Case Of Anaplastic Astrocytoma Research Articles

NIMG-22. QUANTITATIVE BRIGHTNESS ANALYSIS OF 5-ALA FLUORESCENCE IN GLIOMA SURGERY

Abstract OBJECTIVE The 5 aminolevulinic acid (5-ALA) is used for intraoperative tumor visualization in neurosurgery. We hypothesized that glioma may vary in pathology according to the brightness of 5-ALA fluorescence, which we quantified and compared with the pathological results of glioma. METHODS From 2019 to 2023, we investigated 28 glioma patients who underwent surgery with 5-ALA. The pathological diagnosis was based on classification of WHO 2016. The 5-ALA was administered before surgery, and the brightness of 5-ALA fluorescence was quantified. RESULTS Seventeen cases of glioblastoma (GBM), four cases of anaplastic astrocytoma (AA), three cases of oligodendroglioma (OL), and four cases of low grade glioma (LGG) were examined. The mean (SD) brightness of 5-ALA fluorescence was 155.9 (56.0) in GBM, 180.5 (64.7) in AA, and 66.3 (18.8) in OL. The brightness in OL was significantly lower than that in GBM and AA (Scheffe’s test, p<0.05). All LGGs showed negative in the brightness. CONCLUSIONS The brightness of 5-ALA fluorescence was shown to vary by pathology, which may contribute to intraoperative diagnostic support.

AB025. Efficacy of 5-ALA brightness analysis for malignant brain tumor surgery.

For fluorescence-guided neurosurgery, 5-aminolevulinic acid (5-ALA) is widely used for intraoperative tumor visualization. We quantified the brightness of 5-ALA by Image J and report the pathological results of glioma, and non-tumor lesions. From 2019 to 2023, we investigated 27 high-grade glioma patients who underwent surgery with 5-ALA. Twenty-three cases of glioblastoma (GBM) and four cases of anaplastic astrocytoma (AA) were examined. The pathological diagnosis was based on the classification of World Health Organization (WHO) 2016. The 5-ALA was administered before surgery, and the 5-ALA brightness was quantified. Other than high-grade glioma, four low-grade gliomas (LGGs), two radiation necrosis, and one inflammation patients were evaluated by Image J. In GBM, the mean brightness was 134.5±65.4, except for one negative case. AA showed the mean brightness with 180.5±51.6. All LGGs showed negative in the brightness. In two radiation necrosis cases, the mean brightness was 139.5±37.4. In one inflammatory case, the brightness was 239, but after the lesion removed, the adjacent brain parenchyma showed bright, and the border was not clear. In one GBM case, the ventricle was opened, and the brightness difference between the tumor and the ventricular wall was observed. 5-ALA brightness analysis by Image J would be helpful to distinguish between malignant glioma and LGG, and other non-tumor lesions to support rapid pathological diagnosis. Also, it would be useful to distinguish between the tumor and the ventricle wall. As for radiation necrosis and inflammation, border of the lesion is unclear.

Deep Residual Learning-Based Classification with Identification of Incorrect Predictions and Quantification of Cellularity and Nuclear Morphological Features in Digital Pathological Images of Common Astrocytic Tumors.

Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.

NIMG-49. INTRAOPERATIVE 5-ALA INTENSITY ANALYSIS OF GLIOMA USING IMAGE J

Abstract PURPOSE: The 5 aminolevulinic acid (5-ALA) is used for intraoperative tumor visualization in neurosurgery. We hypothesized that glioma may vary in malignancy according to the brightness of 5-ALA. We quantified the brightness of 5-ALA and compared it with the pathological results of glioma. MATERIALS AND METHODS: From 2019 to 2023, we investigated 35 glioma patients who underwent surgery with 5-ALA. Twenty-three cases of glioblastoma (GBM), four cases of anaplastic astrocytoma (AA), three cases of oligodendroglioma (OL), one case of anaplastic oligodendroglioma (AO), and four cases of low grade glioma (LGG) were examined. The pathological diagnosis was based on classification of WHO 2016. The 5-ALA was administered before surgery, and the 5-ALA brightness were quantified. RESULTS: In GBM, the mean brightness was 134.5 ± 65.4, except for one negative case. AA showed the mean brightness with 180.5 ± 51.6. Three cases of OL showed the mean brightness with 78.6 ± 32.7. AO showed the brightness with 153. All LGGs showed negative in the brightness. CONCLUSION: The 5-ALA showed higher brightness in GBM , AA, AO and negative in LGG. In the future, we will accumulate cases and add further studies.

