RESUMO
BACKGROUND: Intravenous thrombolysis (IVT) before endovascular treatment (EVT) for acute ischemic stroke might induce intracerebral hemorrhages which could negatively affect patient outcomes. Measuring white matter lesions size using deep learning (DL-WML) might help safely guide IVT administration. We aimed to develop, validate, and evaluate a DL-WML volume on CT compared to the Fazekas scale (WML-Faz) as a risk factor and IVT effect modifier in patients receiving EVT directly after IVT. METHODS: We developed a deep-learning model for WML segmentation on CT and validated with internal and external test sets. In a post hoc analysis of the MR CLEAN No-IV trial, we associated DL-WML volume and WML-Faz with symptomatic-intracerebral hemorrhage (sICH) and 90-day functional outcome according to the modified Rankin Scale (mRS). We used multiplicative interaction terms between WML measures and IVT administration to evaluate IVT treatment effect modification. Regression models were used to report unadjusted and adjusted common odds ratios (cOR/acOR). RESULTS: In total, 516 patients from the MR CLEAN No-IV trial (male/female, 291/225; age median, 71 [IQR, 62-79]) were analyzed. Both DL-WML volume and WML-Faz are associated with sICH (DL-WML volume acOR, 1.78 [95%CI, 1.17; 2.70]; WML-Faz acOR, 1.53 95%CI [1.02; 2.31]) and mRS (DL-WML volume acOR, 0.70 [95%CI, 0.55; 0.87], WML-Faz acOR, 0.73 [95%CI 0.60; 0.88]). Only in the unadjusted IVT effect modification analysis WML-Faz was associated with more sICH if IVT was given (p = 0.046). Neither WML measure was associated with worse mRS if IVT was given. CONCLUSION: DL-WML volume and WML-Faz had a similar relationship with functional outcome and sICH. Although more sICH might occur in patients with more severe WML-Faz receiving IVT, no worse functional outcome was observed. CLINICAL RELEVANCE STATEMENT: White matter lesion severity on baseline CT in acute ischemic stroke patients has a similar predictive value if measured with deep learning or the Fazekas scale. Safe administration of intravenous thrombolysis using white matter lesion severity should be further studied. KEY POINTS: White matter damage is a predisposing risk factor for intracranial hemorrhage in patients with acute ischemic stroke but remains difficult to measure on CT. White matter lesion volume on CT measured with deep learning had a similar association with symptomatic intracerebral hemorrhages and worse functional outcome as the Fazekas scale. A patient-level meta-analysis is required to study the benefit of white matter lesion severity-based selection for intravenous thrombolysis before endovascular treatment.
Assuntos
Aprendizado Profundo , AVC Isquêmico , Tomografia Computadorizada por Raios X , Substância Branca , Humanos , Feminino , Masculino , Idoso , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Resultado do Tratamento , Terapia Trombolítica/métodos , Hemorragia Cerebral/diagnóstico por imagem , Fibrinolíticos/uso terapêutico , Procedimentos Endovasculares/métodosRESUMO
OBJECTIVES: Model-based health economic evaluations of ischemic stroke are in need of cost- and utility estimates related to relevant outcome measures. This study aims to describe societal cost- and utility estimates per modified Rankin Scale (mRS)-score at different time points within 2 years post stroke. METHODS: Included patients had a stroke between 3 months and 2.5 years ago. mRS and EQ-5D-5L were scored during a telephone interview. Based on the interview date, records were categorized into a time point: 3 months (3M; 3-6 months), 1 year (Y1; 6-18 months), or 2 years (Y2; 18-30 months). Patients completed a questionnaire on healthcare utilization and productivity losses in the previous 3 months. Initial stroke hospitalization costs were assessed. Mean costs and utilities per mRS and time point were derived with multiple imputation nested in bootstrapping. Cost at 3 months post stroke were estimated separately for endovascular treatment (EVT)-/non-EVT-patients. RESULTS: 1106 patients were included from 18 Dutch centers. At each time point, higher mRS-scores were associated with increasing average costs and decreasing average utility. Mean societal costs at 3M ranged from 11 943 (mRS 1, no EVT) to 55 957 (mRS 5, no EVT). For Y1, mean costs in the previous 3 months ranged from 885 (mRS 0) to 23 215 (mRS 5), and from 1655 (mRS 0) to 22 904 (mRS 5) for Y2. Mean utilities ranged from 0.07 to 0.96, depending on mRS and time point. CONCLUSIONS: The mRS-score is a major determinant of costs and utilities at different post-stroke time points. Our estimates may be used to inform future model-based health economic evaluations.
