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Simple Summary: Whole-brain radiation therapy (WBRT) has been a mainstay in the treatment of multiple cerebral metastases for many decades. However, evidence of its negative effects on cognitive functions and quality of life has rendered conventional WBRT unwanted and led to widespread use of local stereotactic therapies instead. However, newer WBRT methods have been proven to be efficient and safe and have become readily available in past years. No clinical trials have compared the oncological and functional outcomes of multiple radiosurgeries with these newer methods. The available data suggest that modern WBRT techniques can play a significant role in the treatment of multiple brain metastases and warrant further prospective research. (1) Background: In recent decades, the use of whole-brain radiation therapy (WBRT) in the treatment of brain metastases has significantly decreased, with clinicians fearing adverse neurocognitive events and data showing limited efficacy regarding local tumor control and overall survival. The present study thus aimed to reassess the role that WBRT holds in the treatment of brain metastases. (2) Methods: This review summarizes the available evidence from 1990 until today supporting the use of WBRT, as well as new developments in WBRT and their clinical implications. (3) Results: While one to four brain metastases should be exclusively treated with radiosurgery, WBRT does remain an option for patients with multiple metastases. In particular, hippocampus-avoidance WBRT, WBRT with dose escalation to the metastases, and their combination have shown promising results and offer valid alternatives to local stereotactic radiotherapy. Ongoing and published prospective trials on the efficacy and toxicity of these new methods are presented. (4) Conclusions: Unlike conventional WBRT, which has limited indications, modern WBRT techniques continue to have a significant role to play in the treatment of multiple brain metastases. In which situations radiosurgery or WBRT should be the first option should be investigated in further studies. Until then, the therapeutic decision must be made individually depending on the oncological context. [ABSTRACT FROM AUTHOR]

Background: Quantitative image analysis based on radiomic feature extraction is an emerging field for survival prediction in oncological patients. 18F-Fluorethyltyrosine positron emission tomography (18F-FET PET) provides important diagnostic and grading information for brain tumors, but data on its use in survival prediction is scarce. In this study, we aim at investigating survival prediction based on multiple radiomic features in glioblastoma patients undergoing radio(chemo)therapy.Methods: A dataset of 37 patients with glioblastoma (WHO grade 4) receiving radio(chemo)therapy was analyzed. Radiomic features were extracted from pre-treatment 18F-FET PET images, following intensity rebinning with a fixed bin width. Principal component analysis (PCA) was applied for variable selection, aiming at the identification of the most relevant features in survival prediction. Random forest classification and prediction algorithms were optimized on an initial set of 25 patients. Testing of the implemented algorithms was carried out in different scenarios, which included additional 12 patients whose images were acquired with a different scanner to check the reproducibility in prediction results.Results: First order intensity variations and shape features were predominant in the selection of most important radiomic signatures for survival prediction in the available dataset. The major axis length of the 18F-FET-PET volume at tumor to background ratio (TBR) 1.4 and 1.6 correlated significantly with reduced probability of survival. Additional radiomic features were identified as potential survival predictors in the PTV region, showing 76% accuracy in independent testing for both classification and regression.Conclusions: 18F-FET PET prior to radiation provides relevant information for survival prediction in glioblastoma patients. Based on our preliminary analysis, radiomic features in the PTV can be considered a robust dataset for survival prediction. [ABSTRACT FROM AUTHOR]

Background: The current study was aimed at investigating the feasibility of hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for metastases and at assessing tumor control in comparison with conventional whole-brain radiation therapy (WBRT) in patients with multiple brain metastases.Methods: Between August 2012 and December 2016, 66 patients were treated within a monocentric feasibility trial with HA-WBRT+SIB: hippocampus-avoidance WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume ≤ 9 Gy) and a simultaneous integrated boost (51 or 42 Gy in 12 fractions) for metastases/resection cavities. Intracranial tumor control, hippocampal failure, and survival were subsequently compared with a retrospective cohort treated with WBRT via propensity score matching analysis.Results: After 1:1 propensity score matching, there were 62 HA-WBRT+SIB patients and 62 WBRT patients. Local tumor control (LTC) of existing metastases was significantly higher after HA-WBRT+SIB (98% vs 82% at 1 year; P = .007), whereas distant intracranial tumor control was significantly higher after WBRT (82% vs 69% at 1 year; P = .016); this corresponded to higher biologically effective doses. Intracranial progression-free survival (PFS; 13.5 vs 6.4 months; P = .03) and overall survival (9.9 vs 6.2 months; P = .001) were significantly better in the HA-WBRT+SIB cohort. Four patients (6.5%) developed hippocampal metastases after hippocampus avoidance. The neurologic death rate after HA-WBRT+SIB was 27.4%.Conclusions: HA-WBRT+SIB can be an efficient therapeutic option for patients with multiple brain metastases and is associated with improved LTC of existing metastases, higher intracranial PFS, a reduction of the neurologic death rate, and an acceptable risk of radiation necrosis. The therapy has the potential to prevent neurocognitive adverse effects, which will be further evaluated in the multicenter, phase 2 HIPPORAD trial. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to validate a new prognostic model (GI-GPA) originally derived from a multi-center database (USA, Canada, Japan).Patients and Methods: This retrospective study included 92 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. The GI-GPA score was calculated as described by Sperduto et al. RESULTS: Median survival was 4 months. The corresponding figures for the 4 different prognostic strata were 2.3, 4.4, 9.4 and 12.7 months, respectively (p = 0.0001). Patients whose management included surgical resection had longer median survival than those who were treated with other approaches (median 11.9 versus 3.0 months, p = 0.002). Comparable results were seen for additional systemic therapy (median 8.5 versus 3.5 months, p = 0.01).Conclusion: These results confirm the validity of the GI-GPA in an independent dataset from a different geographical region, despite the fact that overall survival was shorter in all prognostic strata, compared to Sperduto et al. Potential explanations include differences in molecular tumor characteristics and treatment selection, both brain metastases-directed and extracranially. Long-term survival beyond 5 years is possible in a small minority of patients. [ABSTRACT FROM AUTHOR]

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• First systematic review on (peri-)hippocampal brain metastasis (BM) incidence. • Forty trials included, encompassing 5,374 patients with over 32,570 BMs. • 4.4 % and 9.2 % had hippocampal and perihippocampal BMs, respectively. • 4.5 % failure rate after hippocampal-avoiding (HA) PCI or WBRT. • Hippocampal failure rate not increased in comparison with non-HA PCI or WBRT. In patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy. MEDLINE, Embase, and Scopus were searched with the terms " Hippocampus ", " Brain Neoplasms ", and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included. Forty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 − 27 %) and 9.2 % (3 − 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 − 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17). The overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life. [ABSTRACT FROM AUTHOR]