Meningiomas are the most common intracranial tumor, making up more than a third of all primary central nervous system (CNS) tumors. They are mostly benign tumors that can be observed or preferentially treated with gross total resection that provides good outcomes. Meningiomas with complicated histology or in compromising locations has proved to be a challenge in treating and predicting prognostic outcomes. Advances in genomics and molecular characteristics of meningiomas have uncovered potential use for more accurate grading and prediction of prognosis and recurrence. With the study and detection of genomic aberrancies, specific biologic targets are now being trialed for possible management of meningiomas that are not responsive to standard surgery and radiotherapy treatment. This review summarizes current epidemiology, etiology, molecular characteristics, diagnosis, treatments, and current treatment trials.
The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.
OBJECT: The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. METHODS: A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. RESULTS: A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02–1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95–0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31–0.83]; p = 0.0067) to be significantly associated with survival. CONCLUSION: This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.
Pituitary adenomas are tumors that arise in the anterior pituitary gland. They are the third most common cause of central nervous system (CNS) tumors among adults. Most adenomas are benign and exert their effect via excess hormone secretion or mass effect. Clinical presentation of pituitary adenoma varies based on their size and hormone secreted. Here, we review some of the most common types of pituitary adenomas, their clinical presentation, and current diagnostic and therapeutic strategies.
22 November 2019 in Expert Opinion on Investigational Drugs
Introduction: High grade gliomas (HGG) are extremely aggressive brain malignancies that are usually fatal. Despite maximal resection, chemotherapy and radiation, these tumors inevitably recur and present a poor median overall survival (mOS); hence there is a pressing need for improved treatments. Areas covered: This review assesses DNX-2401 as a treatment of recurrent HGG. Phase I data on efficacy, safety, and tolerability are examined while insights and perspectives on future directions are offered. Expert opinion: This phase I study assessed DNX-2401 in two groups; one group received a one-time intratumoral injection of DNX-2401 without tumor resection while the second group received an intratumoral injection of DNX-2401 followed by surgical resection 14 days later and a second injection of DNX-2401 into the resection cavity. In patients that did not receive resection, the mOS was 9.5 months across all cohorts while patients in the resection group had a mOS of 13 months which is a promising extension of survival compared to historical controls. Furthermore, this study had numerous long-term survivors living for greater than 2 years at the time of recurrence. DNX-2401 was well tolerated with no drug-related Grade 3 or greater adverse events; it demonstrated some ability to provoke an immunologic response to the tumor which may contribute to the complete responses in some patients. Randomized-control trials are necessary and further studies are warranted to identify patients who will benefit most.