The role of single-fraction stereotactic radiosurgery for atypical meningiomas (WHO grade II): treatment results based on a 25-year experience.

PURPOSE: To clarify the role of stereotactic radiosurgery (SRS) for atypical meningiomas (AM). METHODS: A retrospective analysis of 68 patients with AM having SRS from 1995 until 2019. RESULTS: Nineteen patients (28%) had undergone prior external beam radiation therapy (EBRT) (median dose, 54 Gy). The median follow-up period was 52 months. Eighteen (26%), 17 (25%), and 33 (49%) patients received SRS as an upfront adjuvant (≤ 6 months), early salvage (7-18 months), or late salvage treatment (> 18 months), respectively. The 3-, 5-, and 10-year progression-free survivals (PFSs) were 52%, 35%, and 25%, respectively. The 3-, 5-, and 10-year disease-specific survivals were 85%, 78%, and 61%, respectively. Adverse radiation events (AREs) were observed in 12 patients (18%), with increased or new seizures being the most frequent complication (n = 7). Prior EBRT was associated with reduced PFS (HR 5.92, P < 0.01), reduced DSS (HR 5.84, P < 0.01), and an increased risk of ARE (HR 3.31, P = 0.04). Timing of SRS was correlated with reduced PFS for patients having early salvage treatment compared to upfront adjuvant (HR 3.17, P = 0.01) or late salvage treatment (HR 4.39, P < 0.01). CONCLUSION: PFS for patients with residual/recurrent AM remains poor despite SRS. Prior EBRT was associated with worse tumor control, higher tumor-related mortality, and an increased risk of ARE. Further study on the timing of SRS is needed to determine if upfront adjunctive SRS improves tumor control compared to salvage SRS.

A Prospective, Randomized, Double-blind, Placebo-controlled Study of Orbital Radiotherapy for Graves' Ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

Single-fraction stereotactic radiosurgery for spindle cell oncocytoma: preliminary experience and systematic review of the literature.

PURPOSE: Spindle cell oncocytoma (SCO) is a rare benign pituitary tumor. No patient series regarding stereotactic radiosurgery (SRS) for SCO has been published. We report the clinical outcomes of SCO treated with single-fraction SRS, as well as a systematic review of the literature. METHODS: Retrospective cohort series and systematic literature review. RESULTS: Five patients (four male, one female) having single-fraction SRS for persistent or recurrent SCO between 2002 and 2018. Median age was 56 (range 54-79) years. Pre-SRS treatments included transsphenoidal resection (TSR) (n = 3), multiple TSR (n = 1), and TSR, radiotherapy, and craniotomy (n = 1). Median target volume was 4.7 (range 1.8-8.4) cm3, with a median tumor margin dose of 17 (range 14-20) Gy. Median follow-up was 24 (range 10-69) months. All radiation-naïve patients achieved tumor control after SRS; tumor progression was noted 24 months after SRS in one patient who failed prior radiotherapy. No radiation-induced complications were observed after SRS. Systematic literature review of 43 cases in addition to the five cases presented here showed that tumor progression/recurrence was more frequent after STR compared to GTR (P < 0.001). Ten previous cases of radiotherapy for SCO have been reported, but most did not detail radiation volumes, doses, or outcomes. CONCLUSIONS: SCO are uncommon sellar lesions with a propensity for progression or recurrence. Based on the clinically aggressive course of these tumors, adjuvant SRS after STR or at the time of tumor recurrence should be considered. Further case accumulation and follow-up is required to better understand the long-term treatment outcomes after single-fraction SRS for these rare tumors.

Single-fraction stereotactic radiosurgery of meningeal hemangiopericytomas.

