Completion of Gamma Knife radiosurgery for AVM treatment after unplanned interruption-technical note.

BACKGROUND AND IMPORTANCE: Gamma Knife radiosurgery is an established technique for non-urgent treatment of various intracranial pathologies. Intra-procedural dislodgement of the stereotactic frame is an uncommon occurrence that could lead to abortion of ongoing treatment and necessitate more invasive treatment strategies. CLINICAL PRESENTATION: In this case report, we describe a novel method for resumption of Gamma Knife treatment after an unplanned intra-procedural interruption. The case example involves a radiosurgical treatment of a Spetzler-Martin grade I arteriovenous malformation. CONCLUSION: Our technique involves integration of scans and coordinate systems from two imaging sessions using the composite isodose line to resolve translational differences, thereby limiting delivery of remaining shots to the untreated region of the lesion. MRI follow-up at 13 months showed a reduction in the nidus size with no evidence of any radiation injury to the surrounding brain parenchyma. We believe this technique will allow care teams to effectively salvage interrupted Gamma Knife procedures and reduce progression to more invasive treatment options.

Imaging Advances in Stereotactic Radiosurgery.

Novel functional and metabolic MRI imaging provides the ability to analyze tumor tissue properties including tumor vasculature, vascular permeability, tumor cellularity, hypoxia, and tumor proliferation. Stereotactic radiosurgery involves the delivery of a very precise, focal dose of radiation to a target. Recent advances in MR imaging have the potential to improve accuracy for target volume delineation and to potentially improve outcome. Novel MR imaging techniques may also be used in subsequent post-treatment follow-up to distinguish between tumor recurrences versus non-neoplastic treatment-related changes. In this paper, we address multiparametric MR imaging and cerebral angiography as tools to reduce toxicity.

Impact of time of day on outcomes after stereotactic radiosurgery for non-small cell lung cancer brain metastases.

BACKGROUND: This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases. METHODS: At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables. RESULTS: Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS. CONCLUSIONS: Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.

Patient-specific independent 3D GammaPlan quality assurance for Gamma Knife Perfexion radiosurgery.

One of the most important aspects of quality assurance (QA) in radiation therapy is redundancy of patient treatment dose calculation. This work is focused on the patient-specific time and 3D dose treatment plan verification for stereotactic radiosurgery using Leksell Gamma Knife Perfexion (LGK PFX). The virtual model of LGK PFX was developed in MATLAB, based on the physical dimensions provided by the manufacturer. The ring-specific linear attenuation coefficients (LAC) and output factors (OFs) reported by the manufacturer were replaced by the measurement-based collimator size-specific OFs and a single LAC = 0.0065 mm-1. Calculation depths for each LGK PFX shot were obtained by ray-tracing technique, and the dose calculation formalism was similar to the one used by GammaPlan treatment planning software versions 8 and 9. The architecture of the QA process was based on the in-house online database search of the LGK PFX database search for plan-specific information. A series of QA phantom plans was examined to verify geometric and dosimetric accuracy of the software. The accuracy of the QA process was further evaluated through evaluation of a series of patient plans. The shot time/focus point dose verification for each shot took less than 1 sec/shot with full 3D isodose verification taking about 30 sec/shot on a desktop PC. GammaPlan database access time took less than 0.05 sec. The geometric accuracy (location of the point of maximum dose) of the phantom and patient plan was dependent on the resolution of the original dose matrix and was of the order of 1 dose element. Dosimetric accuracy of the independently calculated phantom and patient point (focus) doses was within 3.5% from the GammaPlan, with the mean = 2.3% and SD= 1.1%. The process for independent pretreatment patient-specific Gamma Knife Perfexion time and dose verification was created and validated.

Development of a modified head and neck quality assurance phantom for use in stereotactic radiosurgery trials.

