David P. Friedman

Targeted temperature management after intracerebral hemorrhage (TTM-ICH): methodology of a prospective randomized clinical trial.

Rationale Intracerebral hemorrhage causes 15% of strokes annually in the United States, and there is currently no effective therapy. Aims and hypothesis This is a clinical trial designed to study the safety, feasibility, and efficacy of a protocol of targeted temperature management to moderate hypothermia in intracerebral hemorrhage patients. Methods The targeted temperature management after intracerebral hemorrhage trial is a prospective, single-center, interventional, randomized, parallel, two-arm (1:1) phase-II clinical trial with blinded end-point ascertainment. Intracerebral hemorrhage patients will be randomized within 18 h of symptom onset to either 72 h of targeted temperature management to moderate hypothermia (32–34°C) followed by a controlled rewarming at of 0·05–0·1°C per hour or 72 h of targeted temperature management to normothermia (36–37°C) using endovascular or surface cooling. Outcomes The primary outcome is the development of serious adverse events possibly and probably related to treatment. Secondary outcomes include in-hospital neurological deterioration between day 0–7, in-hospital mortality, functional outcome measured by the modified Rankin scale at discharge and 90 days, and effect of treatment allocation on cerebral edema and hematoma volume. Discussion Intracerebral hemorrhage remains the most severe form of stroke with limited options to improve survival. As the early resuscitation phase in the intensive care unit represents the greatest opportunity for impact on clinical outcome, it also appears to be the most promising window of opportunity to demonstrate a benefit when investigating aggressive treatments. Conclusion More research of novel therapies to improve outcomes after intracerebral hemorrhage is desperately needed. The results of the targeted temperature management after intracerebral hemorrhage clinical trial may provide additional information on the applicability of targeted temperature management after intracerebral hemorrhage.

A Phase I Study of the Combination of Sorafenib With Temozolomide and Radiation Therapy for the Treatment of Primary and Recurrent High-Grade Gliomas

PURPOSE Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. METHODS AND MATERIALS This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m(2)) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). RESULTS Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. CONCLUSIONS Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide.

Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of nonacoustic cranial nerve schwannomas.

OBJECTIVETo review outcomes after fractionated stereotactic radiotherapy (FSR) and stereotactic radiosurgery (SRS) for nonacoustic cranial nerve schwannomas. METHODSWe reviewed medical records of 39 patients who received FSR or SRS for nonacoustic cranial nerve schwannomas at our institution during the period from 1996 to 2007. RESULTSTumors involved Cranial Nerves V (n = 19), III (n = 2), VI (n = 3), VII (n = 5), IX (n = 2), X (n = 5), and XII (n = 2) and the cavernous sinus (n = 1). Irradiation was performed after partial resection, biopsy, or no previous surgery in 16, 2, and 21 patients, respectively. Twenty-four patients received FSR, delivered in 1.8- to 2.0-Gy fractions to a median dose of 50.4 Gy (range, 45.0–54.0 Gy). Fifteen patients received SRS to a median dose of 12.0 Gy (range, 12–15 Gy). Mild acute toxicity occurred in 23% of the patients. The 2-year actuarial tumor control rate after FSR and SRS was 95%. The median follow-up period was 24 months. Changes in cranial nerve deficits after stereotactic irradiation were analyzed for patients with follow-up periods greater than 12 months (n = 26); cranial nerve deficits improved in 50%, were stable in 46%, and worsened in 4% of the patients. No significant difference was observed for FSR compared with SRS with regard to local control or to improvement of cranial nerve-related symptoms (P = 0.17). CONCLUSIONSRS and FSR are both well-tolerated treatments for nonacoustic cranial nerve schwannomas, providing excellent tumor control and a high likelihood of symptomatic improvement.

Role of enhanced MRI in the follow-up of patients with medically refractory trigeminal neuralgia undergoing stereotactic radiosurgery using the gamma knife: initial experience.

Purpose The purpose of this work was to evaluate the early posttreatment MR findings, and their clinical utility, in patients with trigeminal neuralgia undergoing stereotactic radiosurgery using the gamma knife. Method Twenty-six patients with medically refractory trigeminal neuralgia underwent stereotactic radiosurgery. A single dose of 70–90 Gy was administered to the proximal root entry zone (n = 21) or the retrogasserian portion (n = 5) of the trigeminal nerve. Posttreatment enhanced MRI and clinical assessment were performed at 3–6 months. Results Five patients did not have radiologic follow-up. There were no changes identified in the treated trigeminal nerve or adjacent brainstem in 19 of 21 patients. Two patients with multiple sclerosis developed abnormal signal and enhancement in the brainstem and/or trigeminal nerve; neither had clinical complications. Onset of therapeutic effect ranged from 3 weeks to 3 months; 19 patients had a beneficial response. Conclusion Results of enhanced MRI 3–6 months after stereotactic radiosurgical treatment of trigeminal neuralgia do not correlate with the clinical response. Because beneficial clinical responses or treatment failures are apparent by 3 months, routine posttreatment MRI in these patients is not warranted.

