Meningioma transformation to glioblastoma following stereotactic radiosurgery: A case report and review of the literature.

Background: Meningiomas are the most common primary intracranial tumor with increasing incidence. Stereotactic Radiosurgery Gamma Knife (SRS-GK) is a commonly used modality for neoadjuvant and adjuvant treatment of these tumors and is often necessary for long-term disease control, particularly for the World Health Organization grade II/III meningiomas. While there is strong evidence to support the use of SRS-GK for meningioma, there exists a risk of secondary malignancy that is not well understood. We report a case of glioblastoma (GBM) that arose near the bed of a meningioma previously treated with SRS-GK and discuss other cases of GBM that emerged at a site of meningioma reported in the literature. Case Description: A 79-year-old female with a history of a blood-clotting disorder presented to the hospital with sudden facial sensory disturbances. On magnetic resonance imaging (MRI), a homogeneously enhancing lesion was observed in the right temporal lobe, consistent with a meningioma. Following 2 years of surveillance, the patient underwent SRS-GK for enlargement of the lesion. The patient later presented with headache and gait instability 12 years following SRS-GK. MRI revealed a large ring-enhancing lesion with surrounding edema histologically confirmed to be a GBM. At 9 months following initial tumor resection and a combination of radiotherapy and temozolomide, the patient was neurologically intact. Conclusion: There is a very small risk of meningioma to GBM conversion following SRS. Although SRS-GK poses a risk of secondary malignancy, there are some reported cases that underwent malignant transformation without SRS-GK. This suggests that SRS-GK is not the only factor in transformation and is a reasonable therapeutic modality to consider utilizing. Patients and their families should be appropriately counseled on the potential risks of radiation therapy, even for benign lesions like a meningioma.

Neighborhood socioeconomic position, living arrangements, and cardiometabolic disease among older Puerto Ricans: An examination using PREHCO 2002-2007.

Cardiometabolic diseases are among the leading causes of mortality worldwide and are increasingly prevalent in rapidly aging populations. Neighborhood socioeconomic position (SEP) and living arrangements are increasingly recognized as important determinants of cardiometabolic health but have not been examined within Puerto Rico. This study examined the association between neighborhood SEP, living arrangements, and incidence of cardiometabolic conditions among island-dwelling older Puerto Ricans, using longitudinal data from the Puerto Rican Elderly Health Conditions Project (Waves I 2002/03 and II 2006/07) linked with 2000 Census data for neighborhood-level conditions. Our sample consists of non-institutionalized adults aged 60 and older who remained in the same residence over both waves of data collection (N = 2,769). We used multilevel multinomial logistic regression models to examine the relationship between neighborhood SEP and the prevalence and incidence of cardiometabolic disease. Findings show that residence in a socioeconomically advantaged neighborhood was positively associated with reporting having one cardiometabolic condition at baseline, but not associated with the incidence of cardiometabolic conditions at follow-up. Living without a partner was negatively associated with reporting having cardiometabolic conditions compared to living with a partner. Similar results were found for the incidence of cardiometabolic conditions. Living arrangements significantly modified the relationship between neighborhood SEP and cardiometabolic conditions. Compared to living with a partner, living alone in a socioeconomically advantaged neighborhood was associated with a reduced risk of reporting having one condition. Living with children in a socioeconomically advantaged neighborhood was associated with a reduced risk of developing one cardiometabolic condition than living with a partner. Living arrangements are more salient to cardiometabolic health than neighborhood SEP. Social programs and services focused on household composition and familial support are needed to identify older Puerto Ricans potentially at risk of underdiagnosed chronic conditions, especially as ongoing economic, demographic, environmental, and healthcare crises potentially exacerbate social inequalities.

The neighborhood context and all-cause mortality among older adults in Puerto Rico.

