Treatment of Older Adult Patients with Glioblastoma: Moving towards the Inclusion of a Comprehensive Geriatric Assessment for Guiding Management

Chahal, Manik; Thiessen, Brian; Mariano, Caroline

doi:10.3390/curroncol29010032

Cited by 16 publications

(8 citation statements)

References 95 publications

(118 reference statements)

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“…For elderly patients with grade 4 glioma, though the standard of care involves short-course hypofractionated radiation with concurrent and adjuvant temozolomide [ 30 ], there is significant variability in the management of this heterogenous population, and prognosis remains poor. Post-operative adjuvant treatment can range from the standard of care to radiation alone (whether it be hypofractionated radiation or palliative course radiation), to temozolomide alone, to best supportive care, and is largely dependent on performance status and O 6 -methylguanine DNA-methyltransferase (MGMT) methylation status [ 31 ]. Therefore, if the elderly patients in our cohort were presenting later with more severe symptoms, they may have been less likely to be offered treatment.…”

Section: Discussionmentioning

confidence: 99%

Treatment Patterns and Outcomes of Patients with Grade 4 Glioma Treated with Radiation during the COVID-19 Pandemic

Chahal¹,

Aljawi²,

Harrison³

et al. 2023

Current Oncology

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During the first year of the COVID-19 pandemic there was a global disruption in the provision of healthcare. Grade 4 gliomas are rapidly progressive tumors, and these patients are at risk of poorer outcomes due to delays in diagnosis or treatment. We retrospectively evaluated the impact of the pandemic on treatment patterns and outcomes of patients with grade 4 gliomas in British Columbia. We identified a cohort of 85 patients treated with radiotherapy between March 2020–2021 (COVID era) and compared baseline characteristics, treatments, and outcomes with a control cohort of 79 patients treated between March 2018–2019 (pre-COVID era). There were fewer patients treated with radiotherapy over age 65 in the COVID era compared to the pre-COVID era (p = 0.037). Significantly more patients were managed with biopsy relative to partial or gross total resection during the COVID era compared to the pre-COVID era (p = 0.04), but there were no other significant differences in time to assessment, time to treatment, or administration of adjuvant therapy. There was no difference in overall survival between eras (p = 0.189). In this assessment of outcomes of grade 4 gliomas during the pandemic, we found that despite less aggressive surgical intervention during the COVID era, outcomes were similar between eras.

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Section: Discussionmentioning

confidence: 99%

Treatment Patterns and Outcomes of Patients with Grade 4 Glioma Treated with Radiation during the COVID-19 Pandemic

Chahal¹,

Aljawi²,

Harrison³

et al. 2023

Current Oncology

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“…Herein, we employed mass spectrometry-based untargeted plasma metabolomics to gain insights into the rewired metabolic landscape of GBM patients with different clinical outcomes, response to treatment, and disease severity. To avoid selection biases, instead of a population-based estimate, taking into account the sample size of this study and the median OS, 12 months was the cut-off value set for the low- and high-risk groups, as also reported by pivotal studies (RT + TMZ) in GBM and/or clinical trials [ 46 , 47 , 48 ]. To this end, we also interrogated GBM plasma metabotypes and the informative relationships through which metabolites are connected by a mixed-methods content analysis, followed by queries in the Human Metabolome Database (HMDB) [ 28 ], the Metabolomics Workbench, (accessed on 9 October 2020, 9 October 2021 and 29 December 2022) and Metabolights (MTBLS858, MTBLS730, MTBLS3873, MTBLS1558, MTBLS4708) [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

et al. 2023

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The accumulation of cell biomass is associated with dramatically increased bioenergetic and biosynthetic demand. Metabolic reprogramming, once thought as an epiphenomenon, currently relates to disease progression, also in response to extracellular fate-decisive signals. Glioblastoma multiforme patients often suffer misdiagnosis, short survival time, low quality of life, and poor disease management options. Today, tumor genetic testing and histological analysis guide diagnosis and treatment. We and others appreciate that metabolites complement translational biomarkers and molecular signatures in disease profiling and phenotyping. Herein, we coupled a mixed-methods content analysis to a mass spectrometry-based untargeted metabolomic analysis on plasma samples from glioblastoma multiforme patients to delineate the role of metabolic remodeling in biological plasticity and, hence, disease severity. Following data processing and analysis, we established a bioenergetic profile coordinated by the mitochondrial function and redox state, lipids, and energy substrates. Our findings show that epigenetic modulators are key players in glioblastoma multiforme cell metabolism, in particular when microRNAs are considered. We propose that biological plasticity in glioblastoma multiforme is a mechanism of adaptation and resistance to treatment which is eloquently revealed by bioenergetics.

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“…Importantly, our findings show that we can extract a distinct miRNA expression profile for each individual, which reflects disease severity. To avoid selection biases, considering the sample size of this study, instead of a population-based estimate, 12 months was the cut-off value set for the low- and high-risk groups, as reported by pivotal studies (RT+TMZ) in GBM and/or clinical trials for newly diagnosed patients and the age-groups included herein [ 40 , 41 , 42 ]. Our analysis revealed a clear tendency of higher expression levels for our 3-miRNA signature in the high-risk group.…”

Section: Discussionmentioning

confidence: 99%

A 3-miRNA Signature Enables Risk Stratification in Glioblastoma Multiforme Patients with Different Clinical Outcomes

et al. 2022

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Malignant gliomas constitute a complex disease phenotype that demands optimum decision-making as they are highly heterogeneous. Such inter-individual variability also renders optimum patient stratification extremely difficult. microRNA (hsa-miR-20a, hsa-miR-21, hsa-miR-21) expression levels were determined by RT-qPCR, upon FFPE tissue sample collection of glioblastoma multiforme patients (n = 37). In silico validation was then performed through discriminant analysis. Immunohistochemistry images from biopsy material were utilized by a hybrid deep learning system to further cross validate the distinctive capability of patient risk groups. Our standard-of-care treated patient cohort demonstrates no age- or sex- dependence. The expression values of the 3-miRNA signature between the low- (OS > 12 months) and high-risk (OS < 12 months) groups yield a p-value of <0.0001, enabling risk stratification. Risk stratification is validated by a. our random forest model that efficiently classifies (AUC = 97%) patients into two risk groups (low- vs. high-risk) by learning their 3-miRNA expression values, and b. our deep learning scheme, which recognizes those patterns that differentiate the images in question. Molecular-clinical correlations were drawn to classify low- (OS > 12 months) vs. high-risk (OS < 12 months) glioblastoma multiforme patients. Our 3-microRNA signature (hsa-miR-20a, hsa-miR-21, hsa-miR-10a) may further empower glioblastoma multiforme prognostic evaluation in clinical practice and enrich drug repurposing pipelines.

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Treatment of Older Adult Patients with Glioblastoma: Moving towards the Inclusion of a Comprehensive Geriatric Assessment for Guiding Management

Cited by 16 publications

References 95 publications

Treatment Patterns and Outcomes of Patients with Grade 4 Glioma Treated with Radiation during the COVID-19 Pandemic

Treatment Patterns and Outcomes of Patients with Grade 4 Glioma Treated with Radiation during the COVID-19 Pandemic

Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

A 3-miRNA Signature Enables Risk Stratification in Glioblastoma Multiforme Patients with Different Clinical Outcomes

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