Primary Stereotactic Radiosurgery Research Articles

Changes in the muscles of mastication before and after primary stereotactic radiosurgery in patients with idiopathic trigeminal neuralgia.

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. 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. 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). 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.

Long term results of primary radiosurgery for vestibular schwannomas.

Stereotactic radiosurgery (SRS) has become a primary option for management for both newly diagnosed vestibular schwannomas (VS), as well as VS that enlarge after initial observation. A retrospective review of our prospectively maintained data base found 871 patients who underwent Gamma knife® SRS as their initial (primary) management between 1987 and 2008. Follow-up ranged from 1-25years (median = 5.2years) Median tumor volume was 0.9cc (0.02-36) and median margin dose was 13Gy (12-25). Progression free survival (PFS) after SRS was 97% at 3years, 95% at 5years, and 94% at 10years. Freedom from delayed surgical resection was found in 98.7% of patients. Smaller tumor volume was significantly associated with improved PFS. There were 326 patients with serviceable hearing (Gardner-Robertson 1 or 2) at the time of SRS with audiological follow-up of ≥ 1year. Serviceable hearing preservation rates after SRS were 89.8% at 1year, 76.9% at 3years, 68.4% at 5years, 62.5% at 7years, and 51.4% at 10years. Factors associated with improved serviceable hearing preservation included younger age, Gardner-Robertson grade 1 at SRS, and absence of subjective complaints of dysequilibrium or vertigo (vestibulopathy). Fifty-one patients (5.8%) developed trigeminal neuropathy. Fourteen (1.6%) developed a transient House-Brackmann grade 2 or 3 facial neuropathy. In this report with extended follow-up, primary SRS achieved tumor growth control in 94% of patients. Optimization of long- term cranial nerve outcomes remains an important achievement of this management strategy for VS.

Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases.

The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial. To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group. A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan-Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox proportional hazards. Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P=.14). One-year DBF was 27%, 44%, and 40%, respectively (P=.01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume parameters predicted for death, neurologic death or toxicity. SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

Quality of Life in Jugular Paraganglioma Following Radiosurgery.

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. Cross-sectional survey. Tertiary referral center. Adult patients with JP treated with primary SRS or SRS following primary surgery between 1990 and 2017. Surgery and/or Gamma Knife SRS. Global and treatment-related QoL and differences in QoL based on treatment approach. 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). 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.

Primary versus postoperative stereotactic radiosurgery for acromegaly: a multicenter matched cohort study.

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. 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. 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. 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.

P45 Gamma knife radiosurgery for the primary management of acromegaly

ObjectivesReport outcome and morbidity data for the treatment of acromegaly with primary stereotactic radiosurgery (STRS).DesignRetrospective.Subjects20 patients with acromegaly who underwent primary STRS at the National Centre for Radiosurgery, Sheffield (UK) between 1985 and 2015.MethodsReview of notes, database, laboratory results, patient questionnaire and death certification. Guideline-based control was defined as normal age-sex-adjusted IGF1 levels and either random GH <1 µg/L or GH <0.3 µg/L (OGTT) or mean Growth Hormone Day Curve (GHDC) <1 µg/L.ResultsControl at 20 years was 100% and 75% on and off medication respectively. Median time to control on medication was 3 years and 7.4 years off medication. Median marginal radiation dose was 27.5 Gray and median follow-up was 167 months. Seven patients died, median age 65 years. There were no STRS-related deaths. 53% of patients developed new hypopituitarism at median follow-up of 146 months. First onset of hypopituitarism occurred up to 20 years after treatment. No other complications were noted. Three patients underwent trans-sphenoidal surgery due to poor biochemical control at a mean of 35 months.ConclusionsMorbidity from STRS is low. There is significant latency to biochemical control and new onset hypopituitarism. While primary surgical intervention remains the gold standard in acromegaly, primary STRS results should inform discussions with patients considering non-surgical management.

Radiosurgery of vestibular schwannoma: prognostic factors for hearing outcome using 3D-constructive interference in steady state (3D-CISS).

