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Nasser Mohammed, Dale Ding, Yi-Chieh Hung, Zhiyuan Xu, Cheng-Chia Lee, Hideyuki Kano, Roberto Martínez-Álvarez, Nuria Martínez-Moreno, David Mathieu, Mikulas Kosak, Christopher P. Cifarelli, Gennadiy A. Katsevman, L. Dade Lunsford, Mary Lee Vance and Jason P. Sheehan

OBJECTIVE

The role of primary stereotactic radiosurgery (SRS) in patients with medically refractory acromegaly who are not operative candidates or who refuse resection is poorly understood. The aim of this multicenter, matched cohort study was to compare the outcomes of primary versus postoperative SRS for acromegaly.

METHODS

The authors reviewed an International Radiosurgery Research Foundation database of 398 patients with acromegaly who underwent SRS and categorized them into primary or postoperative cohorts. Patients in the primary SRS cohort were matched, in a 1:2 ratio, to those in the postoperative SRS cohort, and the outcomes of the 2 matched cohorts were compared.

RESULTS

The study cohort comprised 78 patients (median follow-up 66.4 months), including 26 and 52 in the matched primary and postoperative SRS cohorts, respectively. In the primary SRS cohort, the actuarial endocrine remission rates at 2 and 5 years were 20% and 42%, respectively. The Cox proportional hazards model showed that a lower pre-SRS insulin-like growth factor–1 level was predictive of initial endocrine remission (p = 0.03), whereas a lower SRS margin dose was predictive of biochemical recurrence after initial remission (p = 0.01). There were no differences in the rates of radiological tumor control (p = 0.34), initial endocrine remission (p = 0.23), biochemical recurrence after initial remission (p = 0.33), recurrence-free survival (p = 0.32), or hypopituitarism (p = 0.67) between the 2 matched cohorts.

CONCLUSIONS

Primary SRS has a reasonable benefit-to-risk profile for patients with acromegaly in whom resection is not possible, and it has similar outcomes to endocrinologically comparable patients who undergo postoperative SRS. SRS with medical therapy in the latent period can be used as an alternative to surgery in selected patients who cannot or do not wish to undergo resection.

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Ching-Jen Chen, Thomas J. Buell, Daniel M. S. Raper, Min S. Park, M. Yashar Kalani, Natasha Ironside, Robert F. James and Dale Ding

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Mayur Sharma, Beatrice Ugiliweneza, Enzo M. Fortuny, Nicolas K. Khattar, Noberto Andaluz, Robert F. James, Brian J. Williams, Maxwell Boakye and Dale Ding

OBJECTIVE

The development and recent widespread dissemination of flow diverters may have reduced the utilization of surgical bypass procedures to treat complex or giant unruptured intracranial aneurysms (UIAs). The aim of this retrospective cohort study was to observe trends in cerebral revascularization procedures for UIAs in the United States before and after the introduction of flow diverters by using the National (Nationwide) Inpatient Sample (NIS).

METHODS

The authors extracted data from the NIS database for the years 1998–2015 using the ICD-9/10 diagnostic and procedure codes. Patients with a primary diagnosis of UIA with a concurrent bypass procedure were included in the study. Outcomes and hospital charges were analyzed.

RESULTS

A total of 216,212 patients had a primary diagnosis of UIA during the study period. The number of patients diagnosed with a UIA increased by 128% from 1998 (n = 7718) to 2015 (n = 17,600). Only 1328 of the UIA patients (0.6%) underwent cerebral bypass. The percentage of patients who underwent bypass in the flow diverter era (2010–2015) remained stable at 0.4%. Most patients who underwent bypass were white (51%), were female (62%), had a median household income in the 3rd or 4th quartiles (57%), and had private insurance (51%). The West (33%) and Midwest/North Central regions (30%) had the highest volume of bypasses, whereas the Northeast region had the lowest (15%). Compared to the period 1998–2011, bypass procedures for UIAs in 2012–2015 shifted entirely to urban teaching hospitals (100%) and to an elective basis (77%). The median hospital stay (9 vs 3 days, p < 0.0001), median hospital charges ($186,746 vs $66,361, p < 0.0001), and rate of any complication (51% vs 17%, p < 0.0001) were approximately threefold higher for the UIA patients with bypass than for those without bypass.

CONCLUSIONS

Despite a significant increase in the diagnosis of UIAs over the 17-year study period, the proportion of bypass procedures performed as part of their treatment has remained stable. Therefore, advances in endovascular aneurysm therapy do not appear to have affected the volume of bypass procedures performed in the UIA population. The authors’ findings suggest a potentially ongoing niche for bypass procedures in the contemporary treatment of UIAs.

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Ching-Jen Chen, Kathryn N. Kearns, Dale Ding, Hideyuki Kano, David Mathieu, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Inga S. Grills, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects.

METHODS

The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome.

RESULTS

The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044).

CONCLUSIONS

SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

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Diogo Cordeiro, Zhiyuan Xu, Gautam U. Mehta, Dale Ding, Mary Lee Vance, Hideyuki Kano, Nathaniel Sisterson, Huai-che Yang, Douglas Kondziolka, L. Dade Lunsford, David Mathieu, Gene H. Barnett, Veronica Chiang, John Lee, Penny Sneed, Yan-Hua Su, Cheng-chia Lee, Michal Krsek, Roman Liscak, Ahmed M. Nabeel, Amr El-Shehaby, Khaled Abdel Karim, Wael A. Reda, Nuria Martinez-Moreno, Roberto Martinez-Alvarez, Kevin Blas, Inga Grills, Kuei C. Lee, Mikulas Kosak, Christopher P. Cifarelli, Gennadiy A. Katsevman and Jason P. Sheehan

OBJECTIVE

Recurrent or residual adenomas are frequently treated with Gamma Knife radiosurgery (GKRS). The most common complication after GKRS for pituitary adenomas is hypopituitarism. In the current study, the authors detail the timing and types of hypopituitarism in a multicenter, international cohort of pituitary adenoma patients treated with GKRS.

