The Clinical Outcome of Hydroxyurea Chemotherapy after Incomplete Resection of Atypical Meningiomas

Abstract

BackgroundThe aim of this study is to investigate the clinical results of adjuvant chemotherapy with hydroxyurea and to compare those with the results of postoperative radiotherapy after incomplete resection of atypical meningiomas (ATMNGs).MethodsWe retrospectively reviewed the medical records of 84 patients with ATMNGs diagnosed in the period from January 2000 to December 2014. Clinical data included patient sex and age at the time of surgery, presenting symptoms at diagnosis, location and size of tumor, extent of surgery, use of postoperative radiotherapy or hydroxyurea chemotherapy, duration of follow-up, and progression. In terms of the extent of surgical resection, incomplete resection was defined as Simpson grade II–V.ResultsAmong the 85 patients, 55 (65.5%) patients underwent incomplete resection; 24 (43.6%) were treated with adjuvant hydroxyurea (group A), and 20 (36.4%) with postoperative radiotherapy (group B), and 11 (20.0%) underwent conservative treatment after surgery (group C). Twenty-five (45.5%) patients experienced the progression of tumors during the follow-up period (mean 47.7 months, range 12.4-132.1 months); 8 of 24 (33.3%) patients in group A, 7 of 20 (35.0%) patients in group B, and 10 of 11 (90.9%) patients in group C. The mean progression-free survival (PFS) was 30.9 months (range 6.4-62.3 months); 46.2 months in group A, 40.4 months in group B, and 11.9 months in group C (p=0.041). Multivariate analysis showed that Simpson grade (p=0.040), adjuvant treatment after surgery (p<0.001), increased Ki67 (p=0.017), mitotic index (p=0.034), and overexpression of p53 (p=0.026) predicted longer PFS.ConclusionThis investigation suggested that adjuvant treatment after incomplete resection of ATMNGs are associated with longer PFS than conservative treatment, and that there is no difference of PFS between hydroxyurea chemotherapy and radiotherapy after surgery. Therefore, hydroxyurea chemotherapy can be considered as another adjuvant tool for the ATMNGs if the postoperative adjuvant radiotherapy cannot be applicable.

Differentially Expressed MicroRNAs in Radioresistant and Radiosensitive Atypical Meningioma: A Clinical Study in Chinese Patients

“…Valproic acid was reported to improve radiation injury to meningioma stemlike cells in vitro, by elevating the G2/M phase of the cell cycle and inducing cell apoptosis (40). Furthermore, hydroxyurea, which could interfere with DNA repair after radiation, has been reported to improve PFS of AM with incomplete resection, which indicates that this drug is a potent radiosensitizer to radioresistant AM (41).…”

Initial management of meningiomas: Analysis of the National Cancer Database

“…Treatment with chemotherapy only (without surgery or radiation therapy) showed the lowest 5-year survival rates (32.7%). This lower survival is expected as chemotherapy is used in cases of surgically inaccessible tumors and in patients who cannot receive further radiation therapy [42]. Hydroxyurea was dropped from the National Comprehensive Cancer Network (NCCN) guideline for WHO grade II meningiomas starting in 2009, based on the lack of survival benefits [42].…”

“…This lower survival is expected as chemotherapy is used in cases of surgically inaccessible tumors and in patients who cannot receive further radiation therapy [42]. Hydroxyurea was dropped from the National Comprehensive Cancer Network (NCCN) guideline for WHO grade II meningiomas starting in 2009, based on the lack of survival benefits [42]. The only systemic therapies that have shown limited efficacy are somatostatin analogues, sunitinib, bevacizumab, everolimus, and interferon-alpha at recurrence [43][44][45].…”

Recent Advances in Meningioma Immunogenetics

“…Hydroxyurea has long been used as an adjuvant therapy for incompletely resected or recurrent meningioma (61,62). Although the benefits vary widely across patients, studies suggest hydroxyurea may have outcomes equivalent to those using radiation therapy (63). The alkylating agent, temozolomide, which is used as standard of care in medical management of glioma, failed to extend progression free survival in clinical trials of recurrent meningioma (64).…”