Oren Berkowitz

Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer

As systemic therapies improve and patients live longer, concerns mount about the toxicity of whole‐brain radiation therapy (WBRT) for treatment of brain metastases. Development of delayed white matter abnormalities indicative of leukoencephalopathy have been correlated with cognitive dysfunction. This study assesses the risk of imaging‐defined leukoencephalopathy in patients whose management included WBRT in addition to stereotactic radiosurgery (SRS). This risk is compared to patients who only underwent SRS.

Repeat gamma knife radiosurgery for trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) may recur after treatment by gamma knife stereotactic radiosurgery (GKSR). OBJECTIVE: To evaluate management outcomes in patients who underwent repeat GKSR for TN. METHODS: The authors reviewed their experience with repeat GKSR in 119 patients with recurrent TN. The median patient age was 74 years (range, 34-96 years). The median interval between procedures was 26 months. The median target dose for repeat GKSR was 70 Gy (range, 50-90 Gy) and the median cumulative dose was 145 Gy (range, 120-170 Gy). The median follow-up was 48 months (range, 6-187 months) after repeat GKSR. RESULTS: After repeat GKSR, 87% of patients achieved initial pain relief (Barrow Neurological Institute pain score I–IIIb). Pain relief was maintained in 87.8% at 1 year, 69.8% at 3 years, and 44.2% at 5 years. Facial sensory dysfunction occurred in 21% of patients within 18 months after GKSR. Longer pain relief was observed in patients who had recurrent pain in a reduced pain distribution of the face compared with the pain distribution at the time of their initial GKSR, and in those who developed additional trigeminal sensory loss after a repeat procedure. A cumulative edge of brainstem dose ≥ 44 Gy was more likely to be associated with the development of sensory loss. CONCLUSION: Repeat GKSR provides a similar rate of pain relief as the first procedure. The best responses were observed in patients who had good pain control after the first procedure and those who developed new sensory dysfunction in the affected trigeminal distribution.

Outcomes of Gamma Knife surgery for trigeminal neuralgia secondary to vertebrobasilar ectasia

OBJECT Vertebrobasilar ectasia (VBE) is an unusual cause of trigeminal neuralgia (TN). The surgical options for patients with medically refractory pain include percutaneous or microsurgical rhizotomy and microvascular decompression (MVD). All such procedures can be technically challenging. This report evaluates the response to a minimally invasive procedure, Gamma Knife surgery (GKS), in patients with TN associated with severe vascular compression caused by VBE. METHODS Twenty patients underwent GKS for medically refractory TN associated with VBE. The median patient age was 74 years (range 48-95 years). Prior surgical procedures had failed in 11 patients (55%). In 9 patients (45%), GKS was the first procedure they had undergone. The median target dose for GKS was 80 Gy (range 75-85 Gy). The median follow-up was 29 months (range 8-123 months) after GKS. The treatment outcomes were compared with 80 case-matched controls who underwent GKS for TN not associated with VBE. RESULTS Intraoperative MR imaging or CT scanning revealed VBE that deformed the brainstem in 50% of patients. The trigeminal nerve was displaced in cephalad or lateral planes in 60%. In 4 patients (20%), the authors could identify only the distal cisternal component of the trigeminal nerve as it entered into the Meckel cave. After GKS, 15 patients (75%) achieved initial pain relief that was adequate or better, with or without medication (Barrow Neurological Institute [BNI] pain scale, Grades I-IIIb). The median time until pain relief was 5 weeks (range 1 day-6 months). Twelve patients (60%) with initial pain relief reported recurrent pain between 3 and 43 months after GKS (median 12 months). Pain relief was maintained in 53% at 1 year, 38% at 2 years, and 10% at 5 years. Some degree of facial sensory dysfunction occurred in 10% of patients. Eventually, 14 (70%) of the 20 patients underwent an additional surgical procedure including repeat GKS, percutaneous procedure, or MVD at a median of 14 months (range 5-50 months) after the initial GKS. At the last follow-up, 15 patients (75%) had satisfactory pain control (BNI Grades I-IIIb), but 5 patients (25%) continued to have unsatisfactory pain control (BNI Grade IV or V). Compared with patients without VBE, patients with VBE were much less likely to have initial (p = 0.025) or lasting (p = 0.006) pain relief. CONCLUSIONS Pain control rates of GKS in patients with TN associated with VBE were inferior to those of patients without VBE. Multimodality surgical or medical management strategies were required in most patients with VBE.

