Advances in multidisciplinary therapy for meningiomas

Abstract

Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas.

Fig. 1

Potential signaling pathways that can be targeted in meningiomas (A, figure modified with permission from Preusser, Brastianos et al Nature Reviews Neurology 2018). (B) Human tumor samples with mutations in SMO and AKT1 are predominantly meningothelial, whereas NF2 mutated tumors are fibroblastic and/or transitional. Immunohistochemistry demonstrates activation of the Hedgehog signaling pathway with GAB1 positivity and the Akt/PI3K pathway with STMN1 positivity (figure modified with permission from Brastianos et al. Nature Genetics 2013).

Fig. 2

Comparisons of external beam radiation therapy (EBRT) and stereotactic radiosurgery (SRS) for the treatment of presumed benign meningiomas.