Endoscopic resection of thalamic lesions via supracerebellar infratentorial approach: a case series and technical note.

The deep location of the thalamus and the complex neural circuits in the surrounding area make surgery extremely challenging. Feasibility and advisability of using a supracerebellar infratentorial approach (SCITA) for endoscopic resection of thalamic lesions remains to be further evaluated. Fifteen patients who underwent endoscopic resection of thalamic via SCITA from 2014 to 2021 were retrospectively collected. We analyzed preoperative tumor-related variables and surgical procedures in detail, as well as postoperative outcomes. Lesions mainly located in the posterior and/or medial part of the thalamus, and some of them expanded downward, or backward. The mean size of them was 30 × 24mm. Five of the nine patients with preoperative hydrocephalus underwent cerebrospinal fluid shunts to relieve increased intracranial pressure. Among the 15 patients, 4 were glioblastoma, 3 were pilocytic astrocytoma, and the rest included 1 case of anaplastic astrocytoma, melanoma, polymorphous low-grade neuroepithelial tumor of the young, rosette-forming glioneuronal tumor, inflammatory lesion, diffuse midline glioma, and cavernous hemangioma. The majority of patients (10/15) achieved gross total resection, which has become more pronounced since paramedian SCITA was used in place of the midline approach in 2020 (6/8). Three patients had unresolved or new onset of clinical symptoms after surgery, resulting in a decreased KPS score at discharge. Neuro-endoscopic techniques can ameliorate many of the shortcomings of the SCITA. With the accumulation of experience and technological progress, more deficiencies of this approach may be improved, enabling safe and effective resection of posterior and/or medial part thalamic lesions.

5-Aminolevulinic acid-enhanced fluorescence-guided treatment of high-grade glioma using angled endoscopic blue light visualization: technical case series with preliminary follow-up.

5-Aminolevulinic acid (5-ALA)-enhanced fluorescence-guided resection of high-grade glioma (HGG) using microscopic blue light visualization offers the ability to improve extent of resection (EOR); however, few descriptions of HGG resection performed using endoscopic blue light visualization are currently available. In this report, the authors sought to describe their surgical experience and patient outcomes of 5-ALA-enhanced fluorescence-guided resection of HGG using primary or adjunctive endoscopic blue light visualization. The authors performed a retrospective review of prospectively collected data from 30 consecutive patients who underwent 5-ALA-enhanced fluorescence-guided biopsy or resection of newly diagnosed HGG was performed. Patient demographic data, tumor characteristics, surgical technique, EOR, tumor fluorescence patterns, and progression-free survival were recorded. In total, 30 newly diagnosed HGG patients were included for analysis. The endoscope was utilized for direct 5-ALA-guided port-based biopsy (n = 9), microscopic to endoscopic (M2E; n = 18) resection, or exoscopic to endoscopic (E2E; n = 3) resection. All endoscopic biopsies of fluorescent tissue were diagnostic. 5-ALA-enhanced tumor fluorescence was visible in all glioblastoma cases, but only in 50% of anaplastic astrocytoma cases and no anaplastic oligodendroglioma cases. Gross-total resection (GTR) was achieved in 10 patients in whom complete resection was considered safe, with 11 patients undergoing subtotal resection. In all cases, endoscopic fluorescence was more avid than microscopic fluorescence. The endoscope offered the ability to diagnose and resect additional tumor not visualized by the microscope in 83.3% (n = 10/12) of glioblastoma cases, driven by angled lenses and increased fluorescence facilitated by light source delivery within the cavity. Mean volumetric EOR was 90.7% in all resection patients and 98.8% in patients undergoing planned GTR. No complications were attributable to 5-ALA or blue light endoscopy. The blue light endoscope is a viable primary or adjunctive visualization platform for optimization of 5-ALA-enhanced HGG fluorescence. Implementation of the blue light endoscope to guide resection of HGG glioma is feasible and ergonomically favorable, with a potential advantage of enabling increased detection of tumor fluorescence in deep surgical cavities compared to the microscope.

