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I. Jonathan Pomeraniec, Davis G. Taylor, Or Cohen-Inbar, Zhiyuan Xu, Mary Lee Vance and Jason P. Sheehan

OBJECTIVE

Gamma Knife radiosurgery (GKRS) provides a safe and effective management option for patients with all types of pituitary adenomas. The long-term adverse effects of targeted radiation to the hypothalamic-pituitary axis in relationship to radiation dose remain unclear. In this retrospective review, the authors investigated the role of differential radiation doses in predicting long-term clinical outcomes and pituitary function after GKRS for pituitary adenomas.

METHODS

A cohort of 236 patients with pituitary tumors (41.5% nonfunctioning, 58.5% functioning adenomas) was treated with GKRS between 1998 and 2015. Point dosimetric measurements, with no minimum volume, to 14 consistent points along the hypothalamus bilaterally, pituitary stalk, and normal pituitary were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiological, and endocrine outcomes.

RESULTS

With a median follow-up duration of 42.9 months, 18.6% of patients developed new loss of pituitary function. The median time to endocrinopathy was 21 months (range 2–157 months). The median dose was 2.1 Gy to the hypothalamus, 9.1 Gy to the pituitary stalk, and 15.3 Gy to the normal pituitary. Increasing age (p = 0.015, HR 0.98) and ratio of maximum dose to the pituitary stalk over the normal pituitary gland (p = 0.013, HR 0.22) were independent predictors of new or worsening hypopituitarism in the multivariate analysis. Sex, margin dose, treatment volume, nonfunctioning adenoma status, or ratio between doses to the pituitary stalk and hypothalamus were not significant predictors.

CONCLUSIONS

GKRS offers a low rate of delayed pituitary insufficiency for pituitary adenomas. Doses to the hypothalamus are low and generally do not portend endocrine deficits. Patients who are treated with a high dose to the pituitary stalk relative to the normal gland are at higher risk of post-GKRS endocrinopathy. Point dosimetry to specific neuroanatomical structures revealed that a ratio of stalk-to-gland radiation dose of 0.8 or more significantly increased the risk of endocrinopathy following GKRS. Improvement in the gradient index toward the stalk and normal gland may help preserve endocrine function.

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Zengpanpan Ye, Xiaolin Ai and Chao You

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Dylan Russell, Travis Peck, Dale Ding, Ching-Jen Chen, Davis G. Taylor, Robert M. Starke, Cheng-Chia Lee and Jason P. Sheehan

OBJECTIVE

Embolization of brain arteriovenous malformations (AVMs) prior to stereotactic radiosurgery (SRS) has been reported to negatively affect obliteration rates. The goal of this systematic review and meta-analysis was to compare the outcomes of AVMs treated with embolization plus SRS (E+SRS group) and those of AVMs treated with SRS alone (SRS group).

METHODS

A literature review was performed using PubMed to identify studies with 10 or more AVM patients and obliteration data for both E+SRS and SRS groups. A meta-analysis was performed to compare obliteration rates between the E+SRS and SRS groups.

RESULTS

Twelve articles comprising 1716 patients were eligible for analysis. Among the patients with radiological follow-up data, complete obliteration was achieved in 48.4% of patients (330/681) in the E+SRS group compared with 62.7% of patients (613/978) in the SRS group. A meta-analysis of the pooled data revealed that the obliteration rate was significantly lower in the E+SRS group (OR 0.51, 95% CI 0.41–0.64, p < 0.00001). Symptomatic adverse radiation effects were observed in 6.6% (27/412 patients) and 11.1% (48/433 patients) of the E+SRS and SRS groups, respectively. The annual post-SRS hemorrhage rate was 2.0%–6.5% and 0%–2.0% for the E+SRS and SRS groups, respectively. The rates of permanent morbidity were 0%–6.7% and 0%–13.5% for the E+SRS and SRS groups, respectively.

CONCLUSIONS

Arteriovenous malformation treatment with combined embolization and SRS is associated with lower obliteration rates than those with SRS treatment alone. However, this comparison does not fully account for differences in the initial AVM characteristics in the E+SRS group as compared with those in the SRS group. Further studies are warranted to address these limitations.

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Adeel Ilyas, Ching-Jen Chen, Dale Ding, Davis G. Taylor, Shayan Moosa, Cheng-Chia Lee, Or Cohen-Inbar and Jason P. Sheehan

OBJECTIVE

Several recent studies have improved our understanding of the outcomes of volume-staged (VS) and dose-staged (DS) stereotactic radiosurgery (SRS) for the treatment of large (volume > 10 cm3) brain arteriovenous malformations (AVMs). In light of these recent additions to the literature, the aim of this systematic review is to provide an updated comparison of VS-SRS and DS-SRS for large AVMs.

METHODS

A systematic review of the literature was performed using PubMed to identify cohorts of 5 or more patients with large AVMs who had been treated with VS-SRS or DS-SRS. Baseline data and post-SRS outcomes were extracted for analysis.

RESULTS

A total of 11 VS-SRS and 10 DS-SRS studies comprising 299 and 219 eligible patients, respectively, were included for analysis. The mean obliteration rates for VS-SRS and DS-SRS were 41.2% (95% CI 31.4%–50.9%) and 32.3% (95% CI 15.9%–48.8%), respectively. Based on pooled individual patient data, the outcomes for patients treated with VS-SRS were obliteration in 40.3% (110/273), symptomatic radiation-induced changes (RICs) in 13.7% (44/322), post-SRS hemorrhage in 19.5% (50/256), and death in 7.4% (24/323); whereas the outcomes for patients treated with DS-SRS were obliteration in 32.7% (72/220), symptomatic RICs in 12.2% (31/254), post-SRS hemorrhage in 10.6% (30/282), and death in 4.6% (13/281).

CONCLUSIONS

Volume-staged SRS appears to afford higher obliteration rates than those achieved with DS-SRS, although with a less favorable complication profile. Therefore, VS-SRS or DS-SRS may be a reasonable treatment approach for large AVMs, either as stand-alone therapy or as a component of a multimodality management strategy.