Superior sagittal sinus thrombosis in the presence of idiopathic bilateral internal jugular vein stenosis.

Cerebral venous outflow obstruction and anomalies in cerebral venous circulation predispose to dural sinus thrombosis. This case report illustrates the magnetic resonance and angiographic findings in a patient who had superior sagittal sinus thrombosis secondary to idiopathic bilateral internal jugular vein stenosis, a previously unrecognized entity. The findings suggest that bilateral stenosis of the internal jugular veins at their junction with the innominate veins causes obstruction to cerebral venous outflow leading to dural sinus thrombosis.

Programmed cell death-1 blockade enhances response to stereotactic radiation in an orthotopic murine model of hepatocellular carcinoma

Small, solitary hepatocellular carcinoma is curable with stereotactic radiation or other methods of tumor ablation, however, regional and systemic tumor recurrence occurs in over 70% of patients. Here we describe the ability of immunoradiotherapy to induce an antitumor immune response and delay the growth of tumors in immunocompetent mice.

Trends in the Utilization of CT Angiography and MR Angiography of the Head and Neck in the Medicare Population

PURPOSE The aim of this study was to analyze trends in the utilization of CT angiography (CTA) and MR angiography (MRA) of the head and neck in the Medicare population over a 6-year interval. METHODS Nationwide Medicare Part B fee-for-service databases were reviewed. Current Procedural Terminology® codes for CTA and MRA of the head and neck were selected. MRA codes included studies without contrast, with contrast, and without and with contrast. Yearly and aggregate procedure volumes were compared for each Current Procedural Terminology code and modality. Data were also analyzed regarding contrast utilization and cost. RESULTS From 2002 to 2007, the volume of head CTA increased by 827%, and the overall volume of head MRA increased by 39%. The year-to-year percentage increase in overall volume of head MRA declined throughout the study period; almost all of the increase in the overall volume of head MRA occurred from 2002 to 2005. The volume of neck CTA increased by 1,074%, and the overall volume of neck MRA increased by 31%. An 18% decrease in the volume of neck MRA without contrast was offset by a 104% increase in the volume of neck MRA using contrast. The year-to-year percentage increase in the overall volume of neck MRA declined from 2002 to 2005; there was a decrease in volume of 3% from 2005 to 2007. From 2002 to 2007, when considering all study types, procedure volume increased by 71%; aggregate allowable charges increased by

Revisiting anaplastic astrocytomas I: An expansive growth pattern is associated with a better prognosis

181 million. Examinations using contrast increased by 235%. In 2002, 23% of examinations used contrast; in 2007, 46% of examinations used contrast. CONCLUSIONS The rate of growth for head and neck CTA was dramatically higher than for MRA. Neck MRA using contrast also showed substantial growth. The Medicare population is now receiving more contrast material and radiation to noninvasively assess the arterial vasculature of the head and neck.

Impact of a Collaborative Radiology Utilization Management Program: Does the Specialty of the Referring Provider Matter?

To study whether anaplastic astrocytomas that are nonenhancing and/or well‐circumscribed (expansive) are associated with a better prognosis.

STING expression and response to treatment with STING ligands in premalignant and malignant disease

OBJECTIVE The purpose of this study was to evaluate the impact of a collaborative radiology utilization management program on the disposition of cases according to provider specialty. MATERIALS AND METHODS A utilization management program directed by a radiology benefit management company provided peer-to-peer decision support for providers ordering advanced outpatient imaging studies. After a radiologist reviewed the cases, based upon provider specialty, the rates of the following dispositions were analyzed: study approved by consensus, study changed by consensus, study not performed by consensus, study approved (no consensus), and study administratively not performed (no callback). Aggregated rates of study changed or not performed by consensus (withdrawals) were used to assess the effect of provider-radiologist collaboration. The rate of no callback was used to assess sentinel effect. The combined rate of withdrawals and no callback represented the overall impact of radiologist participation. The project period was 5 years. RESULTS A total of 168,915 studies were reviewed: 58.6% were approved, 6.8% were changed, and 13.5% were withdrawn by consensus; 6.0% were approved without consensus; 15.2% were withdrawn because of no callback; 35.5% initially ordered were not performed at the time they were ordered. Family practice (25.3%) and internal medicine (23.8%) had the highest aggregated rates of study changed or withdrawn by consensus. Thoracic surgery (13.3%), neurosurgery (11.2%), and orthopedic surgery (9.3%) had the lowest rates. Internal medicine (18.0%), neurology (17.7%), and family practice (17.4%) had the highest rates of study withdrawn owing to no callback. Pediatrics (7.1%) and ophthalmology (7.3%) had the lowest rates. The overall impact was greatest for family practice (42.7%), internal medicine (41.8%), and neurology (33.4%) and least for orthopedic surgery (22.8%) and neurosurgery (24.0%). CONCLUSION Radiologist participation had substantial impact regardless of provider specialty. The impact was greatest on primary care providers who are heavier users of radiology.