Faculty Bibliography

High-grade glioma continues to be a challenging disease with few effective treatment options and a poor prognosis, necessitating intensive research into alternate therapies. The Response Assessment in Neuro-Oncology (RANO) committee was formed to create a robust endpoint assessment criteria in Neuro-Oncology in order to streamline the assessment of new therapies in a uniform fashion. The aim of this committee is to create standardized guidelines to assess clinical and imaging response in the treatment of brain tumors, which can then be applied in clinical trials. Since the first RANO report was published in 2010, its criteria have been widely adopted and utilized in clinical trials worldwide. Standardized application of the RANO response assessment criteria in clinical trials will result in the generation of strong clinical data, which can subsequently be pooled and analyzed to attain a more accurate assessment of treatment efficacy. In this review, we summarize the current RANO guidelines in patients with high-grade glioma, highlighting the key clinical and imaging criteria used for RANO evaluation and introducing the role of newer imaging and biomarkers.

Gamma knife radiosurgery (GKRS) has become a treatment option for intracranial hemangioblastomas, especially in patients with poor clinical status and also high-risk surgical candidates. The objective of this study was to analyze clinical outcome and tumor control rates. Retrospective chart review revealed 12 patients with a total of 20 intracranial hemangioblastomas treated with GKRS from May 1998 until December 2014. Kaplan-Meier plots were used to calculate the actuarial local tumor control rates and rate of recurrence following GKRS. Univariate analysis, including log rank test and Wilcoxon test were used on the Kaplan-Meier plots to evaluate the predictors of tumor progression. Two-tailed p value of <0.05 was considered as significant. Median follow-up was 64months (2-184). Median tumor volume pre-GKRS was 946mm(3) (79-15970), while median tumor volume post-GKRS was 356mm(3) (30-5404). Complications were seen in two patients. Tumor control rates were 100% at 1year, 90% at 3years, and 85% at 5years, using the Kaplan-Meier method. There were no statistically significant univariate predictors of progression identified, although there was a trend towards successful tumor control in solid tumors (p=0.07). GKRS is an effective and safe option for treating intracranial hemangioblastoma with favorable tumor control rates.

OPINION STATEMENT/UNASSIGNED:Intramedullary spinal cord tumors are rare central nervous system tumors with unique challenges due to the eloquence of the surrounding tissue. Their treatment and prognosis is largely dependent on tumor histology and patient functionality. The introduction and advancement of microsurgical techniques have made surgery the mainstay of treatment for intramedullary tumors. Tumors that are well demarcated (e.g., ependymomas, hemangioblastomas) can be resected for cure, while more infiltrative tumors (e.g., high-grade astrocytomas) are typically managed with biopsies or limited resections in order to minimize the significant risk of damage to the spinal cord. The use of more aggressive surgical resection for astrocytoma is controversial but may have an increasing role in select cases. The use of intraoperative neurophysiologic monitoring and intraoperative ultrasound may help guide the extent of surgery while minimizing damage to normal tissue. Advances in MRI technology have greatly aided the diagnosis and preoperative planning of intramedullary tumors. Further advances in intraoperative MRI may make this a useful tool in guiding extent of resection. Preoperative functional status is the most important predictor of neurologic outcome, while histology and extent of resection are the most important predictors of progression-free survival. The use of adjuvant radiation and chemotherapy is dependent on patient age and histology but is largely reserved for high-grade tumor histologies or systemic involvement. Children are particularly at risk of radiation-induced injury, and these cases may benefit from more focused stereotactic radiation where necessary. Further studies are needed to support new surgical strategies minimizing destabilization and to investigate new forms of adjuvant therapy to minimize toxicity.

BACKGROUND:Primary central nervous system lymphoma (PCNSL) is an aggressive type of extra-nodal non-Hodgkin lymphoma. Without treatment, PCNSL is associated with significant morbidity and mortality, including rapid neurological deterioration. In contrast to other high-grade intracranial neoplasms, PCNSL is considered to have a high response rate to conventional medical therapy, especially in younger patients, and therefore warrants particular attention in terms of nonsurgical treatment. CASE DESCRIPTION/METHODS:We report a case of the medical management of acute deterioration due to rapidly growing PCNSL with mass effect to highlight the efficacy of temporization with hyperosmolar therapy while awaiting the known rapid effects of dexamethasone and methotrexate (MTX) treatment. Surgical intervention was avoided, and tumor response was rapid. The patient had corresponding clinical resolution of symptoms of elevated intracranial pressure with return to neurologic baseline. CONCLUSIONS:Despite the evidence that PCNSL responds well to steroids and MTX, the rapidity of onset with which this occurs can vary. In patients presenting with mass effect and rapid neurologic decline, there is little evidence to support medical over surgical intervention. Herein we present an illustrative case of a large PCNSL lesion presenting with rapid decline. With clinical improvement in one day and a 50% reduction in tumor volume over less than seven days, the authors present the specific time frame with which PCNSL responds to medical therapy and a safe strategy for medical temporization.

BACKGROUND:Nonfunctioning pituitary adenomas recur after microsurgery. Gamma Knife radiosurgery (GKRS) has been used to treat recurrent adenomas. OBJECTIVE:To evaluate the long-term rates of tumor control and development of hypopituitarism in patients with nonfunctioning pituitary adenomas after GKRS. METHODS:Forty-eight patients with a nonfunctioning pituitary adenoma treated between 1991 and 2004 at the University of Virginia were studied. All patients had more than 4 years of clinical and imaging follow-up. RESULTS:All patients underwent follow-up imaging and endocrine evaluations, with a duration ranging from 50 to 215 months (median, 80.5 months) and 57 to 201 months (median, 95 months), respectively. New hormone deficiency after GKRS occurred in 19 of 48 patients (39%). Corticotropin/cortisol deficiency developed in 8% of patients, thyroid hormone deficiency in 20.8%, gonadotropin deficiency in 4.2%, growth hormone/insulin-like growth factor 1 in 16.7%, and diabetes insipidus in 2%. Panhypopituitarism including diabetes insipidus developed in 1 patient. Overall, control of tumor volume was 83%. Tumor volume decreased in 36 patients (75%), increased in 8 patients (17%), and was unchanged in 4 patients (8%). Tumor volumes greater than 5 mL at the time of GKRS were associated with a significantly greater rate of growth (P = .003) compared with an adenoma with a volume of 5 mL or less. CONCLUSION/CONCLUSIONS:GKRS resulted in a high and durable rate of tumor control in patients with a nonfunctioning pituitary adenoma. A higher preoperative tumor volume was associated with an increased rate of tumor growth.