Multiple Intracranial Meningiomas Associated with NF2: How Gamma Knife Icon Added Value to a Long Treatment History

By Mayur Sharma, MD, and Lilyana Angelov, MD

History and clinical profile

A 43-year-old man presented to our clinic in 2014 with a history of multiple brain surgeries for neurofibromatosis type 2 (NF2)-associated tumors and a progressively growing left parasagittal meningioma.

He had been diagnosed with NF2 in 1996 when he presented with bilateral vestibular schwanommas and a history of craniotomy for resection of a right frontal meningioma in 1992 that had resulted in permanent left lower extremity weakness. He underwent suboccipital craniotomy with resection of his left and right vestibular schwanommas in 1997 and 1998, respectively; these procedures were complicated by mild left facial weakness and bilateral hearing loss. In 1999, he underwent surgery for resection of foramen magnum meningioma. He then underwent radiosurgery for a parasagittal meningioma and a right frontal meningioma in 2003 and 2007, respectively. He sustained a grand mal seizure in 2008 secondary to multiple intracranial meningiomas; the seizure was preceded by several episodes of aura during which he “felt disconnected from reality” but remained conscious. He was started on antiepileptic medication and his seizures were controlled. He subsequently noticed weakness involving his right hemibody with a follow-up brain MRI in 2012 demonstrating tumor progression. Follow-up MRIs in 2013 showed further progression of a left parafalcine meningioma (from 4.7 to 7.6 mm) and an anterior parafalcine meningioma (from 5.6 to 6.7 mm) as well as a new anterior parafalcine meningioma.

After an interval of observation, he underwent surgery in 2014 with complete recovery of motor strength on the right side of his body. At the time of resection, pathology demonstrated that while one of the tumors was benign (WHO grade I meningioma), a second tumor was of a more aggressive subtype (WHO grade II atypical meningioma).

Presentation at Cleveland Clinic

As all available treatment modalities had been exhausted at the patient’s prior institution, he was referred to Cleveland Clinic’s Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center in 2014 to manage the progressive intracranial meningiomas. Our goal was to provide effective local treatment to the tumor while minimizing radiation injury to surrounding normal brain tissue. On presentation, he was clinically asymptomatic except for baseline weakness and bilateral hearing loss.

In a highly complex case like this with a history of multiple prior treatments, Cleveland Clinic Cancer Center’s multidisciplinary tumor board is engaged to ensure that all pertinent subspecialty expertise is brought to bear in clinical decision-making. Following the board’s recommendation, the patient was managed with EDGE™ hypofractionated radiosurgery over a five-day treatment course in January 2015 targeting six intracranial meningiomas. He fared well clinically and was following up regularly, but in June 2016 he reported progressive weakness of his right leg over the prior few months. The weakness was located proximally on the right and was not associated with leg or back pain or numbness. MRI showed interval increase in the size of the left parasagittal frontoparietal meningioma with increased peritumoral edema (see figure below).

Next treatment step: A new approach to Gamma Knife radiosurgery

Given this clinical conundrum and the patient’s extensive history of treatments, our multidisciplinary tumor board recommendation was to manage the left parasagittal meningioma with fractionated Gamma Knife® radiosurgery. We used Cleveland Clinic’s newly acquired, ultraprecise Leksell Gamma Knife Icon™ machine, making this patient one of the first to benefit from its new frameless technology.

There are multiple advantages to delivering fractionated Gamma Knife therapy with the Icon machine:

• The ability to deliver radiation in a highly precise manner using a frameless stereotactic system and image guidance — i.e., cone-beam CT with a motion tracking system (IFMM, Intra-Fraction Motion Management)
• The ability to use a low radiation dose/fraction in this complex setting of multiple prior radiation treatments to avoid radiation-related side effects
• Use of a face mask for stereotactic guidance (see photo below) to avoid complexities related to frame/pin placement in this patient with multiple prior surgeries

The figure below shows the MRIs (top) and associated CTs (bottom) used to formulate the patient’s Icon treatment plan. The patient tolerated the procedure well, with no neurological complications, even noting that his right leg dysfunction was beginning to improve at the end of the five-day treatment course. He remains fully functional and is able to live independently and work.

Discussion

The presence of multiple intracranial tumors (meningioma and vestibular schwanomma) associated with NF2 is a debilitating condition with significant impact on quality of life. NF2 is an inheritable autosomal dominant disorder associated with mutations in the NF2 (merlin) gene located at chromosome 22. Young age and female gender have been shown to correlate with increased growth rate in NF2-associated meningiomas, and most of these tumors show a saltatory growth pattern (Dirks et al., J Neurosurg. 2012).

Given the unpredictable behavior of these tumors, treatment is usually indicated if the patient secondarily becomes clinically symptomatic. Single-fraction Gamma Knife therapy has been shown to achieve excellent control rates of 96 percent at a median radiographic follow-up of 103 months (Birckhead et al., J Neurooncol. 2016), making it a feasible, safe and effective treatment modality with an acceptable toxicity profile (Liu et al., J Neurosurg. 2015) in patients with NF2-associated meningiomas.

The Leksell Gamma Knife Icon is an advanced platform capable of delivering Gamma Knife radiosurgery with excellent geometrical accuracy (Zeverino et al., Med Phys. 2017). Our case provides insight into the potential role of this fractionated radiosurgery platform in safely managing patients with this type of complex clinical history involving intracranial meningiomas and multiple prior treatments. Many other patients with similarly challenging complex brain tumors are likely to benefit from this new and advanced treatment modality.

Dr. Sharma is a clinical fellow in neurosurgical oncology and Gamma Knife radiosurgery in Cleveland Clinic’s Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center.

Dr. Angelov (angelol@ccf.org) is a neurosurgeon in the Burkhardt Brain Tumor and Neuro-Oncology Center and a staff member of Cleveland Clinic Cancer Center.