scholarly journals Clinicopathologic analysis of microscopic tumor extension in glioma for external beam radiotherapy planning

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shulun Nie ◽  
Yufang Zhu ◽  
Jia Yang ◽  
Tao Xin ◽  
Song Xue ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
External Beam Radiotherapy ◽  
High Grade Glioma ◽  
Tumor Grade ◽  
Radiotherapy Planning ◽  
Low Grade ◽  
Clinical Trial Registry ◽  
Tumor Extension ◽  
Grade Ii ◽  
Grade Iii

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).

Prediction of oligodendroglial tumor subtype and grade using perfusion weighted magnetic resonance imaging

2007 ◽  
Vol 107 (3) ◽  
pp. 600-609 ◽  
Author(s):  
Robert G. Whitmore ◽  
Jaroslaw Krejza ◽  
Gurpreet S. Kapoor ◽  
Jason Huse ◽  
John H. Woo ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Blood Volume ◽  
Tumor Grade ◽  
Grade Ii ◽  
Cytogenetic Profile ◽  
Group 2 ◽  
Oligodendroglial Neoplasms ◽  
Grade Iii ◽  
Group 1

Object Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms. Methods Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade. Results In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96–3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27–2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59–6.26; four patients) and Group 2 (mean 2.83, range 1.81–3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59–6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96–3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively. Conclusions Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.

scholarly journals Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Indrawati Hadi ◽  
Daniel Reitz ◽  
Raphael Bodensohn ◽  
Olarn Roengvoraphoj ◽  
Stefanie Lietke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Radiation Necrosis ◽  
Irradiation Time ◽  
External Beam Radiotherapy ◽  
High Grade Glioma ◽  
Metabolic Imaging ◽  
Time Interval ◽  
Low Grade ◽  
External Beam ◽  
Iodine 125

Abstract Purpose Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown. Methods Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models. Results Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence. Conclusion The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.

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 ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Goodness Of Fit ◽  
Clinical Target Volume ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Grade Glioma ◽  
Target Volume ◽  
Tumor Location ◽  
High Grade ◽  
Clinical Trial Registry

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.

MR Imaging of Hepatocellular Carcinoma

1995 ◽  
Vol 36 (2) ◽  
pp. 163-167 ◽  
Author(s):  
H. Honda ◽  
H. Onitsuka ◽  
Y. Kanazawa ◽  
T. Matsumata ◽  
T. Hayashi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mr Imaging ◽  
Low Grade ◽  
Hepatic Parenchyma ◽  
Grade Ii ◽  
Paramagnetic Ions ◽  
Grade Malignancy ◽  
Histopathologic Findings ◽  
Signal Intensities ◽  
Grade Iii

In order to clarify the factors contributing to the signal intensities (SIs) of HCC on T1-weighted images, the amount of water, lipid, copper (Cu), iron (Fe), and manganese (Mn) was determined in HCC and surrounding hepatic parenchyma of 13 patients. The relationships among these findings, the histopathologic findings, and the SIs of T1-weighted images were evaluated. Among the 13 HCC, 3 had a high SI, 5 were isointense, and 5 had a low SI on T1-weighted images compared to the surrounding hepatic parenchyma. The paramagnetic ions which contributed to the SI patterns were assumed to be Cu in HCC (38.0±62.4 μg/g ww), and Fe in the liver (61.1±42.4 μg/g ww) and HCC (40.0±34.3 μg/g ww). In 8 HCC with high- or isointensity, 2 were grades I, 5 were grade II, and one was grade III according to the Edmondson-Steiner's histopathologic classification. It is concluded that the SI patterns alone can not be a sign of low grade malignancy because of the existence of Fe in livers and HCC.

scholarly journals GENE-35. MGMT PROMOTER METHYLATION IN NEWLY DIAGNOSED LGG AS A POTENTIAL BIOMARKER FOR TMZ-ASSOCIATED HYPERMUTATION AT RECURRENCE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi105-vi105
Author(s):  
Radhika Mathur ◽  
Yalan Zhang ◽  
Matthew Grimmer ◽  
Chibo Hong ◽  
Mitchel Berger ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Methylation Level ◽  
Dna Methyltransferase ◽  
Mgmt Promoter Methylation ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Potential Biomarker ◽  
Mgmt Promoter ◽  
Grade Ii ◽  
Mechanistic Basis