Meningeal hemangiopericytomas (M-HPC) are challenging tumors with a high rate of recurrence despite surgical resection and external beam radiotherapy (EBRT). To better understand the role of single-fraction stereotactic radiosurgery (SRS) for patients with M-HPC, we reviewed our experience with 22 patients (12 men, 10 women) from 1990 until 2010. Twelve patients (55%) underwent a single SRS procedure, whereas 10 patients (45%) had more than one SRS procedure (range 2-6). In total, 47 SRS procedures were performed to treat 64 tumors. Fourteen patients (64%) had undergone prior EBRT (median dose, 56.0 Gy). Follow-up after the initial SRS (median, 66 months) was censored at the time of death (n = 15) or last clinical evaluation (n = 7). Eleven patients (50 %) died of intracranial tumor progression (n = 10) or treatment-related complications (n = 1). One patient (5%) died of systemic disease progression. Disease-specific survival (DSS) at 1-, 3- and 5-years after SRS was 96, 82, and 61%, respectively. Prior EBRT (HR 9.0, 95% CI 1.1-78.1, p < 0.05) and larger initial tumor volume (HR 1.09, 95% CI 1.02-1.2, p = 0.02) were associated with worse DSS. Local tumor control (LTC) after SRS at 1-, 3-, and 5-years was 89, 68, and 59%, respectively. Improved LTC was noted in patients who had not undergone prior EBRT (HR 6.3, 95% CI 2.1-19.5, p = 0.001). One patient (5%) had symptomatic radiation-relation complications after SRS. Overall, single-fraction SRS was effective in providing LTC for more than half of recurrent or residual M-HPC at 5-years after the procedure. Repeat SRS is often required secondary to either distant or local tumor progression.

Pencil Beam Scanning Proton Therapy for Pregnant Patients With Brain and Head and Neck Cancers.

PURPOSE: When radiation therapy is medically necessary for pregnant patients, photon-based treatments (XRT) have traditionally been used, whereas proton radiation therapy (PRT) is avoided due to concerns about neutron dose. This retrospective study analyzes pregnant patients treated with XRT and models the equivalent dose that would have been delivered to the fetus with proton radiation compared with XRT. The purpose of this work is to provide a comprehensive analysis of pencil beam scanning proton therapy (PBS-PRT) for pregnant patients and to evaluate whether PBS-PRT should be the new standard of practice for treating pregnant patients with brain and head and neck cancers. METHODS AND MATERIALS: PBS-PRT plans were made for seven pregnant patients who received XRT: four treated for brain tumors and three for head and neck tumors. Measurements were performed with the patient plans using an anthropomorphic phantom and Wendi-2 meter placed at the phantom's abdomen. Patient-specific measurements were used to determine the total fetal equivalent dose from PBS-PRT compared with XRT. Imaging dose was also evaluated with a Fluke 451 dose meter. RESULTS: The average measured fetal equivalent dose, accounting for photons and neutrons, for the brain plans was 0.4 mSv for PBS-PRT and 7 mSv for XRT. For the head and neck plans, it was 6 mSv and 90 mSv for PBS-PRT and XRT, respectively. The PBS-PRT plans were preferred by the physicians for both tumor coverage and normal-tissue sparing. Daily imaging added between 0.05 and 1.5 mSv to the total dose. CONCLUSIONS: This retrospective study showed that when treating brain or head and neck cancers in pregnant patients, fetal equivalent dose is reduced by approximately a factor of 10 with PBS-PRT compared with XRT without making any compromises in treatment planning objectives. These results support a change of practice to using PBS-PRT as the new standard for treating pregnant patients with brain or head and neck tumors compared with XRT.

The longitudinal risk of hemorrhage of melanoma brain metastases after Gamma Knife radiosurgery.

