Classification of low-grade and high-grade glioma using multi-modal image radiomics features

Abstract INTRODUCTION Tumors arising from the spinal cord are uncommon, especially high-grade tumors in pediatric patients. We report a case of high-grade glioma in the spinal cord harboring NTRK1 gene fusion, who received effective entrectinib therapy. CASE REPORT: A 5-year-old boy presented right hemiparesis and MR imaging revealed an intramedullary enhancing mass at the vertebral body level between C3 and Th1. He underwent microsurgical partial resection and the histological diagnosis was low-grade astrocytoma. After the first-line chemotherapy with vincristine and carboplatin, his right hemiparesis deteriorated and recurrent MR imaging showed growth of the tumor. He underwent microsurgical partial resection again and the histological examination was high-grade glioma with endothelial proliferation and necrosis. The chemoradiotherapy with temozolomide and focal irradiation of 50.4 Gy were given, and his neurological symptom slightly improved. One month later, he presented respiratory disturbance and required assisted ventilation with tracheostomy. MR imaging showed tumor progression invading upward to medulla oblongata. NTRK1 gene fusion was detected in the previous surgical specimen by a gene panel testing, and he received entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK). Since then, no tumor progression has been demonstrated for several months by MRI and he has been stable neurologically. CONCLUSION High-grade spinal cord tumors are rare and effective treatment strategies have not been addressed. Although the frequency of the gene fusion is very low in pediatric gliomas, identification of the driver gene aberration like in this case by a gene panel can provide potential targeted therapies for selected patients.

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OS3.6 Prediagnostic symptoms and signs of adult glioma: the patients’ view

Neuro-Oncology ◽

10.1093/neuonc/noz126.030 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii9-iii10

Author(s):

M C M Peeters ◽

L Dirven ◽

J A F Koekkoek ◽

E G Gortmaker ◽

L Fritz ◽

...

Keyword(s):

Health Care ◽

Health Care Professionals ◽

High Grade Glioma ◽

Median Number ◽

Low Grade ◽

High Grade ◽

Health Care Usage ◽

Patients Experience ◽

Symptoms And Signs ◽

Chronic Complaints

Abstract BACKGROUND Little is known about the symptoms and signs glioma patients experience in the year before diagnosis, either or not resulting in health care usage. The objective of this study was to determine the incidence of several symptoms and signs glioma patients experienced in the year prior to diagnosis, as well as visits to a general practitioner (GP) related to these issues. MATERIAL AND METHODS This was a cross-sectional study, including adults diagnosed with a glioma <12 months ago. Patients were asked to complete a 30-item study-specific questionnaire, if possible with input of a proxy, focusing on symptoms and signs they experienced in the 12 months before diagnosis. For each indicated symptom/sign, patients were asked whether they consulted the GP for this issue. In addition, the presence of comorbidity and other chronic complaints were assessed, as well as consulted health care professionals (HCPs) in the year prior to diagnosis. The statistical analyses were corrected for multiple testing. RESULTS Between July 2016 and March 2019, 58 patients completed the questionnaires, 54 (93%) with input of a proxy. Forty-one (72%) patients were men, with a median age of 60 years (range 43–78), and the median time since diagnosis was 4 months (range 1–12). Forty (69%) patients had a comorbidity or chronic complaint, and the median number of consulted HCPs was 2 (range 0–8). The median number of symptoms/signs experienced in the year before diagnosis was 8 (range 2–19) in low-grade and 5 (range 0–24) in high-grade glioma (p=0.258). The five most frequently mentioned problems were fatigue (34/58, 59%), mental tiredness (28/58, 48%), sleeping disorder (23/58, 40%), headache (22/58, 38%) and stress (20/58, 34%), with no differences between low- and high grade glioma. Twenty-five (43%) patients had visited the GP with at least one issue. We found that patients who did consult their GP reported significantly more often muscle weakness (11 vs 3, p=0.002), paralysis in for example a hand or leg (10 vs 3, p=0.006), or a change in consciousness (9 vs 3, p=0.013) compared to those that did not consult the GP. However, they did not differ with respect to the number of symptoms (median 7 vs 5), comorbidities and chronic complaints (median 1 vs 1), or overall health care usage (median 3 vs 2). CONCLUSION Glioma patients experience a range of problems in the year prior to diagnosis, but patients who consult the GP report significantly more often neurological problems.