An anthropomorphic head phantom, constructed from a water-equivalent plastic shell with only a spherical target, was modified to include a nonspherical target (pituitary) and an adjacent organ at risk (OAR) (optic chiasm), within 2 mm, simulating the anatomy encountered when treating acromegaly. The target and OAR spatial proximity provided a more realistic treatment planning and dose delivery exercise. A separate dosimetry insert contained two TLD for absolute dosimetry and radiochromic film, in the sagittal and coronal planes, for relative dosimetry. The prescription was 25 Gy to 90% of the GTV, with ≤ 10% of the OAR volume receiving ≥ 8 Gy for the phantom trial. The modified phantom was used to test the rigor of the treatment planning process and phantom reproducibility using a Gamma Knife, CyberKnife, and linear accelerator (linac)-based radiosurgery system. Delivery reproducibility was tested by repeating each irradiation three times. TLD results from three irradiations on a CyberKnife and Gamma Knife agreed with the calculated target dose to within ± 4% with a maximum coefficient of variation of ± 2.1%. Gamma analysis in the coronal and sagittal film planes showed an average passing rate of 99.4% and 99.5% using ± 5%/3 mm criteria, respectively. Results from the linac irradiation were within ± 6.2% for TLD with a coefficient of variation of ± 0.1%. Distance to agreement was calculated to be 1.2 mm and 1.3mm along the inferior and superior edges of the target in the sagittal film plane, and 1.2 mm for both superior and inferior edges in the coronal film plane. A modified, anatomically realistic SRS phantom was developed that provided a realistic clinical planning and delivery challenge that can be used to credential institutions wanting to participate in NCI-funded clinical trials.

Recommendations on the practice of calibration, dosimetry, and quality assurance for gamma stereotactic radiosurgery: Report of AAPM Task Group 178.

The American Association of Physicists in Medicine (AAPM) formed Task Group 178 (TG-178) to perform the following tasks: review in-phantom and in-air calibration protocols for gamma stereotactic radiosurgery (GSR), suggest a dose rate calibration protocol that can be successfully utilized with all gamma stereotactic radiosurgery (GSR) devices, and update quality assurance (QA) protocols in TG-42 (AAPM Report 54, 1995) for static GSR devices. The TG-178 report recommends a GSR dose rate calibration formalism and provides tabulated data to implement it for ionization chambers commonly used in GSR dosimetry. The report also describes routine mechanical, dosimetric, and safety checks for GSR devices, and provides treatment process quality assurance recommendations. Sample worksheets, checklists, and practical suggestions regarding some QA procedures are given in appendices. The overall goal of the report is to make recommendations that help standardize GSR physics practices and promote the safe implementation of GSR technologies.

Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases.

BACKGROUND: Patients with limited intracranial metastatic disease traditionally have been treated with surgery followed by WBRT. However, there is growing concern for the debilitating cognitive effects after WBRT in long-term survivors. We present a series of patients treated with surgery followed by SRS, while reserving WBRT as a salvage therapy for disease progression. METHODS: Medical records from 15 patients with 1 to 2 cerebral metastases who underwent both resection and SRS were reviewed. Outcome measures included overall survival, survival by RPA class, EOR, local tumor control, progression of intracranial disease, need for WBRT salvage therapy, and COD. RESULTS: Fifteen patients with cerebral metastases were treated with the combined surgery-SRS paradigm. Eight of the 15 patients (53.3%) were designated RPA class 1, with 6 of 15 (40.0%) in class 2 and 1 of 15 (6.7%) in class 3. Gross total resection was achieved in 12 cases (80.0%). Overall median survival was 20.0 months, with values of 22.0 and 13.0 months for RPA classes 1 and 2, respectively. Local recurrence occurred in 16.7% of those patients with GTR. Six patients (40.0%) went on to receive WBRT at a median of 8.0 months from initial presentation. Twelve patients (80.0%) had died at the completion of the study, and the COD was CNS progression in 33.3%. CONCLUSIONS: Surgical resection combined with SRS is an effective treatment for selected patients with limited cerebral metastatic disease. Survival using this combined treatment was equivalent to or greater than that reported by other studies using surgery + WBRT or SRS + WBRT.

