University of Maryland Medical Center Baltimore, MD
H. R. R. Cherng1, G. F. Woodworth2, H. Ahmad3, L. Pham3, Y. Kwok4, W. F. Regine Jr4, and M. V. Mishra4,5; 1Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, 2Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 3Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, 4Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 5University of Maryland School of Medicine, Baltimore, MD
Purpose/Objective(s): Treating recurrent and progressive meningiomas remains challenging due to the lack of established or effective treatment options. The SWOG S9005 trial evaluated mifepristone in patients with unresectable meningiomas but failed to show oncologic outcome improvements. With a paucity of prospectively collected data on recurrent meningiomas, our aim was to analyze available clinical trial data to identify prognostic risk factors associated with failure-free survival (FFS) and overall survival (OS). Materials/
Methods: We performed a post-hoc analysis of patients with documented evidence of recurrence or progression on SWOG S9005, using data obtained from the NCTN Data Archive. Risk factors associated with FFS and OS were assessed using multivariable Cox proportional hazards modeling (MVA). Kaplan-Meier estimate was used to measure FFS and OS in different subgroups of patients. Results: A total of 130 patients with recurrent or progressive meningiomas were included for analysis. There was an even distribution (50%, 65 patients) for both the placebo and mifepristone arm. 87 (66.9%) of patients were female and the median age of the cohort was 60 years old. Most patients did not receive prior radiation (84, 64.6%). Median FFS for patients who did not receive prior RT was 1.0 years (95% CI: 0.51-1.53) compared to 0.48 years (95% CI: 0.35-0.60) for patients who did receive prior RT (Log-rank p<0.001). Similarly, median survival times (MST) were significantly longer in patients with no prior RT (14.1 years, 95% CI: not reached [NR] vs 2.6 years, 95% CI: 0.82-4.3, p<0.001). Female patients also had significantly improved (p<0.001) median FFS and MST (0.92 years, 95% CI: 0.53-1.31 and 12.2 years, 95% CI: 7.7-16.7, respectively) compared to male patients (0.47 years, 95% CI: 0.35-0.59 and 4.3 years, 95% CI: 2.3-6.3, respectively). Pre-menopausal women had improved survival compared to post-menopausal women (MST NR vs 8.4 years, 95% CI: 3.2-13.6, p=0.048). On MVA, male sex (HR 1.59, p=0.03), prior receipt of radiation therapy (RT) (HR 1.95, p=0.002), increasing age (HR 1.02, p=0.02) and WHO Grade 2 (HR=2.21, p=0.01) were all independently predictive of worse FFS. These same risk factors apart from histology were all also independently associated with worse OS (p<0.01). Treatment arm was not predictive of survival outcomes and there did not appear to be any evidence of heterogeneity of treatment effect. Conclusion: Data on recurrent meningiomas is currently limited and patient outcomes can vary drastically. Our analyses highlight that older patients, males, and those with a history of prior RT, all have worse outcomes. Menopausal status also led to differential survival outcomes in women with recurrent meningiomas irrespective of treatment arm. Therapy escalation may therefore be warranted in some of these patients. These data can help better counsel patients with recurrent meningiomas as well as inform future clinical trials focused on this particular patient population.
