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Martin H. Weiss, Gabriel Zada, John D. Carmichael and William T. Couldwell

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Adomas Bunevicius, Karen Lavezzo, Leah Shabo, Jesse McClure and Jason P. Sheehan

OBJECTIVE

Quality of life (QOL) is an important endpoint measure of cancer treatment. The authors’ goal was to evaluate QOL trajectories and prognostic value in cancer patients treated with stereotactic radiosurgery (SRS) for brain metastases.

METHODS

Patients who underwent Gamma Knife radiosurgery (GKRS) between January 2016 and November 2019 were prospectively evaluated for QOL using the EQ-5D-3L questionnaire before SRS and at follow-up visits. Only patients who had pre-SRS and at least 1 post-SRS QOL assessment were considered.

RESULTS

Fifty-four cancer patients underwent 109 GKRS procedures. The first post-SRS visit was at a median of 2.59 months (range 0.13–21.08 months), and the last post-SRS visit was at 14.72 months (range 2.52–45.21 months) after SRS. There was no statistically significant change in the EQ-5D index score (p = 0.539) at the first compared with last post-SRS visit. The proportion of patients reporting some problems on the EQ-5D dimension of self-care increased during the course of follow-up from 9% (pre-SRS visit) to 18% (last post-SRS visit; p = 0.03). The proportion of patients reporting problems on the EQ-5D dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression remained stable during the course of follow-up (p ≥ 0.106). After adjusting for clinical variables, a higher recursive partitioning analysis (RPA) class (i.e., worse prognostic category) was independently associated with greater odds for EQ-5D index score deterioration (p = 0.050). Upfront whole-brain radiation therapy predicted deterioration of the EQ-5D self-care (p = 0.03) and usual activities (p = 0.024) dimensions, while a greater number of lesions predicted deterioration of the EQ-5D anxiety/depression dimension (p = 0.008). A lower pre-SRS EQ-5D index was associated with shorter survival independently from clinical and demographic variables (OR 18.956, 95% CI 2.793–128.64; p = 0.003).

CONCLUSIONS

QOL is largely preserved in brain metastasis patients treated with SRS. Higher RPA class, upfront whole-brain radiation therapy, and greater intracranial disease burden are independent predictors of post-SRS QOL deterioration. Worse pre-SRS QOL predicts shorter survival. Assessment of QOL is recommended in brain metastasis patients managed with SRS.

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Rebecca M. Burke, Ching-Jen Chen, Dale Ding, Thomas J. Buell, Jennifer D. Sokolowski, Cheng-Chia Lee, Hideyuki Kano, Kathryn N. Kearns, Shih-Wei Tzeng, Huai-che Yang, Paul P. Huang, Douglas Kondziolka, Natasha Ironside, David Mathieu, Christian Iorio-Morin, Inga S. Grills, Caleb Feliciano, Gene H. Barnett, Robert M. Starke, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs.

METHODS

The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared.

RESULTS

The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation.

CONCLUSIONS

Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.

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Yi-Chieh Hung, Cheng-Chia Lee, Huai-che Yang, Nasser Mohammed, Kathryn N. Kearns, Shi-Bin Sun, David Mathieu, Charles J. Touchette, Ahmet F. Atik, Inga S. Grills, Bryan Squires, Dale Ding, Brian J. Williams, Mehran B. Yusuf, Shiao Y. Woo, Roman Liscak, Jaromir Hanuska, Jay C. Shiao, Douglas Kondziolka, L. Dade Lunsford, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors.

METHODS

The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated.

RESULTS

The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022).

CONCLUSIONS

Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

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Adomas Bunevicius, Hideyuki Kano, Cheng-Chia Lee, Michal Krsek, Ahmed M. Nabeel, Amr El-Shehaby, Khaled Abdel Karim, Nuria Martinez-Moreno, David Mathieu, John Y. K. Lee, Inga Grills, Douglas Kondziolka, Roberto Martinez-Alvarez, Wael A. Reda, Roman Liscak, Yan-Hua Su, L. Dade Lunsford, Mary Lee Vance and Jason P. Sheehan

OBJECTIVE

The optimal time to perform stereotactic radiosurgery after incomplete resection of adrenocorticotropic hormone (ACTH)–producing pituitary adenoma in patients with Cushing’s disease (CD) remains unclear. In patients with persistent CD after resection of ACTH-producing pituitary adenoma, the authors evaluated the association of the interval between resection and Gamma Knife radiosurgery (GKRS) with outcomes.

