Faculty Bibliography

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.

Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated. Groups were matched. SCA was characterized by a lack of clinical evidence of Cushing disease, yet with positive immunostaining for corticotroph. Median age was 55.2 years (13.7-87). All patients underwent at least one trans-sphenoidal tumor resection prior to SRS. SRS parameters were comparable as well. Median follow-up 40 months (6-163). Overall tumor control rate (TCR) 91.2% (n = 280). In the SCA group, TCR were 82% (n = 41) versus 94.1% (n = 289) for the control-NFA (p = 0.0065). The SCA group showed a significantly higher incidence of new post-SRS visual deficit (p < 0.0001) assigned to tumor progression and growth, and post-SRS weakness and fatigue (p < 0.0001). In univariate and multivariate analysis, only the status of silent corticotroph staining (p = 0.005, p = 0.009 respectively) and margin dose (p < 0.0005, p = 0.0037 respectively) significantly influenced progression rate. A margin dose of >/=17 Gy was noted to influence the adenoma progression rate in the entire cohort (p = 0.003). Silent corticotroph staining represents an independent factor for adenoma progression and hypopituitarism after SRS. A higher margin dose may convey a greater chance of TCR.

OBJECTIVE Cerebellar arteriovenous malformations (AVMs) represent the majority of infratentorial AVMs and frequently have a hemorrhagic presentation. In this multicenter study, the authors review outcomes of cerebellar AVMs after stereotactic radiosurgery (SRS). METHODS Eight medical centers contributed data from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65% presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent radiation-induced complications (RICs). Patients were followed clinically and radiographically, with a median follow-up of 60 months (range 7-325 months). RESULTS The overall actuarial rates of obliteration at 3, 5, 7, and 10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session SRS. Obliteration and a favorable outcome were more likely to be achieved in patients treated with a margin dose greater than 18 Gy (p < 0.001 for both), demonstrating significantly better rates (83.3% and 79%, respectively). The rate of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable outcome. CONCLUSIONS SRS results in successful obliteration and a favorable outcome in the majority of patients with cerebellar AVMs. Most patients will require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical and not microsurgical scales were predictive of clinical outcome after SRS.