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Interobserver reproducibility of The Paris System for Reporting Urinary Cytology

CytoJournal ◽

10.4103/cytojournal.cytojournal_12_17 ◽

2017 ◽

Vol 14 ◽

pp. 17 ◽

Cited By ~ 25

Author(s):

Theresa Long ◽

Lester J. Layfield ◽

Magda Esebua ◽

Shellaine R. Frazier ◽

D. Tamar Giorgadze ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Urinary Cytology ◽

Low Grade ◽

High Grade ◽

Urothelial Cells ◽

Urothelial Carcinomas ◽

Absolute Agreement ◽

Potential Impact ◽

Urine Specimens

Background: The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm). Methods: Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management. Results: The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact. Conclusions: Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.

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Low and high grade glioma segmentation in multispectral brain MRI data

Acta Universitatis Sapientiae Informatica ◽

10.2478/ausi-2018-0007 ◽

2018 ◽

Vol 10 (1) ◽

pp. 110-132 ◽

Cited By ~ 8

Author(s):

László Szilágyi ◽

David Iclănzan ◽

Zoltán Kapás ◽

Zsófia Szabó ◽

Ágnes Győrfi ◽

...

Keyword(s):

Early Stage ◽

Brain Mri ◽

High Grade Glioma ◽

Detection Algorithm ◽

Gabor Wavelet ◽

Low Grade ◽

Data Sets ◽

Morphological Operations ◽

High Grade ◽

Mass Screening System

Abstract Several hundreds of thousand humans are diagnosed with brain cancer every year, and the majority dies within the next two years. The chances of survival could be easiest improved by early diagnosis. This is why there is a strong need for reliable algorithms that can detect the presence of gliomas in their early stage. While an automatic tumor detection algorithm can support a mass screening system, the precise segmentation of the tumor can assist medical staff at therapy planning and patient monitoring. This paper presents a random forest based procedure trained to segment gliomas in multispectral volumetric MRI records. Beside the four observed features, the proposed solution uses 100 further features extracted via morphological operations and Gabor wavelet filtering. A neighborhood-based post-processing was designed to regularize and improve the output of the classifier. The proposed algorithm was trained and tested separately with the 54 low-grade and 220 high-grade tumor volumes of the MICCAI BRATS 2016 training database. For both data sets, the achieved accuracy is characterized by an overall mean Dice score > 83%, sensitivity > 85%, and specificity > 98%. The proposed method is likely to detect all gliomas larger than 10 mL.

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PATH-41. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG WITH FGFR3-TACC3 FUSION MIMICKING HIGH-GRADE GLIOMA: CASE REPORT AND SERIES OF HIGH-GRADE CORRELATES

Neuro-Oncology ◽

10.1093/neuonc/noab196.493 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi124-vi124

Author(s):

Danielle Golub ◽

Peter C Pan ◽

Benjamin Liechty ◽

Cheyanne Slocum ◽

Tejus Bale ◽

...

Keyword(s):

Progression Free Survival ◽

High Grade Glioma ◽

Proliferation Index ◽

Molecular Profile ◽

Low Grade ◽

High Grade ◽

Molecular Features ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations

Abstract BACKGROUND Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently-described entity that can occasionally histologically and molecularly mimic high-grade glioma. The histologic and molecular features that predict aggressive behavior in FGFR3-TACC3 altered tumors are unclear. CASES We present a rare case of an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of high-grade glioma and analyze common molecular features between this case and a series of high-grade gliomas. After total resection, pathology of the case patient revealed predominantly low-grade cytomorphology, abundant microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34 immunoreactive and harbored both an FGFR3-TACC3 fusion and a TERT promoter mutation. Based on the overall histologic and molecular profile, a diagnosis of PLNTY was favored. The patient was thereafter observed without adjuvant therapy with no evidence of progression at 15-month follow-up. In contrast, a series of eight adult patients with glioblastomas harboring FGFR3-TACC3 fusions and correspondingly aggressive clinical courses are also presented. Common molecular findings included IDH-wildtype status, absence of 1p19q codeletion, and CDKN2A loss. TERT promoter mutations and lack of MGMT promoter methylation were also frequently observed. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival. CONCLUSIONS PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.

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KS02.4.A Olaparib in Recurrent IDH-mutant High-Grade Glioma (OLAGLI)

Neuro-Oncology ◽

10.1093/neuonc/noab180.011 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii4-ii4

Author(s):

F Ducray ◽

M Sanson ◽

O Chinot ◽

M Fontanilles ◽

R Rivoirard ◽

...