OBJECTIVE: The objective of this study was to analyze the hemorrhagic risk of melanoma brain metastases after Gamma Knife radiosurgery (GKRS). METHODS: A prospective institutional database was retrospectively queried to identify patients who underwent GKRS for melanoma brain metastases between 1990 and 2021. Lesional hemorrhage was defined as definite or possible based on radiologists' readings, and severity was graded according to Common Terminology Criteria for Adverse Events. RESULTS: Two hundred ninety-one patients with 1083 lesions treated in 419 sessions were identified. The mean (± SD) patient age was 60 ± 15 years, and 61% were male. The median follow-up period for overall survival (OS) was 11 (range 0-214) months with 581 patient-years. Definite/possible lesional hemorrhages occurred in 13% of lesions, with grade 3 hemorrhages observed in 4% of lesions. Surgical intervention was required in 2% of cases (5% of patients), and all resected lesions were pathologically consistent with melanoma. A decreased risk of definite/possible lesional hemorrhage was associated with a later time period between 2015 and 2021 (OR 0.45, 95% CI 0.266-0.75, p = 0.0021), increased marginal dose (OR 0.91, 95% CI 0.83-0.99, p = 0.037), antiplatelet use post-GKRS (OR 0.195, 95% CI 0.083-0.46, p < 0.001), and whole-brain radiotherapy (WBRT; OR 0.53, 95% CI 0.344-0.82, p = 0.0042). After 2015, more patients received anticoagulation, B-Raf proto-oncogene inhibitors, and immune checkpoint inhibitors, and fewer received bevacizumab (p < 0.001). The cumulative risk of lesional hemorrhage was 17%-20% at 36 months from GKRS, with 95%-96% of cases occurring within 12 months. The median patient OS was 11 (95% CI 9-13) months, and multivariate Cox regression analysis revealed that antiplatelet agents (hazard ratio [HR] 0.66, 95% CI 0.45-0.96, p = 0.031) and immune checkpoint inhibitors (HR 0.35, 95% CI 0.26-0.48, p < 0.001) were associated with longer OS, while WBRT (HR 1.36, 95% CI 1.02-1.81, p = 0.037) and definite/possible hemorrhage (HR 1.39, 95% CI 1.04-1.85, p = 0.024) were associated with shorter OS. CONCLUSIONS: The definite hemorrhage risk of melanoma brain metastases after GKRS was 17% in the first 3 years and 95% of the lesional hemorrhage occurred within the 1st year. Surgical intervention was needed in 5% of patients. Antiplatelet agents and immune checkpoint inhibitors were associated with improved OS, while definite/possible hemorrhage was associated with worse OS.

Stereotactic radiosurgery for intermediate- and high-grade arteriovenous malformations: outcomes stratified by the supplemented Spetzler-Martin grading system.

OBJECTIVE: The supplemented Spetzler-Martin (Supp-SM) grading system was developed to improve the predictive accuracy of surgical risk for patients with brain arteriovenous malformations (AVMs). The aim of this study was to apply the Supp-SM grading system to patients having stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) intermediate- (grade III) or high-grade (grade IV-V) AVMs to enable comparison with published microsurgical series. METHODS: In 219 patients who underwent SRS during the period from 1990 to 2016, the Supp-SM grade was calculated for SM grade III (n = 154) or SM grade IV-V (n = 65) AVMs. The Supp-SM grades in these patients were 4 (n = 14, 6%), 5 (n = 36, 16%), 6 (n = 67, 31%), 7 (n = 76, 35%), and 8-9 (n = 26, 12%). Sixty patients (27%) had deep AVMs (basal ganglia, thalamus, or brainstem). Thirty-nine patients (18%) had volume-staged SRS; 41 patients (19%) underwent repeat SRS. The median follow-up period was 69 months for SM grade III AVMs and 113 months for SM grade IV-V AVMs. RESULTS: AVM obliteration was confirmed in 163 patients (74%) at a median of 38 months after initial SRS. The obliteration rates at 4 and 8 years were 59% and 76%, respectively. Thirty-one patients (14%) had post-SRS deficits from hemorrhage (n = 7, 3%) or radiation injury (n = 24, 11%). Six patients (3%) died after SRS (hemorrhage, n = 5; radiation injury, n = 1). The rates of neurological decline or death at 4 and 8 years were 11% and 18%, respectively. Factors predictive of nonobliteration were deep location (HR 0.57, 95% CI 0.39-0.82, p = 0.003) and increasing AVM volume (HR 0.96, 95% CI 0.93-0.99, p = 0.002). Increasing AVM volume was the only factor associated with neurological decline (HR 1.05, 95% CI 1.02-1.08, p = 0.002). The Supp-SM grading score did not correlate with either obliteration (HR 0.94, 95% CI 0.82-1.09, p = 0.43) or neurological decline (HR 1.15, 95% CI 0.84-1.56, p = 0.38). CONCLUSIONS: The Supp-SM grading system was not predictive of outcomes after SRS of intermediate- or high-grade AVM. In a cohort that included a high percentage (47%) of "inoperable" AVMs according to Supp-SM grade (≥ 7), most patients had obliteration after SRS, although there was a high risk of neurological decline.

