Pollock, Bruce E.

Abstract Background This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management. Methods Using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words “radiosurgery” and “pituitary” and/or “adenoma.” Weighted random effects models were used to calculate pooled outcome estimates. Results Of the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5–35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12–25 Gy, delivered in 3–5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0–96.0%) and 97.0% (95% CI: 93.0–98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0–88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0–27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0–7%). Conclusions SRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Abstract Traditionally, the 50% isodose line (IDL) is used for prescription dose when vestibular schwannomas (VS) are treated with Gamma Knife radiosurgery (GKRS). To compare the effect of IDL on treatment outcomes, propensity score-matched analysis according to age at time of GKRS and tumor volume (TV) between cohorts treated at 40%IDL and 50%IDL was performed. Patients with no history of neurofibromatosis, GKRS prescribed marginal dose of 12–14 Gy and TV ≤ 10 cc were identified. Patients were excluded if follow-up time was < 2 years. Eventually, 30 and 28 patients were included in 40%IDL and 50%IDL cohorts, respectively. Mean age and TV were not significantly different between 40%IDL and 50%IDL groups; 54.5 versus 54.0 years (p=0.891) and 2148.61 versus 2031.10 mm3 (p=0.844), respectively. Median prescription dose was 12 Gy in both groups. At median follow-up times of 111 and 72 months, the 2, 5 and 10-year local control were 100%, 96.4% and 96.4% for 40%IDL and 96.4%, 86.7%, and 86.7% for 50%IDL (p=0.243), respectively. Among 40 patients with accessible follow-up MRIs (40%IDL-n=19, 50%IDL-n=21), volume reduction at last follow-up MRIs and rate of reduction per year for 40%IDL and 50%IDL were 48.1% versus 38.3% (p=0.05) and 5.5% versus 6% (p=0.749), respectively. Of 21 patients with serviceable hearing prior to GKRS and available audiograms after GKRS (40%IDL-n=8, 50%IDL-n=13), the 2, 5 and 10-year hearing preservation rate were 100%, 83.3% and 62.5% for 40%IDL versus 76.2%, 57.1% and 11.4% for 50%IDL (p=0.017). Facial paresthesia, facial palsy and ataxia/gait disturbance requiring steroid and/or shunt were lower in 40%IDL compared to the 50%IDL; 6.7% versus 17.9% (p=0.208) and 3.3% versus 7.1% (p=0.532). To summarize, VS treated at 40%IDL have slightly better local control, although not statistically significant, compared to tumors treated at 50%IDL. However, hearing preservation and safety seem to be more favorable toward 40%IDL group.

OBJECTIVEStereotactic radiosurgery (SRS) is an accepted treatment option for patients with benign parasellar tumors. Here, the authors’ objective was to determine the risk of developing new or progressive internal carotid artery (ICA) stenosis or occlusion after single-fraction SRS for cavernous sinus meningioma (CSM) or growth hormone–secreting pituitary adenoma (GHPA).METHODSThe authors queried their prospectively maintained registry for patients treated with single-fraction SRS for CSM or GHPA in the period from 1990 to 2015. Study criteria included no prior irradiation and ≥ 12 months of post-SRS radiological follow-up. Pre-SRS grading of ICA involvement was applied according to the 1993 classification schemes of Hirsch for CSM or Knosp for GHPA.RESULTSThe authors conducted a retrospective review of 283 patients, 155 with CSMs and 128 with GHPAs. Ninety-three (60%) CSMs were Hirsch category 2 and 3 tumors; 97 (76%) GHPAs were Knosp grade 2–4 tumors. Median follow-up after SRS was 6.6 years (IQR 1–24.9 years). No GHPA or category 1 CSM developed ICA stenosis or occlusion. Three (5.2%) patients with category 2 CSMs had asymptomatic ICA stenosis (n = 2) or occlusion (n = 1); 1 (1.1%) category 2 CSM patient had transient ischemic symptoms. Five (14.3%) category 3 CSMs progressed to ICA occlusion (4 asymptomatic, 1 symptomatic). The median time to stenosis/occlusion was 4.8 years (IQR 1.8–7.6). Five- and 10-year risks of ICA stenosis/occlusion in category 2 and 3 CSM patients were 7.5% and 12.4%, respectively. Five- and 10-year risks of ischemic stroke from ICA stenosis/occlusion in category 2 and 3 CSM patients were both 1.2%. Multivariate analysis showed patient age (HR 0.92, 95% CI 0.86–0.98, p = 0.01), meningioma pathology (HR and 95% CI not defined, p = 0.03), and pre-SRS carotid category (HR 4.51, 95% CI 1.77–14.61, p = 0.004) to be associated with ICA stenosis/occlusion. Internal carotid artery stenosis/occlusion was not related to post-SRS tumor growth (HR and 95% CI not defined, p = 0.41).CONCLUSIONSNew or progressive ICA stenosis/occlusion was common after SRS for CSM but was not observed after SRS for GHPA, suggesting a tumor-specific mechanism unrelated to radiation dose. Pre-SRS ICA encasement or constriction increases the risk of ICA stenosis/occlusion; however, the risk of ischemic complications is very low.