Stereotactic radiosurgery (SRS) is an effective treatment for vestibular schwannoma (VS). Three-dimensional (3D) constructive interference in steady state (CISS) is the preferred magnetic resonance imaging (MRI) sequence for evaluating signal changes in the inner ear endolymph. Previous studies demonstrated acorrelation between pretreatment cochlear signal intensity in 3D-CISS and posttherapeutic hearing outcomes. The purpose of our study was to compare 3D-CISS sequences before and after primary SRS of unilateral VSs to evaluate the effect of radiosurgery on the 3D-CISS signal intensities of cochlea and sacculus/utriculus. We retrospectively reviewed 47patients with unilateral VS treated with SRS. The neuroradiological MRI datasets were analysed to evaluate the signal intensity of the inner ear structure, tumour size, Koos grade, tumour volume, and infiltration of the cochlear aperture before therapy and at follow-up. The differences in these signal intensities before SRS and at follow-up were correlated with clinical symptoms, cochlear radiation dose, tumour volume and infiltration of the cochlear aperture. No differences were found between signal intensities in cochlea and utriculus/sacculus before and after SRS and no correlation with clinical symptoms, cochlear radiation dose, tumour volume, Koos grade or infiltration of the cochlear aperture (all p > 0.05). Our study supports the theory of acomplex interaction causing alteration of the endolymph protein concentration and not adirect dependency on the SRS. Use of modern dosing schemes will have apositive impact on clinical outcome with preservation of hearing in patients with VS.

Repeat Stereotactic Radiosurgery for Recurred Metastatic Brain Tumors.

ObjectiveWe investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. MethodsA total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. ResultsAfter the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. ConclusionThe tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.

Gamma Knife stereotactic radiosurgery for cavernous sinus meningioma: long-term follow-up in 200 patients.

The authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM). The authors retrospectively assessed treatment outcomes 5-18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22-83 years). In total, 120 (60%) patients underwent Gamma Knife SRS as primary management, 46 (23%) for residual tumors, and 34 (17%) for recurrent tumors after one or more surgical procedures. The median tumor target volume was 7.5 cm3 (range 0.1-37.3 cm3), and the median margin dose was 13.0 Gy (range 10-20 Gy). Tumor volume regressed in 121 (61%) patients, was unchanged in 49 (25%), and increased over time in 30 (15%) during a median imaging follow-up of 101 months. Actuarial tumor control rates at the 5-, 10-, and 15-year follow-ups were 92%, 84%, and 75%, respectively. Of the 120 patients who had undergone SRS as a primary treatment (primary SRS), tumor progression was observed in 14 (11.7%) patients at a median of 48.9 months (range 4.8-120.0 months) after SRS, and actuarial tumor control rates were 98%, 93%, 85%, and 85% at the 1-, 5-, 10-, and 15-year follow-ups post-SRS. A history of tumor progression after microsurgery was an independent predictor of an unfavorable response to radiosurgery (p = 0.009, HR = 4.161, 95% CI 1.438-12.045). Forty-four (26%) of 170 patients who had presented with at least one cranial nerve (CN) deficit improved after SRS. Development of new CN deficits after initial microsurgical resection was an unfavorable factor for improvement after SRS (p = 0.014, HR = 0.169, 95% CI 0.041-0.702). Fifteen (7.5%) patients experienced permanent CN deficits without evidence of tumor progression at a median onset of 9 months (range 2.3-85 months) after SRS. Patients with larger tumor volumes (≥ 10 cm3) were more likely to develop permanent CN complications (p = 0.046, HR = 3.629, 95% CI 1.026-12.838). Three patients (1.5%) developed delayed pituitary dysfunction after SRS. This long-term study showed that Gamma Knife radiosurgery provided long-term tumor control for most patients with CSM. Patients who underwent SRS for progressive tumors after prior microsurgery had a greater chance of tumor growth than the patients without prior surgery or those with residual tumor treated after microsurgery.

Cranial nerve outcomes after primary stereotactic radiosurgery for symptomatic skull base meningiomas.

To evaluate cranial nerve (CN) outcomes after primary stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. From our prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12month follow up. Median age at the time of SRS was 58years. Median follow up was 58months (range 12-300months), Median tumor volume treated with SRS was 5.9cm3 (range 0.5-37.5cm3), and median margin dose was 13Gy (range 9-20Gy). Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10years. Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit.

Three or More Courses of Stereotactic Radiosurgery for Patients with Multiply Recurrent Brain Metastases.