Stereotactic radiosurgery of World Health Organization grade II and III intracranial meningiomas: treatment results on the basis of a 22-year experience.

BACKGROUND: A study was undertaken to define the variables associated with tumor control and survival after single-session stereotactic radiosurgery (SRS) for patients with atypical and malignant intracranial meningiomas. METHODS: Fifty patients with World Health Organization (WHO) grade II (n = 37) or grade III (n = 13) meningiomas underwent SRS from 1990 to 2008. Most tumors were located in the falx/parasagittal region or cerebral convexities (n = 35, 70%). Twenty patients (40%) had progressing tumors despite prior external beam radiation therapy (EBRT) (median dose, 54.0 grays [Gy]). The median treatment volume was 14.6 cm(3) ; the median tumor margin dose was 15.0 Gy. Seven patients (14%) received concurrent EBRT (median dose, 50.4 Gy). Follow-up (median, 38 months) was censored at last evaluation (n = 28) or death (n = 22). RESULTS: Tumor grade correlated with disease-specific survival (DSS) (hazard ratio [HR], 3.4; P = .008), local tumor control (HR, 2.4; P = .02), and progression-free survival (PFS) (HR, 2.6; P = .02) on univariate analysis, but not on multivariate analysis. Multivariate analysis showed that having failed EBRT and tumor volume >14.6 cm(3) were negative predictors of DSS and local control (HR, 3.0; P = .02 and HR, 4.4; P = .01; HR, 3.3; P = .001 and HR, 2.3; P = .02;, respectively). Having failed EBRT was a negative predictor of PFS (HR, 3.5; P = .002). Thirteen patients (26%) had radiation-related complications at a median of 6 months after radiosurgery. CONCLUSIONS: Tumor progression despite prior EBRT and larger tumor volume are negative predictors of tumor control and survival for patients having SRS for WHO grade II and III intracranial meningiomas.

Radiation dose to the surgeon during plaque brachytherapy.

PURPOSE: To evaluate the radiation dose to a surgeon's hands during I eye plaque procedures. METHODS: Sixteen consecutive patients with uveal melanomas were scheduled for eye plaque brachytherapy. The same surgeon wore thermoluminescent dosimeters on the dominant index finger and thumb while placing and removing the eye plaque to measure radiation dose. Additional laboratory experiments were performed to measure unobstructed (by surgical gloves or other parts of the hand) radiation exposure from a plaque. RESULTS: Hand radiation doses during eye plaque brachytherapy are very low, but measurable, with plaques containing an average of 1.3 GBq of 125I. CONCLUSION: Using these data, a surgeon would need to perform more than 1,000 cases each year to approach or exceed the annual regulatory radiation dose limits for the extremities.

Intraocular plasmacytoma: A case of iris involvement and a review of the literature.

Purpose: Describe a case of intraocular plasmacytoma in a patient with multiple myeloma successfully treated with photon irradiation. Observations: A 61-year-old man with a history of relapsing/refractory multiple myeloma and left frontal bone plasmacytoma treated with monthly belantamab mafodotin salvage chemotherapy developed bilateral treatment-related corneal keratopathy. An iris mass was incidentally noted in the right eye during a follow-up examination. The mass was amelanotic with diffuse intrinsic vasculature involving the pupillary margin from 1:30 to 10:30. Fundus examination showed an irregularly shaped amelanotic superotemporal scleral lesion in the right eye and two smaller amelanotic scleral lesions in the left eye. Given known systemic multiple myeloma and history of left frontal bone plasmacytoma, a presumed diagnosis of iris and scleral plasmacytoma was made. Due to rapid progression of the iris plasmacytoma despite systemic chemotherapy, the patient was treated with 20 Gy photon irradiation to the anterior and posterior segments of both eyes. One month after photon irradiation, there was complete regression of the iris plasmacytoma, and the scleral lesions in both eyes also appeared to be regressing despite systemic progression of multiple myeloma. Conclusions and importance: Intraocular plasmacytoma is rare and can occur in isolation but typically occurs as a manifestation of systemic multiple myeloma. Intraocular plasmacytoma can be successfully treated with photon irradiation in patients with multiple myeloma who progress on systemic chemotherapy.

