A patient with two gliomas with independent oligodendroglioma and glioblastoma biology proved by DNA-methylation profiling: a case report and review of the literature

Here, we report on a patient presenting with two histopathologically distinct gliomas. At the age of 42, the patient underwent initial resection of a right temporal oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade II followed by adjuvant radiochemotherapy with temozolomide. 15 months after initial diagnosis, the patient showed right hemispheric tumor progression and an additional new left frontal contrast enhancement in the subsequent imaging. A re-resection of the right-sided tumor and resection of the left frontal tumor were conducted. Neuropathological work-up showed recurrence of the right-sided oligodendroglioma with features of an anaplastic oligodendroglioma WHO Grade III, but a glioblastoma WHO grade IV for the left frontal lesion. In depth molecular profiling revealed two independent brain tumors with distinct molecular profiles of anaplastic oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade III and glioblastoma IDH wildtype WHO grade IV. This unique and rare case of a patient with two independent brain tumors revealed by in-depth molecular work-up and epigenomic profiling emphasizes the importance of integrated work-up of brain tumors including methylome profiling for advanced patient care.

Case Report: Detection of Symptomatic Treatment-Related Changes in a Patient With Anaplastic Oligodendroglioma Using FET PET

Following local and systemic treatment of gliomas, the differentiation between glioma relapse and treatment-related changes such as pseudoprogression or radiation necrosis using conventional MRI is limited. To overcome this limitation, various amino acid PET tracers such as O-[2-(18F)-fluoroethyl]-L-tyrosine (FET) are increasingly used and provide valuable additional clinical information. We here report neuroimaging findings in a clincally symptomatic 53-year-old woman with a recurrent anaplastic oligodendroglioma with MRI findings highly suspicious for tumor progression. In contrast, FET PET imaging suggested treatment-related changes considerably earlier than the regression of contrast enhancement on MRI. In patients with oligodendroglioma, the phenomenon of symptomatic treatment-related changes is not well described, making these imaging findings unique and important for clinical decision-making.

INNV-07. TTFIELDS TREATMENT OF GLIOSARCOMA AND RECURRENT ANAPLASTIC OLIGODENDROGLIOMA

INTRODUCTION The Optune device delivers tumor treating fields (TTFields) and is considered as a standard of care for newly diagnosed and recurrent glioblastoma patients. The efficacy of Optune in other glioma subtypes, such as gliosarcoma and anaplastic oligodendroglioma, is still unclear. In this small case series, we present the clinical, pathologic and radiographic findings of two patients who utilized Optune and had improved outcomes compared to historical controls. CASE 1 A 49 year old woman underwent resection of a right temporal lobe gliosarcoma in November 2017. She received conventional radiation therapy with concurrent temozolomide, which was complicated by significant thrombocytopenia and leukopenia. She initiated Optune as monotherapy six weeks after completing radiation, and used the device for 24 months. She still has not had a recurrence, now 3.5 years since her initial diagnosis. CASE 2 A 46 year old woman underwent resection of a right frontal lobe oligodendroglioma, WHO Grade 2, in September 2011. She received one cycle of temozolomide in April 2014, complicated by thrombocytopenia, and no further chemotherapy was administered. In November 2017, she underwent resection of a new focus of enhancement at the margin of the resection cavity, which was confirmed to have transformed to WHO Grade 3. In August 2019, a radiographic progression of an enhancing nodule was observed. She initiated Optune as monotherapy in September 2019, and since that time, has had stable disease for 18 months. Optune treatment is still ongoing. CONCLUSIONS In a case of newly diagnosed gliosarcoma, Optune monotherapy has contributed to progression-free and overall survival of 3.5 years to date. In a case of recurrent anaplastic oligodendroglioma, Optune monotherapy has achieved stable disease for at least 18 months. These cases demonstrate that Optune can be safely utilized in these glioma subtypes and contributed to improved survival outcomes in these two patients.

Incorporating Ensemble approach into Automated Machine Learning in an attempt to predict survival time in patients with anaplastic oligodendroglioma: Analysis on the Surveillance, Epidemiology, and End Results (SEER) database

Automated machine learning is explored to develop survival time predictive models for anaplastic oligodendroglioma by adopted data from the Surveillance, Epidemiology, and End Results (SEER) database. Such models, when incorporated into risk stratification protocols, would optimize the outcomes and translate into the reduction of morbidity and mortality associated with this neoplastic condition.

