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Background Brain metastases (BM) represent the most common intracranial tumor in adults. An estimated 20% of all patients with cancer will develop BM. Stereotactic Radiosurgery (SRS) is a major treatment option for BM. For SRS treatment planning and outcome evaluation, magnetic resonance images (MRI) are acquired before and at multiple stages during the follow-up. Accurate segmentation of brain tumors on MRI is crucial for treatment planning and response evaluation. Detection and segmentation of BM which is a tedious and time-consuming task for many radiologists could be optimized with machine learning. Methods The accuracy of the auto-segmentation, however, is influenced by the presence of false-positive and false-negative segmentation. There are studies which evaluated the segmentation performance of several deep learning algorithms, these were mainly focused on training and testing the models on either the pre-treatment or post-treatment images. The purpose of this study was to investigate a well-known deep learning approach (nnU-Net) for BM segmentation and to evaluate its performance on both pre-treatment and post-treatment images to assess if it could be a handy tool for the clinicians. Methods Pre-treatment T1-weighted brain MRIs which were contrast-enhanced with triple-dose gadolinium were collected retrospectively for 266 patients with BM. Scans were made as part of clinical care at the Gamma Knife Center of the Elisabeth-TweeSteden Hospital (Tilburg, the Netherlands). All patients underwent Gamma Knife Radiosurgery, a form of SRS. This total of 266 patients were randomly split into 210 patients for model training/validation and 56 patients for testing. For these 56 patients used for testing, the post treatment follow-up T1-weighted brain MRI scans which were contrast-enhanced with single-dose gadolinium were also retrospectively collected. The nnU-Net model was trained with the pre-treatment training data, and then tested sepa

Background The aim of this study was to assess long-term multidimensional fatigue and (change in) fatigue as predictor for survival in patients with brain metastases (BM) up to 21 months after Gamma Knife radiosurgery (GKRS). Material and Methods Patients with 1 to 10 BM, expected survival >3 months, and Karnofsky Performance Status ≥70 were included. Fatigue was measured with the Multidimensional Fatigue Inventory (MFI). Linear mixed models were used to evaluate fatigue up to 21 months after GKRS. Fatigue before GKRS and changes in fatigue in the first three months after GKRS were evaluated as predictors for survival duration. Results Patients with BM experienced significantly higher levels of fatigue on all subscales prior to GKRS (n=92) compared to Dutch controls (n=104), all p’s≤.001. Over 21 months, levels of physical fatigue increased significantly (p=.001), and levels of mental fatigue decreased significantly (p=.004). Between pre-GKRS and 3 months, there was a significant increase in levels of general (p<.001) and physical fatigue (p<.001), followed by stable fatigue scores between 3 (n=67) and 6 (n=53) months, 6 and 12 (n=34) months and 12 and 21 (n=21) months. Minimal clinically important (MCI) increases in general (p=.023, time ratio=0.61) and in physical fatigue (p=.008, time ratio=0.56) from pre-GKRS to 3 months thereafter were independent negative predictors of survival time (i.e., an MCI increase in these domains predicted a reduction of 39% and 44% respectively in survival time compared to stable or decreased fatigue). Conclusion Results indicate that up to 21 months after GKRS fatigue is a persistent problem in patients with BM. Except for an increase in general and physical fatigue up to 3 months after treatment, fatigue remained stable up to 21 months after GKRS. In addition, an MCI increase in general or physical fatigue within three months after GKRS may be related to worse survival outcome.

