Adult Brainstem Gliomas Research Articles

Clinical outcome, radiological findings, and genetic features of IDH-mutant brainstem glioma in adults.

With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4months and 85.2months, respectively, longer than that for IDH-wildtype gliomas (5.6months and 12.0months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype.

Clinical characteristics and prognostic factors of adult brainstem gliomas: A retrospective analysis of histologically-proven 40 cases.

To illustrate the clinical characteristics and prognostic factors of adult patients pathologically confirmed with brainstem gliomas (BSGs). Clinical data of 40 adult patients pathologically diagnosed with BSGs admitted to Beijing Shijitan Hospital from 2009 to 2022 were recorded and retrospectively analyzed. The primary parameters included relevant symptoms, duration of symptoms, Karnofsky performance status (KPS), tumor location, type of surgical resection, diagnosis, treatment, and survival. Univariate and multivariate analyses were evaluated by Cox regression models. The gliomas were located in the midbrain of 9 patients, in the pons of 14 cases, in the medulla of 5 cases, in the midbrain and pons of 6 cases and invading the medulla and pons of 6 cases, respectively. The proportion of patients with low-grade BSGs was 42.5%. Relevant symptoms consisted of visual disturbance, facial paralysis, dizziness, extremity weakness, ataxia, paresthesia, headache, bucking, dysphagia, dysacousia, nausea, dysphasia, dysosmia, hypomnesia and nystagmus. 23 (57.5%) patients accepted stereotactic biopsy, 17 (42.5%) patients underwent surgical resection. 39 patients received radiotherapy and 34 cases were treated with temozolomide. The median overall survival (OS) of all patients was 26.2 months and 21.5 months for the median progression-free survival (PFS). Both duration of symptoms (P = .007) and tumor grading (P = .002) were the influencing factors for OS, and tumor grading was significantly associated with PFS (P = .001). Duration of symptoms for more than 2 months and low-grade are favorable prognostic factors for adult patients with BSGs.

Surgical Management of Adult Brainstem Gliomas: A Systematic Review and Meta-Analysis.

The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy.

The Role of Advanced MRI Sequences in the Diagnosis and Follow-Up of Adult Brainstem Gliomas: A Neuroradiological Review.

The 2021 WHO (World Health Organization) classification of brain tumors incorporated the rapid advances in the molecular, genetic, and pathogenesis understanding of brain tumor pathogenesis, behavior, and treatment response. It revolutionized brain tumor classification by placing great emphasis on molecular types and completely splitting adult-type and pediatric-type diffuse gliomas. Brainstem gliomas (BSGs) are the leading primary tumors of the brainstem, although they are quite uncommon in adults compared with the pediatric population, representing less than 2% of adult gliomas. Surgery is not always the treatment of choice since resection is rarely feasible and does not improve overall survival, and biopsies are not generally performed since the location is treacherous. Therefore, MRI (Magnetic Resonance Imaging) without and with gadolinium administration represents the optimal noninvasive radiological technique to suggest brainstem gliomas diagnosis, plan a multidisciplinary treatment and for follow-up evaluations. The MRI protocol encompasses morphological sequences as well as functional and advanced sequences, such as DWI/ADC (Diffusion-Weighted Imaging/Apparent Diffusion Coefficient), DTI (Diffusion Tensor Imaging), PWI (Perfusion-Weighted Imaging), and MRS (Magnetic Resonance Spectroscopy), which improve the accuracy of the diagnosis of BSGs by adding substantial information regarding the cellularity, the infiltrative behavior toward the v fiber tracts, the vascularity, and the molecular changes. Brainstem gliomas have been divided into four categories on the basis of their MRI radiological appearance, including diffuse intrinsic low-grade gliomas, enhancing malignant gliomas, localized tectal gliomas, and other forms. The aim of our review is to provide insight into the role of advanced MRI sequences in the diagnosis and follow-up of adult brainstem gliomas.