Validation of calculations for electrons modulated with conventional photon multileaf collimators.

Treating shallow tumors with a homogeneous dose while simultaneously minimizing the dose to distal critical organs remains a challenge in radiotherapy. One promising approach is modulated electron radiotherapy (MERT). Due to the scattering properties of electron beams, the commercially provided secondary and tertiary photon collimation systems are not conducive for electron beam delivery when standard source-to-surface distances are used. Also, commercial treatment planning systems may not accurately model electron-beam dose distributions when collimated without the standard applicators. However, by using the photon multileaf collimators (MLCs) to create segments to modulate electron beams, the quality of superficial tumor dose distributions may improve substantially. The purpose of this study is to develop and evaluate calculations for the narrow segments needed to modulate megavoltage electron beams using photon beam multileaf collimators. Modulated electron radiotherapy (MERT) will be performed with a conventional linear accelerator equipped with a 120 leaf MLC for 6-20 MeV electron beam energies. To provide a sharp penumbra, segments were delivered with short SSDs (70-85 cm). Segment widths (SW) ranging from 1 to 10 cm were configured for delivery and planning, using BEAMnrc Monte Carlo (MC) code, and the DOSXYZnrc MC dose calculations. Calculations were performed with voxel size of 0.2 x 0.2 x 0.1 cm3. Dosimetry validation was performed using radiographic film and micro- or parallel-plate chambers. Calculated and measured data were compared using technical computing software. Beam sharpness (penumbra) degraded with decreasing incident beam energy and field size (FS), and increasing SSD. A 70 cm SSD was found to be optimal. The PDD decreased significantly with decreasing FS. The comparisons demonstrated excellent agreement for calculations and measurements within 3%, 1 mm. This study shows that accurate calculations for MERT as delivered with existing photon MLC are feasible and allows the opportunity to take advantage of the dynamic leaf motion capabilities and control systems, to provide conformal dose distributions.

Comparison of helical, maximum intensity projection (MIP), and averaged intensity (AI) 4D CT imaging for stereotactic body radiation therapy (SBRT) planning in lung cancer.

BACKGROUND AND PURPOSE: To compare helical, MIP and AI 4D CT imaging, for the purpose of determining the best CT-based volume definition method for encompassing the mobile gross tumor volume (mGTV) within the planning target volume (PTV) for stereotactic body radiation therapy (SBRT) in stage I lung cancer. MATERIALS AND METHODS: Twenty patients with medically inoperable peripheral stage I lung cancer were planned for SBRT. Free-breathing helical and 4D image datasets were obtained for each patient. Two composite images, the MIP and AI, were automatically generated from the 4D image datasets. The mGTV contours were delineated for the MIP, AI and helical image datasets for each patient. The volume for each was calculated and compared using analysis of variance and the Wilcoxon rank test. A spatial analysis for comparing center of mass (COM) (i.e. isocenter) coordinates for each imaging method was also performed using multivariate analysis of variance. RESULTS: The MIP-defined mGTVs were significantly larger than both the helical- (p=0.001) and AI-defined mGTVs (p=0.012). A comparison of COM coordinates demonstrated no significant spatial difference in the x-, y-, and z-coordinates for each tumor as determined by helical, MIP, or AI imaging methods. CONCLUSIONS: In order to incorporate the extent of tumor motion from breathing during SBRT, MIP is superior to either helical or AI images for defining the mGTV. The spatial isocenter coordinates for each tumor were not altered significantly by the imaging methods.

Errors in radiation oncology: a study in pathways and dosimetric impact.