Epidemiology and Environmental Risk Factors Associated with Vestibular Schwannoma

OBJECTIVE Vestibular schwannomas (VS) are tumors originating from the eighth cranial nerve. The etiology and environmental risk factors for VS remain unclear. The goal of this study was to explore some potential environmental risk factors associated with vestibular schwannoma (VS). METHODS A hospital-based case-control study with 1:1 matching based on age and sex was designed. A written questionnaire was administered. Multiple conditional logistic regression models were created to determine odds ratio (OR). RESULTS There were 353 matched pairs with an average age at diagnosis of 53 years (SD ± 12), 50% of participants were female, and >90% were white. Multivariate models revealed significantly increased OR with a history of hay fever (OR = 3.91, 95% confidence interval [CI] = 1.35-11.30) and managerial/professional occupations (OR = 4.41, 95% CI = 2.07-9.40). Tobacco use had a decreased association with VS (<20 pack-years OR = 0.10, 95% CI = 0.04-0.28; ≥ 20 pack-years OR = 0.03, 95% CI = 0.01-0.12). CONCLUSIONS The profile of patients with VS includes white race, age 50-60 years, either sex, and working in a professional occupation. Better access to health care and diagnostic imaging likely plays a role in the diagnosis of this tumor. Hay fever is strongly associated with VS. Tobacco use demonstrates an inverse relationship with VS, but the possible biologic mechanism for this is poorly understood, and tobacco remains a significant public health problem.

The evolution of a clinical registry during 25 years of experience with Gamma Knife radiosurgery in Pittsburgh

OBJECT The first North American 201 cobalt-60 source Gamma Knife surgery (GKS) device was introduced at the University of Pittsburgh Medical Center in 1987. The introduction of this innovative and largely untested surgical procedure prompted the desire to study patient outcomes and evaluate the effectiveness of this technique. The parallel advances in computer software and database technology led to the development of a registry to track patient outcomes at this center. The purpose of this study was to describe the registrys evolution and to evaluate its usefulness. METHODS A team was created to develop a software database and tracking system to organize and retain information on the usage of GKS. All patients undergoing GKS were systematically entered into this database by a clinician familiar with the technology and the clinical indications. Information included patient demographics and diagnosis as well as the anatomical site of the target and details of the procedure. RESULTS There are currently 11,738 patients in the database, which began to be used in August 1987. The University of Pittsburgh Medical Center has pioneered the evaluation and publication of the GKS technique and outcomes. Data derived from this computer database have facilitated the publication of more than 400 peer-reviewed manuscripts, more than 200 book chapters, 8 books, and more than 300 published abstracts and scientific presentations. The use of GKS has become a well-established surgical technique that has been performed more than 700,000 times around the world. CONCLUSIONS The development of a patient registry to track and analyze the use of GKS has given investigators the ability to study patient procedures and outcomes. The future of clinical medical research will rely on the ability of clinical centers to store and to share information.

Are frequent dental x-ray examinations associated with increased risk of vestibular schwannoma?

OBJECT The authors evaluated the potential role of environmental risk factors, including exposure to diagnostic or therapeutic radiation and to wireless phones that emit nonionizing radiation, in the etiology of vestibular schwannoma (VS). METHODS A total of 343 patients with VSs who underwent Gamma Knife surgery performed between 1997 and 2007 were age and sex matched to 343 control patients from the outpatient degenerative spinal disorders service at the University of Pittsburgh Medical Center. The authors obtained information on previous exposure to medical radiation, use of wireless phone technologies, and other environmental factors thought to be associated with the development of a VS. Conditional multivariate logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS After adjusting for race, education, cigarette smoking, alcohol consumption, occupational exposure to noise, use of cell phones, and family history of cancer, the authors identified only a single factor that was associated with a higher risk of VS: individuals exposed to dental x-rays once a year (aOR = 2.27, 95% CI = 1.01-5.09) or once every 2-5 years (aOR = 2.65, 95% CI = 1.20-5.85), compared with those exposed less than once every 5 years. Of interest, a history of exposure to radiation related to head or head-and-neck computed tomography was associated with a reduced risk of VS (aOR = 0.52, 95% CI = 0.30-0.90). No relationship was found between the use of cell phones or cordless phones and VS. CONCLUSIONS Patients with acoustic neuromas reported significantly more exposure to dental x-rays than a matched cohort control group. Reducing the frequency of dental x-ray examinations may decrease the potential risk of VS.

Introduction of an interprofessional oral health curriculum.