Keyword(s):

Median Time ◽

High Grade Glioma ◽

Median Number ◽

Parp Inhibition ◽

Low Grade ◽

Type I ◽

High Grade ◽

Rano Criteria ◽

Anaplastic Gliomas ◽

New Treatments

Abstract BACKGROUND There is a need to develop new treatments in IDH-mutant high-grade gliomas recurring after radiotherapy and chemotherapy. Based on preclinical studies showing that IDH-mutant tumors could be vulnerable to PARP inhibition we launched a phase II study to test the efficacy of olaparib (Lynparza) monotherapy in this population. METHODS Adults with recurrent high-grade IDH-mutant gliomas after radiotherapy and at least one line of alkylating chemotherapy (PCV or TMZ), KPS > 60, normal organ function were enrolled. The primary endpoint was 6 months PFS according to RANO criteria. Patients were treated with olaparib 300 mg twice daily. We used a single-stage Fleming design with p0 = 30%, p1 = 50%, a type I unilateral error rate of 5% and a power of 80%. RESULTS 35 patients with recurrent IDH-mutant gliomas (IDH1R132H-mutant n = 32, other IDH mutation n = 3, 1p/19 codeleted n = 16, 1p/19q non-codeleted n = 14) were enrolled (malignantly transformed low-grade gliomas n = 21, anaplastic gliomas n = 8, glioblastomas n = 6). Median time since diagnosis was 7.4 years (1–22 years), median time since radiotherapy was 2.8 years (0.6–18 years), median number of previous chemotherapy lines was 2 (1–5). With a median follow-up of 11 months, 30 patients had stopped treatment due to tumor progression and 2 patients were still on treatment 16 to 18 months after treatment start. At 6 months, 11/35 patients were progression-free (31 %). According to RANO criteria, based on local investigator analysis, 2 patients (5%) had a partial response and 14 patients a stable disease (37%) with a median duration of response of 9 months (4–18+). Median PFS and OS were 2.3 and 15.9 months and were similar in 1p/19q codeleted and non-codeleted patients. A grade 3 olaparib-related adverse event was observed in 5 patients (14%, lymphopenia n = 3, fatigue n = 2, diarrhea n = 1) and a grade 2 in 15 patients (43%), most frequently consisting in fatigue (23%), gastrointestinal disorders (20%) and lymphopenia (20%). No patient definitively stopped olaparib due to side effects. CONCLUSIONS In this heavily pre-treated population of recurrent IDH-mutant gliomas, olaparib monotherapy was well tolerated and resulted in some activity supporting its evaluation in association with alkylating chemotherapy in recurrent IDH-mutant gliomas in future studies.

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High-grade gliomas and molecular biology of neurosurgical oncology

Oxford Textbook of Neurological Surgery ◽

10.1093/med/9780198746706.003.0007 ◽

2019 ◽

pp. 89-106

Author(s):

Stephen J Price ◽

Harry Bulstrode ◽

Richard Mair

Keyword(s):

Molecular Markers ◽

Who Classification ◽

High Grade Glioma ◽

High Grade ◽

Optimal Management ◽

Who Grade ◽

Normal Human ◽

Who Grade Iii ◽

Grade Iii

The term high-grade glioma (HGG) encompasses a number of histological entities that are considered by the WHO Classification as WHO Grade III and IV tumours. They have traditionally been considered as having similar behaviour and had been treated in a similar manner but recent advances in our understanding of tumour biology have led to the identification of molecular markers that are now central to the classification of these tumours. Normal human cells develop into cancer cells through a stepwise accumulation of genomic and epigenomic alterations and this chapter considers the molecular markers of gliomas and explains their significance before going on to discuss the optimal management.

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SURG-32. THE USE OF 5-AMINOLEVULINIC ACID IN LOW-GRADE GLIOMA RESECTION: A SYSTEMATIC REVIEW

Neuro-Oncology ◽

10.1093/neuonc/noz175.1032 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi246-vi246

Author(s):

Ahmad Almekkawi ◽

Tarek El Ahmadieh ◽

Karl Abi-Aad ◽

Salah Aoun ◽

Najib EL Tecle ◽

...

Keyword(s):

Systematic Review ◽

Quality Index ◽

Aminolevulinic Acid ◽

High Grade Glioma ◽

Extent Of Resection ◽

Low Grade Glioma ◽

Low Grade ◽

High Grade ◽

Visualization Technology ◽

Glioma Resection

Abstract BACKGROUND 5-aminolevulinic acid is a reliable tool for optimizing high-grade glioma resection. However, its efficacy in low-grade glioma resection remains unclear. OBJECTIVE To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and effect on the extent of resection. METHODS A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. Quality index of the selected papers using the Downs and Black criteria checklist was provided. RESULTS Twelve articles met the selection criteria with 244 histologically-confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n=60/244; 24.5%) demonstrated visual intra-operative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies, however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10–17) which correlated with an overall good quality. CONCLUSION There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.

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