MRI-Based Deep Learning Tools for MGMT Promoter Methylation Detection: A Thorough Evaluation

Glioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy temozolomide-based treatment. Upon relapse, one option for treatment is another chemotherapy, lomustine. The efficacy of these chemotherapy reg...

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Published inCancers Vol. 15; no. 8; p. 2253
Main Authors Robinet, Lucas, Siegfried, Aurore, Roques, Margaux, Berjaoui, Ahmad, Cohen-Jonathan Moyal, Elizabeth
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 12.04.2023
MDPI
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ISSN2072-6694
2072-6694
DOI10.3390/cancers15082253

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Abstract Glioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy temozolomide-based treatment. Upon relapse, one option for treatment is another chemotherapy, lomustine. The efficacy of these chemotherapy regimens depends on the methylation of a specific gene promoter known as MGMT, which is the main prognosis factor for glioblastoma. Knowing this biomarker is a key issue for the clinician to personalize and adapt treatment to the patient at primary diagnosis for elderly patients, in particular, and also upon relapse. The association between MRI-derived information and the prediction of MGMT promoter status has been discussed in many studies, and some, more recently, have proposed the use of deep learning algorithms on multimodal scans to extract this information, but they have failed to reach a consensus. Therefore, in this work, beyond the classical performance figures usually displayed, we seek to compute confidence scores to see if a clinical application of such methods can be seriously considered. The systematic approach carried out, using different input configurations and algorithms as well as the exact methylation percentage, led to the following conclusion: current deep learning methods are unable to determine MGMT promoter methylation from MRI data.
AbstractList Simple SummaryA major prognosis factor for glioblastoma patients is the methylation status of the DNA repair enzyme MGMT. Obtaining this information using deep learning models trained on non-invasive MRI data is a major challenge with no scientific consensus to date. In this study, we provide a more rigorous and comprehensive answer to this question by using confidence metrics and relating them to the exact percentage of methylation obtained at biopsy. This systematic approach confirms that the deep learning algorithms developed until now are not suitable for clinical application. We also provide, to the best of our knowledge, the first fully reproducible source code and experiments on this issue.AbstractGlioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy temozolomide-based treatment. Upon relapse, one option for treatment is another chemotherapy, lomustine. The efficacy of these chemotherapy regimens depends on the methylation of a specific gene promoter known as MGMT, which is the main prognosis factor for glioblastoma. Knowing this biomarker is a key issue for the clinician to personalize and adapt treatment to the patient at primary diagnosis for elderly patients, in particular, and also upon relapse. The association between MRI-derived information and the prediction of MGMT promoter status has been discussed in many studies, and some, more recently, have proposed the use of deep learning algorithms on multimodal scans to extract this information, but they have failed to reach a consensus. Therefore, in this work, beyond the classical performance figures usually displayed, we seek to compute confidence scores to see if a clinical application of such methods can be seriously considered. The systematic approach carried out, using different input configurations and algorithms as well as the exact methylation percentage, led to the following conclusion: current deep learning methods are unable to determine MGMT promoter methylation from MRI data.
Glioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy temozolomide-based treatment. Upon relapse, one option for treatment is another chemotherapy, lomustine. The efficacy of these chemotherapy regimens depends on the methylation of a specific gene promoter known as MGMT, which is the main prognosis factor for glioblastoma. Knowing this biomarker is a key issue for the clinician to personalize and adapt treatment to the patient at primary diagnosis for elderly patients, in particular, and also upon relapse. The association between MRI-derived information and the prediction of MGMT promoter status has been discussed in many studies, and some, more recently, have proposed the use of deep learning algorithms on multimodal scans to extract this information, but they have failed to reach a consensus. Therefore, in this work, beyond the classical performance figures usually displayed, we seek to compute confidence scores to see if a clinical application of such methods can be seriously considered. The systematic approach carried out, using different input configurations and algorithms as well as the exact methylation percentage, led to the following conclusion: current deep learning methods are unable to determine MGMT promoter methylation from MRI data.Glioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy temozolomide-based treatment. Upon relapse, one option for treatment is another chemotherapy, lomustine. The efficacy of these chemotherapy regimens depends on the methylation of a specific gene promoter known as MGMT, which is the main prognosis factor for glioblastoma. Knowing this biomarker is a key issue for the clinician to personalize and adapt treatment to the patient at primary diagnosis for elderly patients, in particular, and also upon relapse. The association between MRI-derived information and the prediction of MGMT promoter status has been discussed in many studies, and some, more recently, have proposed the use of deep learning algorithms on multimodal scans to extract this information, but they have failed to reach a consensus. Therefore, in this work, beyond the classical performance figures usually displayed, we seek to compute confidence scores to see if a clinical application of such methods can be seriously considered. The systematic approach carried out, using different input configurations and algorithms as well as the exact methylation percentage, led to the following conclusion: current deep learning methods are unable to determine MGMT promoter methylation from MRI data.
Glioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy temozolomide-based treatment. Upon relapse, one option for treatment is another chemotherapy, lomustine. The efficacy of these chemotherapy regimens depends on the methylation of a specific gene promoter known as MGMT, which is the main prognosis factor for glioblastoma. Knowing this biomarker is a key issue for the clinician to personalize and adapt treatment to the patient at primary diagnosis for elderly patients, in particular, and also upon relapse. The association between MRI-derived information and the prediction of MGMT promoter status has been discussed in many studies, and some, more recently, have proposed the use of deep learning algorithms on multimodal scans to extract this information, but they have failed to reach a consensus. Therefore, in this work, beyond the classical performance figures usually displayed, we seek to compute confidence scores to see if a clinical application of such methods can be seriously considered. The systematic approach carried out, using different input configurations and algorithms as well as the exact methylation percentage, led to the following conclusion: current deep learning methods are unable to determine MGMT promoter methylation from MRI data.
A major prognosis factor for glioblastoma patients is the methylation status of the DNA repair enzyme MGMT. Obtaining this information using deep learning models trained on non-invasive MRI data is a major challenge with no scientific consensus to date. In this study, we provide a more rigorous and comprehensive answer to this question by using confidence metrics and relating them to the exact percentage of methylation obtained at biopsy. This systematic approach confirms that the deep learning algorithms developed until now are not suitable for clinical application. We also provide, to the best of our knowledge, the first fully reproducible source code and experiments on this issue. Glioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy temozolomide-based treatment. Upon relapse, one option for treatment is another chemotherapy, lomustine. The efficacy of these chemotherapy regimens depends on the methylation of a specific gene promoter known as MGMT, which is the main prognosis factor for glioblastoma. Knowing this biomarker is a key issue for the clinician to personalize and adapt treatment to the patient at primary diagnosis for elderly patients, in particular, and also upon relapse. The association between MRI-derived information and the prediction of MGMT promoter status has been discussed in many studies, and some, more recently, have proposed the use of deep learning algorithms on multimodal scans to extract this information, but they have failed to reach a consensus. Therefore, in this work, beyond the classical performance figures usually displayed, we seek to compute confidence scores to see if a clinical application of such methods can be seriously considered. The systematic approach carried out, using different input configurations and algorithms as well as the exact methylation percentage, led to the following conclusion: current deep learning methods are unable to determine MGMT promoter methylation from MRI data.
A major prognosis factor for glioblastoma patients is the methylation status of the DNA repair enzyme MGMT. Obtaining this information using deep learning models trained on non-invasive MRI data is a major challenge with no scientific consensus to date. In this study, we provide a more rigorous and comprehensive answer to this question by using confidence metrics and relating them to the exact percentage of methylation obtained at biopsy. This systematic approach confirms that the deep learning algorithms developed until now are not suitable for clinical application. We also provide, to the best of our knowledge, the first fully reproducible source code and experiments on this issue.
Audience Academic
Author Berjaoui, Ahmad
Robinet, Lucas
Siegfried, Aurore
Roques, Margaux
Cohen-Jonathan Moyal, Elizabeth
AuthorAffiliation 2 IUCT-Oncopole-Institut Claudius Regaud, 31100 Toulouse, France
5 Department of Neuroradiology, Hopital Pierre Paul Riquet, CHU Purpan, 31300 Toulouse, France
1 IRT Saint-Exupéry, 31400 Toulouse, France
3 INSERM UMR 1037, Cancer Research Center of Toulouse (CRCT), University Paul Sabatier Toulouse III, 31100 Toulouse, France
4 Pathology and Cytology Department, CHU Toulouse, IUCT Oncopole, 31100 Toulouse, France
AuthorAffiliation_xml – name: 3 INSERM UMR 1037, Cancer Research Center of Toulouse (CRCT), University Paul Sabatier Toulouse III, 31100 Toulouse, France
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– name: 5 Department of Neuroradiology, Hopital Pierre Paul Riquet, CHU Purpan, 31300 Toulouse, France
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Keywords deep learning
glioblastoma
MGMT promoter
confidence
Language English
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Snippet Glioblastoma is the most aggressive primary brain tumor, which almost systematically relapses despite surgery (when possible) followed by radio-chemotherapy...
A major prognosis factor for glioblastoma patients is the methylation status of the DNA repair enzyme MGMT. Obtaining this information using deep learning...
Simple SummaryA major prognosis factor for glioblastoma patients is the methylation status of the DNA repair enzyme MGMT. Obtaining this information using deep...
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StartPage 2253
SubjectTerms Accuracy
Algorithms
Biopsy
Brain cancer
Brain tumors
Cancer
Chemotherapy
Classification
Computer Science
Data mining
Datasets
Deep Learning
DNA methylation
DNA repair
Enzymes
Genetic aspects
Glioblastoma
Glioblastoma multiforme
Gliomas
Health aspects
Information processing
Learning algorithms
Machine learning
Magnetic resonance imaging
Methods
Methylation
MGMT
MRI
O6-methylguanine-DNA methyltransferase
Patients
Prognosis
Radiation therapy
Radiomics
Temozolomide
Tumors
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Title MRI-Based Deep Learning Tools for MGMT Promoter Methylation Detection: A Thorough Evaluation
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