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 in | Cancers Vol. 15; no. 8; p. 2253 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
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MDPI AG
12.04.2023
MDPI |
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| Online Access | Get full text |
| ISSN | 2072-6694 2072-6694 |
| DOI | 10.3390/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. |
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| 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 |
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| CitedBy_id | crossref_primary_10_1007_s00234_024_03329_8 crossref_primary_10_1007_s00521_024_09757_0 crossref_primary_10_3389_fneur_2025_1493666 crossref_primary_10_3390_diagnostics15070797 crossref_primary_10_3390_diagnostics15030251 crossref_primary_10_1038_s41698_024_00789_2 |
| Cites_doi | 10.1109/TPAMI.2021.3085983 10.1109/3DV.2016.79 10.3174/ajnr.A7029 10.1007/s10278-017-0009-z 10.3390/jpm10030128 10.22489/CinC.2016.025-237 10.3389/fonc.2019.00963 10.1093/jnen/nlaa060 10.3174/ajnr.A5667 10.1007/s10278-013-9622-7 10.1200/JCO.2009.26.3541 10.1109/CVPR.2016.90 10.1016/j.neuroimage.2009.09.049 10.1109/WACV51458.2022.00181 10.1158/1078-0432.CCR-06-2184 10.1038/s41598-022-17707-w 10.1117/1.JMI.5.1.011018 10.1007/978-3-319-46723-8_49 10.1002/hbm.20906 10.1056/NEJMoa043330 10.1109/ACCESS.2019.2952899 10.1109/TMI.2014.2377694 10.1038/nrneurol.2009.197 10.1056/NEJMoa043331 10.1016/j.inffus.2019.02.010 10.1186/s12885-018-4114-2 |
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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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| 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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