Although patients with brain metastasis are treated with primary stereotactic radiosurgery (SRS), the use of salvage therapies and their consequence remains understudied. To study the intracranial recurrence patterns and salvage therapies for patients who underwent multiple SRS courses. A retrospective review was performed of 59 patients with brain metastases who underwent ≥3 SRS courses for new lesions. Cox regression analyzed factors predictive for overall survival. The median age at diagnosis was 52 years. Over time, patients underwent a median of 3 courses of SRS (range: 3-8) to a total of 765 different brain metastases. The 6-month risk of distant intracranial recurrence after the first SRS treatment was 64% (95% confidence interval: 52%-77%). Overall survival was 40% (95% confidence interval: 28%-53%) at 24 months. Only 24 patients (41%) had a decline in their Karnofsky Performance Status ≤70 at last office visit. Quality of life was preserved among 77% of patients at 12months, with 45% experiencing clinically significant improvement during clinical follow-up. Radiation necrosis developed in 10 patients (17%). On multivariate analysis, gender (males, Hazard Ratio [HR]: 2.0, P < .05), Karnofsky Performance Status ≤80 (HR 3.2, P < .001), extracranial metastases (HR: 3.6, P < .001), and a distant intracranial recurrence ≤3 months from initial to repeat SRS (HR: 3.8, P < .001) were associated with a poorer survival. In selected patients, performing ≥3 SRS courses controls intracranial disease. Patients may need salvage SRS for distant intracranial relapse, but focal retreatments are associated with modest toxicity, do not appear to negatively affect a patient's performance status, and help preserve quality of life.

Management of Brain Metastasis in Patients With Pulmonary Neuroendocrine Carcinomas.

The patterns of intracranial failure in patients with brain metastasis from pulmonary neuroendocrine carcinoma (PNEC) remain unknown. From 1998 to 2013, 29 patients with the diagnosis of PNEC were treated for brain metastasis: 16 patients (55%) underwent whole-brain radiation therapy (WBRT), 5 (17%) patients underwent WBRT with a stereotactic radiosurgery (SRS) boost, and 8 (28%) patients underwent primary SRS alone. The median age at treatment was 61 years (range: 44-84 years) and the median follow-up was 9.6 months (0-157.4 months). Of the patients treated with SRS alone, 1 patient had radiographic local progression of disease and 1 patient had a distant intracranial failure. Of the patients treated with WBRT with or without an SRS boost, 9 patients developed intracranial progression, including 1 local failure. No differences in rates of intracranial progression or local failure between the 2 groups (P = .94 and P = .44, respectively) were observed. The actuarial rates of distant intracranial failure at 12 months were 32.9% (95% confidence interval [95% CI] 8.9%-56.8%) and 25% (95% CI 0.0%-67.4%) in patients undergoing primary WBRT or SRS, respectively (P = .31). The median overall survival was 15.8 months in patients treated with WBRT and 20.4 months in patients treated with primary SRS (P = .78). Patients with brain metastasis from PNECs can be effectively treated with either WBRT or SRS alone, with a pattern of failure more consistent with non-small cell lung cancer than small cell lung cancer. In this series, there was not a statistically significant increased risk of distant intracranial failure when patients were treated with primary SRS.

Determining the Optimal Management of Patients With Limited-Brain Metastases: A Cost Analysis Approach

