Dynamic Susceptibility Contrast MRI May Contribute in Prediction of Stereotactic Radiosurgery Outcome in Brain Metastases

Background Following stereotactic radiosurgery (SRS), predicting treatment response is not possible at an early stage using structural imaging alone. Hence, the current study aims at investigating whether dynamic susceptibility contrast (DSC)-MRI estimated prior to SRS can provide predictive biomarkers in response to SRS treatment and characterize vascular characteristics of pseudo-progression. Methods In this retrospective study, perfusion-weighted DSC-MRI image data acquired with a temporal resolution of 1.45 seconds were collected from 41 patients suffering from brain metastases. Outcome was defined based on lesion volume changes in time (determined on structural images) or death. Motion correction and manual lesion delineation were performed prior to semi-automated, voxel-wise perfusion analysis. Statistical testing was performed using linear regression and a significance threshold at P = .05. Age, sex, primary cancers (pulmonary cancer and melanoma), lesion volume, and dichotomized survival time were added as covariates in the linear regression models (ANOVA). Results Relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were found to be significantly lower prior to SRS treatment in patients with increasing lesion volume or early death post-SRS (P ≤ .01). Conclusion Unfavorable treatment outcome may be linked to low perfusion prior to SRS. Pseudo-progression may be preceded by a transient rCBF increase post-SRS. However, results should be verified in different or larger patient material.publishedVersio

A simple score to estimate the likelihood of pseudoprogression vs. recurrence following stereotactic radiosurgery for brain metastases: The Bergen Criteria

Background A major challenge in the follow-up of patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) is to distinguish pseudoprogression (PP) from tumor recurrence (TR). The aim of the study was to develop a clinical risk assessment score. Methods Follow-up images of 87 of 97 consecutive patients treated with SRS for 348 BM were analyzed. Of these, 100 (28.7%) BM in 48 (53.9%) patients responded with either TR (n = 53, 15%) or PP (n = 47, 14%). Differences between the 2 groups were analyzed and used to develop a risk assessment score (the Bergen Criteria). Results Factors associated with a higher incidence of PP vs. TR were as follows: prior radiation with whole brain radiotherapy or SRS (P = .001), target cover ratio ≥98% (P = .048), BM volume ≤2 cm3 (P = .054), and primary lung cancer vs. other cancer types (P = .084). Based on the presence (0) or absence (1) of these 5 characteristics, the Bergen Criteria was established. A total score 3 points were associated with 84% TR and 16% PP, P < .001. Conclusion Based on 5 characteristics at the time of SRS the Bergen Criteria could robustly differentiate between PP vs. TR following SRS. The score is user-friendly and provides a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.publishedVersio

Gamma knife surgery as monotherapy with clinically relevant doses prolongs survival in a Human GBM Xenograft Model

Object. Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs). However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS. Methods. GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12Gy or 18Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test. Results. In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls ( < 0.001). In a second experiment, survival was 72 days in the treatment group versus 54 days in controls ( < 0.006). Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment ( = 0.04). Conclusion.GKS administered with clinically relevant doses prolongs survival in rats harboringGBMxenografts, and the associated toxicity is mild.publishedVersio

Dynamic Susceptibility Contrast MRI May Contribute in Prediction of Stereotactic Radiosurgery Outcome in Brain Metastases

Background Following stereotactic radiosurgery (SRS), predicting treatment response is not possible at an early stage using structural imaging alone. Hence, the current study aims at investigating whether dynamic susceptibility contrast (DSC)-MRI estimated prior to SRS can provide predictive biomarkers in response to SRS treatment and characterize vascular characteristics of pseudo-progression. Methods In this retrospective study, perfusion-weighted DSC-MRI image data acquired with a temporal resolution of 1.45 seconds were collected from 41 patients suffering from brain metastases. Outcome was defined based on lesion volume changes in time (determined on structural images) or death. Motion correction and manual lesion delineation were performed prior to semi-automated, voxel-wise perfusion analysis. Statistical testing was performed using linear regression and a significance threshold at P = .05. Age, sex, primary cancers (pulmonary cancer and melanoma), lesion volume, and dichotomized survival time were added as covariates in the linear regression models (ANOVA). Results Relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were found to be significantly lower prior to SRS treatment in patients with increasing lesion volume or early death post-SRS (P ≤ .01). Conclusion Unfavorable treatment outcome may be linked to low perfusion prior to SRS. Pseudo-progression may be preceded by a transient rCBF increase post-SRS. However, results should be verified in different or larger patient material

A simple score to estimate the likelihood of pseudoprogression vs. recurrence following stereotactic radiosurgery for brain metastases: The Bergen Criteria

Background A major challenge in the follow-up of patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) is to distinguish pseudoprogression (PP) from tumor recurrence (TR). The aim of the study was to develop a clinical risk assessment score. Methods Follow-up images of 87 of 97 consecutive patients treated with SRS for 348 BM were analyzed. Of these, 100 (28.7%) BM in 48 (53.9%) patients responded with either TR (n = 53, 15%) or PP (n = 47, 14%). Differences between the 2 groups were analyzed and used to develop a risk assessment score (the Bergen Criteria). Results Factors associated with a higher incidence of PP vs. TR were as follows: prior radiation with whole brain radiotherapy or SRS (P = .001), target cover ratio ≥98% (P = .048), BM volume ≤2 cm3 (P = .054), and primary lung cancer vs. other cancer types (P = .084). Based on the presence (0) or absence (1) of these 5 characteristics, the Bergen Criteria was established. A total score 3 points were associated with 84% TR and 16% PP, P < .001. Conclusion Based on 5 characteristics at the time of SRS the Bergen Criteria could robustly differentiate between PP vs. TR following SRS. The score is user-friendly and provides a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals

Gamma knife surgery as monotherapy with clinically relevant doses prolongs survival in a Human GBM Xenograft Model

Object. Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs). However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS. Methods. GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12Gy or 18Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test. Results. In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls ( < 0.001). In a second experiment, survival was 72 days in the treatment group versus 54 days in controls ( < 0.006). Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment ( = 0.04). Conclusion.GKS administered with clinically relevant doses prolongs survival in rats harboringGBMxenografts, and the associated toxicity is mild

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature

SIMPLE SUMMARY: Meningiomas are the most common tumours of the central nervous system (CNS). Despite their benign histology, proximity to critical neurovascular structures may lead to significant morbidity with tumour growth. This is the case for cavernous sinus meningiomas (CSMs), as their growth may surround critical neuro-vascular structures and cause significant morbidity. Radical microsurgical resection carries a high risk of additional neurological deficits, as well as the risk of death. Current management of these tumours, where treatment is indicated, has moved away from radical surgery towards radiotherapy/radiosurgery. This is particularly the case for patients who have residual or recurring tumours after previous surgery. There are many reports that describe the effectiveness of using stereotactic radiosurgery (SRS) for CSMs; however, large cohort analyses are lacking. This multicentre analysis reports the outcome data of over 1000 patients with CSMs who were treated with SRS. SRS shows a high local tumour control rate with few complications. These results agree with previous reports in the literature. SRS is a valuable primary or adjuvant treatment option for CSMs. ABSTRACT: Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24–233). Median tumour volume was 6.2 cc (+/−7), and the median marginal dose was 14 Gy (+/−3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6–233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term

External validation and recalibration of an incidental meningioma prognostic model - IMPACT: protocol for an international multicentre retrospective cohort study

Introduction: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. Methods and analysis: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. Ethics and dissemination: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media