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Background EuroQoL EQ-5D-5L is a commonly used measure of health-related quality of life in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D-5L is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes. Methods A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups. Results EQ-5D-5L mean index and VAS score changes between patients who had cognitive failure and those who had preserved cognition showed no statistically significant differences at any timepoint. In contrast, VAS changes at 4 months (1.61 vs -5.13, P  = .05) and 6 months (8.17 vs −0.14, P  = .04) were significantly improved in the patients who survived without intracranial progression. MDASI-BT cognitive factor scores were improved in the cohort of patients with preserved neurocognitive function at 2 months (1.68 vs 2.08, P  = .05) and 4 months (1.35 vs 1.83, P  = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status. Conclusion EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a quality of life metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction. Trial Registration NCT# 02360215. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy (RT) plans deviating from the standard could likely compromise the efficacy of a pre-specified intervention for any clinical trial due either to insufficient coverage of the target area and/or excessive radiation doses to healthy tissues. Knowledge-based machine learning tools utilize high-quality data and generate patient-specific optimization objectives that produce RT plans that comply better with treatment protocol specifications. In this study, we investigated the use of a knowledge-based planning (KBP) model to evaluate the quality of RT plans in two clinical trials, one for glioblastoma and the other for head and neck cancer. The outcomes of this research indicate that this tool can assist RT quality assessments in multi-center clinical trials. The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials. [ABSTRACT FROM AUTHOR]

The article discusses the development of biomarkers for meningioma, the most common primary intracranial tumor. These biomarkers, including DNA mutations, RNA biomarkers, DNA methylation profiling, and gene expression profiling, have provided new insights into the biology and treatment of meningiomas. The article suggests that different biomarker systems may provide complementary information and that gene expression profiling is the most accurate system for risk stratification. The World Health Organization has also revised its grading criteria for meningiomas to incorporate rare DNA mutations. The article concludes by emphasizing the need for clinical trials to determine the best biomarkers and treatments for meningiomas. [Extracted from the article]

Initial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT + memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year. Adult patients with brain metastases were randomized to HA-WBRT + memantine or WBRT + memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L. Between July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT + memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P =.016) and was associated with less deterioration in TMT-B at 4 months (P =.012) and HVLT-R recognition at 4 (P =.055) and 6 months (P =.011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P <.005). Patients who received HA-WBRT + Memantine reported less symptom burden at 6 (P <.001 using imputed data) and 12 months (P =.026 using complete-case data; P <.001 using imputed data), less symptom interference at 6 (P =.003 using complete-case data; P =.0016 using imputed data) and 12 months (P =.0027 using complete-case data; P =.0014 using imputed data), and fewer cognitive symptoms over time (P =.043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity. With median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity. [ABSTRACT FROM AUTHOR]