As complexity for treating patients increases, so does the risk of error. Some publications have suggested that record and verify (R&V) systems may contribute in propagating errors. Direct data transfer has the potential to eliminate most, but not all, errors. And although the dosimetric consequences may be obvious in some cases, a detailed study does not exist. In this effort, we examined potential errors in terms of scenarios, pathways of occurrence, and dosimetry. Our goal was to prioritize error prevention according to likelihood of event and dosimetric impact. For conventional photon treatments, we investigated errors of incorrect source-to-surface distance (SSD), energy, omitted wedge (physical, dynamic, or universal) or compensating filter, incorrect wedge or compensating filter orientation, improper rotational rate for arc therapy, and geometrical misses due to incorrect gantry, collimator or table angle, reversed field settings, and setup errors. For electron beam therapy, errors investigated included incorrect energy, incorrect SSD, along with geometric misses. For special procedures we examined errors for total body irradiation (TBI, incorrect field size, dose rate, treatment distance) and LINAC radiosurgery (incorrect collimation setting, incorrect rotational parameters). Likelihood of error was determined and subsequently rated according to our history of detecting such errors. Dosimetric evaluation was conducted by using dosimetric data, treatment plans, or measurements. We found geometric misses to have the highest error probability. They most often occurred due to improper setup via coordinate shift errors or incorrect field shaping. The dosimetric impact is unique for each case and depends on the proportion of fields in error and volume mistreated. These errors were short-lived due to rapid detection via port films. The most significant dosimetric error was related to a reversed wedge direction. This may occur due to incorrect collimator angle or wedge orientation. For parallel-opposed 60 degrees wedge fields, this error could be as high as 80% to a point off-axis. Other examples of dosimetric impact included the following: SSD, approximately 2%/cm for photons or electrons; photon energy (6 MV vs. 18 MV), on average 16% depending on depth, electron energy, approximately 0.5 cm of depth coverage per MeV (mega-electron volt). Of these examples, incorrect distances were most likely but rapidly detected by in vivo dosimetry. Errors were categorized by occurrence rate, methods and timing of detection, longevity, and dosimetric impact. Solutions were devised according to these criteria. To date, no one has studied the dosimetric impact of global errors in radiation oncology. Although there is heightened awareness that with increased use of ancillary devices and automation, there must be a parallel increase in quality check systems and processes, errors do and will continue to occur. This study has helped us identify and prioritize potential errors in our clinic according to frequency and dosimetric impact. For example, to reduce the use of an incorrect wedge direction, our clinic employs off-axis in vivo dosimetry. To avoid a treatment distance setup error, we use both vertical table settings and optical distance indicator (ODI) values to properly set up fields. As R&V systems become more automated, more accurate and efficient data transfer will occur. This will require further analysis. Finally, we have begun examining potential intensity-modulated radiation therapy (IMRT) errors according to the same criteria.

Specificity of vascular endothelial growth factor treatment for radiation necrosis.

Recently, radiation induced necrosis in the brain has been treated using bevacizumab, an anti-VEGF antibody. We validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, we found that VEGF over-expression and RN developed simultaneously, which precludes preventative anti-VEGF treatment.

A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation Necrosis.

PURPOSE: To develop a Gamma Knife-based mouse model of late time-to-onset, cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance imaging (MRI) and histology. METHODS AND MATERIALS: Mice were irradiated with the Leksell Gamma Knife® (GK) PerfexionTM (Elekta AB; Stockholm, Sweden) with total single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to three fractions. RN was measured using T2-weighted MR images, while confirmation of tissue damage was assessed histologically by hematoxylin & eosin, trichrome, and PTAH staining. RESULTS: MRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation. The development of RN is significantly slower in mice irradiated with 45-Gy than 50- or 60-Gy, where RN development is similar. Irradiated mouse brains demonstrate all of the pathologic features observed clinically in patients with confirmed RN. A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated. Tissue damage, as assessed by a histologic score, correlates well with total necrotic volume measured by MRI (correlation coefficient = 0.948, with p<0.0001), and with post-irradiation time (correlation coefficient = 0.508, with p<0.0001). CONCLUSIONS: Following GK irradiation, mice develop late time-to-onset cerebral RN histology mirroring clinical observations. MR imaging provides reliable quantification of the necrotic volume that correlates well with histologic score. This mouse model of RN will provide a platform for mechanism of action studies, the identification of imaging biomarkers of RN, and the development of clinical studies for improved mitigation and neuroprotection.