Abstract Low-grade gliomas (LGGs), which include grade II astrocytoma and grade II oligodendroglioma, inevitably recur despite aggressive treatment with surgery, and sometimes, with radiation and the chemotherapeutic agent temozolomide (TMZ). The clinical benefit of TMZ in LGG is unclear, and a subset of TMZ-treated LGGs recur with hypermutation in association with malignant progression to high-grade tumors. It is currently unknown why some TMZ-treated LGGs recur with hypermutation while others do not. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that reverses mutagenic lesions induced by TMZ. The amount of MGMT protein in a cell is regulated at the epigenetic level by promoter methylation. Here, we hypothesize that epigenetic silencing of MGMT by promoter methylation facilitates TMZ-induced mutagenesis and contributes to the development of hypermutation. We demonstrate in a cohort of 37 TMZ-treated patients with an initial diagnosis of IDH-mutant LGG that methylation level of the MGMT promoter in initial untreated tumors is significantly associated with hypermutation at recurrence. We also confirm our previous finding that methylation level of the MGMT promoter in recurrent hypermutated tumors is higher than in recurrent tumors that are not hypermutated. These results provide a plausible mechanistic basis for observed differences in propensity of TMZ-treated LGG patients to develop hypermutation at recurrence. Furthermore, they establish the potential of MGMT promoter methylation level to inform treatment decisions in the clinic for patients with newly diagnosed LGG.

scholarly journals Clinicohistopathological study of astrocytomas along with Ki-67 proliferative index

2018 ◽  
Vol 6 (2) ◽  
pp. 665 ◽  
Author(s):  
Basumitra Das ◽  
Kurimella Vamsya Raj ◽  
Bhagyalakshmi Atla
Keyword(s):  
Histological Grade ◽  
Research Work ◽  
Low Grade ◽  
Proliferative Index ◽  
Ki 67 ◽  
Biologic Marker ◽  
Grade Ii ◽  
The Mean ◽  
The Difference ◽  
Grade Iii

Background: Astrocytomas form the largest group of gliomas (>75%) and diffusely infiltrating    accounting for more than 60% of all the primary brain tumors. The ki67 proliferative index is a potent biologic marker that estimates the growth of neoplasms quantitatively and thus will aid in identifying the prognosis for patients with neoplasms.  The aim of the research work was to study various histopathological and clinical features of Astrocytomas in detail, to evaluate Ki-67 proliferative index in patients of Astrocytomas and to compare the results of Immunohistochemistry with histological grade of Astrocytomas.Methods: A   total   number   of    40 cases of   Astrocytomas were included in the study.  Ki-67 immunostaining was done on all cases and compared with WHO histological grading of astrocytomas.Results: The mean Ki‑67 LI in Grade I astrocytomas was 4.66, range 4-5 ,  in Grade II astrocytomas mean was 8.07, range 5-12 ,in Grade III astrocytomas mean was 13.5 , range 8-20,  in Grade IV astrocytomas mean was 22.93, range 15-50. There was a highly significant correlation between the histopathological grade of astrocytomas and Ki-67 LI (p<0.05).Conclusions: The monoclonal antibody Ki-67 has proven its prognostic and diagnostic power in astrocytic tumors. Ki-67 LI is the simplest and the most reliable method for evaluating cell proliferation. Ki-67 LI increased with histological grade and the difference between low grade (I and II astrocytomas) and high grade (grade III and IV) is significant. In the present study Ki-67 LI is not dependent on factors like age and sex and is solely dependent on histological grade.

scholarly journals Meningioma: not always a benign tumor. A review of advances in the treatment of meningiomas

CNS Oncology ◽  
2021 ◽  
pp. CNS72
Author(s):  
Ilaria Maggio ◽  
Enrico Franceschi ◽  
Alicia Tosoni ◽  
Vincenzo Di Nunno ◽  
Lidia Gatto ◽  
...  
Keyword(s):  
Benign Tumor ◽  
Treatment Strategies ◽  
Complete Resection ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Intracranial Tumors ◽  
Review Of The Literature ◽  
Systemic Treatments ◽  
Grade Ii ◽  
Grade Iii