Multiple radiation therapy treatment options exist for patients with limited (1-3) brain metastases including stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT). The natural history, treatment patterns, and cancer-related costs for these patients were analyzed to determine the benefit, if any, of WBRT in the modern era. From 2011-2013, 144 patients were treated with primary SRS, and 22 patients were treated with SRS+WBRT for limited-brain metastasis, at the discretion of the treating physician. A retrospective review was performed of the patient records for determination of clinical outcomes and patterns of failure. Cost analyses were performed using detailed institutional cost data captured by the cancer institute during inpatient and outpatient hospital encounters, including direct and indirect diagnosis-related costs. Survival times were calculated using the Kaplan-Meier method from date of initial radiation procedure. The median age at brain metastasis diagnosis for all patients was 63.5 years, the median KPS was 80, and the median time from diagnosis of the patient's primary disease to brain metastasis was 6.1 months. The 1-year overall survival and distant brain recurrence-free survival were 46% and 50% for patients treated with primary SRS, and 26% and 70% for those treated with SRS+WBRT, respectively (P=.14 and .09). Of the patients treated with primary SRS, 35 (24%) underwent an additional SRS session, 10 (7%) underwent ≥ 2 SRS sessions, and 15 (10%) patients were treated with salvage WBRT at the time of each intracranial relapse. Eight patients (6%) treated with primary SRS and 3 patients (14%) treated with SRS+WBRT were diagnosed with radiation necrosis. Neurologic death occurred in 19 patients (13%) treated with SRS and 6 (27%) treated with SRS+WBRT. The median total cost of care for all patients was $81,142 (R: $8,649 - $429,912): $84,501 for those undergoing primary SRS over a median of 31 clinical encounters and $54,033 ($12,828 - $226,426) over a median of 20 clinical encounters for those undergoing SRS+WBRT (P=.16). The median total cost of care per month survival was similar between the two groups ($10,356 SRS vs $10,285 GKS+WBRT, P=.74). Although patients with limited-brain metastases are at increased risk for distant intracranial failure without upfront WBRT, primary SRS provides comparable local control, risk of neurologic death, and overall survival with a lower risk of treatment-related toxicity. Even when accounting for additional close monitoring, more frequent imaging, and need for salvage therapies for patients undergoing primary GKS, the cost of care per month and overall cost of care remain comparable between single modality and multi-modality radiation treatments.

Long-term dizziness handicap in patients with vestibular schwannoma: a multicenter cross-sectional study.

(1) To characterize long-term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium-sized vestibular schwannoma (VS) using a validated self-assessment inventory; and (2) to identify clinical variables associated with long-term dizziness handicap. Cross-sectional observational study. Two independent tertiary academic referral centers: one located in the United States and one in Norway. All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long-term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long-term dizziness handicap. At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long-term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship.

P08.17 * REPEAT STEREOTACTIC RADIOSURGERY (SRS) FOR RECURRENT BRAIN METASTASES

OBJECTIVES: SRS for brain metastases is an effective treatment for brain metastases with a reported survival of 7-14 months. Local control is in the range of 70-90% at 12 months, with a proportion of patients who recurs locally we have evaluate the efficacy of repeat stereotactic radiosurgery (SRS) as salvage treatment in patients with recurrent brain metastases. PATIENTS AND METHODS: Between May 2008 and December 2012, twenty-seven patients received repeat SRS for a recurrent brain metastasis at University of Rome Sapienza, Sant'Andrea Hospital. All patients had Karnofsky Performance Score ≥ 60 and were previously treated with single-fraction SRS. The median time interval between primary SRS and reirradiation was 13.5 months. At the time of recurrence all patients received multi-fraction SRS (7-8 Gy x 3) RESULTS: Median overall and 12-month survival rates after repeat multifraction SRS were 10.3 months and 37%, respectively. Six patients were alive at the of analysis. The 6-month and 12-month local control rates were 90% and 72%. KPS > 70 (p = 0.04) and presence of extracranial disease (p = 0.01) were significant prognostic factor associated with longer survival. In general the treatment was well tolerated with relatively low treatment-related toxicity. Radionecrosis occurred in 7 reirradiated lesions, and was associated with neurological deterioration in 3 of them. CONCLUSION: Multi-fraction SRS is a feasible treatment option associated with good local control and acceptable radiation-induced toxicity in selected patients with recurrent brain metastases.

Long‐term Dizziness Handicap in Patients with Vestibular Schwannoma: A Multicenter Cross‐Sectional Study

Objectives: Previous studies have demonstrated that ongoing dizziness is a powerful predictor of reduced quality of life for patients with vestibular schwannoma (VS). The purpose of the current study is: (1) to characterize long-term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium sized VS using a validated self-assessment inventory and (2) to identify clinical variables associated with long-term dizziness handicap. Methods: All patients with sporadic &lt;3 cm VS who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. Results: A total of 642 respondents (mean age 56.2 years, 56.9% female) were analyzed and the average time interval between treatment and survey was 7.7 years. Female sex, older age, preexisting diagnosis of migraine, and symptoms of severe dizziness predating treatment were highly statistically significantly associated with a worse DHI score ( P &lt; .001) while type of dizziness (vertiginous vs non vertiginous), tumor size, and treatment strategy were not ( P &gt; .05). The 2 variables that were associated with the greatest deterioration in DHI scores were pre-existing migraine (24.5 vs 15.9 points) and history of severe dizziness prior to treatment (31.1 vs 14.0 points). Conclusions: These data suggest that migraine may play a major role in long-term dizziness in patients with VS. Factors including history of dizziness predating treatment and preexisting diagnosis of migraine most significantly influence dizziness handicap among subjects with VS, while management strategy is not associated with long-term DHI outcome.

