Alireza Mohammad Mohammadi, Pablo F. Recinos, Gene H. Barnett, Robert J. Weil, Michael A. Vogelbaum, Samuel T. Chao, John H. Suh, Nicholas F. Marko, Paul Elson, Gennady Neyman and Lilyana Angelov
The authors evaluated overall survival and factors predicting outcome in patients with ≥ 5 brain metastases who were treated with Gamma Knife surgery (GKS).
Medical records from patients with ≥ 5 brain metastases treated with GKS between 1997 and 2010 at the Cleveland Clinic Gamma Knife Center were retrospectively reviewed. Patient demographics, tumor characteristics, treatment-related factors, and outcome data were evaluated.
One hundred seventy patients were identified, with a median age of 58 years. The female/male ratio was 1.2:1. Gamma Knife surgery was used as an upfront treatment in 35% of patients and as salvage treatment in 65% of patients with multiple brain metastases. The median overall survival after GKS was 6.7 months (95% CI 5.5–8.1). At the time of GKS, 128 patients (75%) had concurrent extracranial metastases, and in 69 patients (41%) multiple extracranial sites were involved. Ninety-two patients (54%) had a history of whole-brain radiation therapy, and 158 patients (93%) had a Karnofsky Performance Scale (KPS) score ≥ 70. The median total intracranial disease volume was 3.2 cm3 (range 0.2–37.2 cm3). A total intracranial tumor volume ≥ 10 cm3 was observed in 32 patients (19%). Lower KPS score at the time of treatment (p < 0.0001), patient age > 60 years (p = 0.004), multiple extracranial metastases (p = 0.0001), and greater intracranial burden of disease (p = 0.03) were prognostic factors for poor outcome in the univariate and multivariate analyses.
In this study, GKS was safe and effective for upfront and salvage treatment in patients with ≥ 5 brain metastases. Gamma Knife surgery should be considered as an additional treatment modality for these patients, especially in the subset of patients with favorable prognostic factors.
Erin S. Murphy, Gene H. Barnett, Michael A. Vogelbaum, Gennady Neyman, Glen H. J. Stevens, Bruce H. Cohen, Paul Elson, Andrew D. Vassil and John H. Suh
The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS).
One hundred seventeen patients with VS underwent GKRS between January 1997 and February 2003. At the time of analysis, at least 5 years had passed since GKRS in all patients. The mean patient age was 60.9 years. The mean maximal tumor diameter was 1.77 ± 0.71 cm. The mean tumor volume was 1.95 ± 2.42 ml. Eighty-two percent of lesions received 1300 cGy and 14% received 1200 cGy. The median dose homogeneity ratio was 1.97 and the median dose conformality ratio was 1.78. Follow-up included MR imaging or CT scanning approximately every 6–12 months. Rates of progression to surgery were calculated using the Kaplan-Meier method.
Of the 117 patients in whom data were analyzed, 103 had follow-up MR or CT images and 14 patients were lost to follow-up. Fifty-three percent of patients had stable tumors and 37.9% had a radiographically documented response. Imaging-documented tumor progression was present in 8 patients (7.8%), but in 3 of these the lesion eventually stabilized. Only 5 patients required a neurosurgical intervention. The estimated 1-, 3-, and 5-year rates of progression to surgery were 1, 4.6, and 8.9%, respectively. One patient (1%) developed trigeminal neuropathy, 4 patients (5%) developed permanent facial neuropathy, 3 patients (4%) reported vertigo, and 7 patients (18%) had new gait imbalance following GKRS.
Gamma Knife radiosurgery results in excellent local control rates with minimal toxicity for patients with VS. The authors recommend standardized follow-up to gain a better understanding of the long-term effects of GKRS.
Mayur Sharma, Jason L. Schroeder, Paul Elson, Antonio Meola, Gene H. Barnett, Michael A. Vogelbaum, John H. Suh, Samuel T. Chao, Alireza M. Mohammadi, Glen H. J. Stevens, Erin S. Murphy and Lilyana Angelov
Glioblastoma (GBM) is the most malignant form of astrocytoma. The average survival is 6–10 months in patients with recurrent GBM (rGBM). In this study, the authors evaluated the role of stereotactic radiosurgery (SRS) in patients with rGBMs.
The authors performed a retrospective review of their brain tumor database (1997–2016). Overall survival (OS) and progression-free survival (PFS) after salvage SRS were the primary endpoints evaluated. Response to SRS was assessed using volumetric MR images.
Fifty-three patients with rGBM underwent salvage SRS targeting 75 lesions. The median tumor diameter and volume were 2.55 cm and 3.80 cm3, respectively. The median prescription dose was 18 Gy (range 12–24 Gy) and the homogeneity index was 1.90 (range 1.11–2.02). The median OS after salvage SRS was estimated to be 11.0 months (95% CI 7.1–12.2) and the median PFS after salvage SRS was 4.4 months (95% CI 3.7–5.0). A Karnofsky Performance Scale score ≥ 80 was independently associated with longer OS, while small tumor volume (< 15 cm3) and less homogeneous treatment plans (homogeneity index > 1.75) were both independently associated with longer OS (p = 0.007 and 0.03) and PFS (p = 0.01 and 0.002, respectively). Based on these factors, 2 prognostic groups were identified for PFS (5.4 vs 3.2 months), while 3 were identified for OS (median OS of 15.2 vs 10.5 vs 5.2 months).
SRS is associated with longer OS and/or PFS in patients with good performance status, small-volume tumor recurrences, and heterogeneous treatment plans. The authors propose a prognostic model to identify a cohort of rGBM patients who may benefit from SRS.
Lilyana Angelov, Alireza M. Mohammadi, Elizabeth E. Bennett, Mahmoud Abbassy, Paul Elson, Samuel T. Chao, Joshua S. Montgomery, Ghaith Habboub, Michael A. Vogelbaum, John H. Suh, Erin S. Murphy, Manmeet S. Ahluwalia, Sean J. Nagel and Gene H. Barnett
Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%–62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy.
Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board–approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient.
Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23–83 years), 23 patients (43%) had non–small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12–18 Gy) and 15 Gy (range 12–15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm3 (range 2.4–31.3 cm3) and 7.0 cm3 (range 1.0–29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1–23.1 cm3). The median change in volume compared with baseline was a decrease of 54.9% (range −98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3–7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively.
2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.