A One-Arm, Open, Single-Center Exploratory Clinical Study on the Safety and Efficacy of Anlotinib in the Treatment of Relapsed High-Grade Gliomas

<h3>Purpose/Objective(s)</h3> There is currently no standard treatment for recurrent high-grade gliomas. The study was conducted through a single-arm, open, single-center clinical study to evaluate the safety and efficacy of anlotinib in the treatment of recurrent high-grade gliomas. <h3>Materials/Methods</h3> Patients with recurrent high-grade glioma (WHO class III-IV) from October 2019 to January 2021 in Sichuan Cancer Hospital were given oral anlotinib 8-12 mg/day, and each course of treatment was taken for 2 consecutive weeks with a break of 1 week. Efficacy is assessed according to response assessment in neuro-oncology (RANO) criteria. The main efficacy indicators were progression-free survival (PFS), 6-month progression-free survival (PFS-6), objective response rate (ORR), and disease control rate (DCR). Secondary indicators of efficacy are overall survival (OS) and drug-related adverse effects are observed. <h3>Results</h3> A total of 14 patients (including 10 cases of glioblastoma, 3 cases of anaplastic astrocytoma, and 1 case of anaplastic oligodendrocyte glioma) were analyzed in a co-enrollment group, and the median follow-up time was 8.8 months (6.3-11.7). According to the THE RANO criteria, 8 patients were in partial remission, 5 patients were stable, and 1 patient was assessed as disease progression. The median PFS was 8.0 months (95% CI: 6.0 to 10.3), PFS-6 was 78.6%, the objective response rate was 57.1%, and the disease control rate was 92.9%. Five cases have not yet been studied. According to the Common Terminology Standard for Adverse Events (CTCAE), no adverse reactions ≥-3 were observed. Grade 1-2 hypertension and fatigue are common adverse reactions, with an incidence rate of 28.6%, of which 4 patients with hypertension, 4 cases of fatigue, 2 cases of short-term memory loss, 1 case of hand and foot skin toxicity, 1 case of drowsiness, 1 case of edema, 1 case of joint pain and hoarseness, all adverse reactions can be alleviated and controlled through symptomatic treatment. <h3>Conclusion</h3> The incidence of adverse reactions of anlotinib in the treatment of recurrent high-grade gliomas is low and the safety is good. At the same time, it shows good short-term efficacy, significantly prolongs the patient's progression-free survival, and may become an effective treatment for recurrent high-grade gliomas, laying the foundation for further clinical research.

Summary of virtual tumor board platforms and implementation in neuro-oncology.

e13604 Background: Virtual tumor board [VTB] platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. VTBs are an emerging resource across various cancer care networks in the United States. Methods: We performed a systematic search of all VTBs incorporating a platform designed for this specific role. We reviewed Xcures, Genomet, Oncolens, Navify Tumor Board, Medical University of South Carolina [MUSC] Virtual Tumor Board, Virtual Tumor Board Tahoe Forest Cancer Center, UC Davis Health Care Center VTB and MassiveBio. Summary data examined include year of launch, demographics, characteristics of cases, average response time, advantages, and how they handle protected health information. Results: 30% of all VTBs examined launched in 2017. All had a HIPAA compliant online environment. Xcures records were reviewed where the median age of female patients was 57yrs and the median age of male patients was 55 years. The data showed that 44% (4.4 out of every 10 patients) with a confirmed treatment chose VTB integrated option. 76% of patients in Xcures registry consist primary CNS tumors. With at least 556 patients in tumor registry which included 46% Glioblastoma cases [96% primary;, 4% secondary], 13% Diffuse midline glioma with H3K27M-mutant cases, 5% Diffuse intrinsic pontine glioma cases, 3% Astrocytoma and Diffuse Astrocytoma cases, 3% Anaplastic astrocytoma cases; Glioma and Diffuse Glioma, 1% Anaplastic Oligodendroglioma cases and &lt; 1% Gliosarcoma, Oligodendroglioma, Pilocytic astrocytoma, Anaplastic pleomorphic Xanthoastrocytoma, Fibrillary astrocytoma, Oligoastrocytoma and Pleomorphic Xanthoastrocytoma cases. In the MUSC VTB, 9 neuro-oncology cases were reviewed. They meet weekly, and average response time was within 24hrs of case review.Patient demographics were not recorded. Genomet Virtual Board de-identifies all patient information; this is a virtual platform primarily focused on neuro-oncology cases. Cases involved a median of 5 specialist most commonly neuro-oncologists, neurosurgeons, radiation oncologists, molecular pathologists and neuroradiologists. Participants had an average of 23 cases reviewed. Case review revealed an age range from 6 months to 84 years [mean age 44.5 years] with 69.6% males and 30.4% females, 43.5% glioblastoma, 8.7% adenocarcinoma, 8.7% infra-tentorial tumor, &lt; 5% each: pineoblastoma, melanoma, hemangioblastoma and pilocytic astrocytoma. Average response time observed in all cases was ≤24 hours. Detailed metrics for number/percentages of brain tumor cases were not available for most other platforms at time of submission. This will be updated at presentation. Conclusions: VTBs have allowed for quicker expert analysis of cases. This has resulted in an accelerated number of cases reviewed with a shortened communication time. More studies are needed to gain additional insight into user engagement

