Faculty Bibliography

The Leksell GammaPlan software version 10 introduces a CT image-based segmentation tool for automatic skull definition and a convolution dose calculation algorithm for tissue inhomogeneity correction. The purpose of this work was to evaluate the impact of these new approaches on routine clinical Gamma Knife treatment planning. Sixty-five patients who underwent CT image-guided Gamma Knife radiosurgeries at the University of Pittsburgh Medical Center in recent years were retrospectively investigated. The diagnoses for these cases include trigeminal neuralgia, meningioma, acoustic neuroma, AVM, glioma, and benign and metastatic brain tumors. Dose calculations were performed for each patient with the same dose prescriptions and the same shot arrangements using three different approaches: 1) TMR 10 dose calculation with imaging skull definition; 2) convolution dose calculation with imaging skull definition; 3) TMR 10 dose calculation with conventional measurement-based skull definition. For each treatment matrix, the total treatment time, the target coverage index, the selectivity index, the gradient index, and a set of dose statistics parameters were compared between the three calculations. The dose statistics parameters investigated include the prescription isodose volume, the 12 Gy isodose volume, the minimum, maximum and mean doses on the treatment targets, and the critical structures under consideration. The difference between the convolution and the TMR 10 dose calculations for the 104 treatment matrices were found to vary with the patient anatomy, location of the treatment shots, and the tissue inhomogeneities around the treatment target. An average difference of 8.4% was observed for the total treatment times between the convolution and the TMR algorithms. The maximum differences in the treatment times, the prescription isodose volumes, the 12 Gy isodose volumes, the target coverage indices, the selectivity indices, and the gradient indices from the convolution and the TMR 10 calculations are 14.9%, 16.4%, 11.1%, 16.8, 6.9%, and 11.4%, respectively. The maximum differences in the minimum and the mean target doses between the two calculation algorithms are 8.1% and 4.2% of the corresponding prescription doses. The maximum differences in the maximum and the mean doses for the critical structures between the two calculation algorithms are 1.3 Gy and 0.7 Gy. The results from the two skull definition methods with the TMR 10 algorithm agree either within ± 2.5% or 0.3 Gy for the dose values, except for a 4.9% difference in the treatment times for a lower cerebellar lesion. The imaging skull definition method does not affect Gamma Knife dose calculation considerably when compared to the conventional measurement-based skull definition method, except in some extreme cases. Large differences were observed between the TMR 10 and the convolution calculation method for the same dose prescription and the same shot arrangements, indicating that the implementation of the convolution algorithm in routine clinical use might be desirable for optimal dose calculation results.

OBJECT Stereotactic radiosurgery (SRS) is a potentially important option for patients with skull base chondrosarcomas. The object of this study was to analyze the outcomes of SRS for chondrosarcoma patients who underwent this treatment as a part of multimodality management. METHODS Seven participating centers of the North American Gamma Knife Consortium (NAGKC) identified 46 patients who underwent SRS for skull base chondrosarcomas. Thirty-six patients had previously undergone tumor resections and 5 had been treated with fractionated radiation therapy (RT). The median tumor volume was 8.0 cm3 (range 0.9-28.2 cm3), and the median margin dose was 15 Gy (range 10.5-20 Gy). Kaplan-Meier analysis was used to calculate progression-free and overall survival rates. RESULTS At a median follow-up of 75 months after SRS, 8 patients were dead. The actuarial overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. Local tumor progression occurred in 10 patients. The rate of progression-free survival (PFS) after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with shorter PFS. Eight patients required salvage resection, and 3 patients (7%) developed adverse radiation effects. Cranial nerve deficits improved in 22 (56%) of the 39 patients who deficits before SRS. Clinical improvement after SRS was noted in patients with abducens nerve paralysis (61%), oculomotor nerve paralysis (50%), lower cranial nerve dysfunction (50%), optic neuropathy (43%), facial neuropathy (38%), trochlear nerve paralysis (33%), trigeminal neuropathy (12%), and hearing loss (10%). CONCLUSIONS Stereotactic radiosurgery for skull base chondrosarcomas is an important adjuvant option for the treatment of these rare tumors, as part of a team approach that includes initial surgical removal of symptomatic larger tumors.

