Bevacizumab as salvage therapy for progressive brain stem gliomas

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Abstract

Objective

There is no standard of care for patients with progredient brain stem gliomas. Therefore, we report about clinical, radiological and metabolic response to anti-angiogenic treatment with bevacizumab in a series of 3 patients with gliomas involving the brain stem.

Patients and methods

Three patients with histologically confirmed gliomas involving the brain stem were treated with bevacizumab for tumor progression. The clinical data, histopathological findings as well as MRI and PET follow up examinations during bevacizumab therapy were retrospectively analyzed.

Results

The histopathological diagnosis revealed an anaplastic astrocytoma WHO grade III in two patients and an astrocytoma WHO grade II in 1 patients with clinical and neuroradiological signs of malignization. One patient is still progression-free 97 weeks after initiation of bevacizumab therapy. Mean progression-free survival and overall survival for the other two patients after initiation of bevacizumab therapy was 34.5 weeks and 43.5 weeks. During bevacizumab therapy mean KPS improved from 60 to 80 and mean dosage of daily dexamathasone was reduced from 7.3 mg to 1.3 mg. MRI showed a decrease of T2 weighted hyperintense lesions in all patients and a decrease of contrast enhancement in two patients. 18F-FET-PET showed a decrease of tracer uptake in all cases (mean maximum decrease: 25%).

Conclusion

In this series treatment of progressive gliomas involving the brain stem with bevacizumab resulted in an improved clinical condition of the patients as well as a reduction of the T2 weighted lesions and reduced amino acid uptake in the tumor area. It therefore may represent a therapeutic salvage option for this type of tumor.

Introduction

Adult brain stem gliomas are a rare tumor entity accounting for 1.5–2.5% of all intracranial tumors. Therapeutic options for intrinsic brain stem gliomas are limited, mainly consisting of radiotherapy with an undefined role of chemotherapy and no standard of care for patient with recurrent brain stem tumors. Recently two case reports about successful treatment of a progressive diffuse brain stem glioma with bevacizumab with or without irinotecan have been published [1], [2]. Therefore we retrospectively analyzed a series of three patients with histological confirmed gliomas involving the brain stem treated with bevacizumab alone as a salvage therapy and report here the clinical, radiological and metabolic findings.

Section snippets

Patients and methods

We performed a retrospective review of the MS ACCESS database of our department and identified three patients with the histopathologically confirmed diagnosis of a glioma with involvement of the brain stem who were treated with bevacizumab as a salvage therapy for tumor progression. The positive experience with bevacizumab therapy in one of these patients was already published as a case report by the author [2]. The patients’ records, histopathological findings and the radiological and

Case 1

The first patient was a 32-year old female with 6 months of nausea and dizziness symptoms. MRI examination showed a homogeneous T2 hyperintense lesion in the medulla oblongata with no contrast enhancement. A stereotactic biopsy was performed with the histological finding of an astrocytoma (WHO II) and initial treatment consisted of external fractionated radiotherapy with 54 Gy. Four months later the patient was admitted to our department due to clinical deterioration with progressive gait ataxia,

Case 2

A 36-year old female patient presented with 3 months of intermittent gait disturbance and headache. MRI examination showed a diffuse, non-contrast-enhancing mass in the left cerebellar peduncle with infiltration of the brain stem. A stereotactic biopsy was performed with the histological finding of a low-grade glioma WHO II. Regarding the young age of the patient and the clear delineation of the tumor no external radiation was planned and it was decided to perform a stereotactic implantation of

Case 3

The third case was a 39-year old male patient with a 1 year progressive eye deviation and 6 months unsteady gait. MRI showed a contrast-enhancing lesion in the pontine tegmentum on both sides with extension to the quadrigeminal plate, pons and cerebellum (Fig. 1). Stereotactic biopsy of the tumor revealed an anaplastic astrocytoma WHO grade III and the patient was treated with external fractionated radiotherapy (54 Gy). The patient remained progression free for 4 months, after which there was an

Clinical course

One patient is still alive and progression free for a period of 97 weeks after initiation of bevacizumab therapy. This patient had initially the diagnosis of a diffuse astrocytoma grade II which showed clinical, radiological and metabolic signs of malignization before administration of bevacizumab. The two other patients died during the observation period and mean progression free and overall survival from start of bevacizumab was 34.5 weeks and 43.5 weeks. Mean total overall survival from time

Discussion

According to the actual literature adult brain stem gliomas are subdivided into four distinct categories with regard to their clinical and radiological patterns [3]. Adult diffuse intrinsic low-grade brain stem gliomas with an onset in the third decade of life and a radiological pattern of diffuse pontomedullary tumor infiltration without contrast enhancement. Therapy consists mainly of radiation therapy and anaplastic transformation occurred in 27% of patients after a long period of stable

Conclusion

In this series treatment of progressive gliomas involving the brain stem with bevacizumab resulted in an improved clinical condition of the patients as well as decrease of the T2-weighted hyperintense lesions and reduced amino acid uptake in the tumor area. It therefore may represent a therapeutic salvage option for this type of tumor.

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