COT-13 Luminance analysis of 5-aminolevulinic acid using Image J for malignant brain tumor

Purpose: For malignant brain tumor surgery, photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) is useful for maximal removal of the tumor. Although it has the advantage of identifying the presence or absence of residual tumors during surgery, there are variations in positive rates, and the classification is limited, based on visual inspection such as Stummer’s classification (strong, vague, none). We analyzed the luminance of positive findings using software Image J for brain tumor surgery using 5-ALA, and we report the results. Materials and Methods: From April 2018 to March 2021, 31 patients with suspected malignant glioma before surgery were included. Intraoperative 5-ALA positive findings were analyzed by software Image J (Wayne Rasband: NIH), the luminance was measured with a histogram, and compared the maximum luminance titer. Results: Among the positive cases, the average maximum luminance value for malignant glioma was 101 (50–168), which consisted of 11 cases of Glioblastoma, 1 case of Oligodendroglioma, and 1 case of anaplastic astrocytoma. The average maximum brightness of metastatic brain tumors is lower than that of malignant gliomas, even if they are visually strong, 83.5 (28–121). Conclusions: Even if it is visually strong in the conventional Stummer classification, it may be possible to classify in detail by analyzing luminance with Image J. In addition, more objective index is necessary to classify the vague findings.

TB-9 An attempt to establish a patient-derived brain tumor culture model by organoid culture method

Background: Molecular heterogeneity among and within tumors are one of the reasons for the poor survival rate of brain tumors even with the current standard therapy. However, monolayer culture and neuro-sphere culture (NS) use exogenous growth factors, so may not show the true nature of the tumor. And the culture establishment rate is low, especially low-grade tumors. Therefore, we used the glioblastoma organoid (GBO) culture method showed by Fadi to create culture models of various brain tumors and investigated their characteristics. Methods: We examined the establishment rate in pathological and genotypic types of 56 patients who underwent brain tumor resection at our hospital between January 2020 and June 2021 and were cultured with GBO or NS. If tumor cells are increased visually at 1 month after culture, we defined establishment. Results: There were 15 cases of glioblastoma, 7 cases of anaplastic astrocytoma, 7 cases of diffuse astrocytoma, 3 cases of diffuse midline glioma, 2 cases of anaplastic oligodendroglioma, 5 cases of oligodendroglioma, and 16 cases of others. The establishment rate was 76.5% by the GBO method and 40% by the N S method. By histological type, GBO: 80% in glioblastoma, NS: 58.3% in glioblastoma, GBO: 83.3% in AA, NS: 40% in AA, and GBO: 100% in DA. The IDH mutation and pTERT mutation were investigated in GBO: IDHwt/TERT+ 87.5%, IDHwt/TERT- 64.3%, IDHmt/TERT- 100%, and in NS: IDHwt/TERT+ 75%, IDHwt/TERT- 33.3%, IDHmt/ TERT- 20% in NS. In addition, establishment was observed in GBO 2 case in medulloblastoma, 1 case in ependymoma. Discussion and Conclusion: This suggest that GBO can be used to establish culture models for low-grade tumors. In addition, GBO can establish culture earlier, so it is expected to be applicable to personalized therapies such as preclinical drug efficacy studies tailored to individual patients.