Management of Primary and Recurrent Endolymphatic Sac Tumors

To report the clinical presentation, management strategies, and outcomes of 14 endolymphatic sac tumors (EST). Retrospective case series. Collective experience accrued from 2 tertiary referral centers. All patients with ESTs. Microsurgery, stereotactic radiosurgery (SRS). Treatment-related morbidity, recurrence. Fourteen ESTs (13 patients) met inclusion criteria. Eight tumors were sporadic, and 6 were associated with von Hippel-Lindau disease (VHL). Twelve lesions were managed primarily, whereas 2 were referred for treatment of sizable recurrences after subtotal resection. Including all patients, the median age at diagnosis was 36 years, and the median duration of posttreatment follow-up was 78 months. Among primary tumors, the median delay between symptom onset and diagnosis was 36 months, and the median tumor diameter at presentation was 23 mm with most lesions demonstrating intracranial involvement. Subjects with VHL frequently presented with smaller, less extensive tumors and were more commonly female compared with patients with sporadic disease. Of the 9 ESTs presenting with normal facial nerve function, 8 maintained good (HB 1-2) posttreatment capacity. Two of 5 ears with useful preoperative hearing maintained pretreatment hearing levels after surgery. One of 12 tumors managed primarily recurred after microsurgical resection. Primary SRS was used in 1 medically infirm patient providing durable tumor control (94 mo) at last follow-up. Among recurrent tumors, 2 were managed successfully with reexcision, whereas 1 underwent salvage surgery followed by 2 sequential treatments of SRS for 2 separate intracranial recurrences; no in-field recurrence has been detected to date. ESTs are rare primary neoplasms of the temporal bone that may occur sporadically or in association with VHL. Outcomes after treatment of small less-extensive tumors are favorable compared with patients with advanced primary or recurrent disease. Furthermore, subtotal resection carries a high risk of bulky or multifocal recurrence. As such, early gross total resection remains the management strategy of choice for primary and recurrent ESTs; however, SRS should be considered in poor surgical candidates or in cases of focal intracranial recurrence when the morbidity of salvage surgery is high.

Stereotactic radiosurgery of cerebral arteriovenous malformations: long-term follow-up in 164 patients of a single institution

This retrospective study aimed to investigate long-term outcome in patients with arteriovenous malformations (AVM) treated with stereotactic radiosurgery (SRS). Between 1998 and 2008, 164 patients with AVM received SRS. Median age was 36 years (range 7-69 years). Before SRS, 39 % of the patients experienced haemorrhage and 27 % suffered from epileptic seizures, whereas 43 % received previously embolization, 7.9 % neurosurgery and 1.8 % proton radiotherapy. Primary SRS was applied in 51.2 % of the patients. Median single dose was 19 Gy (80 % isodose; range 18-20 Gy) and median target volume was 4 cc (range 0.1-24.4). Median follow-up was 93 months (range 12-140). Complete obliteration (CO) was observed in 100 (61 %) patients at a median time of 29 months (range 6.1-88.5). The 3 and 5-year CO rates were 61 and 88 %, respectively. In multivariate analysis, radiation dose ≥ 19 Gy (p = 0.044) and target volume <4 cc (p = 0.015) were associated with significantly higher rates of CO. Intracranial haemorrhage was seen in nine patients (5.5 %) after SRS, whereas three patients (1.8 %) died as a consequence of bleeding. The annual bleeding risk was 1.3 % after 1 year and 1.3 % after 2 years, respectively. In multivariate analysis, only target volume >4 cm(3) (p = 0.031) and Spetzler-Martin grade III-V (p = 0.046) retained significance for increased risk of intracranial bleeding. After SRS an improvement in epileptic episodes, headaches and motor-sensory deficits was found in 8.5, 14 and 15 % of patients, respectively. Our long-term follow-up data show that SRS is an effective treatment option in AVM with low toxicity and bleeding risk, depending on AVM size and Spetzler-Martin grade. An improvement of neurologic symptoms is achievable.

