Concomitant Temozolomide plus radiotherapy for high-grade and recurrent meningioma: a retrospective chart review

Abstract

Background High-grade and recurrent meningiomas are often treatment resistant and pose a therapeutic challenge after surgical and radiation therapy (RT) failure. Temozolomide (TMZ) is a DNA alkylating agent that appears to have a radiosensitizing effect when used in combination with RT and may be worthwhile in meningioma treatment. Thus, we investigated the potential efficacy of concomitant RT plus TMZ compared to historical controls of just RT used in the treatment of high-grade and recurrent meningiomas. Methods We performed a retrospective analysis of patients with meningioma treated at the University of Colorado with TMZ chemoradiation. Progression free survival (PFS) and overall survival (OS) were calculated from the start of chemoradiation to local recurrence or death, respectively. Results Eleven patients (12 tumors) were treated with chemoradiation with a median follow-up of 41.5 months. There were two WHO grade 1, eight grade 2 and two grade 3 meningiomas. Three patients died during the follow-up period—one being disease related (11.1%). Two patients had meningioma recurrence—at 2.3 months (WHO grade 3), and 5.4 years (WHO grade 2). Three-year OS and PFS for grade 2 meningiomas were each 88%. Historical controls demonstrate a 3-year median OS and PFS of 83% and 75.8%, respectively. Conclusions Treatment options are limited for meningiomas after local failure. In this study, TMZ chemoradiation demonstrated no significant difference in PFS and OS in the treatment of grade 2 meningiomas compared to historic controls. Further study is warranted to find novel methods for the treatment of malignant and recurrent meningiomas.

Management of Recurrent Meningiomas: State of the Art and Perspectives

“…N = 41 articles met the inclusion criteria and N = 16 articles failed to assess management of meningioma recurrence. Finally, N = 24 articles were included in our review [ 22 , 29 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 49 , 50 , 51 , 52 , 53 , 55 , 56 , 57 ] ( Flowchart 1 ). The articles were distributed as follows: studies on chemotherapy (N = 14); RT, PT, and SRS (N = 6); BNCT (N = 2); and surgery (N = 3).…”

“…Recently, Belanger et al [ 45 ] retrospectively assessed PFS and OS in N = 11 patients who underwent adjuvant therapy using temozolomide (TMZ) in addition to postoperative RT, with a median follow-up of 41.5 months. While N = 3 patients died during FU, the N = 2 patients with WHO grade 3 meningiomas showed recurrence less than three months after initiation of adjuvant therapy.…”

“…While N = 3 patients died during FU, the N = 2 patients with WHO grade 3 meningiomas showed recurrence less than three months after initiation of adjuvant therapy. Three-year OS and PFS for WHO grade 2 meningiomas were both 88%, with a 3-year median OS and PFS of 83% and 75.8%, respectively [ 45 ].…”

Emerging systemic treatment options in meningioma

“…The efficacy of cytotoxic agents such as hydroxyurea [12][13][14][15], irinotecan [16], temozolomide [17,18], or combination regimens such as vincristine, adriamycin and cyclophosphamide (VAC) [19] has been evaluated, with overall limited efficacy (Table 1). Whereas the DNA-intercalating agent trabectedin has shown promising activity in vitro and in one heavily pretreated patient [20], a prospective randomized phase 2 trial (EORTC 1320) failed to meet its primary endpoint, with no difference to physician's choice in terms of antitumoral activity but significantly higher toxicity [21].…”

Long-Term Follow-Up, Treatment Strategies, Functional Outcome, and Health-Related Quality of Life after Surgery for WHO Grade 2 and 3 Intracranial Meningiomas

“…At the study center, temozolomide, a DNA-alkylating agent, or Bevacizumab, an angiogenesis inhibitor, are used for rescue therapy. However, their utility, especially in high-grade meningiomas, is unclear [ 26 , 27 ].…”