Assuntos
Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Análise Custo-Benefício , Acidente Vascular Cerebral/terapia , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The Plaque At RISK (PARISK) study demonstrated that patients with a carotid plaque with intraplaque hemorrhage (IPH) have an increased risk of recurrent ipsilateral ischemic cerebrovascular events. It was previously reported that symptomatic carotid plaques with IPH showed higher IPH signal intensity ratios (SIR) and larger IPH volumes than asymptomatic plaques. We explored whether IPH SIR and IPH volume are associated with future ipsilateral ischemic cerebrovascular events beyond the presence of IPH. METHODS: Transient ischemic attack and ischemic stroke patients with mild-to-moderate carotid stenosis and an ipsilateral IPH-positive carotid plaque (n = 89) from the PARISK study were included. The clinical endpoint was a new ipsilateral ischemic cerebrovascular event during 5 years of follow-up, while the imaging-based endpoint was a new ipsilateral brain infarct on brain magnetic resonance imaging (MRI) after 2 years (n = 69). Trained observers delineated IPH, a hyperintense region compared to surrounding muscle tissue on hyper T1-weighted magnetic resonance images. The IPH SIR was the maximal signal intensity in the IPH region divided by the mean signal intensity of adjacent muscle tissue. The associations between IPH SIR or volume and the clinical and imaging-based endpoint were investigated using Cox proportional hazard models and logistic regression, respectively. RESULTS: During 5.1 (interquartile range: 3.1-5.6) years of follow-up, 21 ipsilateral cerebrovascular ischemic events were identified. Twelve new ipsilateral brain infarcts were identified on the 2-year neuro MRI. There was no association for IPH SIR or IPH volume with the clinical endpoint (hazard ratio (HR): 0.89 [95% confidence interval: 0.67-1.10] and HR: 0.91 [0.69-1.19] per 100-µL increase, respectively) nor with the imaging-based endpoint (odds ratio (OR): 1.04 [0.75-1.45] and OR: 1.21 [0.87-1.68] per 100-µL increase, respectively). CONCLUSION: IPH SIR and IPH volume were not associated with future ipsilateral ischemic cerebrovascular events. Therefore, quantitative assessment of IPH of SIR and volume does not seem to provide additional value beyond the presence of IPH for stroke risk assessment. TRIAL REGISTRATION: The PARISK study was registered on ClinicalTrials.gov with ID NCT01208025 on September 21, 2010 (https://clinicaltrials.gov/study/NCT01208025).
RESUMO
A disparity exists between spinal cord and brain involvement in multiple sclerosis (MS), each independently contributing to disability. Underlying differences between brain and cord are not just anatomical in nature (volume, white/grey matter organization, vascularization), but also in barrier functions (differences in function and composition of the blood-spinal cord barrier compared to blood-brain barrier) and possibly in repair mechanisms. Also, immunological phenotypes seem to influence localization of inflammatory activity. Whereas the brain has gained a lot of attention in MS research, the spinal cord lags behind. Advanced imaging techniques and biomarkers are improving and providing us with tools to uncover the mechanisms of spinal cord pathology in MS. In the present review, we elaborate on the underlying anatomical and physiological factors driving differences between brain and cord involvement in MS and review current literature on pathophysiology of spinal cord involvement in MS and the observed differences to brain involvement.
