Faculty Bibliography

OBJECTIVE: Dose-response relationships for meningioma radiosurgery are poorly characterized. We evaluated determinants of local recurrence for meningiomas treated with Gamma Knife radiosurgery (GKRS), to guide future treatment approaches to optimize tumor control. MATERIALS AND METHODS: A total of 101 consecutive patients (108 tumors) who underwent GKRS for benign, atypical, or malignant meningiomas between 1998 and 2011 were studied. Local recurrence was assessed. Cox proportional hazards and logistic regression analyses were used to determine the association of patient-related, tumor-related, and treatment-related characteristics with local recurrence. Acute and late toxicity was evaluated. RESULTS: World Health Organization (2007 classification) tumor grade was I (82%), II (11%), or III (7%). Median dose was 14 Gy (range, 10 to 18 Gy) for grade I tumors and 16 Gy (range, 12 to 20 Gy) for grade II and III tumors. Median follow-up was 25 months (maximum, 17 y). Two- /5-year actuarial local control rates were 100%/98% for grade I tumors and 76%/56% for grade II/III tumors. Higher tumor grade and lower GKRS dose were associated with local failure. In this cohort, there was a 42% relative reduction in local recurrence for each 1 Gy of dose escalation. CONCLUSIONS: Treatment was well tolerated with no moderate or severe toxicity. Tumor control was excellent in benign tumors and suboptimal in higher grade tumors. Because the main determinant of local recurrence was GKRS dose, we recommend dose escalation for atypical or malignant tumors to doses between 16 and 20 Gy where critical structures allow.

INTRODUCTION: We expanded upon our previous experience using involved-field fractionated radiotherapy (IFRT) as an alternative to whole brain radiotherapy or stereotactic radiosurgery for patients with surgically resected brain metastases (BM). MATERIALS AND METHODS: All patients with single BM who underwent surgical resection followed by IFRT at our institution from 2006 to 2013 were evaluated. Local recurrence (LR)-free survival, distant failure (DF)-free survival, and overall survival (OS) were determined. Analyses were performed associating clinical variables with LR and DF. Salvage approaches and toxicity of treatment for each patient were also assessed. RESULTS: Median follow-up was 19.1 months. Fifty-six patients were treated with a median dose of 40.05 Gy/15 fractions with IFRT to the resection cavity. LR-free survival was 91.4%, DF-free survival was 68.4%, and OS was 77.7% at 12 months. No variables were associated with increased LR; however, melanoma histopathology and infratentorial location were associated with DF on multivariate analysis. LRs were salvaged in 5/8 patients, and DFs were salvaged in 24/29 patients. Two patients developed radionecrosis. CONCLUSION: Adjuvant IFRT is feasible and safe for well-selected patients with surgically resected single BM. Acceptable rates of local control and salvage of distal intracranial recurrences continue to be achieved with continued follow-up.

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: 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.

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