OBJECTIVERadiation dose to the cochlea has been proposed as a key prognostic factor in hearing preservation following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). However, understanding of the predictive value of cochlear dose on hearing outcomes following SRS for patients with non-VS tumors of the lateral skull base (LSB) is incomplete. The authors investigated rates of hearing loss following high-dose SRS in patients with LSB non-VS lesions compared with patients with VS.METHODSPatients with LSB meningioma or jugular paraganglioma and serviceable pretreatment hearing who underwent SRS treatment during 2007–2016 and received a modiolus dose > 5 Gy were included in a retrospective cohort study, along with a similarly identified control group of consecutive patients with sporadic VS.RESULTSSixteen patients with non-VS tumors and a control group of 43 patients with VS met study criteria. Serviceable hearing, defined as American Academy of Otololaryngology–Head and Neck Surgery class A/B, was maintained in 13 non-VS versus 23 VS patients (81% vs 56%, p = 0.07). All 3 instances of hearing loss in non-VS patients were observed in cerebellopontine angle (CPA) meningiomas. Non-VS with preserved hearing had a median modiolus dose of 6.9 Gy (range 5.7–19.2 Gy), versus 7.4 Gy (range 5.4–7.6 Gy) in those patients with post-SRS hearing loss (p = 0.53). Sporadic VS patients received an overall median modiolus point-dose of 6.8 Gy (range 5.4–11.7 Gy).CONCLUSIONSThe modiolus dose threshold of 5 Gy does not predict hearing loss in patients with non-VS tumors undergoing SRS, suggesting that dosimetric parameters derived from VS may not be applicable to this population. Differential rates of hearing loss appear to vary by pathology, with paragangliomas and petroclival meningiomas demonstrating decreased risk of hearing loss compared to CPA meningiomas that may directly compress the cochlear nerve similarly to VS.

Abstract BACKGROUND Surgical resection is typically cited as the optimal treatment of patients with Spetzler-Martin Grade I-II arteriovenous malformation (AVM). OBJECTIVE To report our experience with single-fraction stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I-II AVM. METHODS A prospectively maintained registry was reviewed for patients with nonsyndromic Spetzler-Martin Grade I-II AVM having SRS from 1990 to 2011. Patients with <24 mo of follow-up or prior radiotherapy/SRS were excluded, resulting in a study population of 173 patients. Actuarial analysis was performed using the Kaplan-Meier method, and Cox proportional hazards modeling was performed with excellent outcomes (obliteration without new deficits) as the dependent variable. RESULTS Median post-SRS follow-up was 68 mo (range, 24-275). AVM obliteration was achieved in 132 (76%) after initial SRS. Eleven additional patients achieved obliteration after repeat SRS for an overall obliteration rate of 83%. The rate of obliteration was 60% at 4 yr and 78% at 8 yr. Post-SRS hemorrhage occurred in 7 patients (4%), resulting in 3 minor deficits (2%) and 1 death (<1%). Radiation-induced complications occurred in 5 patients (3%), resulting in minor deficits only. One hundred and thirty-seven patients (79%) had excellent outcomes at last follow-up. CONCLUSION SRS is a safe and effective treatment for patients with Spetzler-Martin Grade I-II AVM. Selection bias is likely a contributing factor to explain the superior outcomes generally noted in reported series of microsurgery for patients with low grade AVM.

