Gennady Neyman

Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy.

The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole‐brain radiation therapy (WBRT).

Treatment of five or more brain metastases with stereotactic radiosurgery.

PURPOSE To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS). METHODS AND MATERIALS Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS). RESULTS The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60-100). A KPS of ≥ 80 significantly influenced OS (median OS, 4.8 months for KPS ≤ 70 vs. 8.8 months for KPS ≥ 80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191-0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of ≤ 70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157-4.049, p = 0.0157). CONCLUSIONS Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with metastatic cancer, especially for patients previously treated with WBRT. A KPS of ≥ 80 predicts for an improved outcome.

Gamma knife radiosurgery for glomus jugulare tumors: volumetric analysis in 17 patients.

OBJECTIVEStereotactic radiosurgery has been used increasingly for the treatment of glomus jugulare tumors. The authors report their experience treating these tumors using gamma knife radiosurgery (GKRS), documenting the clinical and radiological outcome. METHODSA retrospective analysis identified 17 patients with glomus jugulare tumors who underwent GKRS. Besides analysis of clinical outcome, a radiological volumetric analysis was also performed after treatment. RESULTSThere were 15 women and two men (average age, 63.1 yr) with a median follow-up period of 48 months. The median radiosurgical dose to the tumor margin was 15 Gy (range, 13–18 Gy). Eight patients (47.1%) improved clinically, two (11.8%) worsened, and seven (41.2%) were unchanged. No relationship between internal auditory canal dose and hearing loss was recorded. Tinnitus and otalgia were the symptoms that responded most favorably to GKRS. No patients experienced new lower cranial nerve palsies after GKRS. Tumor volume showed a transient increase in seven patients. Analysis of tumor volume at the time of the last magnetic resonance imaging scan recorded a decrease in eight patients, an increase in four patients, and no change in five patients. CONCLUSIONGKRS is a safe, effective treatment for glomus jugulare tumors, particularly in patients with preserved glossopharyngeal and vagus nerve function, after surgical recurrence, in the elderly, and in patients with serious preexisting medical conditions. Longer follow-up periods are required to assess long-term effects.

Long-term outcomes of Gamma Knife radiosurgery in patients with vestibular schwannomas

OBJECT The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS). METHODS 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. RESULTS 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. CONCLUSIONS 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.

Stereotactic Radiosurgery for Single Brainstem Metastases: The Cleveland Clinic Experience

PURPOSE To assess the imaging and clinical outcomes of patients with single brainstem metastases treated with stereotactic radiosurgery (SRS). MATERIALS AND METHODS We retrospectively reviewed the data from patients with single brainstem metastases treated with SRS. Locoregional control and survival were calculated using the Kaplan-Meier method. Prognostic factors were assessed using a Cox proportional hazards model. RESULTS Between 1997 and 2007, 43 patients with single brainstem metastases were treated with SRS. The median age at treatment was 59 years, the median Karnofsky performance status was 80, and the median follow-up was 5.3 months. The median dose was 15 Gy (range, 9.6-24), and the median conformality and heterogeneity index was 1.7 and 1.9, respectively. The median survival was 5.8 months from the procedure date. Of the 33 patient with post-treatment imaging available, a complete radiographic response was achieved in 2 (4.7%), a partial response in 8 (18.6%), and stable disease in 23 (53.5%). The 1-year actuarial rate of local control, distant brain control, and overall survival was 85%, 38.3%, and 31.5%, respectively. Of the 43 patients, 8 (19%) died within 2 months of undergoing SRS, and 15 (36%) died within 3 months. On multivariate analysis, greater performance status (hazard ratio [HR], 0.95, p = .004), score index for radiosurgery (HR, 0.7; p = .004), graded prognostic assessment score (HR, 0.48; p = .003), and smaller tumor volume (HR, 1.23, p = .002) were associated with improved survival. No Grade 3 or 4 toxicities were observed. CONCLUSION The results of our study have shown that SRS is a safe and effective local therapy for patients with brainstem metastases.