Background: Recent efforts have been made to collect data on neighborhood-level attributes and link them to longitudinal population-based surveys. These linked data have allowed researchers to assess the influence of neighborhood characteristics on the health of older adults in the US. However, these data exclude Puerto Rico. Because of significantly differing historical and political contexts, and widely ranging structural factors between the island and the mainland, it may not be appropriate to apply current knowledge on neighborhood health effects based on studies conducted in the US to Puerto Rico. Thus, we aim to (1) examine the types of neighborhood environments older Puerto Rican adults reside in and (2) explore the association between neighborhood environments and all-cause mortality. Methods: We linked data from the 2000 US Census to the longitudinal Puerto Rican Elderly Health Conditions Project (PREHCO) with mortality follow-up through 2021 to examine the effects of the baseline neighborhood environment on all-cause mortality among 3,469 participants. Latent profile analysis, a model-based clustering technique, classified Puerto Rican neighborhoods based on 19 census block group indicators related to the neighborhood constructs of socioeconomic status, household composition, minority status, and housing and transportation. The associations between the latent classes and all-cause mortality were assessed using multilevel mixed-effects parametric survival models with a Weibull distribution. Results: A five-class model was fit on 2,477 census block groups in Puerto Rico with varying patterns of social (dis)advantage. Our results show that older adults residing in neighborhoods classified as Urban High Deprivation and Urban High-Moderate Deprivation in Puerto Rico were at higher risk of death over the 19-year study period relative to the Urban Low Deprivation cluster, controlling for individual-level covariates. Conclusions: Considering Puerto Rico's socio-structural reality, we recommend that policymakers, healthcare providers, and leaders across industries to (1) understand how individual health and mortality is embedded within larger social, cultural, structural, and historical contexts, and (2) make concerted efforts to reach out to residents living in disadvantaged community contexts to understand better what they need to successfully age in place in Puerto Rico.

Risk of childhood trauma exposure and severity of bipolar disorder in Colombia.

BACKGROUND: Bipolar disorder (BD) is higher in developing countries. Childhood trauma exposure is a common environmental risk factor in Colombia and might be associated with a more severe course of bipolar disorder in Low-Middle Income-Countries. We carried out the first case-control study in Colombia using a structural clinical interview and the Childhood Trauma Questionnaire-Short Form (CTQ-SF) to describe the prevalence and association between trauma exposure during childhood with a severe course of illness (early age onset, rapid cycling, ideation or suicide attempt, or ≥ 3 hospitalization) in a sample of BD patients. RESULTS: A total of 114 cases and 191 controls evaluated showed the following results. Cases included 61.4% BD type I and 38.6% BD type II. The median age was 31.5 years (IQR, 75-24) for BD patients and 31 years old (IQR, 38-24) for healthy controls. A higher prevalence of childhood trauma was evidenced in cases compared to controls. Emotional abuse, physical abuse, sexual abuse, physical neglect and emotional neglect evidenced a strong association with severe bipolar disorder (OR = 3.42, p < .001; OR = 4.68, p < .001; OR = 4.30, p = .003; OR = 5.10, p < .001; OR = 5.64, p < .001, respectively). CONCLUSIONS: This is the first association study between childhood trauma exposure as a higher risk for a severe course of illness in BD patients in Colombian. Our findings highlight the higher prevalence of childhood trauma in bipolar patients and the strong association of childhood trauma with severe bipolar disorder. These findings are relevant for screening and evaluating childhood trauma exposure during the course of BD patients.

Bystander signals from low- and high-dose irradiated human primary fibroblasts and keratinocytes modulate the inflammatory response of peripheral blood mononuclear cells.

Irradiated cells can propagate signals to neighboring cells. Manifestations of these so-called bystander effects (BEs) are thought to be relatively more important after exposure to low- vs high-dose radiation and can be mediated via the release of secreted molecules, including inflammatory cytokines, from irradiated cells. Thus, BEs can potentially modify the inflammatory environment of irradiated cells. To determine whether these modifications could affect the functionality of bystander immune cells and their inflammatory response, we analyzed and compared the in vitro response of primary human fibroblasts and keratinocytes to low and high doses of radiation and assessed their ability to modulate the inflammatory activation of peripheral blood mononuclear cells (PBMCs). Only high-dose exposure resulted in either up- or down-regulation of selected inflammatory genes. In conditioned culture media transfer experiments, radiation-induced bystander signals elicited from irradiated fibroblasts and keratinocytes were found to modulate the transcription of inflammatory mediator genes in resting PBMCs, and after activation of PBMCs stimulated with lipopolysaccharide (LPS), a strong inflammatory agent. Radiation-induced BEs induced from skin cells can therefore act as a modifier of the inflammatory response of bystander immune cells and affect their functionality.

20th Century Puerto Rico and Later-Life Health: The Association Between Multigenerational Education and Chronic Conditions in Island-Dwelling Older Adults.