2-Hydroxyglutarate magnetic resonance spectroscopy in adult brainstem glioma.

Adult brainstem gliomas (BSGs) are rare tumors of the CNS that are poorly understood. Upregulation of the oncometabolite 2-hydroxyglutarate (2HG) in the tumor indicates the mutation of isocitrate dehydrogenase (IDH), which can be detected by magnetic resonance spectroscopy (MRS). Although histological examination is required for the definitive diagnosis of BSG, 2HG-optimized MRS (2HG-MRS) may be useful, considering the difficult nature of brainstem lesion biopsy. The aim of this study was to evaluate the utility of 2HG-MRS for diagnosing IDH-mutant adult BSG. Patients with a radiographically confirmed brainstem tumor underwent 3T MRS. A single voxel was set in the lesion with reference to the T2 or fluid-attenuated inversion recovery image and analyzed according to the 2HG-tailored MRS protocol (point-resolved spectroscopic sequence; echo time 35 msec). All patients underwent intraoperative navigation-guided or CT-guided stereotactic biopsy for histopathological diagnosis. The status of IDH and H3K27M mutations was confirmed by immunohistochemistry and direct DNA sequencing. In addition, the authors examined the relationship between patients' 2HG concentrations and survival time. Ten patients (7 men, 3 women; median age 33.5 years) underwent 2HG-MRS and biopsy. Four patients had an H3K27M mutation and 4 had an IDH1 mutation (1 R132H canonical IDH mutation, 2 R132S and 1 R132G noncanonical IDH mutations). Two had neither H3K27M nor IDH mutations. The H3K27M and IDH mutations were mutually exclusive. Most tumors were located in the pons. There was no significant radiological difference between mutant H3K27M and IDH on a conventional MRI sequence. A 2HG concentration ≥ 1.8 mM on MRS demonstrated 100% (95% CI 28%-100%) sensitivity and 100% (95% CI 42%-100%) specificity for IDH-mutant BSG (p = 0.0048). The median overall survival was 10 months in IDH-wild-type BSG patients (n = 6) and could not be estimated in IDH-mutant BSG patients (n = 4) due to the small number of deaths (p = 0.008). 2HG-MRS demonstrated high sensitivity and specificity for the prediction of IDH-mutant BSG. In addition, 2HG-MRS may be useful for predicting the prognosis of adult BSG patients.

NIMG-38. 2-HYDROXYGLUTARATE MAGNETIC RESONANCE SPECTROSCOPY IN ADULT BRAINSTEM GLIOMA PATIENTS

Abstract INTRODUCTION The onco-metabolite, 2-hydroxyglutarate (2HG), is non-invasive biomarker detected by magnetic resonance spectroscopy (MRS), indicating isocitrate dehydrogenase (IDH) mutant glioma. Especially in patients with brainstem lesions where biopsies are at high risk of causing neurological deficit, 2HG-MRS may be useful. Here, we examined the utility of 2HG-MRS for diagnosing IDH mutant adult diffuse brainstem glioma and the ability of prognosis prediction. METHODS Three tesla -MRS (3T-MRS) was performed on patients with radiographically confirmed brainstem tumor. A single-voxel was set in the lesion with reference to the T2 / FLAIR image, and analyzed according to the 2HG-tailored MRS protocol (Philips, Achieva, PRESS, TE 35 ms). All patients underwent biopsy using an intraoperative navigation system (Brain LABTM) or stereotactic biopsy system (Komai’s CT-stereotactic frame) before initial treatment. IDH and H3K27M mutation status were confirmed by immunohistochemistry and DNA sequence. We examined the relationship between 2HG values and patient survival period. RESULTS Ten patients (7 male and 3 female, median age 33.5) underwent 2HG-MRS and biopsy. Four had H3K27M mutation and 4 had IDH mutation (1 R132H, 2 R132S, and 1 R132G). Two had neither H3K27M nor IDH mutation. H3-K27 and IDH mutations were mutually exclusive. All tumor located at pons mainly. There was no significant radiological difference between H3K27M and IDH mutant in conventional MRI sequence. Pearson's chi-square test demonstrated that 2HG concentrations > 1.5 mM were 100% in sensitivity and 83.3% in specificity for IDH mutant glioma (p = 0.0098). The median overall survival was 130.5 months in IDH mutant glioma (n=4) and 25 months in IDH wild-type glioma (n=6), respectively. CONCLUSIONS 3T-MRS was able to detect 2HG in adult brainstem glioma. A noninvasive 2HG-MRS study may be helpful in the diagnosis and predicting prognosis of adult diffuse brainstem glioma patient.

