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Frailty in Glioblastoma Is Independent From Chronological Age.

ABSTRACT: Objective: Treatment of glioblastoma in elderly patients is particularly challenging due to their general condition and comorbidities. Treatment decisions are often based on chronological age. Frailty screening tests promise an assessment tool to stratify geriatric patients and identify those at risk for an unfavorable outcome. This study aims to evaluate the impact of age and frailty on the surgical outcome and overall survival in geriatric patients with glioblastoma. Methods: Data acquisition was conducted as a single-center retrospective analysis. From January 1st 2015, and December 31st 2019, 104 glioblastoma patients over 70 years of age were included in our study. Demographic data, tumor size, Karnofsky Performance Score (KPS), and Eastern Cooperative Oncology Group Performance Status (ECOG), as well as treatment modalities, were assessed. The Geriatric 8 health status screening tool (G8) and Groningen Frailty Index (GFI) were compiled pre-and postoperatively. Results: The mean patient age was 76.86 ± 4.11 years. Forty-nine (47%) patients were female, 55 (53%) male. Sixty-seven patients underwent microsurgical tumor resection, 37 received tumor biopsy alone. Mean G8 on admission was 12.4 ± 2.0, mean GFI 5.0 ± 2.5. In our cohort, frailty was independent of patient age, tumor size, or localization. Frailty, defined by G8 and GFI, is associated with shorter overall survival (G8: p = 0.0035; GFI: p = 0.0136) and higher numbers of surgical complications (G8: p = 0.0326; GFI: p = 0.0388). Frailer patients are more likely to receive best supportive care (p = 0.004). Nevertheless, frailty did not affect adjuvant treatment decision-making toward either single-use of chemo- or radiation therapy, stratified treatment, or concomitant therapy. The surgical decision on the extent of resection was not based on pre-operative frailty. Conclusion: In our study, frailty is a predictor of poorer surgical outcomes, post-operative complications, and impaired overall survival independent of chronological age. Frailty screening tests offer an additional assessment tool to stratify geriatric patients with glioblastoma and identify those at risk for a detrimental outcome and thus should be implemented in therapeutic decision making.

SUBMITTER: Krenzlin H

PROVIDER: S-EPMC8669893 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEpigenetic clocks can track both chronological age (cAge) and biological age (bAge). The latter is typically defined by physiological biomarkers and risk of adverse health outcomes, including all-cause mortality. As cohort sample sizes increase, estimates of cAge and bAge become more precise. Here, we aim to develop accurate epigenetic predictors of cAge and bAge, whilst improving our understanding of their epigenomic architecture.MethodsFirst, we perform large-scale (N = 18,413) epigenome-wide association studies (EWAS) of chronological age and all-cause mortality. Next, to create a cAge predictor, we use methylation data from 24,674 participants from the Generation Scotland study, the Lothian Birth Cohorts (LBC) of 1921 and 1936, and 8 other cohorts with publicly available data. In addition, we train a predictor of time to all-cause mortality as a proxy for bAge using the Generation Scotland cohort (1214 observed deaths). For this purpose, we use epigenetic surrogates (EpiScores) for 109 plasma proteins and the 8 component parts of GrimAge, one of the current best epigenetic predictors of survival. We test this bAge predictor in four external cohorts (LBC1921, LBC1936, the Framingham Heart Study and the Women's Health Initiative study).ResultsThrough the inclusion of linear and non-linear age-CpG associations from the EWAS, feature pre-selection in advance of elastic net regression, and a leave-one-cohort-out (LOCO) cross-validation framework, we obtain cAge prediction with a median absolute error equal to 2.3 years. Our bAge predictor was found to slightly outperform GrimAge in terms of the strength of its association to survival (HRGrimAge = 1.47 [1.40, 1.54] with p = 1.08 × 10-52, and HRbAge = 1.52 [1.44, 1.59] with p = 2.20 × 10-60). Finally, we introduce MethylBrowsR, an online tool to visualise epigenome-wide CpG-age associations.ConclusionsThe integration of multiple large datasets, EpiScores, non-linear DNAm effects, and new approaches to feature selection has facilitated improvements to the blood-based epigenetic prediction of biological and chronological age.

Project description:BackgroundGiven the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual's kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors.MethodsWe examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years.ResultsIn proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60-69 years, with similar sensitivities for men and women.ConclusionsIn this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women.Trial registrationClinicalTrials.gov NCT00400257 , NCT00604006 , and NCT01581827 .

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Frailty in Glioblastoma Is Independent From Chronological Age.

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