CNS metastases are often terminal for cancer patients and occur at an approximately 10-fold higher rate than primary CNS tumors. The incidence of these tumors is approximately 70,000–400,000 cases annually in the US. Advances that have occurred over the past two decades have led to more personalized treatment approaches. Newer surgical and radiation techniques, as well as targeted and immune therapies, have enanled patient to live longer, thus increasing the risk for the development of CNS, brain, and leptomeningeal metastases (BM and LM). Patients who develop CNS metastases have often been heavily treated, and options for future treatment could best be addressed by multidisciplinary teams. Studies have indicated that patients with brain metastases have improved survival outcomes when cared for in high-volume academic institutions using multidisciplinary teams. This manuscript discusses a multidisciplinary approach for both parenchymal brain metastases as well as leptomeningeal metastases implemented in three academic institutions. Additionally, with the increasing development of healthcare systems, we discuss optimizing the management of CNS metastases across healthcare systems and integrating basic and translational science into our clinical care to further improve outcomes. This paper summarizes the existing therapeutic approaches to the treatment of BM and LM and discusses novel and emerging approaches to optimizing access to neuro-oncologic care while simultaneously integrating multidisciplinary teams in the care of patients with BM and LM. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases (BMs) are the most common brain malignancy and are projected to increase in incidence over the coming decades. Historically, brain metastasis studies have focused on improving survival outcomes, but recently, the importance of evaluating health-related quality of life (HRQOL) and cognitive function has gained recognition. Although there is a myriad of validated HRQOL and cognitive assessments available in the radiation oncology clinic, there is an urgent need to identify tools tailored to patients with BMs and to adopt a uniform set of tests that measure HRQOL and cognition. This review presents various assessments for measuring HRQOL and cognitive function, current recommendations to improve standardization, and treatments known to preserve HRQOL and cognitive function. Brain metastases (BMs) account for a disproportionately high percentage of cancer morbidity and mortality. Historically, studies have focused on improving survival outcomes, and recent radiation oncology clinical trials have incorporated HRQOL and cognitive assessments. We are now equipped with a battery of assessments in the radiation oncology clinic, but there is a lack of consensus regarding how to incorporate them in modern clinical practice. Herein, we present validated assessments for BM patients, current recommendations for future clinical studies, and treatment advances that have improved HRQOL and cognitive outcomes for BM patients. [ABSTRACT FROM AUTHOR]

Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques. [ABSTRACT FROM AUTHOR]

The authors consider the importance of a careful, balanced review of therapeutic options with patients and the current understanding of the therapeutic ratio of whole-brain radiotherapy in patient populations with widespread intracranial disease. The goal of reviewing these options is to provide an unbiased discussion of the potential benefits and risks of whole-brain radiotherapy, particularly with regard to cognitive outcomes. [ABSTRACT FROM AUTHOR]

Primary central nervous system (CNS) lymphoma, a rare CNS neoplasm associated with high mortality, is responsive to therapeutic interventions. In Part 1 of our two-part coverage of this entity, we provided an overview of the epidemiology of primary CNS lymphoma, followed by a discussion of the diagnostic and staging evaluation, and a review of current prognostication systems. In Part 2, we discuss the management of primary CNS lymphoma, focusing in particular on systemic therapies and radiation. With respect to systemic therapies, we provide details of a variety of regimens built around a backbone of high-dose methotrexate. Future directions for the treatment of primary CNS lymphoma are reviewed as well. These include optimization of consolidation regimens and the pursuit of novel agents. [ABSTRACT FROM AUTHOR]

Primary central nervous system (CNS) lymphoma is a rare CNS neoplasm. Its highest incidence is in the elderly and the immunocompromised. The initial steps in establishing a diagnosis involve CNS imaging. Familiarity with the clinical presentation is important in order to limit the risk of a nondiagnostic biopsy. In addition to confirming the diagnosis, it is wise to evaluate for extra-CNS disease. There are important differences in the presentation and evaluation of immunocompetent patients and those of immunocompromised patients; we will delineate these in this review. Appropriate initial clinical evaluations facilitate optimal therapeutic management for patients with primary CNS lymphoma. This is of particular importance because primary CNS lymphoma is a potentially curable disease, despite the high likelihood of recurrence. [ABSTRACT FROM AUTHOR]

Forty years ago, adjuvant treatment of patients with GBM using fractionated radiotherapy following surgery was shown to substantially improve survival compared to surgery alone. However, even with the addition of temozolomide to radiotherapy, overall survival is quite limited and local failure remains a fundamental problem, despite multiple attempts to increase dose to the tumor target. This review presents the historical background and clinical rationale leading to the current standard of care consisting of 60 Gy total dose in 2 Gy fractions to the MRI-defined targets in younger, high performance status patients and more hypofractionated regimens in elderly and/or debilitated patients. Particle therapies offer the potential to increase local control while reducing dose and, potentially, long-term neurocognitive toxicity. However, improvements in systemic therapies for GBM will need to be implemented before the full benefits of improved local control can be realized. [ABSTRACT FROM AUTHOR]