169 Adult brainstem glioma mimicking as a neuro-infectious process: case report and literature review

Background andAimBrainstem gliomas are rare, accounting for less than 2% of adult gliomas. They are difficult to diagnose and challenging to treat [Hu et al, 2016]. Here, we report a patient with an unusual clinical presentation of brainstem glioma, supported by radiological and histopathological findings.Clinical presentationA 61-year old male retired diver presented with 2-month history of worsening occipital headache, described as a constant pressure worse on lying down with migrainous features of nausea and light-sensitivity, and intermittent episodes of double vision and poor balance.Neurological examination on admission was normal. He progressed to develop double vision, left-sided weakness and worsening swallowing and respiratory function.InvestigationsBlood tests for infections and vasculopathy were negative. Two CSF samples taken showed high protein (1.7g and 3.25g respectively) with the first showing 100% lymphocytes and the latter 56% monocytes and 42% lymphocytes. There were no malignant cells on immunophenotyping.MRIs demonstrated progressive of ring-enhancing lesions in brainstem in keeping with inflammatory con- ditions. Biopsy was not possible due to the centrally-located lesions. Despite receiving wide spectrum antimicrobials, steroids and respiratory support, he died 2 months later. Autopsy of the brain showed a glioblastoma with brainstem infiltration and cystic necrosis in the pons.SummaryGliomatosis pattern and leptomeningeal and nerve root spreading of brainstem glioblastoma can be misleading signs with neuro-infections as a differential. Early neurosurgical intervention may aid diagnosis.kitwu@doctors.org.uk

Adult brainstem glioma differential diagnoses: an MRI-based approach in a series of 68 patients.

Brainstem gliomas are rare in adults. The diagnosis is often difficult, as some teams still consider brainstem biopsies dangerous and often avoid this procedure. The aim of this study was to describe differential diagnoses that can mimic brainstem glioma, to help clinicians avoid diagnostic and therapeutic mistakes, and to propose a diagnostic algorithm according to radiological presentations. The French network of adult brainstem gliomas (GLITRAD) retrospectively collected all reported cases of differential diagnoses between 2006 and 2017. The inclusion criteria were as follows: age over 18years, lesion epicenter in the brainstem, radiological pattern suggestive of a glioma and diagnostic confirmation (histopathological or not, depending on the disease). We identified a total of 68 cases. Most cases (58/68, 85%) presented as contrast-enhancing lesions. The most frequent final diagnosis in this group was metastases in 24/58 (41%), followed by central nervous system lymphoma in 8/58 (14%). Conversely, MRI findings revealed 10/68 nonenhancing lesions. The most frequent diagnosis in this group was demyelinating disease (3/10, 30%). The risk of diagnostic mistakes illustrates the need to consider the more systematic use of a brainstem biopsy when reasonably possible. However, we propose an MRI-based approach to the differential diagnosis of gliomas to limit the risk of misdiagnosis in cases where a biopsy is not a reasonable option.

