| Institution: | 1. Swabian Children's Cancer Center, University Hospital Augsburg, Augsburg, Germany;2. Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany
Division of Pathology, Fondazione Policlinico Universitario “A.Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy;3. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong;4. Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany;5. Institute of Diagnostic and Interventional Neuroradiology, University Hospital Wuerzburg, Wuerzburg, Germany;6. Section of Pediatric Neurosurgery, University Hospital Wuerzburg, Wuerzburg, Germany;7. Department of Radio-Oncology, University of Leipzig, Leipzig, Germany;8. Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), German Cancer Consortium (DKTK), Essen, Germany;9. Pediatric Neurosurgery, Charité Universitaetsmedizin Berlin, Berlin, Germany;10. Dr von Hauner Children's Hospital, Ludwig-Maximilians Universitaet, Munich, Germany;11. Professor Hess Children's Hospital, Klinikum Bremen-Mitte, Bremen, Germany;12. Pediatric Oncology and Hematology, Olga Hospital, Stuttgart, Germany;13. Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany |
| Abstract: | 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. |
