RAF and MEK inhibitor therapy in adult patients with brain tumors: a case-based overview and practical management of adverse events.

Targeted therapy has gained mainstream attention with notable successes against specific genetic mutations in many cancers. One particular mutation, the BRAF V600E mutation, is present in a small subset of gliomas in adults. Although clinical experience and trial data of RAF-targeted therapy in adults with glioma are lacking at this time, the poor prognosis of adult high-grade glioma has led neuro-oncology practitioners to consider the use of targeted therapy in these patients. In this manuscript, we describe the use of RAF and MEK inhibitors in adults with recurrent glioma. We discuss the utility of these agents, describe their toxicities, and give examples of management strategies. Given the significant toxicities of RAF and MEK inhibitors, along with the long potential duration of treatment, neuro-oncology providers should counsel patients carefully before initiating therapy and monitor them closely while undergoing treatment with RAF-targeted therapy.

NPH Log: Validation of a New Assessment Tool Leading to Earlier Diagnosis of Normal Pressure Hydrocephalus.

INTRODUCTION: Early treatment of normal pressure hydrocephalus (NPH) yields better postoperative outcomes. Our current tests often fail to detect significant changes at early stages. We developed a new scoring system (LP log score) to determine if this tool is more sensitive in detecting clinical differences than current tests. MATERIAL AND METHODS: Sixty-two consecutive new patients with suspected idiopathic NPH were studied. Secondary, previously treated and obstructive cases were not included. We collected age, pre- and post-lumbar puncture (LP) Tinetti, Timed Up and Go (TUG) Test, European NPH scale, and LP log scores. The LP log score is recorded at baseline and for seven consecutive days after removing 40 cc of cerebrospinal fluid (CSF) via LP. We studied the diagnostic accuracy of the tests for surgical indication. RESULTS: The post-LP log showed improvement in 90% of people with good baseline gait tests and in 93% of people who did not show any pre-LP and post-LP change in gait tests. Sensitivity, specificity, and accuracy to detect intention to treat when positive post-LP improvements were 4%, 100%, and 24%, respectively, for TUG, 21%, 86%, and 34%, respectively, for the Tinetti Mobility Test, 66%, 29%, and 58%, respectively, for Medical College of Virginia (MCV) grade, and 98%, 33%, and 85%, respectively, for LP log score. Pre-LP and post-LP TUG improvement and pre-LP and post-LP Tinetti improvement were not associated with a surgical indication (p > 0.05). LP log improvement was associated with surgical indication odds ratio (OR): 24.5 95% CI (2.4-248.12) (p = 0.007). CONCLUSIONS: LP log showed better sensitivity, diagnostic accuracy, and association with surgical indication than the current diagnostic approach. An LP log may be useful detecting NPH patients at earlier stages and, therefore, yield better surgical outcomes.

Long-term outcomes of vestibular schwannomas treated with fractionated stereotactic radiotherapy: an institutional experience.

PURPOSE: We assessed clinical outcome and long-term tumor control after fractionated stereotactic radiotherapy (FSRT) for unilateral schwannoma. METHODS AND MATERIALS: Between 1995 and 2007, 496 patients were treated with fractionated stereotactic radiotherapy at Johns Hopkins Hospital (Baltimore, MD); 385 patients had radiologic follow-up that met the inclusion criteria. The primary endpoint was treatment failure. Secondary endpoints were radiologic progression and clinical outcome. Logistic regression analysis assessed the association of age, race, tumor side, sex, and pretreatment symptoms. RESULTS: In 11 patients (3%) treatment failed, and they required salvage (microsurgical) treatment. Radiologic progression was observed in 116 patients (30.0%), including 35 patients (9%) in whom the treatment volume more than doubled during the follow-up period, although none required surgical resection. Tumors with baseline volumes of less than 1 cm(3) were 18.02 times more likely to progress than those with tumor volumes of 1 cm(3) or greater (odds ratio, 18.02; 95% confidence interval, 4.25-76.32). Treatment-induced neurologic morbidity included 8 patients (1.6%) with new facial weakness, 12 patients (2.8%) with new trigeminal paresthesias, 4 patients (0.9%) with hydrocephalus (1 communicating and 3 obstructive), and 2 patients (0.5%) with possibly radiation-induced neoplasia. CONCLUSIONS: Although the rate of treatment failure is low (3%), careful follow-up shows that radiologic progression occurs frequently. When reporting outcome, the "no salvage surgery needed" and "no additional treatment needed" criteria for treatment success need to be complemented by the radiologic data.