Radiation Therapy for Grade 3 Gliomas: Correlation of MRI Findings With Prognosis.

Background and objectivePostoperative radiotherapy is usually indicated for both grade 3 glioma and grade 4 glioblastoma. However, the treatment results and tumor features of grade 3 glioma clearly differ from those of glioblastoma. There is limited information on outcomes and tumor progression for grade 3 glioma. In this study, we evaluate the result of postoperative radiotherapy for grade 3 glioma and focus on the correlation of MRI findings with prognosis.MethodsIn this study, 99 of 110 patients with grade 3 glioma who received postoperative radiotherapy and were followed up for more than one year were retrospectively analyzed. The total irradiation dose was 60.0 Gy in 30 fractions, and daily temozolomide or two cycles of nimustine (ACNU) was concurrently administered during radiotherapy. The median follow-up period was 46 months (range: 2-151 months).ResultsIn multivariate analysis, pathology [anaplastic oligodendroglioma (AO) vs. anaplastic astrocytoma (AA)], the status of surgical resection (biopsy vs. partial resection or more), and contrast enhancement (enhanced by MRI image or not) were significant factors for overall survival (OS). The five-year OS for AO vs. AA cases were 76.8% vs. 46.1%, total to partial resection vs. biopsy cases were 72.7% vs. 21.0%, and non-enhanced vs. enhanced cases were 82.5% vs. 45.6%, respectively. In multivariate analysis, the status of surgical resection and longer extension of preoperative edema (PE) were significant factors for progression-free survival (PFS). The five-year PFS for the total to partial resection vs. biopsy cases were 52.9% vs. 10.7%, and non-extensive PE vs. extensive PE (EPE) cases were 62.2% vs. 19.1%, respectively.ConclusionOur results suggest that a contrast-enhanced tumor on MRI and a longer PE may also be significantly associated with OS and PFS among grade 3 glioma patients.

Assessment of Isocitrate Dehydrogenase 1 Mutation by Immunohistochemistry in Egyptian Patients with High-grade Gliomas

BACKGROUND: At present, the classification of central nervous system tumors relies on molecular factors in addition to histologic features to identify many tumor types. This should subsequently results in more accurate diagnosis as well as addressing specific markers of potential prognostic and predictive value. AIM: This study was conducted to emphasize the importance of including isocitrate dehydrogenase 1 (IDH1) evaluation as a crucial part of the diagnosis and categorization of high-grade glioma cases. This also may help to individualize the treatment of high-grade glioma patients. MATERIALS AND METHODS: The current study included 60 cases of high-grade gliomas, studied histologically and immunohistochemically for the detection of IDH1 mutation. The results were correlated with different clinicopathologic variables and course of the disease. RESULTS: IDH1 immunohistochemical expression was positive in 46.67% of the studied high-grade glioma cases. A statistically significant relationship was detected between IDH1 expression and tumor histologic grade as 100% of Grade III anaplastic oligodendroglioma cases and 80% of the Grade III anaplastic astrocytoma cases were IDH1 positive while only 40.4% of Grade IV glioblastoma cases were IDH1 positive (p = 0.03). In addition, patients who were IDH1 mutant were in a better category of response to radiotherapy (p = 0.019) and also to chemotherapy (p &lt; 0.001). Moreover, patients who expressed IDH1 had prolonged overall survival (OS) and progression-free survival than those who showed negative IDH1expression (p &lt; 0.001). On the other hand, no statistically significant relationship was detected between IDH1 expression and patients age, sex, tumor site, tumor size, motor symptoms, sensory symptoms, and increased intracranial tension (p &gt; 0.05). CONCLUSIONS: It is suggested that IDH1 is a good prognostic marker for gliomas and is a good predictive marker for response to treatment. IDH1 is a promising target for therapy in high-grade gliomas through the emerging IDH1 inhibitors. Immunohistochemical testing for IDH1 is a practical and cost-effective method that should be applied in all glioma cases. Further study on a larger sample size is recommended to validate the current results. Moreover, applying molecular analysis to detect IDH1 mutation is recommended to be able to precisely detect the IDH1 wild-type tumor

Can quantifying the extent of ‘high grade’ features help explain prognostic variability in anaplastic astrocytoma?

