) represent the most common childhood brain tumors and are a histologically heterogenous group of tumors. Most LGGs are surgically resectable with excellent 10-year overall survival outcomes of more than 90 % with surgery alone. Tumors not amenable to surgical resection and those with an aggressive biology are more challenging to treat. Conventional radiotherapy is a more efficacious method of long-term tumor control than chemotherapy. However, radiation is associated with significant cognitive, endocrine, and cerebrovascular late effects, making chemotherapy an often-preferred modality over radiotherapy, especially in younger children. Multiple chemotherapy regimens have been evaluated over the past few decades with comparable survival outcomes and differing toxicity profiles. Newer regimens containing antiangiogenic agents also show promise. Recent molecular studies have implicated the BRAF oncogene, a key regulator of the MAPK pathway, and the AKT/mTOR pathway in pediatric LGG tumorigenesis. This has opened up promising new avenues for targeted therapy, with many agents currently under investigation.

Wisoff JH et al. Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children's Oncology Group. Neurosurgery. 2011;68(6):1548–54. Discussion 1554-5.PubMedCrossRef

Louis DN et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.PubMedCentralPubMedCrossRef

Rodriguez FJ et al. Pathological and molecular advances in pediatric low-grade astrocytoma. Annu Rev Pathol. 2013;8:361–79.PubMedCentralPubMedCrossRef

4.•

Bandopadhayay P, et al. Long-term outcome of 4,040 children diagnosed with pediatric low-grade gliomas: an analysis of the Surveillance Epidemiology and End Results (SEER) database. Pediatr Blood Cancer. 2014;61(7):1173–9. A large study of of 4,040 children showed that pediatric LGGs are associated with excellent long term survival with low likelihood of pedaitric LGG related death in adult survivors thereby emphazising the need for treatment strategies that will minimize long term sequelae.

Mirow C et al. 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. 2014;61(3):457–63.PubMedCrossRef

Qaddoumi I, Sultan I, Gajjar A. Outcome and prognostic features in pediatric gliomas: a review of 6212 cases from the Surveillance, Epidemiology, and End Results database. Cancer. 2009;115(24):5761–70.PubMedCentralPubMedCrossRef

Youland RS et al. Prognostic factors and survival patterns in pediatric low-grade gliomas over 4 decades. J Pediatr Hematol Oncol. 2013;35(3):197–205.PubMedCrossRef

Terashima K et al. Long-term outcome of centrally located low-grade glioma in children. Cancer. 2013;119(14):2630–8.PubMedCrossRef

Fisher PG et al. Outcome analysis of childhood low-grade astrocytomas. Pediatr Blood Cancer. 2008;51(2):245–50.PubMedCrossRef

10.

Gnekow AK et al. 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. 2012;14(10):1265–84.PubMedCentralPubMedCrossRef

11.

Pollack IF et al. Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg. 1995;82(4):536–47.PubMedCrossRef

12.

Gajjar A et al. Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital. J Clin Oncol Off J Am Soc Clin Oncol. 1997;15(8):2792–9.

13.

Steinbok P et al. Neurological morbidity of surgical resection of pediatric cerebellar astrocytomas. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg. 2013;29(8):1269–75.CrossRef

14.

Mishra KK et al. The role of up-front radiation therapy for incompletely resected pediatric WHO grade II low-grade gliomas. Neuro-Oncology. 2006;8(2):166–74.PubMedCentralPubMedCrossRef

15.

Fisher BJ et al. Results of a policy of surveillance alone after surgical management of pediatric low grade gliomas. Int J Radiat Oncol Biol Phys. 2001;51(3):704–10.PubMedCrossRef

16.

Merchant TE et al. Phase II trial of conformal radiation therapy for pediatric low-grade glioma. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(22):3598–604.CrossRef

17.

Armstrong GT et al. Survival and long-term health and cognitive outcomes after low-grade glioma. Neuro-Oncology. 2011;13(2):223–34.PubMedCentralPubMedCrossRef

18.

Grill J et al. Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol. 1999;45(3):393–6.PubMedCrossRef

19.

Epstein MA et al. Vascular malformation with radiation vasculopathy after treatment of chiasmatic/hypothalamic glioma. Cancer. 1992;70(4):887–93.PubMedCrossRef

20.

