High-grade (World Health Organization Grade II and III) meningiomas (HGMs), which
comprise ~18% of all meningioma diagnoses, are challenging to manage due to their
heterogeneity and increased likelihood of recurrence. Current standard of care is
limited to gross surgical resection and adjuvant chemo/radiation therapy. However,
certain tumors at the skull base are challenging to reach surgically and even after
Simpson I resections, HGMs can have recurrence rates of up to 80%. Tumor treating
fields (TTFs), an antimitotic treatment that employ alternating electrical currents
to interrupt tumor proliferation, have emerged as a promising treatment for brain
tumors. We sought out to understand and evaluate the current literature on TTF use
in aggressive brain cancers and their potential utility in HGM. A search was performed
on PubMed, Embase, Cochrane, and ClinicalTrials.gov databases using the keywords:
(“tumor treating fields”) and (“meningioma”). In total, 6 articles met the final eligibility criteria for our study.
TTFs have currently been approved as a treatment of recurrent glioblastoma (GBM) as
a standalone therapy. In vitro experiments have demonstrated that TTFs reduce proliferation
and clonogenicity of patient-derived anaplastic meningioma cells. Two clinical trials
have begun investigating the use of TTFs in HGM patients. The first trial, which has
yet to report preliminary outcomes, involves a combination therapy of TTF and Bevacizumab,
an anti-angiogenic drug. In another trial, the Optune TTF device was used as a monotherapy
according to standard treatment protocols. Six HGM patients (50% female), with a median
age of 60.4 years and who had all undergone prior surgery and radiation, were enrolled.
The median PFS was 3.3 months. Radiographic responses indicated stable disease in
four patients and progressive disease in two patients. The treatment protocol was
also well-tolerated with no major complications reported. While TTFs seem promising,
drawbacks in design and ergonomics prevent the broader reach and impact of these devices.
Implantable TTFs present a solution by eliminating wiring issues, delivering more
precise field control, enhancing treatment efficiency, consuming less energy, and
overcoming the barriers associated with wearing the device. A study that looked at
the effect of skull remodeling surgery (burr holes and craniectomy) on the safety
and field strength of TTFs showed that skull remodeling in conjunction with TTFs was
safe and improved field strength by 32%, which suggests that implantable devices are
the natural next step in innovation. To this end, researchers in the United Kingdom
have engineered an implantable device to deliver fields directly to the margins of
the resection cavity, similar in design to current deep brain stimulator (DBS) platforms.
Other preliminary work has suggested that there are implantation targets within the
skull base that could be used to direct TTFs for HGMs of the middle and posterior
fossae. TTFs represent an intriguing but inadequately studied treatment paradigm that
warrants further investigation for the treatment of hard-to-treat intracranial HGM,
including lesions of the skull base.
