Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II-Report from the German/Swiss SIOP-LGG 2004 cohort.
Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment.
['Falkenstein|Fabian|F|', 'Gessi|Marco|M|', 'Kandels|Daniela|D|', 'Ng|Ho-Keung|HK|', 'Schmidt|René|R|', 'Warmuth-Metz|Monika|M|', 'Bison|Brigitte|B|', 'Krauss|Juergen|J|', 'Kortmann|Rolf-Dieter|RD|', 'Timmermann|Beate|B|', 'Thomale|Ulrich-Wilhelm|UW|', 'Albert|Michael H|MH|', 'Pekrun|Arnulf|A|', 'Maaß|Eberhard|E|', 'Gnekow|Astrid K|AK|0000-0002-7356-6887', 'Pietsch|Torsten|T|']
D000293:Adolescent D001932:Brain Neoplasms D002648:Child D002675:Child, Preschool D015331:Cohort Studies D005260:Female D005858:Germany D005910:Glioma D006801:Humans D007223:Infant D008297:Male D009154:Mutation D060787:Neoplasm Grading D011379:Prognosis D000077982:Progression-Free Survival D011446:Prospective Studies D016879:Salvage Therapy D013557:Switzerland D014944:World Health Organization
genetics diffuse glioma WHO-grade II Histone3 gene mutation astrocytoma child