OBJECTIVES: Previous research on the association between education and older adult health in the U.S. has not included Puerto Rico. We investigated the effects of multigenerational educational attainment and chronic conditions among older Puerto Ricans residing on the archipelago's main island. METHODS: Data were from the longitudinal Puerto Rican Elderly Health Conditions Project. Generalized Poisson regression models were used to examine if multigenerational educational attainment was associated with chronic disease. RESULTS: Findings show that parental educational attainment was associated with fewer chronic conditions among females at baseline but not at follow-up, suggesting that the effects of parental education on health over time are less pronounced. For males, educational attainment across the three generations was not significantly associated with chronic disease at baseline or follow-up. DISCUSSION: Multigenerational education is an important determinant of older adult health that continues to be relevant in Puerto Rico and the Latin American and Hispanic-Caribbean region.

Global Ocean Particulate Organic Phosphorus, Carbon, Oxygen for Respiration, and Nitrogen (GO-POPCORN).

Concentrations and elemental stoichiometry of suspended particulate organic carbon, nitrogen, phosphorus, and oxygen demand for respiration (C:N:P:-O2) play a vital role in characterizing and quantifying marine elemental cycles. Here, we present Version 2 of the Global Ocean Particulate Organic Phosphorus, Carbon, Oxygen for Respiration, and Nitrogen (GO-POPCORN) dataset. Version 1 is a previously published dataset of particulate organic matter from 70 different studies between 1971 and 2010, while Version 2 is comprised of data collected from recent cruises between 2011 and 2020. The combined GO-POPCORN dataset contains 2673 paired surface POC/N/P measurements from 70°S to 73°N across all major ocean basins at high spatial resolution. Version 2 also includes 965 measurements of oxygen demand for organic carbon respiration. This new dataset can help validate and calibrate the next generation of global ocean biogeochemical models with flexible elemental stoichiometry. We expect that incorporating variable C:N:P:-O2 into models will help improve our estimates of key ocean biogeochemical fluxes such as carbon export, nitrogen fixation, and organic matter remineralization.

Global patterns and predictors of C:N:P in marine ecosystems.

Oceanic nutrient cycles are coupled, yet carbon-nitrogen-phosphorus (C:N:P) stoichiometry in marine ecosystems is variable through space and time, with no clear consensus on the controls on variability. Here, we analyze hydrographic, plankton genomic diversity, and particulate organic matter data from 1970 stations sampled during a global ocean observation program (Bio-GO-SHIP) to investigate the biogeography of surface ocean particulate organic matter stoichiometry. We find latitudinal variability in C:N:P stoichiometry, with surface temperature and macronutrient availability as strong predictors of stoichiometry at high latitudes. Genomic observations indicated community nutrient stress and suggested that nutrient supply rate and nitrogen-versus-phosphorus stress are predictive of hemispheric and regional variations in stoichiometry. Our data-derived statistical model suggests that C:P and N:P ratios will increase at high latitudes in the future, however, changes at low latitudes are uncertain. Our findings suggest systematic regulation of elemental stoichiometry among ocean ecosystems, but that future changes remain highly uncertain.

"Guttmann Cognitest"®, preliminary validation of a digital solution to test cognitive performance.

Thanks to technological advances, the administration of cognitive assessments via digital solutions continues to increase, both in research and clinical practice. "Guttmann Cognitest"°ledR is a digital solution for cognitive assessment which includes seven computerized tasks designed to assess main cognitive functions requiring approximately 20 min to be completed. The purpose of the present study was to validate it against standard and more extensive in-person neuropsychological assessments in the context of the Barcelona Brain Health Initiative (BBHI) cohort study. We studied 274 participants of the BBHI (126 women, mean age = 56.14, age range 44-69), who underwent an extensive in-person assessment, including a classical paper-and-pencil neuropsychological assessment and a cognitive assessment via the "Guttmann Cognitest"°ledR. Principal component analysis indicated that "Guttmann Cognitest"°ledR measures four main cognitive domains and convergent validity analysis demonstrated that cognitive performance was associated with gold standard paper and pencil tests. Results also showed an expected negative correlation with age, a relation with educational level as well as a gender effect. Regression-based norming equations for the sample tested are also reported. Performing a cognitive assessment with this digital solution is feasible and potentially useful to gather information about cognitive functioning in large samples and experimental settings.

Cranial Irradiation for Childhood Cancers and Adult Risk of Meningioma.

