Impact of histopathological transformation and overall survival in patients with progressive anaplastic glioma

Allen L Ho; Matthew J Koch; Shota Tanaka; April F Eichler; Tracy T Batchelor; Jantima Tanboon; David N Louis; Daniel P Cahill; Andrew S Chi; William T Curry Jr

doi:10.1016/j.jocn.2016.02.019

Impact of histopathological transformation and overall survival in patients with progressive anaplastic glioma

J Clin Neurosci. 2016 Sep:31:99-105. doi: 10.1016/j.jocn.2016.02.019. Epub 2016 Jun 6.

Authors

Affiliations

¹ Department of Neurosurgery, Stanford University, Palo Alto, CA, USA.
² Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
³ University of Tokyo Hospital, Tokyo, Japan.
⁴ Stephen E. and Catherine Pappas Center for Neuro-Oncology and Division of Hematology/Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, 55 Fruit Street/Y9E, Boston, MA 02114, USA; Harvard Medical School, Boston, MA, USA.
⁵ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
⁶ Stephen E. and Catherine Pappas Center for Neuro-Oncology and Division of Hematology/Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, 55 Fruit Street/Y9E, Boston, MA 02114, USA; Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
⁷ Stephen E. and Catherine Pappas Center for Neuro-Oncology and Division of Hematology/Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, 55 Fruit Street/Y9E, Boston, MA 02114, USA; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁸ Stephen E. and Catherine Pappas Center for Neuro-Oncology and Division of Hematology/Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, 55 Fruit Street/Y9E, Boston, MA 02114, USA; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: wcurry@mgh.harvard.edu.

PMID: 27279154
DOI: 10.1016/j.jocn.2016.02.019

Abstract

Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9years, p=0.0005) and second surgery (1.0 vs. 3.5years, p<0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4years, p=0.008) and OS (median 10.0 vs. 4.2years, p=0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population.

Keywords: Anaplastic glioma; Glioblastoma; Malignant glioma; Recurrent glioma; Transformation.

MeSH terms

Adult
Aged
Brain Neoplasms / genetics
Brain Neoplasms / mortality
Brain Neoplasms / pathology*
Cell Transformation, Neoplastic / pathology*
Combined Modality Therapy
Disease Progression
Female
Glioma / genetics
Glioma / mortality
Glioma / pathology*
Humans
Isocitrate Dehydrogenase / genetics
Male
Middle Aged
Mutation
Prognosis
Retrospective Studies

Substances

Isocitrate Dehydrogenase