Merchant TE et al. Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(22):3691–7.CrossRef

21.

Ruge MI et al. Stereotactic brachytherapy with iodine-125 seeds for the treatment of inoperable low-grade gliomas in children: long-term outcome. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(31):4151–9.CrossRef

22.

Kirsch DG, Tarbell NJ. New technologies in radiation therapy for pediatric brain tumors: the rationale for proton radiation therapy. Pediatr Blood Cancer. 2004;42(5):461–4.PubMedCrossRef

23.

Packer RJ et al. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997;86(5):747–54.PubMedCrossRef

24.

Packer RJ et al. Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol Off J Am Soc Clin Oncol. 1993;11(5):850–6.

25.

Gururangan S et al. Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(13):2951–8.CrossRef

26.

Massimino M et al. High response rate to cisplatin/etoposide regimen in childhood low-grade glioma. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(20):4209–16.CrossRef

27.

Massimino M et al. A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma. J Neuro-Oncol. 2010;100(1):65–71.CrossRef

28.

Sardi I et al. Successful treatment with a low-dose cisplatin–etoposide regimen for patients with diencephalic syndrome. J Neuro-Oncol. 2012;109(2):375–83.CrossRef

29.

Laithier V et al. Progression-free survival in children with optic pathway tumors: dependence on age and the quality of the response to chemotherapy–results of the first French prospective study for the French Society of Pediatric Oncology. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21(24):4572–8.CrossRef

30.

Prados MD et al. Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. J Neuro-Oncol. 1997;32(3):235–41.CrossRef

31.

Mishra KK et al. Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update. J Neuro-Oncol. 2010;100(1):121–7.CrossRef

32.•

Bouffet E et al. Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(12):1358–63. This phase II study demonstrated that vinblastine can be considered as an alternative to radiotherapy in patients with recurrent LGGs that have failed first-line chemotherapy.CrossRef

33.

Jakacki RI et al. A phase 1 study of vinblastine in combination with carboplatin for children with low-grade gliomas: a Children's Oncology Group phase 1 consortium study. Neuro-Oncology. 2011;13(8):910–5.PubMedCentralPubMedCrossRef

34.

Villanueva MT. Pediatric oncology: vinblastine in low-grade glioma. Nat Rev Clin Oncol. 2012;9(5):248.PubMedCrossRef

35.

Khaw SL et al. Temozolomide in pediatric low-grade glioma. Pediatr Blood Cancer. 2007;49(6):808–11.PubMedCrossRef

36.

Gururangan S et al. Temozolomide in children with progressive low-grade glioma. Neuro-Oncology. 2007;9(2):161–8.PubMedCentralPubMedCrossRef

37.

Liu R et al. Quality of life in low-grade glioma patients receiving temozolomide. Neuro-Oncology. 2009;11(1):59–68.PubMedCentralPubMedCrossRef

38.

Sutton LN et al. Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery. J Neurosurg. 1995;83(4):583–9.PubMedCrossRef

39.••

Ater JL et al. 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 Off J Am Soc Clin Oncol. 2012;30(21):2641–7. This randomized controlled trial of the carboplatin/vincristine and thioguanine/procarbazine/lomustine and vincristine showed that both regimens are effective in the treatment of LGGs and the differences in the toxicity profiles may influence physician choice of treatment regimens.CrossRef

40.

Sie M et al. Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma? Neuropathol Appl Neurobiol. 2010;36(7):636–47.PubMedCrossRef

41.

Packer RJ et al. Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan. Pediatr Blood Cancer. 2009;52(7):791–5.PubMedCrossRef

42.•

Hwang EI et al. Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas. Pediatr Blood Cancer. 2013;60(5):776–82. This study showed that antiangiogenic agents can be used in the treatment of LGGs with rapid clinical responses but however may not result in sustained stable disease.PubMedCrossRef

43.••

Gururangan S et al. Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas–a Pediatric Brain Tumor Consortium study. Neuro-Oncology. 2014;16(2):310–7. This phase II study showed that a combination of antiangiogenic agent bevacizumab and irinotecan can result in sustained disease control in some children with recurrent LGGs.PubMedCrossRef

44.