INTRODUCTION: Following cranial irradiation, there is an increased risk of developing secondary neoplasms, especially meningiomas. Despite childhood cancer survivors who have undergone cranial irradiation having an increased risk of acquiring radiation-induced meningioma (RIM), there is no widely used standard guideline for meningioma screening. METHODS: At a single institution, we reviewed three adult survivors of childhood cancer who were treated for RIM between 2010 and 2020. We recorded age at diagnosis for the primary lesion, the radiation dose, age at RIM diagnosis, and tumor characteristics including treatment, pathology, and outcome. Two had had T-cell acute lymphocytic leukemia and one a rhabdomyosarcoma. The age of diagnosis of the RIM ranged from 20 to 40 years, with latencies ranging from 18 to 33 years. All lesions were classified as WHO Grade I meningiomas, and only 1 patient had a subsequent recurrence. A literature search identified articles that address RIM: a total of 684 cases were identified in 36 publications. RESULTS: Mean radiation doses ranged from 1.4 gray to 70 gray. Mean age of diagnosis for secondary meningioma ranged from 8 to 53.4 years old, with latency periods ranging from 2.8 to 44 years. Given variability in the way that investigators have published their results, it is difficult to make a single recommendation for RIM screening. Using our experience and the literature, we devised two different screening protocols and calculated their expense. CONCLUSIONS: We recommend that data be standardized in a registry to provide greater insight into the clinical and resource allocation questions, especially as long-term survival of children with pediatric cancer into full adulthood becomes more commonplace worldwide.

Sense of Coherence Mediates the Relationship Between Cognitive Reserve and Cognition in Middle-Aged Adults.

In recent years, supported by new scientific evidence, the conceptualization of cognitive reserve (CR) has been progressively enriched and now encompasses not only cognitive stimulating activities or educational level, but also lifestyle activities, such as leisure physical activity and socialization. In this context, there is increasing interest in understanding the role of psychological factors in brain health and cognitive functioning. In a previous study, we have found that these factors mediated the relationship between CR and self-reported cognitive functioning. In this study, we have confirmed an association between two important constructs included in the psychological wellbeing and salutogenic models, "purpose in life" and "sense of coherence," CR, as assessed using a questionnaire, and cognitive functioning, as evaluated using a comprehensive neuropsychological battery. Results from 888 middle-aged healthy participants from the Barcelona Brain Health Initiative indicate that both sense of coherence (SoC) and CR were positively associated with verbal memory, reasoning and attention, working memory, and global cognition. Moreover, the relation between CR and cognitive functioning in the different domains is partially mediated by SoC. When we controlled for brain integrity, introducing into the model neurofilament light chain measures, the mediator role of SoC was confirmed for reasoning and attention and global cognition. However, purpose in life was not associated with cognitive functioning. These results reveal the central role of the SoC construct, which mediates the association between classic CR estimates and cognitive functions, potentially representing a modifiable target for interventions that aim to promote brain health.

Stress is a Latent Construct: Exploring the Differential Experience of Stress and Discrimination on Depressive Symptoms Among Black Older Adults.

Objectives: While evidence highlights the detrimental mental health consequences of chronic stress exposure, the impact of this stress exposure on older Black Americans' mental health varies by exposure to other types of stressors like discrimination as well as subjective evaluations of stress like chronic stress appraisal. Methods: Using data from the 2010/2012 Health and Retirement Study, we use latent profile analysis (LPA) to describe 2,415 Black older adults experience with chronic stress exposure, appraisal, and discrimination and examine which stress contexts are associated with depressive symptomology. Results: Analyses revealed five stress clusters-demonstrating the diversity in the stress experience for older Black adults. Black older adults with stress profiles that include lower stress appraisal report fewer depressive symptoms regardless of number of stress exposures. Discussion: LPA is as an alternative approach to examining the stress-mental health link that can define stress profiles by both exposure and appraisal-based measures.

Living Arrangements and Intergenerational Support in Puerto Rico: Are Fathers Disadvantaged?

OBJECTIVES: To examine how intergenerational support varies by parents' living arrangements and whether there are gender differences in received support in Puerto Rico. METHODS: Data come from the 2006-2007 Puerto Rican Elderly and Health Conditions Project, a representative longitudinal study of adults aged 60 and older in Puerto Rico (n = 2,288). We examined the association between parents' living arrangements (alone, with spouse/partner only, with children) and their receipt of functional (help with errands/housework/transport) and health (help when sick) support from children, and whether parents' gender moderates the association. RESULTS: Intergenerational coresidence was associated with higher odds of receiving functional and health support than living alone. Women were more likely than men to receive both forms of support. Parents' gender significantly moderated the association between living arrangements and receiving health support-men living with their partners were less likely to receive health support from children than women in similar living arrangements. These associations persisted when analyses were restricted to those with disability. DISCUSSION: Our findings suggest that parents' receipt of support from children is conditioned upon their living arrangement and gender, even when their functional health is jeopardized. We discuss these results in relation to the heterogeneous influence of living arrangements for older adults' support needs and provide suggestions for policy and directions for future research in rapidly aging Puerto Rico.