Assuntos
Esclerose Múltipla , Substância Branca , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Substância Cinzenta/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Branca/patologia , Imageamento por Ressonância MagnéticaRESUMO
Introduction: Intracranial multiple myeloma (MM) is a rare manifestation of MM, a malignant plasma cell disorder that primarily affects bone marrow. Dural involvement in MM is even rarer and can manifest as a dural mass. We present a case of MM presenting as an intracranial dural tumor with primary hemi-dural involvement. Research question: This case report aims to investigate the clinical presentation, diagnostic challenges, and treatment approaches for intracranial multiple myeloma, with a focus on the extensive hemi-dural thickening and enhancement seen in this case. Material and methods: A 73-year-old male presented with progressive dysphasia and weakness. MRI revealed a solid left frontal mass with significant mass-effect. Hemi-dural thickening and enhancement was present along with invasion of the skull. The patient underwent surgical resection of the tumor with dural and bone reconstruction. Results: Histopathological examination confirmed MM diagnosis. Chemotherapy was started. Follow-up MRI showed complete tumor resection, but extensive hemi-dural thickening and enhancement persisted. Postoperative radiation therapy was considered. Discussion and conclusion: MM with primary dural involvement is rare and poses diagnostic challenges. Postoperative treatment involves chemotherapy, the role of surgery and radiotherapy is not established. The extensive hemi-dural thickening and enhancement observed in this case require further investigation, and a wait-and-scan policy was recommended instead of radiotherapy.
RESUMO
BACKGROUND AND PURPOSE: Endovascular treatment (EVT) is the preferred treatment option in eligible acute ischemic stroke (AIS) patients with a large vessel occlusion of the anterior circulation. Several comorbidities have been identified that can affect clinical outcomes. Various studies have investigated the association between anemia and clinical outcome and found conflicting. RESULTS: . The aim is to investigate the association between pre-EVT anemia and clinical outcomes at different time points post-EVT, primarily focusing on the National Institutes of Health Stroke Scale (NIHSS) at 24-48 hours. METHODS: We prospectively included 560 AIS patients who received EVT in the Maastricht University Medical Center+. Hemoglobin levels (Hb; g/dL) were determined on admission. Hb levels were also categorized into two groups: anemia (male: Hb ≤12.9 g/dL; female: Hb ≤11.9 g/dL) and no anemia. Multiple imputation was used to handle missing data. Multivariable regression was used to investigate the association between anemia or Hb levels and clinical outcomes. RESULTS: Anemia was present in 26% of the patients. Multivariable regression did not show a significant association between anemia or Hb levels and NIHSS at 24-48 hours (adjusted ß [aß]anemia: 1.44, 95% confidence interval [CI]: -0.47 to 3.36; aßHb: -0.37, 95% CI: -0.88 to 0.13). However, multivariable regression showed significant associations with modified Rankin Scale (adjusted common odds ratio [acOR]anemia: 1.66, 95% CI: 1.12 to 2.48; acORHb: 0.83, 95% CI: 0.75 to 0.93) and poor functional outcome at 90 days (adjusted OR [aOR]anemia: 2.09, 95% CI: 1.21 to 3.63; aORHb: 0.80, 95% CI: 0.69 to 0.92). CONCLUSION: Anemia was not independently associated with early neurological deficit (NIHSS) post-AIS, suggesting it is more suitable as a general frailty marker.
RESUMO
Perfusion measures of the total vasculature are commonly derived with gradient-echo (GE) dynamic susceptibility contrast (DSC) MR images, which are acquired during the early passes of a contrast agent. Alternatively, spin-echo (SE) DSC can be used to achieve specific sensitivity to the capillary signal. For an improved contrast-to-noise ratio, ultra-high-field MRI makes this technique more appealing to study cerebral microvascular physiology. Therefore, this study assessed the applicability of SE-DSC MRI at 7 T. Forty-one elderly adults underwent 7 T MRI using a multi-slice SE-EPI DSC sequence. The cerebral blood volume (CBV) and cerebral blood flow (CBF) were determined in the cortical grey matter (CGM) and white matter (WM) and compared to values from the literature. The relation of CBV and CBF with age and sex was investigated. Higher CBV and CBF values were found in CGM compared to WM, whereby the CGM-to-WM ratios depended on the amount of largest vessels excluded from the analysis. CBF was negatively associated with age in the CGM, while no significant association was found with CBV. Both CBV and CBF were higher in women compared to men in both CGM and WM. The current study verifies the possibility of quantifying cerebral microvascular perfusion with SE-DSC MRI at 7 T.