Anti-VEGF antibodies mitigate the development of radiation necrosis in mouse brain.

PURPOSE: To quantify the effectiveness of anti-VEGF antibodies (bevacizumab and B20-4.1.1) as mitigators of radiation-induced, central nervous system (brain) necrosis in a mouse model. EXPERIMENTAL DESIGN: Cohorts of mice were irradiated with single-fraction 50- or 60-Gy doses of radiation targeted to the left hemisphere (brain) using the Leksell Perfexion Gamma Knife. The onset and progression of radiation necrosis were monitored longitudinally by in vivo, small-animal MRI, beginning 4 weeks after irradiation. MRI-derived necrotic volumes for antibody (Ab)-treated and untreated mice were compared. MRI results were supported by correlative histology. RESULTS: Hematoxylin and eosin-stained sections of brains from irradiated, non-Ab-treated mice confirmed profound tissue damage, including regions of fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, loss of neurons, and edema. Treatment with the murine anti-VEGF antibody B20-4.1.1 mitigated radiation-induced changes in an extraordinary, highly statistically significant manner. The development of radiation necrosis in mice under treatment with bevacizumab (a humanized anti-VEGF antibody) was intermediate between that for B20-4.1.1-treated and non-Ab-treated animals. MRI findings were validated by histologic assessment, which confirmed that anti-VEGF antibody treatment dramatically reduced late-onset necrosis in irradiated brain. CONCLUSIONS: The single-hemispheric irradiation mouse model, with longitudinal MRI monitoring, provides a powerful platform for studying the onset and progression of radiation necrosis and for developing and testing new therapies. The observation that anti-VEGF antibodies are effective mitigants of necrosis in our mouse model will enable a wide variety of studies aimed at dose optimization and timing and mechanism of action with direct relevance to ongoing clinical trials of bevacizumab as a treatment for radiation necrosis.

Toward distinguishing recurrent tumor from radiation necrosis: DWI and MTC in a Gamma Knife--irradiated mouse glioma model.

PURPOSE: Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose. METHODS AND MATERIALS: Two MRI contrasts that are widely used in the clinic were chosen for application to a glioma/radiation-injury model: diffusion weighted imaging, from which the apparent diffusion coefficient (ADC) is obtained, and magnetization transfer contrast, from which the magnetization transfer ratio (MTR) is obtained. These metrics were evaluated longitudinally, first in each lesion type alone-glioma versus irradiation - and then in a combined irradiated glioma model. RESULTS: MTR was found to be consistently decreased in all lesions compared to nonlesion brain tissue (contralateral hemisphere), with limited specificity between lesion types. In contrast, ADC, though less sensitive to the presence of pathology, was increased in radiation injury and decreased in tumors. In the irradiated glioma model, ADC also increased immediately after irradiation, but decreased as the tumor regrew. CONCLUSIONS: ADC is a better metric than MTR for differentiating glioma from radiation injury. However, MTR was more sensitive to both tumor and radiation injury than ADC, suggesting a possible role in detecting lesions that do not enhance strongly on T1-weighted images.

Predictors of individual tumor local control after stereotactic radiosurgery for non-small cell lung cancer brain metastases.

PURPOSE: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. RESULTS: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥ 1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. CONCLUSIONS: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

A GSK-3ß inhibitor protects against radiation necrosis in mouse brain.