METHODS

Seventeen institutions pooled clinical data obtained from pituitary adenoma patients who were treated with GKRS from 1988 to 2016. Patients who had undergone prior radiotherapy were excluded. A total of 1023 patients met the study inclusion criteria. The treated lesions included 410 nonfunctioning pituitary adenomas (NFPAs), 262 cases of Cushing’s disease (CD), and 251 cases of acromegaly. The median follow-up was 51 months (range 6–246 months). Statistical analysis was performed using a Cox proportional hazards model to evaluate factors associated with the development of new-onset hypopituitarism.

RESULTS

At last follow-up, 248 patients had developed new pituitary hormone deficiency (86 with NFPA, 66 with CD, and 96 with acromegaly). Among these patients, 150 (60.5%) had single and 98 (39.5%) had multiple hormone deficiencies. New hormonal changes included 82 cortisol (21.6%), 135 thyrotropin (35.6%), 92 gonadotropin (24.3%), 59 growth hormone (15.6%), and 11 vasopressin (2.9%) deficiencies. The actuarial 1-year, 3-year, 5-year, 7-year, and 10-year rates of hypopituitarism were 7.8%, 16.2%, 22.4%, 27.5%, and 31.3%, respectively. The median time to hypopituitarism onset was 39 months.

In univariate analyses, an increased rate of new-onset hypopituitarism was significantly associated with a lower isodose line (p = 0.006, HR = 8.695), whole sellar targeting (p = 0.033, HR = 1.452), and treatment of a functional pituitary adenoma as compared with an NFPA (p = 0.008, HR = 1.510). In multivariate analyses, only a lower isodose line was found to be an independent predictor of new-onset hypopituitarism (p = 0.001, HR = 1.38).

CONCLUSIONS

Hypopituitarism remains the most common unintended effect of GKRS for a pituitary adenoma. Treating the target volume at an isodose line of 50% or greater and avoiding whole-sellar radiosurgery, unless necessary, will likely mitigate the risk of post-GKRS hypopituitarism. Follow-up of these patients is required to detect and treat latent endocrinopathies.

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I. Jonathan Pomeraniec, Dale Ding, Robert M. Starke, Kenneth C. Liu, E. Kelly Mrachek, M. Beatriz Lopes and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is a commonly employed treatment modality for brain arteriovenous malformations (AVMs). However, due to the low frequency of delayed cyst formation after AVM SRS, as well as the prolonged time interval between treatment and its occurrence, the characteristics of post-SRS cyst formation are not well defined. Therefore, the aims of this retrospective cohort study are to determine the rate of cyst formation after SRS for AVMs, identify predictive factors, and evaluate the clinical sequelae of post-SRS cysts.

METHODS

The authors analyzed an SRS database for AVM patients who underwent SRS at the University of Virginia and identified those who developed post-SRS cysts. Statistical analyses were performed to determine predictors of post-SRS cyst formation and the effect of cyst formation on new or worsening seizures after SRS.

RESULTS

The study cohort comprised 1159 AVM patients treated with SRS; cyst formation occurred in 17 patients (post-SRS cyst rate of 1.5%). Compared with patients who did not develop post-SRS cysts, those with cyst formation were treated with a greater number of radiosurgical isocenters (mean 3.8 vs 2.8, p = 0.047), had a longer follow-up (mean 132 vs 71 months, p < 0.001), were more likely to develop radiological radiation-induced changes (RIC) (64.7% vs 36.1%, p = 0.021), and had a longer duration of RIC (57 vs 21 months, p < 0.001). A higher number of isocenters (p = 0.014), radiological RIC (p = 0.002), and longer follow-up (p = 0.034) were found to be independent predictors of post-SRS cyst formation in the multivariate analysis. There was a trend toward a significant association between cyst formation and new or worsening seizures in univariate analysis (p = 0.054).

CONCLUSIONS

Patients with greater nidal complexity appear to be more prone to post-SRS cyst formation. The findings of this study emphasize the importance of long-term follow-up for patients who have undergone AVM SRS, even after nidal obliteration is achieved. Post-SRS cysts may be epileptogenic, although seizure outcomes after AVM SRS are multifactorial.

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Ching-Jen Chen, Pedro Norat, Dale Ding, George A. C. Mendes, Petr Tvrdik, Min S. Park and M. Yashar Kalani

Endovascular embolization of brain arteriovenous malformations (AVMs) is conventionally performed from a transarterial approach. Transarterial AVM embolization can be a standalone treatment or, more commonly, used as a neoadjuvant therapy prior to microsurgery or stereotactic radiosurgery. In contrast to the transarterial approach, curative embolization of AVMs may be more readily achieved from a transvenous approach. Transvenous embolization is considered a salvage therapy in contemporary AVM management. Proposed indications for this approach include a small (diameter < 3 cm) and compact AVM nidus, deep AVM location, hemorrhagic presentation, single draining vein, lack of an accessible arterial pedicle, exclusive arterial supply by perforators, and en passage feeding arteries. Available studies of transvenous AVM embolization in the literature have reported high complete obliteration rates, with reasonably low complication rates. However, evaluating the efficacy and safety of this approach is challenging due to the limited number of published cases. In this review the authors describe the technical considerations, indications, and outcomes of transvenous AVM embolization.

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Zengpanpan Ye, Xiaolin Ai and Chao You