Purpose Physician assistants can incorporate a variety of oral health services into their practices, but many physician assistant programs do not dedicate adequate time to oral health education. Our goal was to develop a novel and interprofessional oral health education curriculum model for our physician assistant students that could be adopted by other physician assistant programs and dental schools in the United States. Methods Curricula were created collaboratively and taught by dental school faculty with a focus on the primary care setting. Prewritten and postwritten tests were administered along with a clinical skills examination. Student and faculty evaluations were administered for pedagogical evaluation. Results Pretests and posttests demonstrated a 25% increase in knowledge acquisition (paired t test: P < .001). Physical examination skills testing achieved a 95% completion rate. Student and faculty evaluations demonstrated high satisfaction rates with the curricula delivery. Conclusions Initial evaluation of this novel interprofessional curriculum for physician assistant students demonstrates that it was successful. It was well-received by the students and the faculty members and resulted in measurable knowledge acquisition. This model could feasibly be reproduced in other institutions for oral health education.

Determining the elements of procedural quality

OBJECT The definition and determination of quality health care is an important topic. The purpose of this study was to develop a longitudinal method to define a quality procedure by creating a formal approach to pre- and postoperative outcomes documentation. The authors worked to define quality outcomes by first documenting the patients condition. Goals were determined together by the surgeon and the patient and then were evaluated to see if those goals were met. METHODS The population consisted of cancer patients with newly diagnosed metastatic brain disease who were scheduled to undergo stereotactic radiosurgery. Surgeons recorded perioperatively objective information related to preoperative goals, clinical findings, surgical performance and/or error, and whether goals were met. In addition, patients completed pre- and postprocedure questionnaires (Rand 36-Item Short-Form Health Survey 1.0 [SF-36]). RESULTS Procedural goals, defined as completing radiosurgery without error or complication and same-day discharge, were met in all patients. The clinically predetermined goal of tumor palliation was met in all but 1 patient at follow-up. The SF-36 scores remained stable except for the general health domain, which was lower (p = 0.006). CONCLUSIONS Procedural goals can be defined and objectively measured serially. The authors think that quality care can be defined as a process that achieves predefined goals without significant error and maintains or improves health.

The art and science of selecting graduate students in the biomedical sciences: Performance in doctoral study of the foundational sciences

The goal of this study was to investigate associations between admissions criteria and performance in Ph.D. programs at Boston University School of Medicine. The initial phase of this project examined student performance in the classroom component of a newly established curriculum named “Foundations in Biomedical Sciences (FiBS)”. Quantitative measures including undergraduate grade point average (GPA), graduate record examination (GRE; a standardized, computer-based test) scores for the verbal (assessment of test takers’ ability to analyze, evaluate, and synthesize information and concepts provided in writing) and quantitative (assessment of test takers’ problem-solving ability) components of the examination, previous research experience, and competitiveness of previous research institution were used in the study. These criteria were compared with competencies in the program defined as students who pass the curriculum as well as students categorized as High Performers. These data indicated that there is a significant positive correlation between FiBS performance and undergraduate GPA, GRE scores, and competitiveness of undergraduate institution. No significant correlations were found between FiBS performance and research background. By taking a data-driven approach to examine admissions and performance, we hope to refine our admissions criteria to facilitate an unbiased approach to recruitment of students in the life sciences and to share our strategy to support similar goals at other institutions.

Gamma Knife Radiosurgery for Vestibular Schwannomas and Quality of Life Evaluation.

Background: Further investigation is needed to look at the impact of vestibular schwannoma (VS) on the health-related quality of life (QOL) of participants who undergo Gamma Knife® radiosurgery (GKRS). Objectives: Investigators compared the QOL for VS participants to reported US population norms in order to evaluate disease burden and long-term QOL several years after GKRS. Methods: This cross-sectional study surveyed participants to assess hearing status, tinnitus, imbalance, vertigo, as well as the Short-Form 36-item Health Questionnaire (SF-36). The data were normalized, age adjusted, and functional status was correlated to determine clinically significant differences. Results: A total of 353 participants who underwent GKRS between 1997 and 2007 were included in this study with a median postoperative period of 5 years. SF-36 scores were very similar to population norms, and age-adjusted scores for participants followed the US population curve. Frequent vertigo and balance problems had the largest statistically and clinically significant effect on physical and mental component summary scores followed by nonuseful hearing in the tumor ear. Conclusions: Participants reported a good long-term QOL that was very similar to the QOL of US population norms. Of the common VS symptoms, vertigo had the greatest impact on QOL followed by imbalance and then hearing loss.