Assuntos
Volume Sanguíneo Cerebral , Substância Branca , Adulto , Idoso , Masculino , Feminino , Humanos , Perfusão , Imageamento por Ressonância MagnéticaRESUMO
Background: Glioblastoma (GBM) is widely treated using large radiotherapy margins, resulting in substantial irradiation of the surrounding cerebral structures. In this context, the question arises whether these margins could be safely reduced. In 2018, clinical target volume (CTV) expansion was reduced in our institution from 20 to 15 mm around the gross target volume (GTV) (ie, the contrast-enhancing tumor/cavity). We sought to retrospectively analyze the impact of this reduction. Methods: All adult patients with GBM treated between January 2015 and December 2020 with concurrent chemoradiation (60Gy/2Gy or 59.4Gy/1.8Gy) were analyzed. Patients treated using a 20 (CTV20, nâ =â 57) or 15 mm (CTV15, nâ =â 56) CTV margin were compared for target volumes, dose parameters to the surrounding organs, pattern of recurrence, and survival outcome. Results: Mean GTV was similar in both groups (ie, CTV20: 39.7cm3; CTV15: 37.8cm3; Pâ =â .71). Mean CTV and PTV were reduced from 238.9cm3 to 176.7cm3 (Pâ =â .001) and from 292.6cm3 to 217.0cm3 (Pâ <â .001), for CTV20 and CTV15, respectively. As a result, average brain mean dose (Dmean) was reduced from 25.2Gy to 21.0Gy (Pâ =â .002). Significantly lower values were also observed for left hippocampus Dmean, brainstem D0.03cc, cochleas Dmean, and pituitary Dmean. Pattern of recurrence was similar, as well as patient outcome, ie, median progression-free survival was 8.0 and 7.0 months (Pâ =â .80), and median overall survival was 11.0 and 14.0 months (Pâ =â .61) for CTV20 and CTV15, respectively. Conclusions: In GBM patients treated with chemoradiation, reducing the CTV margin from 20 to 15 mm appears to be safe and offers the potential for less treatment toxicity.
RESUMO
Glioblastoma (GBM) continues to exhibit a discouraging survival rate despite extensive research into new treatments. One factor contributing to its poor prognosis is the tumor's immunosuppressive microenvironment, in which the kynurenine pathway (KP) plays a significant role. This study aimed to explore how KP impacts the survival of newly diagnosed GBM patients. We examined tissue samples from 108 GBM patients to assess the expression levels of key KP markers-tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenase (IDO1/2), and the aryl hydrocarbon receptor (AhR). Using immunohistochemistry and QuPath software, three tumor cores were analyzed per patient to evaluate KP marker expression. Kaplan-Meier survival analysis and stepwise multivariate Cox regression were used to determine the effect of these markers on patient survival. Results showed that patients with high expression of TDO2, IDO1/2, and AhR had significantly shorter survival times. This finding held true even when controlling for other known prognostic variables, with a hazard ratio of 3.393 for IDO1, 2.775 for IDO2, 1.891 for TDO2, and 1.902 for AhR. We suggest that KP markers could serve as useful tools for patient stratification, potentially guiding future immunomodulating trials and personalized treatment approaches for GBM patients.
