Faculty Bibliography

OBJECTIVEThe role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.METHODSThe authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988-2000) or modern (2001-2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).RESULTSThe study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.CONCLUSIONSDespite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.

OBJECTIVE The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease. Stereotactic radiosurgery (SRS) is a first-line management option for brain metastases. The purpose of this study was to determine if there is a threshold tumor size below which local control (LC) rates approach 100%, and to relate these findings to the use of routine surveillance brain imaging. METHODS From a prospective registry, 200 patients with 1237 brain metastases were identified who underwent SRS between December 2012 and May 2015. The median imaging follow-up duration was 7.9 months, and the median margin dose was 18 Gy. The maximal diameter and volume of tumors were measured. Histological analysis included 96 patients with non-small cell lung cancers (NSCLCs), 40 with melanoma, 35 with breast cancer, and 29 with other histologies. RESULTS Almost 50% of brain metastases were NSCLCs and commonly measured less than 6 mm in maximal diameter or 70 mm3 in volume. Thirty-three of 1237 tumors had local progression at a median of 8.8 months. The 1- and 2-year actuarial LC rates were 97% and 93%, respectively. LC of 100% was achieved for all intracranial metastases less than 100 mm3 in volume or 6 mm in diameter. Patients whose tumors at first SRS were less than 10 mm maximal diameter or a volume of 250 mm3 had improved overall survival. CONCLUSIONS SRS can achieve LC rates approaching 100% for subcentimeter metastases. The earlier initial detection and prompt treatment of small intracranial metastases may prevent the development of neurological symptoms and the need for resection, and improve overall survival. To identify tumors when they are small, routine surveillance brain imaging should be considered as part of the standard of care for lung, breast, and melanoma metastases. CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort; evidence: Class II.

Stereotactic radiosurgery has revolutionized the management of brain metastases. It delivers focused, highly conformal, ionizing radiation to a tumor delineated using high-resolution imaging, with low toxicity to adjacent brain structures. Randomized controlled and prospective trials have demonstrated a survival advantage and high local control rates after stereotactic radiosurgery for metastatic disease to the central nervous system, including for up to 10 brain metastases. Its minimal-access nature makes it an attractive alternative to surgical resection. Furthermore, in addition to chemotherapy, newer targeted therapies and immunotherapies with improved side-effect profiles allow for the concurrent delivery of systemic therapy with radiosurgery, with possible additive or synergistic effects, expediting the treatment of both extracranial and intracranial disease. The modern management of brain metastasis patients should include consideration of routine staging and surveillance magnetic resonance imaging scans in patients with higher-stage cancer to detect intracranial metastases earlier and treat promptly with radiosurgery in order to prevent the development of neurologic symptoms and the need for surgical resection.

BACKGROUND: The management of brainstem arteriovenous malformations (bAVMs) is a formidable challenge. bAVMs harbor higher morbidity and mortality compared to other locations. OBJECTIVE: To review the outcomes following stereotactic radiosurgery (SRS) of bAVMs in a multicenter study. METHODS: Six medical centers contributed data from 205 patients through the International Gamma Knife Research Foundation. Median age was 32 yr (6-81). Median nidus volume was 1.4 mL (0.1-69 mL). Favorable outcome (FO) was defined as AVM obliteration and no post-treatment hemorrhage or permanent symptomatic radiation-induced complications. RESULTS: Overall obliteration was reported in 65.4% (n = 134) at a mean follow-up of 69 mo. Obliteration was angiographically proven in 53.2% (n = 109) and on MRA in 12.2% (n = 25). Actuarial rate of obliteration at 2, 3, 5, 7, and 10 yr after SRS was 24.5%, 43.3%, 62.3%, 73%, and 81.8% respectively. Patients treated with a margin dose >20 Gy were more likely to achieve obliteration ( P = .001). Obliteration occurred earlier in patients who received a higher prescribed margin dose ( P = .05) and maximum dose ( P = .041). Post-SRS hemorrhage occurred in 8.8% (n = 18). Annual postgamma knife latency period hemorrhage was 1.5%. Radiation-induced complications were radiologically evident in 35.6% (n = 73), symptomatic in 14.6% (n = 30), and permanent in 14.6% (n = 30, which included long-tract signs and new cranial nerve deficits). FO was achieved in 64.4% (n = 132). Predictors of an FO were a higher Virginia radiosurgery AVM scale score ( P = .003), prior hemorrhage ( P = .045), and a lower prescribed maximum dose ( P = .006). CONCLUSION: SRS for bAVMs results in obliteration and avoids permanent complications in the majority of patients.

Context: Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge. Objective: To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management. Design: International, multicenter, retrospective cohort analysis. Setting: Ten medical centers participating in the International Gamma Knife Research Foundation. Patients: Patients with CD with >6 months endocrine follow-up. Intervention: SRS using Gamma Knife radiosurgery. Main Outcome Measures: The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded. Results: In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation. Conclusions: SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS.