Medical Management of Meningioma in the Era of Precision Medicine

Saksham Gupta, BA; Wenya Linda Bi, MD, PhD; Ian F. Dunn, MD

Disclosures

Neurosurg Focus. 2018;44(4):e3 

In This Article

Abstract and Introduction

Abstract

Surgery is curative for most meningiomas, but a minority of these tumors recur and progress after resection. Initial trials of medical therapies for meningioma utilized nonspecific cytotoxic chemotherapies. The presence of hormone receptors on meningioma ushered in trials of hormone-mimicking agents. While these trials expanded clinical understanding of meningioma, they ultimately had limited efficacy in managing aggressive lesions. Subsequent detection of misregulated proteins and genomic aberrancies motivated the study of therapies targeting specific biological disturbances observed in meningioma. These advances led to trials of targeted kinase inhibitors and immunotherapies, as well as combinations of these agents together with chemotherapies. Prospective trials currently recruiting participants are testing a diverse range of medical therapies for meningioma, and some studies now require the presence of a specific protein alteration or genetic mutation as an inclusion criterion. Increasing understanding of the unique and heterogeneous nature of meningiomas will continue to spur the development of novel medical therapies for the arsenal against aggressive tumors.

Introduction

Meningiomas are the most common primary central nervous tumors in adults, comprising more than a third of all brain tumors. Most are WHO grade I, while 15%–20% are considered high grade (WHO grade II or III). While grade I meningiomas largely express an indolent course, high-grade meningiomas are associated with poor prognoses: 10-year overall survival (OS) ranges from 53%–79% for patients with WHO grade II lesions to 14%–34% for those with grade III tumors. Patients with meningioma refractory to conventional surgery or radiation have limited pharmacotherapeutic options.[72]

Clinical trials for meningioma are challenged not only by a dearth of targets, but also by several qualities of the tumor's growth pattern and epidemiology. First, the relatively indolent nature of WHO grade I meningiomas and the wide variability in the natural history of grade II meningiomas challenge our ability to define consistent outcome measures within a reasonable time frame. The amount of time necessary to reflect true disease control or progression may exceed that budgeted for a typical clinical trial. Second, the relative efficacy of surgery and adjuvant radiation for meningiomas constrains the burden of progressive meningiomas, especially WHO grade I subtypes, which might be studied in clinical trials. These constraints have frequently prompted the accrual of tumors of different grades and with prior treatments into the same trial to allow sufficient power for the end points, which may then confound the interpretation of results.

Additionally, approaches for measuring meningioma growth vary across studies of tumor progression, with some investigators utilizing maximum diameter; others, maximum area; and still others, three-dimensional volumetric analysis. The lack of consistent clinical end points across studies has limited comparisons between trials and raised calls for standardization of trial techniques.

Medical management of meningioma has continued to evolve in the last 2 decades, mirroring the expansion of therapeutic strategies in human cancers. Studies of nonspecific agents have given way to trials that leverage our understanding of specific molecular alterations and the immune environment. These discoveries have motivated trials of novel molecular inhibitors and immunotherapies. In the present review, we summarize the medical management strategies studied for meningioma to date and avenues for future therapeutic development in light of biological insights.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....