Purpose Both phenotypic and genotypic variations now underpin glioma classification, thus helping to more accurately guide their clinical management. However, WHO Grade III anaplastic astrocytoma (AA) remains an unpredictable, heterogeneous entity; displaying a variable prognosis, clinical course and treatment response. This study aims to examine whether additional tumour characteristics influence either overall survival (OS) or 3-year survival in AA. Materials and methods Data were collected on all newly diagnosed cases of AA between 2003 and 2014, followed up for a minimum of 3 years. Molecular information was obtained from case records and if missing, was re-analysed. Histological slides were independently examined for Ki-67 proliferation index, cellularity and number of mitotic figures. Kaplan–Meier and Cox regression analyses were used to assess OS. Results In total, 50 cases were included with a median OS of 14.5 months (range: 1–150 months). Cumulative 3-year survival was 31.5%. Median age was 50 years (range: 24 − 77). Age, IDH1 mutation status, lobar location, oncological therapy and surgical resection were significant independent prognostic indicators for OS. In cases demonstrating an OS ≥ 3 years (n = 15), Ki-67 index, number of mitotic figures and percentage areas of ‘high cellularity’ were significantly reduced, i.e. more characteristic of lower-grade/WHO Grade II glioma. Conclusions IDH1 status, age, treatment and location remain the most significant prognostic indicators for patients with AA. However, Ki-67 index, mitotic figures and cellularity may help identify AA cases more likely to survive < 3 years, i.e. AA cases more similar to glioblastoma and those cases more likely to survive > 3 years, i.e. more similar to a low-grade glioma.

A pediatric case of anaplastic astrocytoma with a gliomatosis cerebri; the growth pattern and changes in serum VEGF-121 levels after bevacizumab treatment

Gliomatosis cerebri (GC) is a rare diffusely infiltrating glial neoplasm that carries a poor prognosis. Because tumors are undetectable in most patients at early-stage of the onset, a useful diagnostic method is expected. We compared serum vascular endothelial growth factor (VEGF)-121 levels in patients with GC or glioblastoma and controls. VEGF-121 levels were significantly higher in one patient with GC and patients with glioblastoma than in controls. VEGF-121 levels decreased in a patient with GC after bevacizumab-based therapy. Thus, VEGF-121 may be useful for diagnosing GC, its disease-monitoring and understanding its etiology.

Subgroup stratification of adult diffuse gliomas and outcomes: an adaptation of the updated WHO classification in a resource-constrained environment

AbstractIntroduction:The updated World Health Organization 2016 classification of central nervous system tumours recommends the addition of molecular parameters to histological diagnosis. In a resource-constrained setting, molecular testing such as gene sequencing and fluorescence in situ hybridisation is not feasible for all the patients. We assessed the utility of immunohistochemistry (IHC) for isocitrate dehydrogenase (IDH1/R132H) gene and alpha thalassemia/mental retardation syndrome X linked gene (ATRX) to stratify adult diffuse gliomas into subgroups and analysed the outcomes.Materials/Methods:Fifty-eight patients with grades III/IV astrocytic gliomas were tested by IHC for IDH1/R132H and ATRX mutation as per the standard protocol and were later stratified into three subgroups based on IHC. IDH1/R132H positive/ATRX retained gliomas were stratified as group 1 (G1), IDH1/R132H positive/ATRX lost were grouped as G2 and IDH1/R132H negative (with or without ATRX loss) as G3. All patients underwent adjuvant therapy as per the Stupp regimen. Outcomes and survival were analysed by Kaplan–Meier analysis using SPSS 21.v.Results:Median age of the cohort of 58 patients (male: 39, female: 19) was 40 years. Histologically, glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) and anaplastic oligodendroglioma (AOD) were seen in 23:17:18 patients. Forty-eight percent were tested positive for IDH1/R132H, 62% had retained ATRX protein stratifying patients into three subgroups (G1:14, G2:14, G3:30). The G3 group contained both AA and GBM cases. At median follow-up of 18 months, overall survival (OS) of the entire cohort was 76%, higher in G1, compared to G2 and G3 (log-rank p = 0·01). In comparison to various factors such as age, gender, location of the lesion and presenting symptom on survival among various groups, we found that gender of the patient in group I (men vs. women, p = 0·02), laterality of the tumour in group II (right vs. left, p = 0·07) and age of the patient in group III (&lt;45 vs. &gt;45, p = 0·01) demonstrated significant impact on OS.Conclusion:Subgroup stratification of adult diffuse gliomas based on IHC for IDH/R132H and ATRX demonstrates that group 1 was the most favourable prognostic factor. In a resource-constrained environment, IHC alone may guide appropriate management decision for the majority of adult diffuse gliomas, gene sequencing reserved for IDH1/R132H negative GBM in patients less than 45 years of age.