Salvage Radiosurgery for Optic Nerve Sheath Meningioma.

Optic nerve sheath meningiomas (ONSMs) are rare and benign tumors that affect the optic nerve. Although surgical decompression may be used for large tumors that cause mass effect on the surrounding structures, the mainstay of treatment is radiotherapy. We report the case of a 54-year-old female patient who presented with progressive vision loss due to a recurrent right ONSM despite fractionated radiotherapy eight years prior and the subsequent interval regression of the tumor. The optical coherence tomography at the time of recurrence revealed thinning of the right retinal nerve fiber layer. She underwent salvage stereotactic radiosurgery using a marginal dose of 15 Gy. At six months post-radiosurgery, the patient had a dramatic improvement in visual acuity and visual fields despite persistent thinning of the retinal nerve fiber layer. This case illustrates how salvage radiosurgery can be a useful treatment modality in these challenging situations. This tumor's exophytic growth and the steep dose fall-off of Gamma Knife radiosurgery might favorably affect visual recovery. However, the outcomes of single-session radiosurgery for ONSMs should be further evaluated.

The Role of Biological Effective Dose in Predicting Obliteration After Stereotactic Radiosurgery of Cerebral Arteriovenous Malformations.

OBJECTIVE: To determine whether biological effective dose (BED) was predictive of obliteration after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs). PATIENTS AND METHODS: We studied patients undergoing single-session AVM SRS between January 1, 1990, and December 31, 2014, with at least 2 years of imaging follow-up. Excluded were patients with syndromic AVM, previous SRS or embolization, and patients treated with volume-staged SRS. Biological effective dose was calculated using a mono-exponential model described by Jones and Hopewell. The primary outcome was likelihood of total obliteration defined by digital subtraction angiography or magnetic resonance imaging (MRI). Variables were analyzed as continuous and dichotomous variables based on the maximum value of (sensitivity-[1-specificity]). RESULTS: This study included 352 patients (360 AVM, median follow-up, 5.9 years). The median margin dose prescribed was 18.75 Gy (interquartile range [IQR]: 18 to 20 Gy). Two hundred fifty-nine patients (71.9%) had obliteration shown by angiography (n=176) or MRI (n=83) at a median of 36 months after SRS (IQR: 26 to 44 months). Higher BED was associated with increased likelihood of obliteration in univariate Cox regression analyses, when treated as either a dichotomous (≥133 Gy; hazard ratio [HR],1.52; 95% confidence interval [CI], 1.19 to 1.95; P<.001) or continuous variable (HR, 1.00, 95% CI, 1.0002 to 1.005; P=.04). In multivariable analyses including dichotomized BED and location, BED remained associated with obliteration (P=.001). CONCLUSION: Biological effective dose ≥133 Gy was predictive of AVM obliteration after single-session SRS within the prescribed margin dose range 15 to 25 Gy. Further study is warranted to determine whether BED optimization should be considered as well as treatment dose for AVM SRS planning.

More II It than Meets the Eye: Outcomes After Single-Fraction Stereotactic Radiosurgery in a Case Series of Low-Grade Arteriovenous Malformations.

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.

Analysis and impact of a multidisciplinary lymphoma virtual tumor board.

The aim is to prospectively evaluate the impact of a multidisciplinary lymphoma virtual tumor board. The utility of multi-site interactive lymphoma-specific tumor boards has not been reported. The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN). The format includes the clinical case presentation, presentation of radiology and hematopathology findings by the appropriate subspecialist, proposed treatment options, review of the literature pertinent to the case, pharmacy contributions, and discussion followed by recommendations. Three hundred and nine consecutive highly selected real-time cases with a diagnosis of lymphoma were presented at the Mayo Clinic Lymphoma Tumor Board from January 2014 to June 2018 and decisions were prospectively tracked to assess its impact on the treatment decisions. A total of 309 cases were prospectively evaluated. One hundred and forty (45.3%) cases had some changes made or recommended. The total changes suggested were 179, as some cases had more than one recommendation. There were 93 (30%) clinical management recommendations, 45 (14.6%) additional testing recommendations, 29 (9.4%) pathology changes, and 6 (1.9%) radiology changes. In an electronic evaluation process, 93% of the responders reported an improvement in knowledge and competence, and 100% recommended no change in format of the board. A multidisciplinary lymphoma tumor board approach was found to have a meaningful impact on lymphoma patients while enhancing interdisciplinary interactions and education for multiple levels of the clinical care team.