Meningiomas are the most common primary intracranial tumors. The majority of meningiomas are benign, but they can present different grades of dedifferentiation from grade I to grade III (anaplastic/malignant) that are associated with different outcomes. Radiological surveillance is a valid option for low-grade asymptomatic meningiomas. In other cases, the treatment is usually surgical, aimed at achieving a complete resection. The use of adjuvant radiotherapy is the gold standard for grade III, is debated for grade II and is not generally indicated for radically resected grade I meningiomas. The use of systemic treatments is not standardized. Here we report a review of the literature on the clinical, radiological and molecular characteristics of meningiomas, available treatment strategies and ongoing clinical trials.

scholarly journals Classification and Treatment of Pediatric Gliomas in the Molecular Era

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 739
Author(s):  
Peter Hauser
Keyword(s):  
Wide Spectrum ◽  
High Grade Glioma ◽  
Tumor Grade ◽  
Primary Treatment ◽  
Low Grade ◽  
High Grade ◽  
Therapeutic Approaches ◽  
Term Survival ◽  
Low Grade Gliomas ◽  
Leading Role

The overall survival of pediatric gliomas varies over a wide spectrum depending on the tumor grade. Low-grade gliomas have an excellent long-term survival, with a possible burden of surgery, irradiation, and chemotherapy; in contrast, high-grade gliomas generally have a short-term, devastating lethal outcome. Recent advances in understanding their molecular background will transform the classification and therapeutic approaches of pediatric gliomas. Molecularly targeted treatments may acquire a leading role in the primary treatment of low-grade gliomas and may provide alternative therapeutic strategies for high-grade glioma cases in the attempt to avoid the highly unsuccessful conventional therapeutic approaches. This review aims to overview this progress.

scholarly journals Immuno-Phenotyping of High-Grade Glioma Infiltrating Immune Cells Reveals Grade Specific Differences in Cells of Myeloid Origin

2020 ◽  
Author(s):  
Raksha A. Ganesh ◽  
Jayashree V. Raghavan ◽  
Pranali Sonpatki ◽  
Divya Naik ◽  
Priyanka Arunachalam ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
High Grade Gliomas ◽  
Cell Phenotypes ◽  
Grade Iii

AbstractGliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade III and IV) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, grade IV) or grade III gliomas. Our data show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade III glioma tissue. In addition, we observe that neutrophils are highly heterogeneous among individuals with glioma, and a greater proportion of granulocytic myeloid-derived suppressor cells are present in grade III gliomas when compared to GBM. Finally, we show that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor, and suggest that these may be used as possible markers for prognosis.

scholarly journals RADIOMICS BASED SINGLE AND MULTI-CLASS GLIOMA CLASSIFICATION USING SUPPORT VECTOR MACHINE VARIANTS

2021 ◽  
Vol 57 (2) ◽  
pp. 265-273
Author(s):  
P.D. Seema ◽  
◽  
T. Bobby Christy ◽  
K.R. Anandh ◽  
◽  
...  
Keyword(s):  
Support Vector Machine ◽  
Classification Accuracy ◽  
Clinical Decision Making ◽  
World Health ◽  
Support Vector ◽  
Low Grade ◽  
Whole Brain ◽  
Grade Ii ◽  
Linear Svm ◽  
Grade Iii

The common type of primary brain tumor is glioma. The mortality rate of glioma patients is high due to delayed diagnosis, incorrect grading and treatment planning. Traditionally, gliomas were classified into Low Grade (grade-I and grade-II) and High Grade (grade-III and grade-IV). However, World Health Organization has insisted to classify the grades into grade-I(G-I), grade II(G-II), grade III(G-III) and grade IV(G-IV) individually to aid the physicians in clinical decision-making. Although there are limited number of studies reported to differentiate individual grades, the classification accuracy was low. Consequently, in this work single-class (G-II vs. G-III, G-II vs. G-IV and G-III vs. G-IV) and multi-class (G-II vs. G-III+IV, G-III vs. G-II+IV and G-IV vs. G-II+III) analysis was performed using specific region of tumor and whole brain as Regions of Interest(ROI) by extracting radiomic features. The images for this study (N=75) were obtained from The Cancer Imaging Archive. Further, the statistically significant features were used in the classification of individual grades by implementing variants of Support Vector Machine (SVM) algorithm: SVM, Linear-SVM and Least-Squared SVM. Among these, Linear-SVM resulted in the highest classification accuracy (>80%) with average sensitivity, specificity and AUC values of >70%. The comparative analysis of whole brain versus tumor ROI showed that the latter yielded better classification accuracy.

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