Outcomes for Adults with Metabolic Syndrome Undergoing Elective Carotid Endarterectomy.

BACKGROUND: Metabolic syndrome (MetS) is a disorder characterized by a constellation of cardiometabolic risk factors including abdominal obesity, dyslipidemia, hypertension, and glucose intolerance that has been associated with adverse perioperative outcomes. We evaluated outcomes for patients with MetS after carotid endarterectomy (CEA) in the largest population to date. METHODS: We performed a matched cohort analysis using clinical data from 2012 to 2018 in the American College of Surgeons National Surgical Quality Improvement Program. We used propensity scores to match patients to attain covariate balance and used logistic regression to assess odds of unfavorable outcomes, including a predefined primary outcome of composite cardiovascular incident. RESULTS: We identified 50,423 eligible adult patients, of whom 14.2% qualified for MetS (n = 7156). Patients with MetS tended to have CEA at an earlier age, more functional dependence, and longer operative durations. After matching, MetS remained associated with the primary outcome of combined cardiovascular incident (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.18-1.72; P < 0.001), stroke (OR, 1.44; 95% CI, 1.12-1.85; P = 0.004), prolonged length of stay (OR, 1.31; 95% CI, 1.18-1.44; P < 0.001), and discharge to facility (OR, 1.32; 95% CI, 1.08-1.61; P = 0.007). We also found that obesity alone is protective against combined cardiovascular incident, whereas hypertension with diabetes and MetS increase odds of a cardiovascular complication. CONCLUSIONS: Metabolic syndrome is associated with adverse outcomes for adult patients undergoing elective CEA.

Validation and Normative Data of the Spanish Version of the Rey Auditory Verbal Learning Test and Associated Long-Term Forgetting Measures in Middle-Aged Adults.

Rey Auditory Verbal Learning Test (RAVLT) is an episodic memory helpful measure to detect changes associated with abnormal aging. There is a lack of RAVLT validation and normalization studies in Spain. The aim was to determine its psychometric properties and explore long-term forgetting (LTF) performance through 1-week delayed recall under three different modes of administration. The RAVLT was administered to 602 cognitively healthy volunteers, aged between 41 and 65 years, of whom 251 completed the LTF assessment. Findings reveal a factorial structure of four components, with satisfactory goodness of fit, and adequate convergent and divergent validity. We also demonstrated the differential effect of three methodologies used in LTF assessment, supporting that test expectancy positively influences long-term storage. Finally, normative data were generated according to age, sex, and education. The test, including the LTF measure, is a promising tool to estimate memory in middle-aged adults and develop predictive brain aging models.

Local Prefrontal Cortex TMS-Induced Reactivity Is Related to Working Memory and Reasoning in Middle-Aged Adults.

INTRODUCTION: The prefrontal cortex (PFC) plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this study, we investigated the associations between cognitive measures and TMS evoked EEG reactivity and explored whether the effects of this relationship were related to neurofilament light chain levels (NfL), a marker of neuroaxonal damage. METHODS: Fifty two healthy middle-aged adults (41-65 years) from the Barcelona Brain Health Initiative cohort underwent TMS-EEG, a comprehensive neuropsychological assessment, and a blood test for NfL levels. Global and Local Mean-Field Power (GMFP/LMFP), two measures of cortical reactivity, were quantified after left prefrontal cortex (L-PFC) stimulation, and cognition was set as the outcome of the regression analysis. The left inferior parietal lobe (L-IPL) was used as a control stimulation condition. RESULTS: Local reactivity was significantly associated with working memory and reasoning only after L-PFC stimulation. No associations were found between NfL and cognition. These specific associations were independent of the status of neuroaxonal damage indexed by the NfL biomarker and remained after adjusting for age, biological sex, and education. CONCLUSION: Our results demonstrate that TMS evoked EEG reactivity at the L-PFC, but not the L-IPL, is related to the cognitive status of middle-aged individuals and independent of NfL levels, and may become a valuable biomarker of frontal lobe-associated cognitive function.

Demographic and Health Characteristics of Older Latino Birth Cohorts in the Health and Retirement Study.

