Antiangiogenic Therapies and Extracranial Metastasis in Glioblastoma: A Case Report and Review of the Literature

Abstract

We present a case report of a patient with glioblastoma multiforme (GBM) complicated by extracranial metastasis (ECM) whose survival of nearly four years surpassed the anticipated life expectancy given numerous negative prognostic factors including EGFRvIII-mutation, unmethylated MGMT promoter status, and ECM. Interestingly, while this patient suffered from locally aggressive disease with multiple intracranial recurrences, the proximal cause of death was progressive extracranial disease and complications related to pulmonary metastases. Herein, we review potential mechanisms of ECM with an emphasis upon glioblastoma molecular and genetic profiles and the potential implications of targeted agents such as bevacizumab.

Figure 1

Surgical pathological specimens from (a) initial craniotomy and (b-c) repeat craniotomy for recurrent intracranial disease. Histopathological analysis of the initial (a) right temporal lobe specimen demonstrated glioblastoma with small cell features. The pathological specimen after second resection (b) demonstrated active glioblastoma, almost entirely viable with <5% necrosis. Following the third and final (c) craniotomy for locally recurrent disease, predominantly viable (approximately 15% necrosis) active glioblastoma was identified. Molecular studies were negative for MGMT methylation and EGFR amplification was detected by FISH.

Figure 2

(a) Whole body FDG PET imaging demonstrating hypermetabolic osseous and visceral metastases including bilateral pulmonary nodules and hilar adenopathy. (b) CT imaging demonstrating mediastinal adenopathy, multiple pulmonary nodules, and right pleural effusion. (c) Coregistered PET/CT imaging demonstrating intense FDG uptake within GBM lung metastases.

Figure 3

Intracranial imaging during final course of salvage therapy with bevacizumab and carboplatin. (a) FLAIR, (b) T1-weighted axial, and (c) T2-weighted axial magnetic resonance imaging demonstrating stable intracranial disease at time of respiratory decline. Postsurgical hyperintensity surrounds area of resection in the right temporal and occipital lobes communicating with the right occipital horn, unchanged with respect to prior imaging.