Assuntos
Biomarcadores Tumorais , Glioblastoma , Indolamina-Pirrol 2,3,-Dioxigenase , Cinurenina , Receptores de Hidrocarboneto Arílico , Triptofano Oxigenase , Humanos , Cinurenina/metabolismo , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Glioblastoma/patologia , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Biomarcadores Tumorais/metabolismo , Triptofano Oxigenase/metabolismo , Idoso , Adulto , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Estimativa de Kaplan-Meier , Microambiente Tumoral , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
BACKGROUND: The MR CLEAN-LATE trial has shown that patient selection for endovascular treatment (EVT) in the late window (6-24 h after onset or last-seen-well) based on the presence of collateral flow on CT-angiography is safe and effective. We aimed to assess the cost-effectiveness of late-window collateral-based EVT-selection compared to best medical management (BMM) over a lifetime horizon (until 95 years of age). MATERIALS AND METHODS: A model-based economic evaluation was performed from a societal perspective in The Netherlands. A decision tree was combined with a state-transition (Markov) model. Health states were defined by the modified Rankin Scale (mRS). Initial probabilities at 3-months post-stroke were based on MR CLEAN-LATE data. Transition probabilities were derived from previous literature. Information on short- and long-term resource use and utilities was obtained from a study using MR CLEAN-LATE and cross-sectional data. All costs are expressed in 2022 euros. Costs and quality-adjusted life years (QALYs) were discounted at a rate of 4% and 1.5%, respectively. The effect of parameter uncertainty was assessed using probabilistic sensitivity analysis (PSA). RESULTS: On average, the EVT strategy cost 159,592 (95% CI: 140,830-180,154) and generated 3.46 QALYs (95% CI: 3.04-3.90) per patient, whereas the costs and QALYs associated with BMM were 149,935 (95% CI: 130,841-171,776) and 2.88 (95% CI: 2.48-3.29), respectively. The incremental cost-effectiveness ratio per QALY and the incremental net monetary benefit were 16,442 and 19,710, respectively. At a cost-effectiveness threshold of 50,000/QALY, EVT was cost-effective in 87% of replications. DISCUSSION AND CONCLUSION: Collateral-based selection for late-window EVT is likely cost-effective from a societal perspective in The Netherlands.
Assuntos
Angiografia por Tomografia Computadorizada , Análise Custo-Benefício , Procedimentos Endovasculares , AVC Isquêmico , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Procedimentos Endovasculares/economia , Procedimentos Endovasculares/métodos , AVC Isquêmico/economia , AVC Isquêmico/terapia , AVC Isquêmico/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/economia , Idoso , Masculino , Feminino , Circulação Colateral/fisiologia , Países Baixos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Modelos EconômicosRESUMO
BACKGROUND: The MR CLEAN-LATE trial provided evidence for the safety and efficacy of endovascular treatment for acute ischaemic stroke within the late window (after 6-24 h) in patients who were preselected based on the presence of collateral flow on CT angiography. We aimed to evaluate clinical outcomes 2 years after randomisation. METHODS: MR CLEAN-LATE was a phase 3, multicentre, open-label, blinded-endpoint, randomised controlled trial conducted at 18 stroke intervention centres in the Netherlands. If endovascular treatment could be initiated within 6-24 h of symptom onset or last seen well, patients (aged 18 years or older) with an acute ischaemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery territory on CT angiography were randomly assigned (1:1) to either endovascular treatment with best medical treatment (endovascular treatment group) or best medical treatment alone (control group). Web-based randomisation, stratified by centre, was performed with the use of permuted blocks (block size eight to 20). The researchers who collected clinical outcomes and analysed the results were masked to treatment allocation; treating physicians, local investigators, and patients were aware of the received treatment. The primary outcome of MR CLEAN-LATE was the modified Rankin Scale (mRS) score at 90 days after randomisation. For this 2-year prespecified analysis, the primary outcome was mRS score at 2 years (minus 3 months to plus 6 months). Primary and safety analyses were performed based on the modified intention-to-treat principle, and included patients who provided (deferred) consent or died before consent could be obtained. Missing data were handled with multiple imputation by chained equations. The trial is completed and is registered at ISRCTN, ISRCTN19922220. FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned in the MR CLEAN-LATE trial, of whom 502 (94%) gave deferred consent and comprised the modified intention-to-treat population (255 in the endovascular treatment group and 247 in the control group). 261 (52%) patients were female and 241 (48%) were male. Data for mRS score at 2 years were available for 226 (89%) patients in the endovascular treatment group and for 202 (82%) patients in the control group. The median mRS score at 2 years was 4 (IQR 2-6) in the endovascular treatment group and 6 (2-6) in the control group. The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common odds ratio 1·41 [95% CI 1·00-1·99]; p=0·049). All-cause mortality at 2 years was 34% (87 of 255) in the endovascular treatment group and 41% (101 of 247) in the control group (adjusted hazard ratio 0·81 [95% CI 0·60-1·08]; p=0·15). Major vascular events (ie, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, and cardiac events) were reported between 90 days and 2 years in 23 patients in the endovascular treatment group and 13 patients in the control group. INTERPRETATION: Our results show that the effectiveness of late-window (after 6-24 h) endovascular treatment in improving clinical outcomes is sustained for up to 2 years in a population preselected based on the presence of collateral flow on CT angiography. This finding might be important for prompting further evaluations of cost-effectiveness, health-care policy development, and clinical decision making. FUNDING: The Dutch Organization for Health Research and Health Innovation (ZonMW), Collaboration for New Treatments of Acute Stroke Consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Health Holland Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.
