Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II—Report from the German/Swiss SIOP-LGG 2004 cohort

Fabian Falkenstein, Marco Gessi, Daniela Kandels, Ho Keung Ng, René Schmidt, Monika Warmuth-Metz, Brigitte Bison, Juergen Krauss, Rolf Dieter Kortmann, Beate Timmermann, Ulrich Wilhelm Thomale, Michael H. Albert, Arnulf Pekrun, Eberhard Maaß, Astrid K. Gnekow, Torsten Pietsch

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2159-2175
Number of pages17
JournalInternational Journal of Cancer
Issue number8
Publication statusPublished - Oct 15 2020


  • astrocytoma
  • child
  • diffuse glioma WHO-grade II
  • genetics
  • Histone3 gene mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II—Report from the German/Swiss SIOP-LGG 2004 cohort'. Together they form a unique fingerprint.

Cite this