Exploring Tumor Treating Fields as a Potential Therapy for High-Grade Meningiomas: A Review of Literature and Clinical Trials

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.

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Artikel online veröffentlicht:
07. Februar 2025