The role of stereotactic radiosurgery in the treatment of renal cell carcinoma patients with five or more brain metastases.

410 Background: Whole brain radiation therapy (WBRT) is considered standard treatment in patients with multiple brain metastases (BM). However, WBRT has limited efficacy in patients with BM from radio resistant tumors like renal cell carcinoma (RCC) where median survival is 2–4 months. The aim of this study is to evaluate outcomes in RCC patients with ≥5 BM treated with Stereotactic Radio-surgery (SRS) monotherapy or as part of a multimodality regimen. Methods: Data from 16 consecutive RCC patients with ≥5 simultaneous BM (99 lesions) treated with SRS at our institution (1999–2010) were analyzed. Patient demographics, tumor characteristics, treatment related factors and outcomes were statistically evaluated. Results: 12 male and 4 female patients (median age of 59) were treated. 62% of patients had concurrent systemic metastases to multiple organs at the time of treatment. 31% of patients were on active systemic treatment before SRS. Patients had prior cranial surgery 2(12%), WBRT 6(37%) and SRS 2(12%) previous to their presentation with ≥5 BM. Median interval between primary diagnoses and SRS was 2years (range 0–16). At the time of current SRS treatment 75% of patients had only mild neurological symptoms and median KPS was 80; 87% of patients were Recursive Partitioning Analysis Class II. Median number of lesion was 5 (max 10), and median total intracranial disease burden was 2cc (range 0.2–36.4). Post SRS for ≥5 BM, 9 of 16 patients required further intracranial therapy for new lesions, WBRT 3(19%) and SRS 6(37%). Mean follow up was 6.5 months from SRS for ≥5 BM (range 1-19). 12 patients (75%) died during follow up with neurological cause of death in 3(25%). Median overall survival (OS) was 7.1 months (range1–21). OS was 50% after 6 month and 31% after 1 year. Local control rate was achieved in 91% of targets in all evaluated patients. Conclusions: SRS is traditionally used to treat patients with a limited number of BM. This is the first series to evaluate the role of SRS in the management ≥5 BM in RCC. We demonstrate that using SRS in these patients results in excellent local disease control (91%) and acceptable OS. Hence, SRS should be considered in the ongoing management of patients even with extensive intracranial disease.

Stereotactic radiosurgery for pineal tumours

Objectives. Pineal tumours continue to present considerable clinical dilemmas and challenges. We were, therefore, interested to review our cumulative experience with a view to formulating a potential treatment strategy. Methods. A retrospective analysis of all patients treated with Stereotactic radiosurgery (SRS) for pineal tumours in one centre between 1987 and 2009. Forty-four patients (66% male) were treated radiosurgically with a mean age(± 1sd) of 33.6 (16.4) years. Eleven had biopsy-proven pineal parenchymal tumours (PPT), six astrocytomas, three ependymomas, two papillary epithelial tumours and two germ cell tumours. Twenty (45%) patients had no definitive histology despite attempted surgical biopsy in 11. Prior to radiosurgery, 17 had undergone craniotomy, 10 radiotherapy and four chemotherapy. Nine patients were referred for primary SRS. Results. Fifty Gamma knife treatments were performed on 44 patients prescribing 18.1 (4.2) Gy with a treatment volume of 3.8 (3.8) cm. Routine clinical and MRI assessments were reviewed to calculate control rates. Mean follow up was 62.5 (52.9) months. Five patients (two ependymomas and three PPT) died at 36.2 (36.7) months after initial radiosurgical treatment. Overall progression-free survival (PFS) results were 93% at 1 year, 77% at 5 years, 67% at 10 and 20 years. Log-rank analysis revealed that higher initial tumour grade (P = 0.04), previous radiotherapy (P = 0.002) and radiological evidence of necrosis (P = 0.03) were associated with worse outcomes. The 5-year PFS for patients who possessed these ‘aggressive’ features was 47.1% compared with 91% for those patients who did not have these features. No persistent complications were attributed to SRS. Conclusions. These results further demonstrate the increasingly significant role played by STRS in the treatment of pineal tumours. Based on our findings, we believe a re-examination of the role of more established therapies for this patient group may be warranted.