Abstract
Pediatric malignant gliomas represent a heterogeneous group of tumors. This publication reviews data from the first three HIT-GBM® protocols. One important question is whether it makes sense to include both histologically confirmed high-grade glial tumors (HGG), and radiologically confirmed diffuse intrinsic pontine gliomas in a single study. Three-hundred-and ten patients (173 male, median age 10.0 years) were enrolled. Tumor locations were cerebral hemispheres: 80, basal ganglia: 38, pons: 134, non-pontine brain stem: 14, cerebellum: 14, spinal: 8, and overlapping areas: 22. Surgical resection was complete in 49, subtotal in 35, partial in 58, biopsy in 99, and no surgery in 69 cases. One-hundred-and twenty-three cases corresponded to WHO grade IV, 101 to III, and 15 to I/II. Two-hundred-and twenty-eight patients could be evaluated for response: CR: 8, PR: 32, SD: 116, and PD: 72. Median overall survival time was 1.03 years, and median event free survival was 0.54 years. Five year OS-rate was 10.28 ± 2.1%. In the total database, tumor location, grading, and extent of surgical resection were prognostic factors, but the relevance differed in location subgroups with no relevance for sex, histological grading or extend of surgical resection in pontine tumors. Possible prognostic factors were not distributed homogeneously. Pontine tumors differed from cerebral hemisphere tumors concerning the frequency of previous diseases, the age at diagnosis (median age pons 7.9 years versus cerebral hemispheres 11.4 years), and the frequency of WHO grade III versus Grade IV (III:IV = 1.6 for pons, and 0.7 for cerebral hemispheres). We conclude that the biology of pontine glioma differs significantly from other HGG, and clinical studies should be separate with different endpoints.
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References
Bouffet E, Khelfaoui F, Philip I, Biron P, Brunat-Mentigny M, Philip T (1997) High-dose carmustine for high-grade gliomas in childhood. Cancer Chemother Pharmacol 39(4):376–379
Estlin EJ, Lashford L, Ablett S, Price L, Gowing R, Gholkar A, Kohler J,Lewis IJ, Morland B, Pinkerton CR, Stevens MC, Mott M, Stevens R, Newell DR,Walker D, Dicks-Mireaux C, McDowell H, Reidenberg P, Statkevich P, Marco A, Batra V, Dugan M, Pearson AD (1998) Phase I study of temozolomide in paediatric patients with advanced cancer. Br J Cancer 78(5):652–661
Liu L, Vapiwala N, Munoz LK, Winick NJ, Weitman S, Strauss LC, Frankel LS, Rosenthal DI (2001) A phase I study of cranial radiation therapy with concomitant continuous infusion paclitaxel in children with brain tumors. Med Pediatr Oncol 37(4):390–392
Broniscer A, Gajjar A (2004) Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist 9(2):197–206
Donaldson SS, Laningham F, Fisher PG (2006) Advances toward an understanding of brainstem gliomas. J Clin Oncol 24(8):1266–1272
Kramm CM, Wagner S, Van Gool S, Schmid HJ, Sträter R, Gnekow A, Rutkowski S, Wolff JEA (2006) Improved survival after gross total resection of primary and relapsed malignant gliomas in pediatric patients. Anticancer Res 26(5B):3773–3779
Sposto R, Ertel IJ, Jenkin RD, Boesel CP, Venes JL, Ortega JA, Evans AE, Wara W, Hammond D (1989) The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. J Neurooncol 7(2):165–177
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) European organisation for research and treatment of cancer brain tumor and radiotherapy groups; national cancer institute of Canada clinical trials group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996
Albright AL, Packer RJ, Zimmerman R, Rorke LB, Boyett J, Hammond GD (1993) Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the children’s cancer group. Neurosurgery 33:1026–1029
Wagner S, Warmuth-Metz M, Gnekow A, Sträter R, Rutkowski S, Jorch N, Schmid H-J, Berthold F, Graf N, Peters O, Wolff JEA (2006) Treatment options of pontine gliomas: a retrospective analysis of the HIT-GBM data base. J Neurooncol 79(3):281–287
Wolff JE, Wagner S, Sindichakis M, Pietsch T, Gnekow A, Kortmann RD, Sträter R, Kühl J (2002) Simultaneous radiochemotherapy in pediatric patients with high-grade glioma: a phase I study. Anticancer Res 22(6B):3569–3572
Wolff JEA, Boos J, Krähling KH, Jürgens H (1996) Second temporal remission in a malignant glioma with trofosfamide and etoposide: a case report. Klin Padiatr 208:190–192
Wolff JE, Westphal S, Mölenkamp G, Gnekow A, Warmuth-Metz M, Rating D, Kühl J (2002) Treatment of pediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87(9):945–949
Wolff JEA, Gnekow A, Kortmann RD, Kühl J, Urban C, Graf N (2002) Preradiation Chemotherapy for pediatric patients with high-grade Glioma. Cancer 94:264–271
Wolff JEA, Mölenkamp G, Westphal S, Pietsch T, Gnekow A, Kortmann RD, Kühl J (2000) Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme. Cancer 89(10):2131–2137
Wolff JEA, Wagner S, Reinert C, Gnekow A, Kortmann R-D, Kühl J, Van Gool S (2006) Maintenance treatment with Interferon-gamma and low dose cyclophosphamide for Pediatric high-grade Glioma. J Neurooncol 79(3):315–321
Shinojima N, Kochi M, Hamada J, Nakamura H, Yano S, Makino K, Tsuiki H, Tada K, Kuratsu J, Ishimaru Y, Ushio Y (2004) The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme. J Neurosurg 101:219–226
Pope WB, Sayre J, Perlina A, Villablanca JP, Mischel PS, Cloughesy TF (2005) MR imaging correlates of survival in patients with high-grade gliomas. AJNR Am J Neuroradiol 26(10):2466–2474
Wolff JEA, Boos J, Kühl J (1996) (HIT-GBM: multicenter study for children with malignant glioma). HIT-GBM: multizentrische studie zur behandlung von kindern mit malignen gliomen. Klin Pädiatr 208:193–196
Benesch M, Wagner S, Berthold F, Wolff Johannes EA (2005) Primary dissemination of high-grade gliomas in children: experiences from four studies of the pediatric oncology and hematology society of the German language group (GPOH). J Neurooncol 72(2):179–183
Classen CF, Warmuth-Metz M, Papke K, Trotter A, Wolff JEA,Wagner S (2006) Late response to radiochemotherapy in pediatric glioblastoma: report on two patients treated according to HIT-GBM protocols. Pediatr Hematol Oncol 23(8):631–637
Wagner S, Reinert C, Schmid H-J, Liebeskind A-K, Jorch N, Peters O, Wolff JE (2005) High dose methotrexate prior to simultaneous radiochemotherapy in children with malignant high-grade gliomas. Anticancer Res 25:2583–2588
Acknowledgments
Supported by Deutsche Kinderkrebsstiftung, Germany. The original HIT-GBM-database has been used as source for analyses with different focuses and different subsets of data before [6, 10–12, 14, 20, 22]. This analysis only uses the data generated prospectively for that question and updated 2006. The other HIT-GBM publications have been based on overlapping but not identical patient populations.
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Joachim Kühl passed away since finishing work on this study.
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Wolff, J.E.A., Classen, C.F., Wagner, S. et al. Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database. J Neurooncol 87, 155–164 (2008). https://doi.org/10.1007/s11060-007-9495-z
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DOI: https://doi.org/10.1007/s11060-007-9495-z