Background Both stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) have proven to be effective treatments for multiple brain metastases (BM) with similar overall survival. Cognition and Radiation (CAR) Study B is a randomized trial on the effect of Gamma Knife radiosurgery (GKRS) or WBRT on cognitive performance in patients with 11-20 BM. The primary and secondary aim of this interim analysis were to check whether Bayesian stopping rules for cognitive failure were met, and to compare cognitive changes after treatment respectively, for the first 45 patients enrolled. Material and Methods Patients with 11-20 newly diagnosed BM on a triple-dose contrast-enhanced MRI-scan, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70, were stratified by age, histology, total BM volume, systemic treatment, KPS, and baseline Hopkins Verbal Learning total recall (HVLT-R TR) score, and randomized 1:1 (minimization) to GKRS or WBRT. Neuropsychological tests were administered before (T0) treatment (n=21 vs n=20), and at 3 (T3; n=16 vs n=14) and 6 (T6; n=9 vs n=9) months thereafter. A decline of ≥5 points in HVLT-R TR score was considered a cognitive failure. The trial would be halted if the posterior probability for a higher cognitive failure rate in one group versus the other was >0·975 at T3 or T6 according to the employed beta (2.09,2.91) prior (prior mean of 42%), based on the average failure rates at 4 months reported by Chang et al. (2009). Between-group differences in changes of test performances over 6 months were analyzed using mixed ANOVAs. Proportions of cognitive changes (T0-T6) at the individual level based on reliable change indices correcting for practice effects, were determined. Results HVLT-R TR failure rates in the GKRS versus WBRT group were 31% versus 29% at T3, and 0% versus 33% at T6. The observed failure rates after WBRT at T3 and T6 were lower than the average failure rates of Chang et

Purpose A growing number of patients with brain metastases (BM) are being treated with stereotactic radiosurgery (SRS), and the importance of evaluating the impact of SRS on the health-related quality of life (HRQoL) in these patients has been increasingly acknowledged. This systematic review summarizes the current knowledge about the HRQoL of patients with BM after SRS. Methods We searched EMBASE, Medline Ovid, Web-of-Science, the Cochrane Database, PsycINFO Ovid, and Google Scholar up to November 15, 2018. Studies in patients with BM in which HRQoL was assessed before and after SRS and analyzed over time were included. Studies including populations of several types of brain cancer and/or several types of treatments were included if the results for patients with BM and treatment with SRS alone were described separately. Results Out of 3638 published articles, 9 studies met the eligibility criteria and were included. In 4 out of 7 studies on group results, overall HRQoL of patients with BM remained stable after SRS. In small study samples of longer-term survivors, overall HRQoL remained stable up to 12 months post-SRS. Contradictory results were reported for physical and general/global HRQoL, which might be explained by the different questionnaires that were used. Conclusions In general, SRS does not have significant negative effects on patients’ overall HRQoL over time. Future research is needed to analyze different aspects of HRQoL, differences in individual changes in HRQoL after SRS, and factors that influence these changes. These studies should take into account several methodological issues as discussed in this review.

Purpose: Stereotactic radiation surgery (SRS) is increasingly applied in patients with brain metastases (BM) and is expected to have fewer adverse effects on cognitive functioning than whole brain radiation therapy (WBRT). Patients with BM are often confronted with a relatively short life expectancy, and the prevention or delay of cognitive decline to maintain quality of life is a clinically and highly relevant treatment goal. This review systematically and specifically evaluates the current literature on the cognitive effects of SRS in patients with BM.Methods and materials: Published trials on SRS alone or in combination with WBRT, including objective assessment of cognitive functioning, were identified through a systematic search of the PubMed database up to March 2018.Results: Of the 241 records screened, 14 studies matched the selection criteria: 2 pilot studies, 7 single-group/observational trials (1 study update), and 5 randomized trials (1 secondary analysis).Conclusions: In general, the results show little to no objective cognitive decline up to 4 months after SRS compared with WBRT. However, most trials suffered from methodologic limitations that hindered reliable conclusions. Most importantly, few studies investigated the specific cognitive effects of SRS alone or versus WBRT. Furthermore, disentangling the cognitive effects of SRS from the effects of the disease itself and from the effects of other treatments remains very difficult. By presenting this comprehensive review, we aim to encourage researchers to probe deeper into this area and to do so in a standardized and methodologically optimal manner. The ultimate objective of this line of research is to inform both doctors and patients more precisely about the cognitive effects they can expect from treatment. This study is expected to improve the quality of decision-making and maximize clinical outcomes for each individual patient.

Background Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing. Methods CAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11–20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months. Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery. Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment. Discussion Knowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups.