Clinical and radiologic outcomes after stereotactic radiosurgery for meningiomas in direct contact with the optic apparatus: an international multicenter study.

OBJECTIVE: Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus. METHODS: The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression. RESULTS: SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9-1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0-1.02, adjusted p = 0.02). CONCLUSIONS: In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.

Stereotactic radiosurgery for clinoid meningiomas: a multi-institutional study.

PURPOSE: Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas. METHODS: From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas. RESULTS: Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR = 2.938, p = 0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy. CONCLUSIONS: SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas. OBJECTIVE: To study the safety and effectiveness of SRS for perioptic meningiomas. METHODS: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus. RESULTS: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline. CONCLUSION: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.

Intraoperative radiotherapy (IORT) for surgically resected brain metastases: outcome analysis of an international cooperative study.

BACKGROUND AND OBJECTIVE: The ideal delivery of radiation to the surgical cavity of brain metastases (BMs) remains the subject of debate. Risks of local failure (LF) and radiation necrosis (RN) have prompted a reappraisal of the timing and/or modality of this critical component of BM management. IORT delivered at the time of resection for BMs requiring surgery offers the potential for improved local control (LC) afforded by the elimination of delay in time to initiation of radiation following surgery, decreased uncertainty in target delineation, and the possibility of dose escalation beyond that seen in stereotactic radiosurgery (SRS). This study provides a retrospective analysis with identification of potential predictors of outcomes. METHODS: Retrospective data was collected on patients treated with IORT immediately following surgical resection of BMs at three institutions according to the approval of individual IRBs. All patients were treated with 50kV portable linear accelerator using spherical applicators ranging from 1.5 to 4.0 cm. Statistical analyses were performed using IBM SPSS with endpoints of LC, DBC, incidence of RN, and overall survival (OS) and p < 0.05 considered significant. RESULTS: 54 patients were treated with IORT with a median age of 64 years. The most common primary diagnosis was non-small cell lung cancer (40%) with the most common location in the frontal lobe (38%). Median follow-up was 7.2 months and 1-year LC, DBC, and OS were 88%, 58%, and 73%, respectively. LMD was identified in 2 patients (3%) and RN present in 4 patients (7%). The only predictor of LC was extent of resection with 1-year LC of 94% for GTR versus 62% for STR (p = 0.049). CONCLUSIONS: IORT is a safe and effective means of delivering adjuvant radiation to the BM resection cavities with high rates of LC and low incidence of RN. Further studies are warranted directly comparing LC outcomes to SRS.

Tumor Cavity Recurrence after Stereotactic Radiosurgery of Surgically Resected Brain Metastases: Implication of Deviations from Contouring Guidelines.

BACKGROUND: Significant heterogeneity exists in target volumes for postoperative stereotactic radiosurgery (SRS) for brain metastases. A set of contouring guidelines was recently published, and we investigated the impact of deviations. METHODS: Patients (n = 41) undergoing single-fraction Gamma Knife SRS following surgical resection of brain metastases from 2011 to 2017 were retrospectively reviewed. SRS included the entire contrast-enhancing cavity with heterogeneity in inclusion of the surgical tract and no routine margin along the dura or clinical target volume margin. Follow-up MR imaging was fused with SRS plans to assess patterns of failure. RESULTS: The median follow-up was 11.1 months with a median prescription of 18 Gy. There were 5 local failures: infield (n = 3, 60%), surgical tract (n = 1, 20%), and marginal > 5 mm from the resection cavity (n = 1, 20%). No marginal failures < 5 mm or dural margin failures were noted. For deep lesions (n = 13), 62% (n = 8) had the entire tract covered. The only tract recurrence was in a deep lesion without coverage of the surgical tract (n = 1/5). CONCLUSION: In this small preliminary experience, despite no routine inclusion of the dural tract or bone flap, no failures were noted in these locations. Omission of the surgical tract in deep lesions may increase failure rates.

Gamma Knife Radiosurgery for Arteriovenous Malformations Using a Four-Dimensional Dynamic Volume Computed Tomography Angiography Planning System as an Alternative to Traditional Catheter Angiogram.