Third Ventricle Anaplastic Oligodendroglioma: A Case Report

Background and Importance: Anaplastic Oligodendroglioma (ODG) constitutes 24% of all pediatric ODG. The mean age of presentation of ODG is 12±6 years. They are most common in frontal and temporal lobes; however, rare cases of intraventricular ODGs are reported. Most commonly they arise from the anterior part of lateral ventricles. Third ventricle ODG is extremely rare and only a few cases of lateral and third ventricle anaplastic ODG are reported. ODGs infiltrate locally to meninges and rarely have leptomeningeal spread. Thus, ODG forms a differential diagnosis of pediatric intraventricular tumor. Case Presentation: Here we present a case of a 15-month-old male child with raised intracranial pressure due to obstructive hydrocephalus. The patient was detected to be COVID-19 RT–PCR (Reverse Transcriptase Polymerase Chain Reaction) positive in the preoperative period and underwent emergency Right-sided Ventriculo Peritoneal (VP) shunt. His contrast MRI (Magnetic Resonance Imaging) Brain showed a 50×24×39 mm heterogeneously enhancing mass epicenter at third ventricle and extending to lateral and fourth ventricle with spinal drop metastasis. Preoperative differential diagnosis of Ependymoma was made and definitive surgery was done once the child recovered from COVID-19. However, his biopsy specimen pathology and Immunohistochemistry (IHC) were suggestive of anaplastic oligodendrogliomas and the child responded well to chemotherapy. Conclusion: Intraventricular ODG is an extremely rare pediatric tumor. Patients usually present with obstructive hydrocephalus. Contrast MRI findings are nonspecific and help in detecting leptomeningeal spread to the spine. IHC and chromosomal analysis are important diagnostic and treatment prognostication tools. These tumors have a high recurrence and poor prognosis despite gross total resection.

A single institution retrospective analysis on survival based on treatment paradigms for patients with anaplastic oligodendroglioma

Introduction Anaplastic oligodendrogliomas are high-grade gliomas defined molecularly by 1p19q co-deletion. There is no curative therapy, and standard of care includes surgical resection followed by radiation and chemotherapy. However, the benefit of up-front radiation with chemotherapy compared to chemotherapy alone has not been demonstrated in a randomized control trial. Given the potential long-term consequences of radiation therapy, such as cognitive impairment, arteriopathy, endocrinopathy, and hearing/visual impairment, there is an effort to balance longevity with radiation toxicity. Methods We performed a retrospective single institution analysis of survival of patients with anaplastic oligodendroglioma over 20 years. Results 159 patients were identified as diagnosed with an anaplastic oligodendroglioma between 1996 and 2016. Of those, 40 patients were found to have AO at original diagnosis and had documented 1p19q co-deletion with a median of 7.1 years of follow-up (range: 0.6–16.7 years). After surgery, 45 % of patients were treated with radiation and chemotherapy at diagnosis, and 50 % were treated with adjuvant chemotherapy alone. The group treated with chemotherapy alone had a trend of receiving more cycles of chemotherapy than patients treated with radiation and chemotherapy upfront (p = 0.051). Median overall survival has not yet been reached. The related risk of progression in the upfront, adjuvant chemotherapy only group was almost 5-fold higher than the patients who received radiation and chemotherapy (hazard ratio = 4.85 (1.74–13.49), p = 0.002). However, there was no significant difference in overall survival in patients treated with upfront chemotherapy compared to patients treated upfront with chemotherapy and radiation (p = 0.8). Univariate analysis of age, KPS, extent of resection, or upfront versus delayed radiation was not associated with improved survival. Conclusions Initial treatment with adjuvant chemotherapy alone, rather than radiation and chemotherapy, may be an option for some patients with anaplastic oligodendroglioma, as it is associated with similar overall survival despite shorter progression free survival.

Formation of primary cell line collections of glial tumors for cancer research.