OBJECTIVES: Latinos are the fastest aging racial/ethnic minority group in the United States. One limitation to understanding the diverse experiences of older Latinos is the lack of nationally representative data necessary to examine factors contributing to changes in population-level health over time. This is needed to provide a more comprehensive picture of the demographic characteristics that influence the health and well-being of older Latinos. METHODS: We utilized the steady-state design of the Health and Retirement Study (HRS) from 1992 to 2016 to examine the demographic and health characteristics of five entry birth cohorts of older Latinos aged 51-56 years (n = 2,882). Adjusted Wald tests were used to assess statistically significant differences in demographic and health characteristics across the HRS birth cohorts. RESULTS: Cross-cohort comparisons of demographic and health characteristics of older Latinos indicate significant change over time, with later-born HRS birth cohorts less likely to identify as Mexican-origin, more likely to identify as a racial "other," and more likely to be foreign-born. In addition, we find that later-born cohorts are more educated and exhibit a higher prevalence of hypertension, diabetes, and obesity. DISCUSSION: Increasing growth and diversity among the older U.S. Latino population make it imperative that researchers document changes in the demographic composition and health characteristics of this population as it will have implications for researchers, policymakers, health care professionals, and others seeking to anticipate the needs of this rapidly aging population.

Validation and Normative Data of the Spanish Version of the Face Name Associative Memory Exam (S-FNAME).

OBJECTIVE: The relevance of the episodic memory in the prediction of brain aging is well known. The Face Name Associative Memory Exam (FNAME) is a valued associative memory measure related to Alzheimer's disease (AD) biomarkers, such as amyloid-ß deposition preclinical AD individuals. Previous validation of the Spanish version of the FNAME test (S-FNAME) provided normative data and psychometric characteristics. The study was limited to subjects attending a memory clinic and included a reduced sample with gender inequality distribution. The purpose of this study was to assess S-FNAME psychometric properties and provide normative data in a larger independent sample of cognitively healthy individuals. METHOD: S-FNAME was administered to 511 cognitively healthy volunteers (242 women, aged 41-65 years) participating in the Barcelona Brain Health Initiative cohort study. RESULTS: Factor analysis supported construct validity revealing two underlying components: face-name and face-occupation and explaining 95.34% of the total variance, with satisfactory goodness of fit. Correlations between S-FNAME and Rey Auditory-Verbal Learning Test were statistically significant and confirmed its convergent validity. We also found weak correlations with non-memory tests supporting divergent validity. Women showed better scores, and S-FNAME was positively correlated with education and negatively with age. Finally, we generated normative data. CONCLUSIONS: The S-FNAME test exhibits good psychometric properties, consistent with previous findings, resulting in a valid and reliable tool to assess episodic memory in cognitively healthy middle-aged adults. It is a promising test for the early detection of subtle memory dysfunction associated with abnormal brain aging.

Hematological adverse events in the management of glioblastoma.

BACKGROUND: Hematological adverse events (HAEs) are common during treatment for glioblastoma (GBM), usually associated with temozolomide (TMZ). Their clinical value is uncertain, as few investigations have focused on outcomes for HAEs during GBM treatment. METHODS: We combined data from two randomized clinical trials, RTOG 0525 and RTOG 0825, to analyze HAEs during treatment for GBM. We investigated differences between chemoradiation and adjuvant therapy, and by regimen received during adjuvant treatment. RESULTS: 1454 patients participated in these trials, of which 1154 (79.4%) developed HAEs. During chemoradiation, 44.4% of patients developed HAEs (54% involving more than one cell line), and were most commonly lymphopenia (50.6%), and thrombocytopenia (47.5%). During adjuvant treatment, 45% of patients presented HAEs (78.6% involving more than one cell line), and were more commonly leukopenia (62.7%), and thrombocytopenia (62.3%). Median overall survival (OS) and progression free survival (PFS) were longer in patients with HAEs (OS 19.4 months and PFS 9.9 months) compared to those with other or no adverse events (OS 14.1 months and PFS 5.9 months). There was no significant difference in survival between grade 1 and/or 2 versus grade 3 and/or 4 HAEs. History of HAEs during chemoradiation was a protective factor for presentation of HAEs during adjuvant therapy. CONCLUSION: HAEs are common during GBM treatment, and often involve more than one cell line (more likely during adjuvant therapy). HAEs may be associated with prolonged OS and PFS, particularly during adjuvant therapy. HAEs during chemoradiation was a protective factor for HAEs during adjuvant therapy.