Role of Gamma Knife surgery in patients with 5 or more brain metastases

OBJECT The authors evaluated overall survival and factors predicting outcome in patients with ≥ 5 brain metastases who were treated with Gamma Knife surgery (GKS). METHODS 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. RESULTS 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 cm(3) (range 0.2-37.2 cm(3)). A total intracranial tumor volume ≥ 10 cm(3) 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. CONCLUSIONS 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.

Repeat trigeminal nerve radiosurgery for refractory cluster headache fails to provide long-term pain relief

Objective/Background.—Medically refractory cluster headache (MRCH) is a debilitating condition that has proven resistant to many modalities. Previous reports have indicated that radiosurgery for MRCH provides little long‐term pain relief, with moderate/significant morbidity. However, there have been no reports of repeated radiosurgery in this patient population. We present our findings from the first reports of repeat radiosurgery for MRCH.

The importance of the conformality, heterogeneity, and gradient indices in evaluating Gamma Knife radiosurgery treatment plans for intracranial meningiomas.

PURPOSE To investigate the relationship between the conformality index (CIn), heterogeneity index (HIn), and gradient index (GIn) and the development of toxicity in patients treated with Gamma Knife radiosurgery (GKRS) for intracranial meningiomas. METHODS AND MATERIALS Treatment records of patients treated from 1997 to 2009 with at least 6 months of follow-up were reviewed. The following parameters were collected: CIn, HIn, GIn (ratio of the volume receiving half the prescription isodose to the volume receiving the full prescription isodose), brainstem (BS) maximum dose (MD), BS volume receiving ≥ 12 Gy (V12), optic apparatus (OA) MD, OA V8 Gy, OA V10, number of isocenters, number of isocenters outside target volume, and the occurrence of six toxicities. Univariate and multivariate logistic regression modeling were used for analysis. RESULTS This study included 145 patients (148 meningiomas) with a median follow-up time of 27 months (range, 6-113.9 months). The majority of meningiomas were located in the skull base (53%). The median prescription dose was 13 Gy (range, 10-24 Gy) to the 51.50% (range, 50-92%) isodose. A lower HIn was correlated with a higher GIn (p = 0.007). CIn was not associated with any toxicity. Higher HIn was associated with the development of dizziness (odds ratio [OR] 1.9; p = 0.02), whereas a lower GIn was associated with motor deficits (OR 0.38; p = 0.04) and auditory changes (OR 0.59; p = 0.04). The OA MD, V8, and V12 were not associated with visual changes, but visual changes were associated with a higher number of isocenters outside the target volume (OR 1.93; p = 0.07). BS V12 was correlated with the development of auditory changes (OR 1.05; p = 0.05), whereas patients with higher BS MD tended to have increased toxicity. CONCLUSIONS Close attention must be paid to all three indices (CIn, HIn, GIn) when optimal treatment plans are determined. We recommend that the target CIn should be ≤ 2.0, the HIn ≤ 2.0, and the GIn ≥ 3.0 for intracranial meningiomas.

Impact of the radiosurgery prescription dose on the local control of small (2 cm or smaller) brain metastases