Objective: The treatment paradigm for jugular paraganglioma (JP) has changed considerably over time with the wider adoption of stereotactic radiosurgery (SRS). To the best of the authors’ knowledge, there are no published studies that use validated patient-reported outcome measures to ascertain quality of life (QoL) outcomes following SRS for JP when used in single or combined modality treatment regimens. Study Design: Cross-sectional survey. Setting: Tertiary referral center. Patients: Adult patients with JP treated with primary SRS or SRS following primary surgery between 1990 and 2017. Interventions(S): Surgery and/or Gamma Knife SRS. Main Outcome Measures: Global and treatment-related QoL and differences in QoL based on treatment approach. Results: Sixty-nine surveys were distributed and a total of 26 completed surveys were received (38% response rate). Among respondents, the median age at SRS was 53 years and 16 of the 26 patients (62%) were female. Median follow-up was 97 months. Nineteen patients (73%) were treated with primary SRS or staged SRS following intentional subtotal resection (STR; hereafter referred to as “staged SRS”), while the remainder (n = 7, 27%) were treated with SRS for recurrent JP. Median physical and mental health QoL PROMIS-10 T-scores regardless of treatment strategy were 39.8 and 38.8, respectively, while median SF36 physical and mental component subscores were similar to national averages and non-tumor controls. When comparing general physical and mental health QoL scores, there was no significant difference between patients treated with primary or staged SRS and those treated with SRS for recurrent JP. However, age-adjusted swallowing function among patients treated with primary or staged SRS was better than in those patients treated with SRS for recurrent JP (p = 0.05). Conclusions: Patients treated with primary or staged SRS for JP tend to exhibit better swallowing outcomes than those treated with SRS for recurrent JP. However, the majority of overall and disease-specific quality of life measures were not different between groups. Based on the low incidence of new cranial neuropathy following SRS, it is likely that initial surgical morbidity is the primary contributor to this outcome. Disease-specific overall quality of life measures, akin to those already used for other benign skull base tumors, are necessary to better gauge physical and mental health outcomes following treatment for JP. Though limited by small sample size, this represents the first study to gauge QoL outcomes following treatment for JP.

OBJECTIVEThe goal of this study was to evaluate the outcomes of Gamma Knife stereotactic radiosurgery (SRS) when used for patients with intractable idiopathic glossopharyngeal neuralgia.METHODSSix participating centers of the International Gamma Knife Research Foundation identified 22 patients who underwent SRS for intractable glossopharyngeal neuralgia between 1998 and 2015. The median patient age was 60 years (range 34–83 years). The median duration of symptoms before SRS was 46 months (range 1–240 months). Three patients had unsuccessful prior surgical procedures, including microvascular decompression (MVD) (n = 2) and balloon compression (n = 1). The radiosurgical target was the glossopharyngeal meatus. The median maximum dose was 80 Gy.RESULTSThe median follow-up was 45 months after SRS (range 6–120 months). Twelve patients (55%) had < 4 years of follow-up. Thirteen patients (59%) had initial complete pain relief at a median of 12 days after SRS (range 1–60 days). Three patients (14%) had partial pain relief at a median of 70 days after SRS (range 60–90 days). Six patients (27%) had no pain relief. Among 16 patients with initial pain relief, 5 maintained complete pain relief without medication (Barrow Neurological Institute [BNI] pain intensity score Grade I), 1 maintained occasional pain relief without medication (BNI Grade II), 3 maintained complete pain relief with medication (BNI Grade IIIb), and 7 patients had pain recurrence at a median of 20 months after SRS (range 6–120 months). The rates of maintenance of adequate pain relief (BNI Grades I–IIIb) were 63% at 1 year, 49% at 2 years, 38% at 3 years, 38% at 5 years, and 28% at 7 years. When 7 patients without pain recurrence within 4 years of follow-up were excluded, the rates of maintenance of adequate pain relief were 38% at 5 years and 28% at 7 years. Ten patients required additional procedures (MVD, n = 4; repeat SRS, n = 5; glossopharyngeal nerve block, n = 1). Four of 5 patients who underwent repeat SRS maintained pain relief (BNI Grade I, n = 3; and BNI Grade IIIb, n = 1). No adverse effects of radiation were observed after a single SRS. Two patients developed hyperesthesia in the palatoglossal arch 5 and 8 months after repeat SRS, respectively.CONCLUSIONSStereotactic radiosurgery for intractable, medically refractory glossopharyngeal neuralgia provided lasting pain reduction in 55% of patients after 1 or 2 SRS procedures. Patients who had a poor response or pain recurrence may require additional procedures such as repeat SRS, MVD, nerve blocks, or nerve section. No patient developed changes in vocal cord function or swallowing disorders after SRS in this study.

