scholarly journals Determining optimal clinical target volume margins in high-grade glioma based on microscopic tumor extension and magnetic resonance imaging

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shulun Nie ◽  
Yufang Zhu ◽  
Jia Yang ◽  
Tao Xin ◽  
Song Xue ◽  
...  

Abstract Introduction In this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy. Materials and methods The study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. Results Between June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001). Conclusion ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.

2021 ◽  
Author(s):  
Shulun Nie ◽  
Yufang Zhu ◽  
Jia Yang ◽  
Tao Xin ◽  
Song Xue ◽  
...  

Abstract Introduction: One of the most difficult steps of radiotherapy is to determine the clinical target volume (CTV) based on microscopic extension (ME). In this study, we performed a consecutive macropathologic analysis to assess ME in high-grade glioma (HGG) to determine appropriate CTV margins for radiotherapy.Material and methods: The study included 30 HGG patients with tumors located in non-functional areas, and supra total resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. Meanwhile, in order to validate the feasibility and safety of this model, we prospectively recruited another 30 HGG patients in a 1:1 ratio to receive guideline-based radiotherapy (RT) or model-based RT. The overall response rate (ORR) was evaluated during a follow-up of 14 months.Results: Between June 2017 and July 2019, 652 pathologic slides were analyzed. The mean ME distance was 1.70cm (range, 0.63 to 2.87cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. In our validation cohort, after a mean follow-up of 7.65months, patients in the model RT group had a higher ORR than those in the guideline RT group (66.7% vs. 20%, P = 0.01).Conclusion: ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients.


2001 ◽  
Vol 58 (2) ◽  
pp. 219
Author(s):  
Chun-Ru Chien ◽  
Shang-Wen Chen ◽  
Fang-Jen Lin

2019 ◽  
Vol 6 (5) ◽  
pp. 364-374 ◽  
Author(s):  
Christopher H Chapman ◽  
Jared H Hara ◽  
Annette M Molinaro ◽  
Jennifer L Clarke ◽  
Nancy Ann Oberheim Bush ◽  
...  

Abstract Background Optimal techniques and patient selection for salvage reirradiation of high-grade glioma (HGG) are unclear. In this study, we identify prognostic factors for freedom from progression (FFP) and overall survival (OS) after reirradiation, risk factors for high-grade toxicity, and validate clinical prognostic scores. Methods A total of 116 patients evaluated between 2000 and 2018 received reirradiation for HGG (99 WHO grade IV, 17 WHO grade III). Median time to first progression after initial therapy was 10.6 months. Salvage therapies before reirradiation included surgery (31%) and systemic therapy (41%). Sixty-five patients (56%) received single-fraction stereotactic radiosurgery (SRS) as reirradiation. The median biologically effective dose (BED) was 47.25 Gy, and the median planning target volume (PTV) was 4.8 cc for SRS and 95.0 cc for non-SRS treatments. Systemic therapy was given concurrently to 52% and adjuvantly to 74% of patients. Results Median FFP was 4.9 months, and median OS was 11.0 months. Significant multivariable prognostic factors for FFP were performance status, time to initial progression, and BED; for OS they were age, time to initial progression, and PTV volume at recurrence. High-grade toxicity was correlated to PTV size at recurrence. Three-level prognostic scores were generated for FFP and OS, with cross-validated receiver operating characteristic area under the curve (AUC) of 0.640 and 0.687, respectively. Conclusions Clinical variables at the time of reirradiation for HGG can be used to prognosticate FFP and OS.


2014 ◽  
Vol 112 (3) ◽  
pp. 425-429 ◽  
Author(s):  
Pierina Navarria ◽  
Giacomo Reggiori ◽  
Federico Pessina ◽  
Anna Maria Ascolese ◽  
Stefano Tomatis ◽  
...  

2019 ◽  
Vol 21 ◽  
pp. 101658 ◽  
Author(s):  
Lisa Millgård Sagberg ◽  
Daniel Høyer Iversen ◽  
Even Hovig Fyllingen ◽  
Asgeir Store Jakola ◽  
Ingerid Reinertsen ◽  
...  

2020 ◽  
Vol 10 (23) ◽  
pp. 8591
Author(s):  
Michael Saminsky ◽  
Anat Ben Dor ◽  
Jacob Horwitz

The aim of this study is to evaluate factors associated with long-term peri-implant bone-loss and to create a statistical model explaining bone-loss. The dental records in a private periodontal practice were screened for implant-patients with a minimal follow-up period of 8 years with periapical radiographs at implant-placement (T0) and last follow-up (Tf). Collected data included demographics, general health, medications, periodontal parameters, implant parameters, bone augmentation procedures, restoration and antagonist data, number of supportive periodontal appointments (SPT), and radiographic bone-loss between T0 and Tf. Bivariate and Mixed Logistic Regression analyses were performed. “Goodness-of-fit” of the model was elaborated with Receiver Operating Characteristic Curve (ROC) analyses. Thirty-seven patients receiving 142 implants were included. Mean clinical follow-up period was 11.7 ± 3.7 years (range 8–23). Most implants 64.4% were SPT-maintained more than twice a year. Patients with osteoporosis and smokers were prone to increased radiographic peri-implant bone-loss. External-hex implants placed without guided bone regeneration (GBR) and implants 10–12 mm long and diameter of 3.7–4 mm showed less peri-implant bone-loss. The model’s Area Under the Curve (AUC) was 76.9% (Standard Error 4.6%, CI 67.8%–86%).


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shulun Nie ◽  
Yufang Zhu ◽  
Jia Yang ◽  
Tao Xin ◽  
Song Xue ◽  
...  

Abstract 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).


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