Avery RA et al. Marked recovery of vision in children with optic pathway gliomas treated with bevacizumab. JAMA Ophthalmol. 2014;132(1):111–4.PubMedCrossRef

45.

Nageswara Rao AA et al. Biologically targeted therapeutics in pediatric brain tumors. Pediatr Neurol. 2012;46(4):203–11.PubMedCentralPubMedCrossRef

46.

Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev. 2010;24 Suppl 1:S13–9.PubMedCrossRef

47.

Warren KE et al. 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 Off J Am Soc Clin Oncol. 2011;29(3):324–9.CrossRef

48.

Gottfried ON, Viskochil DH, Couldwell WT. Neurofibromatosis type 1 and tumorigenesis: molecular mechanisms and therapeutic implications. Neurosurg Focus. 2010;28(1):E8.PubMedCrossRef

49.

Hawkins C et al. BRAF-KIAA1549 fusion predicts better clinical outcome in pediatric low-grade astrocytoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(14):4790–8.CrossRef

50.

Jones DT et al. Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma. Oncogene. 2009;28(20):2119–23.PubMedCentralPubMedCrossRef

51.

Cin H et al. Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol. 2011;121(6):763–74.PubMedCrossRef

52.

Dougherty MJ et al. Activating mutations in BRAF characterize a spectrum of pediatric low-grade gliomas. Neuro-Oncology. 2010;12(7):621–30.PubMedCentralPubMedCrossRef

53.

Janzarik WG et al. Further evidence for a somatic KRAS mutation in a pilocytic astrocytoma. Neuropediatrics. 2007;38(2):61–3.PubMedCrossRef

54.

Morita H, Nagai R. Vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;365(15):1448. Author reply 1450.PubMedCrossRef

55.

Farina-Sarasqueta A et al. The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2010;21(12):2396–402.CrossRef

56.•

Schindler G et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 2011;121(3):397–405. This large study demonstrated the high frequency of BRAF V600E mutations in different LGGs, thereby opening up the possibility of using targeted therapy in BRAF V600E mutated tumors.PubMedCrossRef

57.

Horbinski C et al. Interplay among BRAF, p16, p53, and MIB1 in pediatric low-grade gliomas. Neuro-Oncology. 2012;14(6):777–89.PubMedCentralPubMedCrossRef

58.

Chapman PB et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.PubMedCentralPubMedCrossRef

59.

Long GV et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(11):1087–95.PubMedCrossRef

60.

Hauschild A et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–65.PubMedCrossRef

61.

Kolar GR et al. Neoadjuvant treatment of a solitary melanoma brain metastasis with vemurafenib. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(3):e40–3.CrossRef

62.

McArthur GA et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014;15(3):323–32.PubMedCrossRef

63.

West ES, Williams VL, Morelli JG. Vemurafenib-induced neutrophilic panniculitis in a child with a brainstem glioma. Pediatr Dermatol. 2014. doi:10.1111/pde.12316.PubMed

64.

Hatzivassiliou G et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature. 2010;464(7287):431–5.PubMedCrossRef

65.

Heidorn SJ et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell. 2010;140(2):209–21.PubMedCentralPubMedCrossRef

66.

Sievert AJ et al. Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas. Proc Natl Acad Sci U S A. 2013;110(15):5957–62.PubMedCentralPubMedCrossRef

67.•

Karajannis MA, Fisher MJ, Milla SS, Cohen KJ, Legault G, Wisoff JH, et al. Phase II study of sorafenib in children with recurrent/progressive low-grade astrocytomas. Neuro-Oncology. 2012; 14(supplement 6). This phase II study showed that sorefanib may be associated with tumor progression through paradoxical ERK activation.

68.

Lito P et al. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell. 2012;22(5):668–82.PubMedCentralPubMedCrossRef

69.

Poulikakos PI et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011;480(7377):387–90.PubMedCentralPubMedCrossRef

70.

Prabowo AS et al. BRAF V600E mutation is associated with mTOR signaling activation in glioneuronal tumors. Brain Pathol. 2014;24(1):52–66.PubMedCrossRef

71.

Prahallad A et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483(7387):100–3.PubMedCrossRef

72.

Rush S, Foreman N, Liu A. Brainstem ganglioglioma successfully treated with vemurafenib. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(10):e159–60.CrossRef

73.