Assuntos
Circulação Colateral , Procedimentos Endovasculares , AVC Isquêmico , Humanos , Procedimentos Endovasculares/métodos , Masculino , Feminino , AVC Isquêmico/terapia , AVC Isquêmico/cirurgia , Países Baixos , Idoso , Pessoa de Meia-Idade , Seguimentos , Circulação Colateral/fisiologia , Resultado do Tratamento , Seleção de Pacientes , Idoso de 80 Anos ou maisRESUMO
Accurate preoperative localization is crucial for successful minimally invasive parathyroidectomy in primary hyperparathyroidism (PHPT). Preoperative localization can be challenging in patients with recurrent and/or multigland disease (MGD). This has led clinicians to investigate multiple imaging techniques, most of which are associated with radiation exposure. Magnetic resonance imaging (MRI) offers ionizing radiation-free and accurate imaging, making it an attractive alternative imaging modality. The objective of this systematic review is to provide an overview of the diagnostic performance of MRI in the localization of PHPT. PubMed and Embase libraries were searched from 1 January 2000 to 31 March 2023. Studies were included that investigated MRI techniques for the localization of PHPT. The exclusion criteria were (1) secondary/tertiary hyperparathyroidism, (2) studies that provided no diagnostic performance values, (3) studies published before 2000, and (4) studies using 0.5 Tesla MRI scanners. Twenty-four articles were included in the systematic review, with a total of 1127 patients with PHPT. In 14 studies investigating conventional MRI for PHPT localization, sensitivities varied between 39.1% and 94.3%. When employing more advanced MRI protocols like 4D MRI for PHPT localization in 11 studies, sensitivities ranged from 55.6% to 100%. The combination of MR imaging with functional techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy, with sensitivities ranging from 84.2% to 100% in five studies. Despite the limitations of the available evidence, the results of this review indicate that the combination of MR imaging with functional imaging techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy. Further research on emerging MR imaging modalities, such as 4D MRI and PET/MRI, is warranted, as MRI exposes patients to minimal or no ionizing radiation compared to other imaging modalities.
RESUMO
Background: Treatment resistance and tumor relapse are the primary causes of mortality in glioblastoma (GBM), with intratumoral heterogeneity playing a significant role. Patient-derived cancer organoids have emerged as a promising model capable of recapitulating tumor heterogeneity. Our objective was to develop patient-derived GBM organoids (PGO) to investigate treatment response and resistance. Methods: GBM samples were used to generate PGOs and analyzed using whole-exome sequencing (WES) and single-cell karyotype sequencing. PGOs were subjected to temozolomide (TMZ) to assess viability. Bulk RNA sequencing was performed before and after TMZ. Results: WES analysis on individual PGOs cultured for 3 time points (1-3 months) showed a high inter-organoid correlation and retention of genetic variants (range 92.3%-97.7%). Most variants were retained in the PGO compared to the tumor (range 58%-90%) and exhibited similar copy number variations. Single-cell karyotype sequencing demonstrated preservation of genetic heterogeneity. Single-cell multiplex immunofluorescence showed maintenance of cellular states. TMZ treatment of PGOs showed a differential response, which largely corresponded with MGMT promoter methylation. Differentially expressed genes before and after TMZ revealed an upregulation of the JNK kinase pathway. Notably, the combination treatment of a JNK kinase inhibitor and TMZ demonstrated a synergistic effect. Conclusions: Overall, these findings demonstrate the robustness of PGOs in retaining the genetic and phenotypic heterogeneity in culture and the application of measuring clinically relevant drug responses. These data show that PGOs have the potential to be further developed into avatars for personalized adaptive treatment selection and actionable drug target discovery and as a platform to study GBM biology.