RADT-16. CLINICAL CHARACTERISTICS AND PROGNOSIS OF ADULT BRAIN STEM GLIOMA: A SINGLE-CENTER 10-YEAR RETROSPECTIVE STUDY OF 81 PATIENTS

OBJECTIVE Adult brain stem glioma (ABSG) is a subset of brain tumor with a low incidence rate. This study reviewed the clinical characteristics and the risk factors affecting the prognosis of ABSG in a single center and explored the proper therapeutic mode for ABSG. METHODS The clinical data of adult patients (age over 18 years old) with brain stem gliomas from January 2010 to January 2021 of Guangdong Sanjiu brain hospital were retrospectively analyzed. Overall survival (OS) were determined by the Kaplan-Meier method, and Log-rank test was used for univariate analysis, COX proportion hazards regression was used for multivariate analysis. P < 0.05 was considered to be statistically significant. RESULTS Eighty-one ABSGs, including 46 males and 35 females, were analyzed. The median age of patients was 37 years (range, 19 to 67), and the median follow-up time was 17 months (range, 3 to 108) . The median OS of 81 patients was 18 months, and the OS for 1, 2, 3, and 5 years was 87.4%, 75.8%, 61.0%, and 36.5%, respectively. Univariate analysis demonstrated that the lesions enhancement on MRI, the WHO classifications, the expression status of H3K27M, radiotherapy status, and the status of adjuvant chemotherapy were related to prognosis. Multivariate Cox regression analysis revealed that age, the WHO classifications, radiotherapy status, and the maintenance chemotherapy followed radiotherapy were independent predictors for OS. CONCLUSIONS Radiotherapy is still the main treatment of ABSGs, and patients can be benefit from maintenance chemotherapy followed radiotherapy. The age > 40 years and WHO IV grade were two independent unfavorable prognostic factors. Research with expanded patient volume would help to further explore the influence of H3K27M expression on ABSG prognosis.

RADT-19. CLINICAL OUTCOMES OF RADIATION THERAPY FOR BRAIN STEM GLIOMA

PURPOSE/OBJECTIVES Brain stem gliomas are up to 20% of all brain tumor in children and unusual in adults. Radiotherapy is mainstay of treatment. Surgery for brain stem glioma is difficult because of anatomical location. This study was performed to evaluate the clinical outcomes of radiotherapy in brain stem glioma. METHODS Retrospective analysis of brain stem glioma patients treated with radiation therapy (54Gy/30 fractions of IMRT/ 3D CRT) with or without surgery or chemotherapy or other agents. RESULTS Twenty-four patients (median age 11.8 years) were treated between 2016 and 2020. Male to female ratio was 2:3. Surgical approach (biopsy and partial removal) was done in 16 patients. Histology revealed that anaplastic ependymoma in 2 patients, low grade astrocytoma in 2 patients, anaplastic astrocytoma in 8 patients, glioblastoma in 4 patients and remaining 8 patients had no histologic diagnosis. Radiotherapy (dose- 54Gy/ 30 fractions) was given with the technique of IMRT or 3D CRT. At the time of follow up, 8 patients had local recurrence, 10 patients died of due to disease and recurrence, 14 patients were alive. Among alive patients, 2 patients were treated with chemotherapy and 12 patients with temozolomide for 12 cycles. Patients who received temozolomide got improvement in performance status and reduced clinical symptoms; among them, 6 patients had more than 50% objective tumor response in radiological findings for follow-up 3-6 months after radiotherapy. The 2-years overall survival (OS) rate was 58.3% and 2-years Event-free Survival (EFS) rate was 50%. The median survival time was 14 months. There is no grade 3 or greater acute and late toxicities. CONCLUSION As the LMIC country with limited resources, our results of radiotherapy followed by temozolomide in brain stem glioma have optimal outcomes. However, prospective studies of this select group of patients with larger number and longer follow up is required.

Partial Regression of Congenital Brain Stem Glioma and Its Outcome

Congenital brain stem gliomas are rare in neonates and are difficult to diagnose given their subtle clinical presentation. They are usually associated with poor prognosis by their location and behavior. However, there are few reports of spontaneous regression of brain stem glioma with favorable long-term outcome. In this article, we reported a case of congenital brain stem glioma with a normal long-term outcome where a wait and watch approach allowed observation of spontaneous partial regression of the tumor with normal neurodevelopmental outcome at 40 months of age. The optimal approach to the management of children with brain stem glioma is difficult to define as, in general, the prognosis is considered poor. Selecting an “early intervention” or “wait and watch” approach depends on the nature, size, and progression of the lesion, and the risk versus benefits of early intervention. The clinical course of our case suggests that a conservative approach may be justified in selected cases as long as the parents have been counselled and regular frequent follow-up is assured.

A Risk Stratification Model Based on a Population Analysis for Predicting Cancer Specific Survival in Pediatric Brain Stem Glioma.