Abstract BACKGROUND Patients with persistent or recurrent Cushing disease (CD) after prior transsphenoidal surgery require further treatment to reduce the disease's metabolic consequences. OBJECTIVE To assess patient outcomes after stereotactic radiosurgery (SRS) for persistent or recurrent CD from adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas and propose a management algorithm. METHODS Retrospective review of 38 patients without prior radiation treatment having SRS for ACTH-secreting pituitary adenomas from 1990 to 2015. Favorable outcome was defined as biochemical remission and tumor growth control. Patients were evaluated separately if they underwent bilateral adrenalectomy (Adx). RESULTS Twenty patients (53%) were treated with Adx and SRS (median margin dose, 25 Gy) and 18 patients (47%) received SRS alone (median margin dose, 22.5 Gy). Median follow-up after SRS was 76 mo. Of patients undergoing Adx, 18/20 (90%) had a favorable outcome. Two patients (10%) had tumor growth requiring additional treatment. A favorable outcome was achieved in 13/18 patients (72%) having SRS alone (median, 14 mo; interquartile range, 8-23). Five patients (28%) required additional treatment due to persistent hypercortisolemia (n = 4) or hypercortisolemia and tumor growth (n = 1). Favorable outcomes were more frequent in the Adx and SRS group at 1 yr (100% vs 33%; P < .001) and 3 yr (100% vs 62%; P < .01), but no different at 5 yr (88% vs 77%; P = .63). CONCLUSION SRS was effective for patients with persistent or recurrent CD. Patients with mild to moderate CD can be safely managed with SRS alone; patients with severe CD should be considered for Adx with either concurrent SRS or SRS performed at a later date if tumor growth occurs.

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a common treatment modality for vestibular schwannoma (VS), with a role in primary and recurrent/progressive algorithms. At our institution, routine magnetic resonance imaging (MRI) is obtained at 6 and 12 mo following SRS for VS. OBJECTIVE To analyze the safety and financial impact of eliminating the 6-mo post-SRS MRI in asymptomatic VS patients. METHODS A prospectively maintained SRS database was retrospectively reviewed for VS patients with 1 yr of post-treatment follow-up, 2005 to 2015. Decisions at 6-mo MRI were binarily categorized as routine follow-up vs clinical action —defined as a clinical visit, additional imaging, or an operation as a direct result of the 6-mo study. RESULTS A total of 296 patients met screening criteria, of whom 53 were excluded for incomplete follow-up and 8 for NF-2. Nine were reimaged prior to 6 mo due to clinical symptoms. Routine 6-mo post-SRS MRI was completed by 226 patients (76% of screened cohort), following from which zero instances of clinical action occurred. When scaled using national insurance database-derived financials—which estimated the mean per-study charge for MRI of the brain with and without contrast at $1767—the potential annualized national charge reduction was approximated as $1 611 504. CONCLUSION For clinically stable VS, 6-mo post-SRS MRI does not contribute significantly to management. We recommend omitting routine MRI before 12 mo, in patients without new or progressive neurological symptoms. If extrapolated nationally to the more than 100 active SRS centers, thousands of patients would be spared an inconvenient, nonindicated study, and national savings in health care dollars would be on the order of millions annually.