Neuropediatrics 2012; 43 - FV11_11
DOI: 10.1055/s-0032-1307055

Analysis of risk factors for pediatric low-grade glioma patients after long term follow-up of the HIT-LGG 1996 trial

P Hernáiz Driever 1, F Falkenstein 2, S von Hornstein 2, I Zwiener 3, M Warmuth-Metz 4, R Kortmann 5, T Pietsch 6, A Faldum 7, A Gnekow 2
  • 1Klinik für Pädiatrie mS Onkologie/Hämatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
  • 2Kinderklinik Augsburg, Augsburg, Germany
  • 3IMBEI Universität Mainz, Mainz, Germany
  • 4Abteilung für Neuroradiologie, Universitätsklinik, Würzburg, Germany
  • 5Klinik für Strahlentherapie, Universitätsklinik, Leipzig, Germany
  • 6Institut für Neuropathologie, Universitätsklinik, Bonn, Germany
  • 7Institut für Biometrie und klinische Forschung, Universitätsklinik, Münster, Germany

Aims: HIT-LGG 1996 was the first nationwide comprehensive treatment strategy for children and adolescents with a low grade glioma (LGG) integrating observation, radio-(RT) and chemotherapy (CT) recommendations.

Methods: 1031 patients were recruited from 10/1996 to 03/2004 (median age 6.89 years, 6.5% <1 year, 52.9% male, 10.5% NF1, 28 diencephalic syndrome, 45 dissemination). Location: supratentorial midline 40.4% (22.4% visual pathways), cerebellum 28.1%, cerebral hemispheres 18.1%, caudal brain stem 8.3%, spinal cord 3.5%. Resection was complete in 34.8%, subtotal/partial in 34.2%, biopsy in 19.9% tumours, 11.1% were diagnosed radiologically. Histology revealed 67.9% pilocytic astrocytoma, 9.8% grade II glioma, 8.9% glioneural tumours.

668 patients remained observed, while 363 started non-surgical therapy as external beam-RT/brachytherapy in 147 or vincristine/carboplatin-CT in 216 patients.

Results: Overall survival (OS) remains at 0.94at 10 years, while event free survival (EFS) declines to 0.47. 10-year progression free survival following first non-surgical treatment is 0.62 for RT and 0.438 for CT. 28/51 RT- and 104/130 CT-patients received further non-surgical treatment. At last follow-up 59/216 children in the CT-arm had been irradiated 0.3–8.7 years after initial diagnosis.

Multivariable analysis identifies diencephalic syndrome in infants and incomplete resection as unfavourable risk factors for survival and event following diagnosis as well as older age (OS) and supratentorial midline localisation (EFS). Dissemination, young age and non-pilocytic histology prove unfavourable for progression following RT, while diencephalic syndrome, dissemination, and older age are risk factors for progression following CT. NF1-patients experience prolonged tumour stabilisation with chemotherapy.

Conclusion: Extended follow-up confirms high survival rates following diagnosis and radio- as well as chemotherapy of paediatric LGG. Infants with/without diencephalic syndrome and dissemination represent a high risk group as opposed to older children with pilocytic astrocytoma, or diffuse astrocytoma or NF-1.

Children - Adolescents - Low-grade glioma - Risk factors