- Department of Neurosurgery, Christchurch, New Zealand.
- Department of Medicine Christchurch Hospital, Christchurch, New Zealand.
Ethan John Kilmister, Department of Neurosurgery, Christchurch Hospital, Christchurch, New Zealand.
DOI:10.25259/SNI_788_2021Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Ethan John Kilmister1, Bridget Robinson2, Claudio De Tommasi1. Treatment of BRAF V600E mutated ganglioglioma of the third ventricle with dabrafenib. 19-Oct-2021;12:529
How to cite this URL: Ethan John Kilmister1, Bridget Robinson2, Claudio De Tommasi1. Treatment of BRAF V600E mutated ganglioglioma of the third ventricle with dabrafenib. 19-Oct-2021;12:529. Available from: https://surgicalneurologyint.com/?post_type=surgicalint_articles&p=11183
Background: Ganglioglioma (GG) of the third ventricle is rare. Surgical excision of tumors in this location is associated with high morbidity due to nearby eloquent brain centers. Alternative treatments, when available, should be considered to reduce risks of surgical treatment.
Case Description: We present the case of a 21-year-old female diagnosed with a BRAF V600E mutated GG of the third ventricle. After an endoscopic biopsy and insertion of a ventriculoperitoneal shunt, the patient was started on the BRAF inhibitor dabrafenib, as an alternative to surgery or radiation. Nearly 2 years after starting dabrafenib, her tumor appearance on serial magnetic resonance imaging is stable, and she has maintained a good quality of life with no new neurological symptoms.
Conclusion: The disease control thus far suggests targeted medical therapy of GG of the third ventricle with BRAF inhibitors may have efficacy and should be a considered treatment modality.
Keywords: BRAF inhibitor, Dabrafenib, Ganglioglioma, Targeted therapy, Third ventricle
Gangliogliomas (GGs) are rare, well-differentiated tumors comprising dysplastic cells of neuronal and glial origin, accounting for 1.3% of central nervous system (CNS) tumors in adults.[
Ten to sixty percent of GGs, depending on anatomic location have an activating p.V600E mutation in the BRAF oncogene.[
We present the case of a young patient with a third ventricle GG treated with the BRAF inhibitor dabrafenib.
A 21-year-old female presented to the emergency department in November 2017 with a 2-month history of a worsening headache in the frontal and occipital regions. This was associated with photophobia and nausea, blurred vision, neck stiffness, and vomiting. She had no significant background medical history. The neurological examination was clinically unremarkable.
Computed tomography imaging demonstrated hydrocephalus with severe lateral ventriculomegaly with a deviation of the septum pellucidum to the left, effacement of the sulcal spaces, basal cisterns, and tonsillar herniation. Subsequent magnetic resonance imaging (MRI) demonstrated a lobulated mass within the third ventricle which demonstrated mildly increased signal on T2 weighted imaging [
Serial magnetic resonance imaging (MRI) images of the ganglioglioma. Sagittal T2 weighted MRI (a), Sagittal T1 weighted MRI (b), diffusion-weighted imaging (c), Sagittal T1 weighted MRI (d), Sagittal T1 weighted MRI from October 2019 showing a reduction in tumor size (e), and a Sagittal T1 weighted MRI from March 2021 showing a stable tumor appearance (f).
The patient underwent endoscopic exploration with biopsy of the mass protruding through the foramen of Monroe followed by septum pellucidotomy and ventriculoperitoneal shunt insertion (Codman Certas plus programmable valve set at 5).
Following the operation and given the anatomic location and tumor grade, conservative management with serial MRIs was initially undertaken in consideration of the potential morbidity of a surgical approach to the third ventricle. An MRI in February 2018, and in July 2018, demonstrated a stable appearance of the GG and reduced ventricular size. The patient remained neurologically well with resolution of her headaches and maintained her normal daily functioning. Follow-up MRI in March 2019 showed subtle tumor growth. There was increased mass effect on the midbrain and tectal plate due to the increased size of the dorsal cystic component of the tumor (from 11 × 4 × 8 mm to 24 × 12 × 14 mm) [
In consideration of the tumor growth and the presence of a BRAF p.V600E mutation, we suggested the use of the BRAF inhibitor dabrafenib. After discussion with the patient, a final decision was made to proceed with medical treatment. The patient commenced dabrafenib at 150 mg twice daily in July 2019. MRI 4 months later in October 2019 demonstrated a significant reduction in tumor size from 22 × 12 mm to 17 × 8 mm [
Histology was consistent with a WHO grade I GG [
This case presented shows the multidisciplinary management of a third ventricle GG. Although surgery was initially considered, the patient’s young age and the potential high post-operative morbidity led the multidisciplinary team to consider targeted therapy with the BRAF inhibitor dabrafenib.
Patients with third ventricle GGs may present with symptoms of raised intracranial pressure secondary to obstruction of CSF circulation. Their treatment includes surgical resection and drainage of CSF to decrease intracerebral pressure. As the third ventricle is located centrally in the brain, GGs here present a surgical challenge, with a limited potential for complete resection due to nearby eloquent brain structures.
In avoiding the potential complications from surgery, our patient had a good treatment response to dabrafenib. However, she experienced some mild complications that prompted a dosage reduction. This finding is supported by case reports in the literature for the BRAF inhibitors dabrafenib and vemurafenib. Higa et al. reported a case of a third ventricle GG and reviewed the available literature.[
We did not find a report of a third ventricle GG treated with BRAF inhibitors. Although surgically accessible, we felt that a surgical approach was associated with a high risk of complications. The literature evidence for the management of other GGs prompted us to consider the use of BRAF inhibitors in the presented case. Conservative management was attempted initially, but tumor growth prompted us to begin medical treatment. A good response with tumor control was observed with the sole use of dabrafenib at 2 years. Mild side effects were successfully controlled with a reduction in the dosage of dabrafenib.
BRAF mutated GGs have been treated successfully with BRAF inhibitors, in multiple anatomic locations.[
This raises an important question: what is the appropriate treatment duration for BRAF inhibitors in treating GGs to achieve a sustained response? Further studies are required but BRAF inhibitors should be considered within the armamentarium of the treating physician.
This case demonstrates the efficacy of BRAF inhibitors against GGs in the third ventricle and highlights the need for further investigation of this treatment modality. It also highlights the importance of a multidisciplinary approach towards complex lesions like these. Targeted medical treatment for GGs of the third ventricle, which avoids high morbidity surgery and maximizes their quality of life, is a promising treatment method for third ventricle GGs.
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