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Xiaoguang Qiu
Beijing Tiantan Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6806-9827
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Background: Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethyaltion (MGMT-non-pM) have a particularly short survival and are greatly resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM.
Methods: 269 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005-2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariable analyses were performed using the cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose-response on MGMT status defined subtypes was analyzed.
Results: On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas（p = 0.002 and p = 0.005）, high-dose RT (> 54 Gy) （p = 0.017 and p = 0.023） and 1p/19q codeletion （p <0.001 and p = 0.001）. On multivariable analyses, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.44; 95%CI, 0.21-0.92; p = 0.029; and HR, 0.43; 95%CI, 0.20-0.90; p = 0.025, respectively) and PFS (HR, 0.48; 95%CI, 0.27-0.90; p = 0.021; and HR, 0.52; 95%CI, 0.27-0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.55; 95%CI, 0.32-0.93; p = 0.026) and PFS (HR, 0.57; 95%CI, 0.35-0.93; p = 0.026) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype.
Conclusions: High-dose RT (> 54 Gy) is an independently protective factor for LGGs and associated with improved survival in patients with MGMT-non-pM.
Keywords
Low-grade gliomas, Radiation dose, Survival, MGMT
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryFigure1.jpg
Supplementary Fig. 1. The distribution of RT doses in LGG patients.
- SupplementaryFigure2.tif
Supplementary Fig. 2. MGMT promoter methylation was analyzed by pyrosequencing. > 10% in average was considered to be methylation.
- SupplementaryFigure3.tif
Supplementary Fig. 3. Chemotherapy effects on MGMT status defined subtypes. Patients with MGMT-pM (A and B) or MGMT-non-pM did not benefit from additional chemotherapy (C and D).
- SupplementaryTable1.docx
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View the published article at Radiation Oncology.
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On 27 Jun, 2021
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Reviewer #6 agreed
On 24 Jun, 2021
Reviewer #5 agreed
On 23 Jun, 2021
Reviewer #4 agreed
On 23 Jun, 2021
Reviewer #2 agreed
On 22 Jun, 2021
Reviewer #3 agreed
On 22 Jun, 2021
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Received 22 Jun, 2021
Reviewer #1 agreed
On 22 Jun, 2021
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On 04 May, 2021
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See the published version of this preprint at Radiation Oncology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Xiaoguang Qiu
Beijing Tiantan Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6806-9827
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Radiation Oncology.
Version 1
Posted 12 May, 2021
No community comments so far
Editorial decision: Minor revision
On 08 Jul, 2021
Review #6 received
Received 08 Jul, 2021
Review #7 received
Received 07 Jul, 2021
Review #3 received
Received 07 Jul, 2021
Review #5 received
Received 05 Jul, 2021
Reviewer #8 agreed
On 27 Jun, 2021
Review #1 received
Received 27 Jun, 2021
Review #2 received
Received 27 Jun, 2021
Reviewer #7 agreed
On 26 Jun, 2021
Review #4 received
Received 24 Jun, 2021
Reviewer #6 agreed
On 24 Jun, 2021
Reviewer #5 agreed
On 23 Jun, 2021
Reviewer #4 agreed
On 23 Jun, 2021
Reviewer #2 agreed
On 22 Jun, 2021
Reviewer #3 agreed
On 22 Jun, 2021
Reviewers invited
Invitations sent on 22 Jun, 2021
Reviews received
Received 22 Jun, 2021
Reviewer #1 agreed
On 22 Jun, 2021
Editor assigned
On 04 May, 2021
Submission checks complete
On 04 May, 2021
Editor invited
On 04 May, 2021
First submitted
On 30 Apr, 2021
Metrics
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PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Radiation Oncology.
Background: Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethyaltion (MGMT-non-pM) have a particularly short survival and are greatly resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM.
Methods: 269 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005-2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariable analyses were performed using the cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose-response on MGMT status defined subtypes was analyzed.
Results: On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas（p = 0.002 and p = 0.005）, high-dose RT (> 54 Gy) （p = 0.017 and p = 0.023） and 1p/19q codeletion （p <0.001 and p = 0.001）. On multivariable analyses, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.44; 95%CI, 0.21-0.92; p = 0.029; and HR, 0.43; 95%CI, 0.20-0.90; p = 0.025, respectively) and PFS (HR, 0.48; 95%CI, 0.27-0.90; p = 0.021; and HR, 0.52; 95%CI, 0.27-0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.55; 95%CI, 0.32-0.93; p = 0.026) and PFS (HR, 0.57; 95%CI, 0.35-0.93; p = 0.026) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype.
Conclusions: High-dose RT (> 54 Gy) is an independently protective factor for LGGs and associated with improved survival in patients with MGMT-non-pM.
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryFigure1.jpg
Supplementary Fig. 1. The distribution of RT doses in LGG patients.
- SupplementaryFigure2.tif
Supplementary Fig. 2. MGMT promoter methylation was analyzed by pyrosequencing. > 10% in average was considered to be methylation.
- SupplementaryFigure3.tif
Supplementary Fig. 3. Chemotherapy effects on MGMT status defined subtypes. Patients with MGMT-pM (A and B) or MGMT-non-pM did not benefit from additional chemotherapy (C and D).
- SupplementaryTable1.docx
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