Risk of internal carotid artery stenosis or occlusion after single-fraction radiosurgery for benign parasellar tumors.

OBJECTIVE: Stereotactic 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). METHODS: The 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. RESULTS: The 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). CONCLUSIONS: New 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.

Gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas: results from a 15-year experience.

PURPOSE: To evaluate the efficacy and complications of stereotactic radiosurgery for patients with nonfunctioning pituitary adenomas (NFA). METHODS AND MATERIALS: This was a retrospective review of 62 patients with NFA undergoing radiosurgery between 1992 and 2004, of whom 59 (95%) underwent prior tumor resection. The median treatment volume was 4.0 cm(3) (range, 0.8-12.9). The median treatment dose to the tumor margin was 16 Gy (range, 11-20). The median maximum point dose to the optic apparatus was 9.5 Gy (range, 5.0-12.6). The median follow-up period after radiosurgery was 64 months (range, 23-161). RESULTS: Tumor size decreased for 37 patients (60%) and remained unchanged for 23 patients (37%). Two patients (3%) had tumor growth outside the prescribed treatment volume and required additional treatment (fractionated radiation therapy, n = 1; repeat radiosurgery, n = 1). Tumor growth control was 95% at 3 and 7 years after radiosurgery. Eleven (27%) of 41 patients with normal (n = 30) or partial (n = 11) anterior pituitary function before radiosurgery developed new deficits at a median of 24 months after radiosurgery. The risk of developing new anterior pituitary deficits at 5 years was 32%. The 5-year risk of developing new anterior pituitary deficits was 18% for patients with a tumor volume of < or = 4.0 cm(3) compared with 58% for patients with a tumor volume >4.0 cm(3) (risk ratio = 4.5; 95% confidence interval = 1.3-14.9, p = 0.02). No patient had a decline in visual function. CONCLUSIONS: Stereotactic radiosurgery is effective in the management of patients with residual or recurrent NFA, although longer follow-up is needed to evaluate long-term outcomes. The primary complication is hypopituitarism, and the risk of developing new anterior pituitary deficits correlates with the size of the irradiated tumor.

Stereotactic radiosurgery for brainstem metastases: Survival, tumor control, and patient outcomes.

PURPOSE: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. METHODS AND MATERIALS: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). RESULTS: Median survival time after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. CONCLUSIONS: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS.

Central neurocytoma: management recommendations based on a 35-year experience.

PURPOSE: To examine the outcomes of patients with histologically confirmed central neurocytomas. METHODS AND MATERIALS: The data from 45 patients with central neurocytomas diagnosed between 1971 and 2003 were retrospectively evaluated. Various combinations of surgery, radiotherapy (RT), and chemotherapy had been used for treatment. RESULTS: The median follow-up was 10.0 years. The 10-year overall survival and local control rate was 83% and 60%, respectively. Patients whose tumor had a mitotic index of <3 (per 10 high-power fields) experienced a 10-year survival and local control rate of 89% and 74%, respectively, compared with 57% (p = 0.040) and 46% (p = 0.14) for patients with a tumor mitotic index of > or =3. The 10-year survival and local control rate was 90% and 74% for patients with typical tumors compared with 63% (p = 0.055) and 46% (p = 0.41) for those with atypical tumors. A comparison of gross total resection with subtotal resection showed no significant difference in survival or local control. Postoperative RT improved local control at 10 years (75% with RT vs. 51% without RT, p = 0.045); however, this did not translate into a survival benefit. No 1p19q deletions were found in the 19 tumors tested. CONCLUSION: Although the overall prognosis is quite favorable, one-third of patients experienced tumor recurrence or progression at 10 years, regardless of the extent of the initial resection. Postoperative RT significantly improved local control but not survival, most likely because of the effectiveness of salvage RT. For incompletely resected atypical tumors and/or those with a high mitotic index, consideration should be given to adjuvant RT because of the more aggressive nature.

