Combined Modality Approaches in the Management of Adult Glioblastoma

Over the past two decades, management of newly diagnosed glioblastoma has undergone significant evolution. While surgery has long been a mainstay of management for this disease, and while radiotherapy has a proven survival role, initial efforts at radiotherapy dose escalation, use of radiosurgery, brachytherapy, and altered fractionation did not improve patient survival. Recently, multiple modality therapy integrating maximal safe resection, postoperative radiation, and new systemic therapies have resulted in improved patient outcomes compared with older regimens utilizing surgery and postoperative radiation alone. Numerous trials are currently underway investigating the combination of surgery, radiation, and systemic therapy with targeted agents to find ways to further improve outcomes for adults with glioblastoma

Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme

Purpose : Loss of PTEN, which is common in glioblastoma multiforme (GBM), results in activation of the mammalian target of rapapmycin (mTOR), thereby increasing mRNA translation of a number of key proteins required for cell-cycle progression. CCI-779 is an inhibitor of mTOR. The primary objectives of this study were to determine the efficacy of CCI-779 in patients with recurrent GBM and to further assess the toxicity of the drug. Experimental Design : CCI-779 was administered weekly at a dose of 250 mg intravenously for patients on enzyme-inducing anti-epileptic drugs (EIAEDs). Patients not on EIAEDs were initially treated at 250 mg; however, the dose was reduced to 170 mg because of intolerable side effects. Treatment was continued until unacceptable toxicity, tumor progression, or patient withdrawal. The primary endpoint was 6-month progression-free survival. Results : Forty-three patients were enrolled; 29 were not on EIAEDs. The expected toxicity profile of increased lipids, lymphopenia, and stomatitis was seen. There were no grade IV hematological toxicities and no toxic deaths. One patient was progression free at 6 months. Of the patients assessable for response, there were 2 partial responses and 20 with stabilization of disease. The median time to progression was 9 weeks. Conclusions : CCI-779 was well tolerated at this dose schedule; however, there was no evidence of efficacy in patients with recurrent GBM. Despite initial disease stabilization in approximately 50% of patients, the durability of response was short. Because of the low toxicity profile, CCI-779 may merit exploration in combination with other modalities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45273/1/10637_2005_Article_1444.pd

Recent advances in managing/understanding meningioma [version 1; referees: 2 approved]

Meningiomas are the most common adult primary intracranial tumor. Despite their higher incidence, there have not—until recently—been as many advances in understanding and managing meningiomas. Thus far, two broad classes of meningiomas have emerged on the basis of their mutational profile: those driven by neurofibromatosis 2 (NF2) inactivation and those with non-NF2 driver gene alterations, such as mammalian target of rapamycin and Hedgehog, Wingless/b-catenin, Notch, transforming growth factor-b receptor, mitogen-activated protein kinase, and phospholipase C pathway alterations. In addition to improvements in molecular diagnostics, advances in imaging are being studied to better predict tumor behavior, stratify risk, and potentially monitor for disease response. Management consists primarily of surgery and radiation therapy and there has been limited success from medical therapies, although novel targeted agents are now in clinical trials. Advances in imaging and understanding of the genetic makeup of meningiomas demonstrate the huge potential in revolutionizing the classification, diagnosis, management, and prognosis of meningiomas.