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Updated: Oct 13, 2025
Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Clinicopathologic analysis of microscopic tumor extension in glioma for external beam radiotherapy planning
Shulun Nie1,2, Yufang Zhu3, Jia Yang2
1Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao Road 6699, Jinan, 250117, Shandong, China.
Background:
There is no consensus regarding the clinical target volume (CTV) margins in radiotherapy for glioma. In this study, we aimed to perform a complete macropathologic analysis examining microscopic tumor extension (ME) to more accurately define the CTV in glioma.
Methods:
Thirty-eight supra-total resection specimens of glioma patients were examined on histologic sections. The ME distance, defined as the maximum linear distance from the tumor border to the invasive tumor cells, was measured at each section. We defined the CTV based on the relationships between ME distance and clinicopathologic features.
Results:
Between February 2016 and July 2020, a total of 814 slides were examined, corresponding to 162 slides for low-grade glioma (LGG) and 652 slides for high-grade glioma (HGG). The ME value was 0.69 ± 0.43 cm for LGG and 1.29 ± 0.54 cm for HGG (P < 0.001). After multivariate analysis, tumor grade, O6-methylguanine-DNA-methyltransferase promoter methylated status (MGMTm), isocitrate dehydrogenase wild-type status (IDHwt), and 1p/19q non-co-deleted status (non-codel) were positively correlated with ME distance (all P < 0.05). We defined the CTV of glioma based on tumor grade. To take into account approximately 95% of the ME, a margin of 1.00 cm, 1.50 cm, and 2.00 cm were chosen for grade II, grade III, and grade IV glioma, respectively. Paired analysis of molecularly defined patients confirmed that tumors that had all three molecular alterations (i.e., MGMTm/IDHwt/non-codel) were the most aggressive subgroups (all P < 0.05). For these patients, the margin could be up to 1.50 cm, 2.00 cm, and 2.50 cm for grade II, grade III, and grade IV glioma, respectively, to cover the subclinical lesions in 95% of cases.
Conclusions:
The ME was different between the grades of gliomas. It may be reasonable to recommend 1.00 cm, 1.50 cm, and 2.00 cm CTV margins for grade II, grade III, and grade IV glioma, respectively. Considering the highly aggressive nature of MGMTm/IDHwt/non-codel tumors, for these patients, the margin could be further expanded by 0.5 cm. These recommendations would encompass microscopic disease extension in 95% of cases.
Trial Registration:
The trial was registered with Chinese Clinical Trial Registry ( ChiCTR2100049376 ).
Insights
This study analyzed microscopic tumor extension in glioma to define radiotherapy clinical target volume (CTV) margins. Recommended margins vary by grade, with expanded options for aggressive molecular subtypes to cover 95% of microscopic disease.
Area of Science:
- Neuro-oncology
- Radiation Oncology
- Surgical Pathology
Background:
- Lack of consensus on clinical target volume (CTV) margins for glioma radiotherapy.
- Need for accurate definition of CTV based on microscopic tumor spread.
Purpose of the Study:
- To perform macropathologic analysis of microscopic extension (ME) in glioma.
- To define optimal CTV margins for glioma radiotherapy based on ME and clinicopathologic features.
Main Methods:
- Macropathologic analysis of 38 glioma resection specimens.
- Measurement of maximum linear distance of ME from tumor border.
- Correlation of ME with tumor grade and molecular markers (MGMT promoter methylation, IDH wild-type, 1p/19q non-co-deletion).
Main Results:
- ME was significantly greater in high-grade gliomas (HGG) than low-grade gliomas (LGG) (1.29 cm vs. 0.69 cm).
- Tumor grade, MGMT promoter methylated status (MGMTm), IDH wild-type status (IDHwt), and 1p/19q non-co-deleted status (non-codel) correlated with ME.
- Proposed CTV margins: 1.00 cm (Grade II), 1.50 cm (Grade III), 2.00 cm (Grade IV).
Conclusions:
- Recommended CTV margins of 1.00 cm, 1.50 cm, and 2.00 cm for glioma grades II, III, and IV, respectively.
- For aggressive MGMTm/IDHwt/non-codel tumors, an additional 0.5 cm margin is suggested.
- These margins aim to encompass microscopic disease extension in 95% of cases.