The Risk of Radiation-Induced Tumors or Malignant Transformation After Single-Fraction Intracranial Radiosurgery: Results Based on a 25-Year Experience.

PURPOSE: To determine the risk of radiation-induced tumors or malignant transformation after single-fraction intracranial stereotactic radiosurgery (SRS). METHODS AND MATERIALS: We performed a retrospective review of 1837 patients who received single-fraction SRS for arteriovenous malformation or benign tumor (meningioma, vestibular schwannoma, pituitary adenoma, glomus tumor) at a single center between 1990 and 2009. Patients were excluded if they refused research authorization (n=31), had a genetic predisposition to tumor development (n=84), received prior or concurrent radiation therapy (n=79), or had less than 5 years of imaging follow-up after SRS (n=501). The median imaging follow-up period for the remaining 1142 patients was 9.0 years (range, 5-24.9 years). RESULTS: No radiation-induced tumors were identified in 11,264 patient-years of follow-up after SRS. The risk of a radiation-induced tumor developing after SRS was 0.0% at 5 years (95% confidence interval [CI], 0.0%-0.4%), 0.0% at 10 years (95% CI, 0.0%-0.9%), and 0.0% at 15 years (95% CI, 0.0%-2.8%). Malignant transformation occurred in 7 of 316 meningioma patients (2.2%) and 1 of 358 vestibular schwannoma patients (0.3%) at a median of 4.9 years (range, 2.8-13.8 years) after SRS. No cases of malignant transformation were noted in patients with pituitary adenomas (n=188) or glomus tumors (n=47). The 5-, 10-, and 15-year risk of malignant transformation was 0.5% (95% CI, 0.0%-0.9%), 0.8% (95% CI, 0.0%-1.8%), and 2.4% (95% CI, 0.0%-5.5%), respectively. Patients who underwent prior resection (hazard ratio, 14.56; 95% CI, 1.79-118.33; P=.01) and who had meningioma pathology (hazard ratio, 11.72; 95% CI, 1.44-96.15; P=.02) were at increased risk of malignant transformation. CONCLUSIONS: The risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation) over SRS for appropriate patients.

Volume-Staged Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: Outcomes Based on an 18-Year Experience.

BACKGROUND: Radiation-based treatment options of large intracranial arteriovenous malformations (AVM) must balance the likelihood of obliteration with the risk of adverse radiation effects (ARE). OBJECTIVE: To analyze the efficacy and risks of volume-staged stereotactic radiosurgery (VS-SRS) for AVM. METHODS: Retrospective study of 34 AVM patients having VS-SRS between 1997 and 2012. A median of 2 stages (range, 2-4) was used to treat a median AVM volume of 22.2 cm 3 (range, 7.4-56.7). The median AVM margin dose was 16 Gy (range, 14-18); the median radiosurgery-based AVM score was 2.81 (range, 1.54-6.45). The median follow-up after VS-SRS was 8.2 years (range, 3-13.3). RESULTS: Nidus obliteration was noted in 18 patients (53%) after VS-SRS. The rate of obliteration was 14% at 3 years, 54% at 5 years, and 75% at 7 years. Six patients (18%) had 11 bleeds after VS-SRS. Two patients (6%) remained neurologically stable, 2 (6%) patients had significant deficits, and 2 patients (6%) died. The actuarial risk of a first bleed after VS-SRS was 6% at 1 year, 12% at 3 years, and 19% at 7 years. Six patients (18%) underwent repeat SRS; all achieved nidus obliteration for an overall cure rate of 71%. Two patients (6%) had a permanent ARE after VS-SRS or repeat SRS. CONCLUSION: VS-SRS permitted large volume intracranial AVM to be treated with a low rate of ARE. Further study is needed on dose escalation and decreasing the treatment volume per stage to determine if this will increase the rate of obliteration with this technique.