METHODS

Pooled data from 10 institutions participating in the International Radiosurgery Research Foundation were used in this study.

RESULTS

Data from 255 patients with a mean follow-up of 65.59 ± 49.01 months (mean ± SD) were analyzed. Seventy-seven patients (30%) underwent GKRS within 3 months; 46 (18%) from 4 to 6 months; 34 (13%) from 7 to 12 months; and 98 (38%) at > 12 months after the resection. Actuarial endocrine remission rates were higher in patients who underwent GKRS ≤ 3 months than when treatment was > 3 months after the resection (78% and 65%, respectively; p = 0.017). Endocrine remission rates were lower in patients who underwent GKRS at > 12 months versus ≤ 12 months after the resection (57% vs 76%, respectively; p = 0.006). In multivariate Cox regression analyses adjusted for clinical and treatment characteristics, early GKRS was associated with increased probability of endocrine remission (hazard ratio [HR] 1.518, 95% CI 1.039–2.218; p = 0.031), whereas late GKRS (HR 0.641, 95% CI 0.448–0.919; p = 0.015) was associated with reduced probability of endocrine remission. The incidence of some degree of new pituitary deficiency (p = 0.922), new visual deficits (p = 0.740), and other cranial nerve deficits (p = 0.610) was not significantly related to time from resection to GKRS.

CONCLUSIONS

Early GKRS is associated with an improved endocrine remission rate, whereas later GKRS is associated with a lower rate of endocrine remission after pituitary adenoma resection. Early GKRS should be considered for patients with CD after incomplete pituitary adenoma resection.

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Ching-Jen Chen, Cheng-Chia Lee, Hideyuki Kano, Kathryn N. Kearns, Dale Ding, Shih-Wei Tzeng, Ahmet Atik, Krishna Joshi, Gene H. Barnett, Paul P. Huang, Douglas Kondziolka, David Mathieu, Christian Iorio-Morin, Inga S. Grills, Thomas J. Quinn, Zaid A. Siddiqui, Kim Marvin, Caleb Feliciano, Andrew Faramand, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years).

METHODS

The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated.

RESULTS

The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%–68.0%), 77.1% (95% CI 72.1%–81.3%), and 88.1% (95% CI 82.5%–92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%–7.2%), 9.7% (95% CI 6.4%–13.7%), and 14.5% (95% CI 9.5%–20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%–10.7%) and 6.9% (95% CI 3.1%–12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%–9.7%) over 15 years.

CONCLUSIONS

AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.

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Adomas Bunevicius, Darrah Sheehan, Mary Lee Vance, David Schlesinger and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is used for the management of residual or recurrent Cushing’s disease (CD). Increasing experience and technological advancements of Gamma Knife radiosurgery (GKRS) systems can impact the outcomes of CD patients. The authors evaluated the association of their center’s growing experience and the era in which GKRS was performed with treatment success and adverse events in patients with CD.

METHODS

The authors studied consecutive patients with CD treated with GKRS at the University of Virginia since installation of the first Gamma Knife system in March 1989 through August 2019. They compared endocrine remission and complication rates between patients treated before 2000 (early cohort) and those who were treated in 2000 and later (contemporary cohort).

RESULTS

One hundred thirty-four patients with CD underwent GKRS during the study period: 55 patients (41%) comprised the early cohort, and 79 patients (59%) comprised the contemporary cohort. The contemporary cohort, compared with the early cohort, had a significantly greater treatment volume, radiation prescription dose, maximal dose to the optic chiasm, and number of isocenters, and they more often had cavernous sinus involvement. Endocrine remission rates were higher in the contemporary cohort when compared with the early cohort (82% vs 66%, respectively; p = 0.01). In a Cox regression analysis adjusted for demographic, clinical, and SRS characteristics, the contemporary GKRS cohort had a higher probability of endocrine remission than the early cohort (HR 1.987, 95% CI 1.234–3.199; p = 0.005). The tumor control rate, incidence of cranial nerve neuropathy, and new anterior pituitary deficiency were similar between the two groups.

CONCLUSIONS

Technological advancements over the years and growing center experience were important factors for improved endocrine remission rates in patients with CD. Technological aspects and results of contemporary Gamma Knife systems should be considered when counseling patients, planning treatment, and reporting treatment results. Studies exploring the learning curve for GKRS are warranted.