e14030 Background: Gliomas are the most common primary intracranial tumors. Primary cell cultures are obtained directly from patient’s tumor after surgery, so they display tumor properties in vivo much better than established cell lines. This advantage makes it possible to use primary cell cultures in development of individualized cancer treatment. The aim of the study was to obtain primary cell lines of malignant brain tumors using the explant method. Methods: Twenty-six patients of both sexes aged 22 to 66 years with such diagnoses as glioblastoma, glioblastoma with anaplastic astrocytoma, anaplastic oligodendroglioma, diffuse astrocytoma, anaplastic astrocytoma, oligoastrocytoma and diffuse protoplasmic astrocytoma were recruited for the study. Tumor samples obtained during surgery was disintegrated with sterile scalpels in a Petri dish with 5 ml of DMEM. Further cultivation of fragmented tumor tissue was in a culture flask with 5 ml of complete media contained DMEM (Gibco, USA), 10% FBS (HyClone, USA), 1% penicillin/streptomycin (BioLot, Russia), 1% NEAA (Sigma-Aldrich, USA), 1 ng/ml FGF (Sigma-Aldrich, USA). Microscopic investigation and media replacement were carried out once in 3-5 days. Cell counting was executed with automatic cell counter EVE (NanoEnTek, Korea). Results: At the zero passage, the rate of a 100% confluence monolayer formation varied from 22 to 85 days (46.3 days in average). At the zero passage, glioblastoma lines formed a 100% confluence monolayer longer than all the other lines, with an average of 57.1 days. Diffuse astrocytoma, anaplastic oligodendroglioma, and glioblastoma with anaplastic astrocytoma lines took the shortest time to reach a 100% confluence - 22-24 days. However, at the first passage, the cells reached a full monolayer within 4 to 25 days (7.1 days in average). It demonstrates a tendency in increase of the cell proliferation rate by 6.5 times at the first passage which indirectly indicates the effectiveness of the used cultivation conditions. Success in the cell cultivation is particularly important for creating a bank of primary cell lines for further screening of anticancer therapeutic agents. Glioblastoma samples had a tendency for more active cell proliferation at the first passage compared with other glial tumors: 5.7 days against 8.5 days in average. At the same time, glioblastoma with anaplastic astrocytoma lines showed a tendency for 2-4 times decrease in the rate of monolayer formation compared with glioblastoma samples: 19.5 days against 5.7 days in average. Conclusions: Twenty-six primary human brain cancer cell lines were obtained: four diffuse astrocytoma lines, five anaplastic astrocytoma lines, anaplastic oligodendroglioma line, thirteen glioblastoma lines, two glioblastoma with anaplastic astrocytoma lines, oligoastrocytoma line. The explant method was shown to be more effective for obtaining of glioblastoma cell lines in comparison with other glial tumors.

Preparation of primary glial tumor cell lines

Objective. The aim of this work was to obtain the primary cell lines of brain malignant tumors using the explant method. Materials and methods. Thirteen patients of both sexes, aged 22 to 66, were recruited. The tumor material of the patients was fragmented and placed in flasks with complete nutrient medium for glial tumor cells. Subsequently, the material was photographed at various stages of cultivation, the cell morphology was determined, and the rate of monolayer formation at the zero and first passages was assessed. Results. As a result, thirteen primary human cell lines of glial tumors were obtained: six glioblastoma lines, two glioblastoma lines with anaplastic astrocytoma, one anaplastic oligodendroglioma line, one diffuse astrocytoma line, one oligoastrocytoma line and one diffuse protoplasmic astrocytoma line, one anaplastic astrocytoma line. In the culture of diffuse astrocytoma, there were observed the cells forming a network at the bottom of the flask. In the culture of anaplastic astrocytoma at a confluence of 3050 %, fibroblast-like cells were presented, and at a confluence of 100 %, a monolayer was formed with cells intimately adjacent to each other. In the culture of oligoastrocytoma, both fibroblast-like cells and islets of closely intertwined fusiform cells were observed. The same was typical for the cells of diffuse protoplasmic astrocytoma. Anaplastic oligodendroglioma during the first week of cultivation was represented mainly by round cells with a contrast agent, which subsequently attached and actively proliferated. At a confluence of 3080 %, fibroblast-like cells were observed, and at 100 %, spindle-shaped cells closely adjacent to each other. In cultures of glioblastomas, no specific character of cell growth was revealed: spindle-shaped, fibroblast-like cells and cells with long processes forming a network were encountered. Glioblastoma cultures against the background of anaplastic astrocytoma were represented by a network of cells with long processes. At the zero passage, the rate of formation of a 100 % confluence monolayer ranged from 22 to 85 days. At the first passage, the cells reached a full monolayer within 4 to 25 days. At the zero passage, the longest time among all the samples to form the monolayer with a 100 % confluence needed glioblastoma lines on average 59 days. The shortest time to reach a 100 % confluence was required for cells of diffuse astrocytoma, anaplastic oligodendroglioma and glioblastoma against the background of anaplastic astrocytoma 2224 days. Conclusions. In our work, it was shown that the explant method ensures the production of viable cells of glial tumors and the possibility of their further cultivation.