PURPOSE: To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3ß, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model. METHODS AND MATERIALS: Cohorts of mice were treated with SB415286 or dimethyl sulfoxide (DMSO) prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using a gamma knife machine. The onset and progression of radiation necrosis (RN) were monitored longitudinally by noninvasive in vivo small-animal magnetic resonance imaging (MRI) beginning 13 weeks postirradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology. RESULTS: Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all postirradiation time points in SB415286-treated animals. Although the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemispheres of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3ß inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain. CONCLUSIONS: The unilateral cerebral hemispheric stereotactic radiation surgery mouse model in concert with longitudinal MRI monitoring provided a powerful platform for studying the onset and progression of RN and for developing and testing new neuroprotectants. Effectiveness of SB415286 as a neuroprotectant against necrosis motivates potential clinical trials of it or other GSK-3ß inhibitors.

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas.

BACKGROUND: While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution's Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. METHODS: Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. RESULTS: Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. CONCLUSION: Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly predictive of recurrence and survival on multivariate analysis in aggressive meningioma patients treated with radiosurgery. Larger tumor size predicts poor survival, while nuclear atypia, necrosis, and increased mitotic rate are risk factors for recurrence. Clinical and pathologic predictors may help identify patients that are at higher risk for recurrence.

Acute Hemorrhage Following Gamma Knife Radiosurgery to a Clival Meningioma.

BACKGROUND: Gamma Knife radiosurgery (GKS) is a primary treatment modality for small, surgically-challenging meningiomas of the skull base in carefully selected patients. Despite the overall low incidence of complications from this procedure, rare instances of hemorrhagic events following GKS have been reported. In fact, only a single, probable case of acute hemorrhage after GKS for a meningioma exists in the literature. CASE DESCRIPTION: The authors present the case of a 59-year-old female treated with GKS to a clival meningioma who suffered an acute intra- and peritumoral hemorrhage within three hours after the procedure. The patient also had an ST-elevation myocardial infarction associated with the hemorrhage. At the time of her GKS she was taking aspirin and clopidogrel for treatment of coronary artery disease with multiple cardiac stents. Cerebral catheter angiography failed to reveal a source for the hemorrhage. CONCLUSION: Acute hemorrhage following GKS to a meningioma is a rare, but potentially serious, complication and consideration should be given to counseling patients of this risk prior to treatment. We hypothesize that acute change to the structural integrity of the vascular endothelium after GKS may have precipitated cerebrovascular dysfunction resulting in hemorrhage. While the administration of anti-platelet therapy may have been a contributing factor to his event, it appears that the low incidence of acute tumoral bleeding after GKS does not justify routinely discontinuing anti-platelet and/or anti-coagulation in patients with severe associated medical co-morbidities.

Survival following gamma knife radiosurgery for brain metastasis from breast cancer.

BACKGROUND: Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. METHODS: A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. RESULTS: Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. CONCLUSION: Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival.

Dosimetric predictors of chest wall pain after lung stereotactic body radiotherapy.

PURPOSE: To identify risk factors for the development of chest wall (CW) pain after thoracic stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: A registry of patients with lung lesions treated with lung SBRT was explored to identify patients treated with 54 Gy in three fractions or 50 Gy in five fractions. One hundred and forty-six lesions in 140 patients were identified; complete electronic treatment plans were available on 86 CWs. The CW was contoured as a 3 cm outward expansion from the involved lung. Univariate and multivariate analyses were used to correlate patient, tumor, and dosimetric factors to the development of CW toxicity. RESULTS: CW pain occurred in 22 patients (15.7%). The Kaplan-Meier estimated risk of CW pain at 2 years was 20.1% (95% C.I., 13.2-28.8%). On univariate analysis of patient factors, elevated BMI (p=0.026) and connective tissue disease (p=0.036) correlated with CW pain. The percent of CW receiving 30, 35, or 40 Gy was most predictive of CW pain on multivariate analysis using logistic regression, while V40 alone was predictive using Cox regression. A V30 threshold of 0.7% and V40 threshold of 0.19% was correlated with a 15% risk of CW pain. CONCLUSIONS: We have described patient and dosimetric parameters that correlate with CW pain after lung SBRT. The risk of CW pain may be mitigated by attempting to reduce the relative proportion of CW receiving 30-40 Gy during treatment planning.