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Erin S. Murphy, Shireen Parsai, Hideyuki Kano, Jason P. Sheehan, Roberto Martinez-Alvarez, Nuria Martinez-Moreno, Douglas Kondziolka, Gabriela Simonova, Roman Liscak, David Mathieu, Cheng-Chia Lee, Huai-Che Yang, John Y. Lee, Brendan J. McShane, Fang Fang, Daniel M. Trifiletti, Mayur Sharma and Gene H. Barnett

OBJECTIVE

The current standard initial therapy for pilocytic astrocytoma is maximal safe resection. Radiation therapy is considered for residual, recurrent, or unresectable pilocytic astrocytomas. However, the optimal radiation strategy has not yet been established. Here, the authors describe the outcomes of stereotactic radiosurgery (SRS) for pilocytic astrocytoma in a large multiinstitutional cohort.

METHODS

An institutional review board–approved multiinstitutional database of patients treated with Gamma Knife radiosurgery (GKRS) between 1990 and 2016 was queried. Data were gathered from 9 participating International Radiosurgery Research Foundation (IRRF) centers. Patients with a histological diagnosis of pilocytic astrocytoma treated using a single session of GKRS and with at least 6 months of follow-up were included in the analysis.

RESULTS

A total of 141 patients were analyzed in the study. The median patient age was 14 years (range 2–84 years) at the time of GKRS. The median follow-up was 67.3 months. Thirty-nine percent of patients underwent SRS as the initial therapy, whereas 61% underwent SRS as salvage treatment. The median tumor volume was 3.45 cm3. The tumor location was the brainstem in 30% of cases, with a nonbrainstem location in the remainder. Five- and 10-year overall survival rates at the last follow-up were 95.7% and 92.5%, respectively. Five- and 10-year progression-free survival (PFS) rates were 74.0% and 69.7%, respectively. On univariate analysis, an age < 18 years, tumor volumes < 4.5 cm3, and no prior radiotherapy or chemotherapy were identified as positive prognostic factors for improved PFS. On multivariate analysis, only prior radiotherapy was significant for worse PFS.

CONCLUSIONS

This represents the largest study of single-session GKRS for pilocytic astrocytoma to date. Favorable long-term PFS and overall survival were observed with GKRS. Further prospective studies should be performed to evaluate appropriate radiosurgery dosing, timing, and sequencing of treatment along with their impact on toxicity and the quality of life of patients with pilocytic astrocytoma.

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Nasser Mohammed, Yi-Chieh Hung, Thomas J. Eluvathingal Muttikkal, Roy C. Bliley, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

The motor root of the trigeminal nerve runs close to the sensory root and receives considerable radiation during Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The object of this study was to evaluate via MRI the changes in the muscles of mastication before and after upfront GKRS in patients with idiopathic TN.

METHODS

In this single-institution retrospective cohort study, all patients with idiopathic unilateral TN treated with primary GKRS at the University of Virginia in the period from 2007 to 2017 were included provided that they had pre- and post-GKRS MRI data. The thicknesses of the temporalis, pterygoid, and masseter muscles were measured on both pre- and post-GKRS MRI in a blinded fashion. Changes in the muscles like fatty infiltration, MRI signal, or atrophy were noted.

RESULTS

Among the 68 patients eligible for inclusion in the study, 136 temporalis muscles, 136 medial pterygoid muscles, 136 lateral pterygoid muscles, and 136 masseter muscles were assessed. A subset of patients was found to have muscle atrophy even prior to GKRS. Pre-GKRS atrophy of the masseter, medial pterygoid, lateral pterygoid, and temporalis muscles was seen in 18 (26%), 16 (24%), 9 (13%), and 16 (24%) patients, respectively. Logistic regression analysis showed that distribution of pain in the V3 territory (p = 0.01, OR 5.43, 95% CI 1.46–20.12) and significant pain on chewing (p = 0.02, OR 5.32, 95% CI 1.25–22.48) were predictive of pre-GKRS atrophy. Reversal of atrophy of these muscles occurred after GKRS in a majority of the patients. The incidence of new-onset permanent post-GKRS muscle atrophy was 1.5%. The median follow-up was 39 months (range 6–108 months).

CONCLUSIONS

A subset of patients with TN with significant pain on chewing have pre-GKRS disuse atrophy of the muscles of mastication. A reversal of the atrophy occurs in a majority of the patients following GKRS. New-onset motor neuropathy post-GKRS was rare.