BACKGROUND: Competency-based medical education (CBME) is gaining momentum in postgraduate residency and fellowship training. While randomized trials, consensus statements, and practice guidelines can help delineate some of the core competencies for CBME, they are not applicable to all clinical scenarios. OBJECTIVE: To propose and assess the feasibility of a practical methodology for addressing this issue using radiosurgery for vestibular schwannoma (VS) science as an example. METHODS: The Web of Science electronic database was searched using relevant terms. A 3-step review of titles and abstracts was used. Studies were classified independently and in duplicate as either efficacy or effectiveness analyses. Cohen's kappa score was used to assess inter-rater agreement. RESULTS: Overall, 1818 surgical and 943 radiosurgical publications were identified. The number of effectiveness studies surpassed that of efficacy studies in the late 1980s for surgical studies, and in the early-to-mid 1990s among radiosurgical studies. The publication rate was higher for radiosurgery in the mid 1990s, but it paralleled that of surgical studies beyond the early 2000s. Variations in this overall trend corresponded to the emergence of studies that assessed the role of endoscopy and the utility of dose reduction in radiosurgery. CONCLUSION: We have confirmed the feasibility and accuracy of this objective methodological approach. By understanding how the peer-reviewed literature reflects actual practice interests, educators can tailor curricula to ensure that trainees remain current. While further validation studies are needed, this methodology can serve as a supplemental strategy for identifying additional core competencies in CBME.

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.

BACKGROUND: Embolization before stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVM) has been shown to negatively affect obliteration rates, but its impact on the risks of radiosurgery-induced complications and latency period hemorrhage is poorly defined. OBJECTIVE: To determine, in a case-control study, the effect of prior embolization on AVM SRS outcomes. METHODS: We evaluated a database of AVM patients who underwent SRS. Propensity score analysis was used to match the case (embolized nidi) and control (nonembolized nidi) cohorts. AVM angioarchitectural complexity was defined as the sum of the number of major feeding arteries and draining veins to the nidus. Multivariate Cox proportional hazards regression analyses were performed on the overall study population to determine independent predictors of obliteration and radiation-induced changes. RESULTS: The matching process yielded 242 patients in each cohort. The actuarial obliteration rates were significantly lower in the embolized (31%, 49% at 5, 10 years, respectively) compared with the nonembolized (48%, 64% at 5, 10 years, respectively) cohort (P = .003). In the multivariate analysis for obliteration, lower angioarchitectural complexity (P < .001) and radiologically evident radiation-induced changes (P = .016) were independent predictors, but embolization was not significant (P = .744). In the multivariate analysis for radiologic radiation-induced changes, lack of prior embolization (P = .009) and fewer draining veins (P = .011) were independent predictors. CONCLUSION: The effect of prior embolization on AVM obliteration after SRS may be significantly confounded by nidus angioarchitectural complexity. Additionally, embolization could reduce the risk of radiation-induced changes. Thus, combined embolization and SRS may be warranted for appropriately selected nidi. ABBREVIATIONS: AVM, arteriovenous malformationRBAS, radiosurgery-based AVM scoreSRS, stereotactic radiosurgeryVRAS, Virginia Radiosurgery AVM Scale.

BACKGROUND: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published. METHODS: Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Asberg Depression Rating Scale from baseline. RESULTS: There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Asberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively. CONCLUSION: The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed.

OBJECT Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. Resection can be undertaken, but the tumor's intimate association with the facial nerve makes resection with neurological preservation quite challenging. Stereotactic radiosurgery (SRS) has been used to treat FNSs, and this study evaluates the outcome of this approach. METHODS At 8 medical centers participating in the North American Gamma Knife Consortium (NAGKC), 42 patients undergoing SRS for an FNS were identified, and clinical and radiographic data were obtained for these cases. Males outnumbered females at a ratio of 1.2:1, and the patients' median age was 48 years (range 11-76 years). Prior resection was performed in 36% of cases. The mean tumor volume was 1.8 cm(3), and a mean margin dose of 12.5 Gy (range 11-15 Gy) was delivered to the tumor. RESULTS At a median follow-up of 28 months, tumor control was achieved in 36 (90%) of the 40 patients with reliable radiographic follow-up. Actuarial tumor control was 97%, 97%, 97%, and 90% at 1, 2, 3, and 5 years postradiosurgery. Preoperative facial nerve function was preserved in 38 of 42 patients, with 60% of evaluable patients having House-Brackmann scores of 1 or 2 at last follow-up. Treated patients with a House-Brackmann score of 1 to 3 were more likely to demonstrate this level of facial nerve function at last evaluation (OR 6.09, 95% CI 1.7-22.0, p = 0.006). Avoidance of temporary or permanent neurological symptoms was more likely to be achieved in patients who received a tumor margin dose of 12.5 Gy or less (log-rank test, p = 0.024) delivered to a tumor of