OBJECTIVE The impact of the stereotactic radiosurgery (SRS) prescription dose (PD) on local progression and radiation necrosis for small (≤ 2 cm) brain metastases was evaluated. METHODS An institutional review board-approved retrospective review was performed on 896 patients with brain metastases ≤ 2 cm (3034 tumors) who were treated with 1229 SRS procedures between 2000 and 2012. Local progression and/or radiation necrosis were the primary end points. Each tumor was followed from the date of radiosurgery until one of the end points was reached or the last MRI follow-up. Various criteria were used to differentiate tumor progression and radiation necrosis, including the evaluation of serial MRIs, cerebral blood volume on perfusion MR, FDG-PET scans, and, in some cases, surgical pathology. The median radiographic follow-up per lesion was 6.2 months. RESULTS The median patient age was 56 years, and 56% of the patients were female. The most common primary pathology was non-small cell lung cancer (44%), followed by breast cancer (19%), renal cell carcinoma (14%), melanoma (11%), and small cell lung cancer (5%). The median tumor volume and median largest diameter were 0.16 cm3 and 0.8 cm, respectively. In total, 1018 lesions (34%) were larger than 1 cm in maximum diameter. The PD for 2410 tumors (80%) was 24 Gy, for 408 tumors (13%) it was 19 to 23 Gy, and for 216 tumors (7%) it was 15 to 18 Gy. In total, 87 patients (10%) had local progression of 104 tumors (3%), and 148 patients (17%) had at least radiographic evidence of radiation necrosis involving 199 tumors (7%; 4% were symptomatic). Univariate and multivariate analyses were performed for local progression and radiation necrosis. For local progression, tumors less than 1 cm (subhazard ratio [SHR] 2.32; p < 0.001), PD of 24 Gy (SHR 1.84; p = 0.01), and additional whole-brain radiation therapy (SHR 2.53; p = 0.001) were independently associated with better outcome. For the development of radiographic radiation necrosis, independent prognostic factors included size greater than 1 cm (SHR 2.13; p < 0.001), location in the corpus callosum (SHR 5.72; p < 0.001), and uncommon pathologies (SHR 1.65; p = 0.05). Size (SHR 4.78; p < 0.001) and location (SHR 7.62; p < 0.001)-but not uncommon pathologies-were independent prognostic factors for the subgroup with symptomatic radiation necrosis. CONCLUSIONS A PD of 24 Gy results in significantly better local control of metastases measuring < 2 cm than lower doses. In addition, tumor size is an independent prognostic factor for both local progression and radiation necrosis. Some tumor pathologies and locations may also contribute to an increased risk of radiation necrosis.

Using higher isodose lines for gamma knife treatment of 1 to 3 brain metastases is safe and effective.

BACKGROUND Higher isodose lines (IDLs) in Gamma Knife (GK) Perfexion treatment of brain metastases (BMet) could result in lower local control (LC) or higher radiation necrosis (RN) rates, but reduce treatment time. OBJECTIVE To assess the impact of the heterogeneity index (HI) and conformality index (CFI) ion local failure (LF) for patients treated with GK for 1 to 3 BMet. METHODS From an institutional review board-approved database, 320 patients with 496 BMet were identified, treated for 1 to 3 BMet from July 2007 to April 2011 on GK Perfexion. Cox proportional hazards regression was used to analyze significance of HI, CFI, IDL, dose, tumor diameter, recursive partitioning analysis class, tumor radioresistance, primary, smoking history, metastasis location, and whole-brain radiation therapy (WBRT) history with LF and RN. RESULTS Median follow-up by lesion was 6.8 months (range, 0-49.6). The series median survival was 14.2 months. Per RECIST, 9.5% of lesions failed, 33.9% were stable, 38.3% partially responded, 17.1% responded completely, and 1.2% could not be assessed. The 12-month LC rate was 87.3%. On univariate analysis, a dose less than 20 Gy (hazard ratio [HR]: 2.940, P < .001); tumor size (HR: 1.674, P < .001); and cerebellum/brainstem location vs other (HR: 1.891, P = .043) were significant for LF. Non-small cell lung cancer (HR: 0.333, P = .0097) was associated with better LC. On multivariate analysis, tumor size (HR: 1.696, P < .001) and cerebellum/brainstem location vs other (HR: 1.959, P = .033) remained significant for LF. Variables not significant for LF included CI, IDL, and HI. CONCLUSION Our study of patients with 1 to 3 BMet treated with GK demonstrated no difference in LC or RN with varying HI, indicating that physicians can treat to IDL at 70% or higher IDL to reduce treatment time without increased LF or RN.