Kolb EA et al. Initial testing (stage 1) of AZD6244 (ARRY-142886) by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2010;55(4):668–77.PubMedCentralPubMedCrossRef

74.

Bid HK et al. Development, characterization, and reversal of acquired resistance to the MEK1 inhibitor selumetinib (AZD6244) in an in vivo model of childhood astrocytoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2013;19(24):6716–29.CrossRef

75.

Manning BD, Cantley LC. United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling. Biochem Soc Trans. 2003;31(Pt 3):573–8.PubMedCrossRef

76.

Johannessen CM et al. The NF1 tumor suppressor critically regulates TSC2 and mTOR. Proc Natl Acad Sci U S A. 2005;102(24):8573–8.PubMedCentralPubMedCrossRef

77.

Jentoft M et al. Phenotypic variations in NF1-associated low grade astrocytomas: possible role for increased mTOR activation in a subset. Int J Clin Exp Pathol. 2010;4(1):43–57.PubMedCentralPubMed

78.

Brundage ME et al. MAF mediates crosstalk between Ras-MAPK and mTOR signaling in NF1. Oncogene. 2014. doi:10.1038/onc.2013.506.PubMed

79.

Kaul A et al. Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner. Genes Dev. 2012;26(23):2561–6.PubMedCentralPubMedCrossRef

80.

Hutt-Cabezas M et al. Activation of mTORC1/mTORC2 signaling in pediatric low-grade glioma and pilocytic astrocytoma reveals mTOR as a therapeutic target. Neuro-Oncology. 2013;15(12):1604–14.PubMedCrossRef

81.

Franz DN et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006;59(3):490–8.PubMedCrossRef

82.

Franz DN. Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex. Biologics Targets Ther. 2013;7:211–21.CrossRef

83.••

Krueger DA et al. Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma. Neurology. 2013;80(6):574–80. This study showed that everolimus is safe and effective in the treatment of SEGAs in patients 3 years and older with TS.PubMedCentralPubMedCrossRef

84.

Franz DN et al. 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(9861):125–32.PubMedCrossRef

85.•

Kieran M, Yao X, Macy M, Geyer R, Cohen K, MacDonald T, et al. A prospective multi-institutional phase II study of everolimus (RAD001), a mTOR inhibitor, in pediatric patients with recurrent or progressive low-grade gliomas. A POETIC consortium trial. Pediatr Blood Cancer. 2013;60(S3):19. This study showed that everolimus is well-tolerated and maybe effective in the treatment of pediatric recurrent LGGs.

86.

Yalon M et al. A feasibility and efficacy study of rapamycin and erlotinib for recurrent pediatric low-grade glioma (LGG). Pediatr Blood Cancer. 2013;60(1):71–6.PubMedCrossRef

87.

Saurez G et al. Clinical experience with nimotuzumab in cuban pediatric patients with brain tumors, 2005 to 2007. MEDICC Rev. 2009;11(3):27–33.PubMed

88.••

Zhang J et al. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet. 2013;45(6):602–12. Whole-genome sequencing has helped identify multiple genomic alterations in 151 pediatric LGGs and potential therapeutic targets.PubMedCentralPubMedCrossRef

Titel: Advances in the Management of Low-Grade Gliomas
verfasst von: Amulya A. Nageswara Rao
Roger J. Packer
Publikationsdatum: 01.08.2014
Verlag: Springer US
Erschienen in: Current Oncology Reports / Ausgabe 8/2014
Print ISSN: 1523-3790
Elektronische ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-014-0398-9

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Advances in the Management of Low-Grade Gliomas

Abstract

Neu im Fachgebiet Onkologie

Blutdrucksenkung könnte Uterusmyome verhindern

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Update Onkologie

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2014

Post-Treatment Imaging Changes in Primary Brain Tumors

Cardiotoxicity of Antineoplastic Agents: What Is the Present and Future Role for Imaging?

Revisiting Oxaliplatin-based Regimens for Advanced Hepatocellular Carcinoma

Imaging Mimics of Primary Malignant Tumors of the Central Nervous System (CNS)

Advances in Therapy for Pediatric Sarcomas

Neu im Fachgebiet Onkologie

Blutdrucksenkung könnte Uterusmyome verhindern

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Update Onkologie