Background Gamma knife radiosurgery (GKRS) remains a critical intervention in the long-term management of arteriovenous malformations (AVMs). For planning a treatment, identification of the nidus is essential, and it is dependent on high-resolution blood flow imaging, usually in the form of a traditional angiogram. The development of dynamic 320-slice computed tomography (CT) angiography has offered a noninvasive alternative to intra-arterial fluoroscopic imaging, and it is capable of providing equivalent temporal resolution. In this study, we describe the feasibility of using four-dimensional CT angiography (4D-CTA) in GKRS planning for AVM treatment and a comparative analysis with a traditional angiogram. Methods A retrospective review was performed on AVM patients treated via GKRS with a 4D-CTA prior to the day of treatment, on the day of treatment, or with a day-of-treatment angiogram. Treatment times, along with total times in the Leksell® coordinate frame G, were obtained from the medical records. The frame-on time was calculated by subtracting the treatment time from the total time starting from application to removal, and the statistical analysis was performed across groups using analysis of variance (ANOVA). All treatments were performed on the Perfexion™ model with a dynamic flow imaging procured via a 320-slice CT scanner or traditional angiography platform. Results Some 27 patients underwent a total of 29 GKRS procedures for AVM treatment at our institution between September 2011 and January 2017. Mean age at the time of treatment was 35.5 (6-65) years, and male:female ratio was 5:4. Some 12 patients had 4D-CTA performed prior to the day of treatment, eight patients had the same CTA completed after frame placement on the day of treatment, while seven patients underwent traditional angiography. The mean frame-on times of each group were 190, 336, and 426 minutes, respectively (p < 0.0001). No procedures were aborted based on the image quality. Conclusions 4D-CTA is an effective tool in identifying the AVM nidus for GKRS planning. These studies can be performed prior to the day of treatment, allowing for a significant reduction in frame-on time and eliminating the risk of angiogram complication on the day of GKRS.

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Post-operative SRS (stereotactic radiosurgery) for large brain metastases is challenged by risks of radiation necrosis that limit SRS dose. Intraoperative radiotherapy (IORT) is a potential alternative, however standard dose recommendations are lacking. METHODS AND MATERIALS: Twenty consecutive brain metastases treated with post-operative SRS were retrospectively compared to IORT plans generated for 10-30 Gy in 1 fraction to 0-5 mm by estimating the applicator size and distance from critical organs using pre-operative and post-operative MRI. Additionally, 7 consecutive patients treated with IORT 30 Gy to surface were compared to retrospectively generated SRS plans using the post-operative MRI to 15-20 Gy and 30 Gy in 1 fraction marginal dose. RESULTS: For the 20 resection cavities treated with SRS and retrospectively compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly different doses to the optic apparatus and brainstem. Comparatively for the 7 patients treated with IORT 30 Gy to retrospective SRS plans to standard 15-20 Gy and 30 Gy marginal dose, IORT resulted in significantly lower doses to the optic apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients treated with surgery and IORT achieved local control and 0% developed radiographic or symptomatic radiation necrosis. CONCLUSIONS: Critical organ dosimetry for IORT remains generally lower than that achieved with single fraction SRS following resection of large brain metastases. We recommend 30 Gy to surface as the preferred prescription, consistent with the dose recommendation for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early clinical outcomes appear promising for surgery and IORT.

Efficacy of Stereotactic Radiosurgery in Patients with Multiple Metastases: Importance of Volume Rather Than Number of Lesions.

The role of stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases is controversial. While whole brain radiation therapy (WBRT) has historically been the mainstay of treatment, its value is increasingly being questioned as emerging data supports that SRS alone can provide comparable therapeutic outcomes for limited (one to three) intracranial metastases with fewer adverse effects, including neurocognitive decline. Multiple recent studies have also demonstrated that patients with multiple (> 3) intracranial metastases with a low overall tumor volume have a favorable therapeutic response to SRS, with no significant difference compared to patients with limited metastases. Herein, we present a patient with previously controlled breast cancer who presented with multiple recurrences of intracranial metastases but low total intracranial tumor volume each time. This patient underwent SRS alone for a total of 40 metastatic lesions over three separate procedures with good local control and without any significant cognitive toxicity. The patient eventually opted for enrollment in the NRG-CC001 clinical trial after multiple cranial recurrences. She received conventional WBRT with six months of memantine and developed significant neurocognitive side effects. This case highlights the growing body of literature supporting the role of SRS alone in the management of multiple brain metastases and the importance of maximizing neurocognition as advances in systemic therapies prolong survival in Stage IV cancer.

Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity.

PURPOSE: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. RESULTS: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. CONCLUSIONS: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.