Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Standard Protocol Approvals, Registrations, and Patient Consents
2.2. Patient Population
2.3. Data Analysis
2.4. Statistics
2.5. Data Availability
3. Results
3.1. Patient Population
3.2. Impact of Quantitative MGMT Status on Survival
3.3. Predictive Cut-Off of Quantitative MGMT Status
4. Discussion
4.1. Prognostic Threshold of Quantitative MGMT Testing
4.2. MGMT Promoter Methylation: The More, the Better?
4.3. Can TMZ Be Omitted According to MGMT Promoter Methylation?
4.4. Method for MGMT Methylation Assessment
4.5. Clinical Implications
4.6. Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviation
Abbreviation | Meaning |
95% CI | 95% confidence interval |
AUC | Area under the curve |
CpG | Cytosine–phosphate–guanine |
CRET | Complete resection of enhancing tumor |
EGFR | Epidermal growth factor receptor |
GTR | Gross total resection |
HR | Hazard ratio |
IDH | Isocitrate dehydrogenase |
KPS | Karnofsky performance status |
MGMT | O(6)-methylguanine-DNA methyltransferase |
mPCR | Methylation-specific polymerase chain reaction |
NIHSS | National Institutes of Health Stroke Scale |
ROC | Receiver operating characteristics |
STR | Subtotal resection |
TERT | Telomerase reverse transcriptase |
TMZ | Temozolomide |
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Percentage Methylation | 0% n = 165 | 1–15% n = 14 | 16–30% n = 18 | 31–60% n = 24 | 61–100% n = 100 | p-Value |
---|---|---|---|---|---|---|
Female sex | 43 (26%) | 10 (71%) | 6 (33%) | 8 (33%) | 42 (42%) | 0.003 |
Age (years) | 63 (±12) | 61 (±9.3) | 67 (±8.7) | 62 (±13) | 66 (±10) | 0.06 |
KPS ≥ 70% | 139 (84%) | 10 (71%) | 18 (100%) | 18 (75%) | 80 (80%) | 0.15 |
Surgery | 0.44 | |||||
-biopsy | 48 (29%) | 5 (36%) | 7 (39%) | 8 (33%) | 29 (29%) | |
-CRET | 70 (42%) | 4 (29%) | 7 (39%) | 4 (17%) | 38 (38%) | |
-GTR | 11 (6.7%) | 0 (0%) | 0 (0%) | 2 (8.3%) | 5 (5%) | |
-subtotal | 33 (20%) | 5 (36%) | 3 (17%) | 9 (38%) | 28 (28%) | |
Chemotherapy | 126 (76%) | 10 (71%) | 14 (78%) | 19 (79%) | 83 (83%) | 0.72 |
Radiotherapy | 141 (85%) | 12 (86%) | 14 (78%) | 21 (88%) | 90 (90%) | 0.66 |
Promoter Methylation | Unadjusted HR (95% CI) | p-Value | Adjusted HR (95% CI) | p-Value |
---|---|---|---|---|
0% | reference | n/a | reference | n/a |
1–15% | 1.32 (0.75–2.32) | 0.340 | 1.47 (0.81–2.66) | 0.204 |
16–30% | 0.47 (0.28–0.78) | 0.004 | 0.50 (0.29–0.85) | 0.010 |
31–60% | 0.45 (0.28–0.72) | 0.001 | 0.39 (0.25–0.63) | <0.001 |
61–100% | 0.52 (0.40–0.67) | <0.001 | 0.54 (0.41–0.72) | <0.001 |
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Häni, L.; Kopcic, M.; Branca, M.; Schütz, A.; Murek, M.; Söll, N.; Vassella, E.; Raabe, A.; Hewer, E.; Schucht, P. Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification. Cancers 2022, 14, 3149. https://doi.org/10.3390/cancers14133149
Häni L, Kopcic M, Branca M, Schütz A, Murek M, Söll N, Vassella E, Raabe A, Hewer E, Schucht P. Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification. Cancers. 2022; 14(13):3149. https://doi.org/10.3390/cancers14133149
Chicago/Turabian StyleHäni, Levin, Monika Kopcic, Mattia Branca, Alessa Schütz, Michael Murek, Nicole Söll, Erik Vassella, Andreas Raabe, Ekkehard Hewer, and Philippe Schucht. 2022. "Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification" Cancers 14, no. 13: 3149. https://doi.org/10.3390/cancers14133149