Atypical clinical manifestations and prognosis analysis of pediatric diffuse intrinsic pontine glioma

Objective To analyze the atypical clinical manifestations and clinical prognosis of pediatric diffuse intrinsic pontine glioma (DIPG). Methods A total of 27 patients with complete clinical data of DIPG undergoing clinical treatment at Neurosurgery Department of Beijing Tiantan Hospital, Capital Medical University from November 2015 to November 2017 were retrospectively enrolled into this study. All patients were divided into 2 groups according to the presence of atypical manifestations: atypical clinical manifestation group (17 cases) and the control group (10 cases). Among the 27 cases, 16 patients underwent stereotactic biopsy or open cranial biopsy, and the other 11 patients underwent tumor excision through craniotomy. All the children were followed up clinically or by telephone after operation to study the clinical outcomes. Comparative analysis was conducted on those clinical data. Prognosis was compared between the 2 groups through Kaplan-Meier survival analysis. Results Among the 27 cases, 20 were pathologically identified as high grade gliomas (including 4 cases of diffuse midline glioma, 6 cases of glioblastoma, 6 cases of anaplastic oligoastrocytoma, 4 cases of anaplastic astrocytoma) and 7 as low grade glioma (including 4 cases of oligoastrocytoma and 3 cases of astrocytoma). One child suffered from pneumonia and finally recovered postoperatively. No statistically significant difference (all P>0.05) was identified between 2 groups in the age, gender, clinical manifestation (including cranial nerve palsy, long tract dysfunction and cerebellum signs), clinical imaging features (including lesion enhancement, supratentorial ventricle enlargement and brachium pontis involvement), clinical treatment or pathology. Kaplan-Meier survival analysis showed that patients with atypical clinical manifestation had significantly higher cumulative survival rate than those in the control group (P=0.045). Conclusion Atypical clinical manifestation could be identified in some pediatric DIPG patients, which might be predictive of a better prognosis. Key words: Brainstem tumor; Child; Atypical clinical manifestation

Neuroendoscopic Cylinder Surgery and 5-Aminolevulinic Acid Photodynamic Diagnosis of Deep-Seated Intracranial Lesions

Microscopic detection of intracranial brain tumors with 5-aminolevulinic acid (5-ALA) has proven extremely useful, and reports the use of 5-ALA have recently increased. However, few reports have described 5-ALA photodynamic diagnosis (PDD) using a neuroendoscope. We performed neuroendoscopic 5-ALA PDD for various brain lesions and present a procedure using only a neuroendoscope. We describe the diagnosis of 20 intracranial brain lesion cases with a 5-ALA-guided fluorescence endoscope. A light-emitting diode that emitted either white light or 400- to 410-nm violet light was attached to a neuroendoscope. We performed cylinder surgery with a transparent sheath under observation with a rigid neuroendoscope. Neuroendoscopic biopsies were performed in 11 patients, and resections were performed in 9 patients. All lesions were observed with a neuroendoscope under sequential white light and violet light. We confirmed the presence of a red fluorescent lesion under violet light in 15 patients, including 4 of 5 glioblastoma cases (80%); 1 of 2 anaplastic astrocytoma cases (50%); 4 of 5 diffuse large B cell lymphoma cases (80%); 2 of 2 metastatic brain tumors; 1 of 1 case each of diffuse astrocytoma, pilocytic astrocytoma, inflammatory change, and germinoma (100%); and no cases of anaplastic ependymoma or cysticercosis. Pretargeted lesions were accurately harvested from all biopsy specimens. Gross total resection was achieved in 5 of 9 patients using a resection procedure. Our described method offers a promising technique for achieving precise brain tumor biopsies and safe resection.

