Dataset Information

Brain atlas for assessing the impact of tumor location on perioperative quality of life in patients with high-grade glioma: A prospective population-based cohort study.

ABSTRACT:

Background

Tumor location is important for surgical decision making. Particular attention is paid to regions that contain sensorimotor and language functions, but it is unknown if these are the most important regions from the patients' perspective.

Objective

To develop an atlas for depicting and assessing the potential importance of tumor location for perioperative health-related quality of life (HRQoL) in patients with newly diagnosed high-grade glioma.

Methods

Patient-reported HRQoL data and semi-automatically segmented preoperative 3D MRI-images were combined in 170 patients. The images were registered to a standardized space where the individual tumors were given the values and color intensity of the corresponding HRQoL. Descriptive brain maps of HRQoL, defined quantitative analyses, and voxel-based lesion symptom mapping comparing patients with tumors in different locations were made.

Results

There was no statistical difference in overall perioperative HRQoL between patients with tumors located in left or right hemisphere, between patients with tumors in different lobes, or between patients with tumors located in non-eloquent, near eloquent, or eloquent areas. Patients with tumors involving the internal capsule, and patients with preoperative motor symptoms and postoperative motor deficits, reported significantly worse overall HRQoL-scores.

Conclusions

The impact of anatomical tumor location on overall perioperative HRQoL seems less than frequently believed, and the distinction between critical and less critical brain regions seems more unclear according to the patients than perhaps when judged by physicians. However, worse HRQoL was found in patients with tumors in motor-related regions, indicating that these areas are crucial also from the patients' perspective.

SUBMITTER: Sagberg LM

PROVIDER: S-EPMC6412075 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Brain atlas for assessing the impact of tumor location on perioperative quality of life in patients with high-grade glioma: A prospective population-based cohort study.

Sagberg Lisa Millgård LM Iversen Daniel Høyer DH Fyllingen Even Hovig EH Jakola Asgeir Store AS Reinertsen Ingerid I Solheim Ole O

NeuroImage. Clinical 20190108

<h4>Background</h4>Tumor location is important for surgical decision making. Particular attention is paid to regions that contain sensorimotor and language functions, but it is unknown if these are the most important regions from the patients' perspective.<h4>Objective</h4>To develop an atlas for depicting and assessing the potential importance of tumor location for perioperative health-related quality of life (HRQoL) in patients with newly diagnosed high-grade glioma.<h4>Methods</h4>Patient-rep ...[more]

PMID: 30655192

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Project description:A phase-1, multi-center study in recurrent non-enhancing gliomas with IDH1 R132H mutation for patients who require surgery. The purpose of this study is to evaluate the suppression of 2-HG (2-hydroxyglutarate) by comparing the concentration of 2-HG in resected tumors from IDH1 mutant glioma subjects following AG-120 or AG-881 treatment with the 2-HG concentration in untreated, control tumors. The safety, tolerability, PK/PD, and anti tumor activity data from the study in subjects with recurrent non-enhancing Grade 2/3 LGG with an IDH1 R132H mutation for whom surgical resection is indicated will identify the recommended dose of AG-120 and AG-881 for future studies in glioma. Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) and have shown preliminary clinical activity against mIDHglioma. We evaluated both agents in a perioperative phase 1 trial to explore the mechanism of action in recurrent low-grade glioma (IGG) and select a molecule for phase 3 testing. Primary end-point was concentration ofD-2-hydroxyglutarate (2-HG), the metabolic product of mIDH enzymes, measured in tumor tissue from 49 patients with mIDH1-R132H nonenhancing gliomas following randomized treatment with vorasidenib (50 mg or 10 mg once daily, q.d.), ivosidenib (500 mg q.d. or 250 mg twice daily) or no treatment before surgery. Tumor 2-HG concentrations were reduced by 92.6% (95% credible interval (CrI), 76.1–97.6) and 91.1% (95% CrI, 72.0–97.0) in patients treated with vorasidenib 50 mg q.d. and ivosidenib 500 mg q.d., respectively. Both agents were well tolerated and follow-up is ongoing. In exploratory analyses, 2-HG reduction was associated with increased DNA 5-hydroxymethylcytosine, reversal of ‘proneural’ and ‘stemness’ gene expression signatures, decreased tumor cell proliferation and immune cell activation. Vorasidenib, which showed brain penetrance and more consistent 2-HG suppression than ivosidenib, was advanced to phase 3 testing in patients with mIDHLGGs. Funded by Agios Pharmaceuticals, Inc. and Servier Pharmaceuticals LLC; ClinicalTrials.gov number NCT03343197.

Project description:PurposeClinical trials in glioma patients with neurocognitive deficits face challenges due to lacking or unreliable patient self-reports on their health-related quality of life (HRQOL). Patient-proxy data could help solve this issue. We determined whether patient-proxy concordance levels were affected by patients' neurocognitive functioning.MethodsPatient and patient-by-proxy HRQOL ratings were assessed via SF-36 and EORTC QLQ-BN20, respectively, in 246 patients. Data on neurocognitive functioning were collected on a subgroup of 195 patients. Patient-proxy agreement was measured using the Bland-Altman limit of agreement, the mean difference, the concordance correlation coefficient (CCC), and the percentage difference (PD, ±0, 5, or 10 points). We defined patients to be cognitively impaired (n = 66) or cognitively intact (n = 129) based on their neurocognitive performance.ResultsPatients rated their physical function and general health to be better than their proxies did, while at the same time, patients reported more visual disorders, communication deficits, itchy skin, and problems with bladder control. The cognitively impaired subgroup reported poorer physical functioning, more visual disorders, headaches, itchy skin, and issues with bladder control. In the cognitively intact group, no statistical significant differences were observed between patients and proxies. Not surprisingly, Bland-Altman plots revealed a high agreement between the patient and patient-by-proxy rating in all HRQOL domains ranging from 95 to 99 %. The CCC was fairly high in all HRQOL domains (0.37-0.80), and the percentage of perfect agreement (PD ± 0) ranged from 8.5 to 76.8 %. In the cognitively impaired patients, the mean difference between patients and proxies was overall larger, and accordingly, agreement based on Bland-Altman plots was lower.ConclusionsThe level of agreement between patient and patient-by-proxy ratings of low-grade glioma patients' HRQOL is generally high. However, patient-proxy agreement is lower in patients with neurocognitive deficits than in patients without neurocognitive deficits.

Dataset Information

Brain atlas for assessing the impact of tumor location on perioperative quality of life in patients with high-grade glioma: A prospective population-based cohort study.

Background

Objective

Methods

Results

Conclusions

Publications

Brain atlas for assessing the impact of tumor location on perioperative quality of life in patients with high-grade glioma: A prospective population-based cohort study.

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