Introduction: The aim of this study was to construct and validate a nomogram and risk stratification model for predicting cancer-specific survival (CSS) of pediatric brainstem glioma patients. Methods: Cases of pediatric brainstem glioma patients (<12 years) from 1998 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and demographic, clinicopathologic characteristics, treatments, and survival outcomes were analyzed. The total cohort was randomly divided into training and validation sets, followed by univariate and multivariate Cox regression analyses. A nomogram was constructed and risk stratification analysis incorporated using the selected variables from the multivariate analysis. The accuracy of the model was assessed using C-index and calibration curves. Results: A total of 806 pediatric cases with histologically confirmed diagnosis of brainstem glioma were selected and analyzed. Multivariate analysis showed that age, race, tumor size, grade and radiotherapy (P<0.05) were independent prognostic indicators of pediatric gliomas. For prediction of CSS, the C-index of the nomogram was 0.75, which shows a good predictive probability. Conclusion: The nomogram developed in this study for predicting survival of pediatric patients with histologically confirmed stem gliomas is the first to incorporate risk stratification. Combining nomogram and risk stratification system is a convenient tool to aid clinicians in the identification of high-risk patients and to perform targeted adjuvant treatment.

To study histopathological features, GFAP staining and Ki 67/ MIB-1 labelling index in diagnoses and histological grading of gliomas

: A group of tumors that develops in the brain and spinal cord is called glioma. Histologically gliomas are classified into astrocytoma, ependymoma, oligodendroglioma, brain stem glioma and oligoastrocytoma. The present study was conducted to study histological grading of gliomas and correlate it with patient’s age, sex, GFAP staining, role of the Ki-67/MIB-1 labelling indices (PIs). The present retrospective study was conducted on 50 biopsies received. All specimens were subjected to immunohistochemistory for GFAP and MIB-1 and correlated with WHO grading for glioma.: High incidence of glial tumours was seen in the 3 and 4 decade with slight male predominance (60%), with commonest site being frontal lobe. Glioblastomas (Grade IV) constitute the most common glial tumour. A statistically significant correlation was observed between GFAP staining and Ki-67/MIB-1 with histological grading.: The study can prove helpful in diagnosis and histological grading of gliomas and in planning treatment protocols and strategies.

RONC-13. RADIATION INDUCED BRAIN STEM GLIOMA AFTER RADIATION THERAPY FOR MIXED GERM CELL TUMOR

We report a case of radiation-induced glioma in the pons after radiation therapy for germ cell tumor. A 17-year-old man was diagnosed as HCG and AFP secreting germ cell tumor at the age of 9. The tumor was located in the suprasellar region, which filled up most part of the third ventricle. Five courses of chemotherapy with cisplatin, etoposide, and cyclophosphamide, and whole ventricle plus local radiation therapy (total 51.2 Gy / 32Fr) were performed. After the treatment, most part of the tumor was regressed, and only small enhanced lesion remained. Six years after the treatment, he started to be ataxic, and worsened. An MRI revealed an enhanced lesion in the pons. Lesion biopsy was performed via the right cerebellar peduncle. Histopathological diagnosis confirmed the lesion was high grade glioma. He underwent extended local radiation therapy (50.4 Gy / 28 Fr) and administered temozolomide. Later, bevacizumab was added, and 3 months after treatment started, the size of the tumor was reduced and his symptoms were improving. There is no established treatment for radiation induced glioma. However, additional radiation therapy, temozolomide and bevacizumab appears to be useful to reduce tumor size and resolve the symptoms, even if it is transient.

A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma

Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression suggested the tumours were distinct from primary DIPG. Additional gene expression analysis demonstrated concordance with a published RIG expression profile. Multiple genetic alterations that enhance PI3K/AKT and Ras/Raf/MEK/ERK signalling were discovered in TK-RIG915 including an activating mutation in PIK3CA, upregulation of PDGFRA and AKT2, inactivating mutations in NF1, and a gain-of-function mutation in PTPN11. Additionally, deletion of CDKN2A/B, increased IDH1 expression, and decreased ARID1A expression were observed. Detection of phosphorylated S6, 4EBP1 and ERK via immunohistochemistry confirmed PI3K pathway and ERK activation. Here, we report one of the first PDX models for RIG, which recapitulates the patient disease and is molecularly distinct from primary brain stem glioma. Genetic interrogation of this model has enabled the identification of potential therapeutic vulnerabilities in this currently incurable disease.

Pediatric low grade focal brainstem glioma: outcomes of different treatment strategies and prognostic factors

Background: This study explores the prognostic factors and outcomes of different treatment modalities in focal brain stem glioma (FBSG). Materials & methods: Pediatric FBSG patients diagnosed during 2010–2017 were retrospectively reviewed for clinical and therapeutic data. Results: A total of 71 cases were identified and the median age was 6.4 years. The 5-year overall- and progression-free survival were 74.5 and 70.6%, respectively. Radiotherapy was the main line of treatment (66.2%) and there were no survival differences between radiotherapy, chemotherapy and surveillance groups. Two independent poor prognostic factors were identified on multivariate analysis: age <8 years and cervicomedullary tumor site (p = 0.02 for both). Conclusion: Surveillance, radiotherapy and chemotherapy have comparable clinical outcomes in pediatric FBSG.