Phosphorylated Hsp27 is mutually exclusive with ATRX loss and the IDH1R132H mutation and may predict better prognosis among glioblastomas without the IDH1 mutation and ATRX loss

AimTo identify biomarkers for accurate classification of glioma.Patients and methodsWe evaluated the heat shock protein 27 (Hsp27), phosphorylated Hsp27 (p-Hsp27), ATRX and IDH1R132Hproteins using immunohistochemistry in 421 glioma tissues. The...

Disease progression patterns of bevacizumab responders with recurrent malignant gliomas.

Tumor progression in patients with recurrent malignant glioma who respond to bevacizumab (BEV) is difficult to assess. The current study reviewed the clinical and radiological results of patients following a BEV-based chemotherapy regimen, and evaluated disease progression patterns in patients who responded to BEV therapy. From August 2011 to November 2015, 24 patients (18 glioblastoma cases and 6 anaplastic astrocytoma cases) were treated with BEV-based chemotherapy. In total, 6 patients were treated with BEV alone and 18 patients were treated with BEV combined with irinotecan. The male-female ratio was 10:14, and the median age was 47.5 years (range, 29–69). Patient performance status (PS) was classified using the Eastern Cooperative Oncology Group PS scores as follows: PS 1 (n=3), PS 2 (n=9), PS 3 (n=9) and PS 4 (n=3). Treatment-associated complications were also analyzed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Treatment responses were estimated using the Response Assessment in Neuro-Oncology Criteria. Progression-free survival (PFS) following treatment, patterns of disease progression and overall survival following treatment failure were also analyzed. The median PFS was 2.8 months (range, 0.6–10.1). In total, 2 patients did not continue treatment due to rectal bleeding and severe hematologic toxicity. Amongst the BEV responders (n=16, 72.7%), there was clinical deterioration without significant radiological progression in 2 patients (n=2, 12.5%). Radiological progression of non-enhancing lesions without enhancement flare-ups was observed in 6 patients (42.9%). A total of 3 of those lesions were diffuse and 3 were focal. Increased lesion enhancement was observed in 8 patients (57.1%). Of the non-responders (n=6, 27.3%), diffuse enlargement of non-enhancing lesions was detected in 2 patients and an increase in lesion enhancement occurred in 4 patients. BEV complete responders (n=3) radiologically progressed with enlarged T2/fluid attenuation inversion recovery lesions without enhancement, followed by enhancement flare-ups. Following BEV treatment failure, 8 patients received a number of adjuvant treatments and the overall survival was 4.5 months (range, 0.4–34.0). Clinical symptoms and radiological alterations of non-enhancing lesions must be evaluated in order to assess tumor progression in the BEV responders, particularly in patients who have achieved complete remission.

Anaplastic astrocytoma mimicking progressive multifocal leucoencephalopathy: a case report and review of the overlapping syndromes

BackgroundCo-occurrence of multiple sclerosis (MS) and glial tumours (GT) is uncommon although occasionally reported in medical literature. Interpreting the overlapping radiologic and clinical characteristics of glial tumours, MS lesions, and progressive multifocal leukoencephalopathy (PML) can be a significant diagnostic challenge.Case presentationWe report a case of anaplastic astrocytoma mimicking PML in a 27-year-old patient with a 15-year history of MS. She was treated with interferon, natalizumab and finally fingolimod due to active MS. Follow-up MRI, blood and cerebrospinal fluid examinations, and biopsy were conducted, but only the latter was able to reveal the cause of progressive worsening of patient’s disease.ConclusionsAnaplastic astrocytoma misdiagnosed as PML has not yet been described. We suppose that the astrocytoma could have evolved from a low grade glioma to anaplastic astrocytoma over time, as the tumour developed adjacent to typical MS plaques. The role of the immunomodulatory treatment as well as other immunological factors in the malignant transformation can only be hypothesised. We discuss clinical, laboratory and diagnostic aspects of a malignant GT, MS lesions and PML. The diagnosis of malignant GT must be kept in mind when an atypical lesion develops in a patient with MS.