A 25-year-female with Diffuse Intrinsic Pontine Glioma Surviving for More than Nine Years Following Treatment with Antineoplastons

Rationale: Diffuse intrinsic pontine glioma (DIPG) is a lethal brain tumor and leading cause of brain tumor–related death in children. Over the past few decades, clinical trials have shown no improvement in outcome. Most DIPGs occur in the pediatric population. Adult brainstem gliomas are rare, constitute less than 2% of adult gliomas, and show a slight male predominance. The case of this 25-year-old female is presented to detail and discuss the use of Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal) in the treatment of DIPG that persisted despite radiation therapy (RT) and temozolomide. Objectives: The patient described was treated at the Burzynski Clinic (BC), as a special exception, according to the phase II protocol, BT-09, which utilized Antineoplastons A10 and AS2-1 (ANP therapy) in the treatment of brain tumors. The delivery of ANP therapy was via a subclavian catheter and infusion pump. Tumor response to therapy was measured by sequential magnetic resonance imaging (MRI) of the brain. Overall Survival (OS) and Adverse Events (AES) were also documented. Findings: At her presentation to the BC, the patient complained of diplopia, left-sided weakness, and difficulty walking. On physical exam, she was alert and orientated. Her cranial nerves were intact. There was weakness of the left-sided extremities. Deep tendon reflexes were equal bilaterally with down-going toes bilaterally. Reports of the original brain MRIs in Argentina suggested a DIPG with extension to the medulla and cerebellum. In addition, tumor biopsy confirmed a grade 3 astrocytoma. Following radiation therapy (RT) and temozolomide in Argentina, the patient was treated at BC for persistent disease with ANP therapy. Sequential MRI imaging of the residual tumor, which was non-enhancing, showed no change in size during therapy. However, the patient did achieve resolution of her neurologic signs and symptoms and has survived more than nine years since first being seen at BC. Correspondence with the patient on September 9, 2021 indicated she was feeling fine, had a healthy child, and was enjoying life. Conclusions: We have presented here the case of an adult female with a DIPG who had resolution of signs and symptoms and survived more than nine years after ANP therapy. For patients with DIPG (or other high-grade astrocytoma), who do not qualify for/refuse RT or show persistent or progressive disease following RT and/or chemotherapy, ANP therapy is an effective therapeutic option. In collaboration with the FDA confirmatory Phase II and Phase III studies have been developed.

NIMG-15. 2-HYDROXYGLUTARATE MAGNETIC RESONANCE SPECTROSCOPY IN ADULT BRAINSTEM GLIOMA PATIENTS

Abstract OBJECTIVE The onco-metabolite, 2-Hydroxyglutarate (2HG), is non-invasive biomarker for detecting isocitrate dehydrogenase (IDH) mutant glioma by MR-Spectroscopy. Especially 2HG-MRS may be useful in patients with brainstem lesions, where surgical biopsy presents high risk of neurological injury. Here, we examined the utility of 2HG-MRS for diagnosis of IDH mutant adult brainstem glioma. METHODS We conducted 3 tesla -MRS (3T-MRS) in 8 radiographically identified brainstem tumor (7 male and 1 female, median age 39). Single-voxel was localized from the T2-FLAIR using a 2HG-tailored MRS protocol (Philips, Achieva, PRESS, TE 35 ms). All patients underwent tumor biopsy using an intraoperative navigation system (Brain LABTM) or stereotactic biopsy system (Komai’s CT-stereotactic frame) before initial treatment. IDH and H3K27M status were diagnosed by IHC and DNA sequence. RESULTS 3 cases were H3K27M and 4 cases were IDH mutant (R132H 1 case, R132S 2 cases, and R132G 1 case). 1 case were neither H3K27M nor IDH mutant. H3-K27 and IDH1 mutations were mutually exclusive. All tumor located at pons. There were no significant radiological difference between H3K27M and IDH mutant in conventional MRI sequence. Pearson's chi-square test demonstrated that 2HG concentrations >1.5 mM were 100% sensitive and 75% specific for IDH mutant glioma (p = 0.0285). The median overall survival survival were 127 month in IDH mutant glioma (n=4) and 22.5 months in IDH wild-type glioma (n=4), respectively. CONCLUSIONS 2HG in adult brainstem glioma was detected by conventional 3T-MRS successfully. A noninvasive 2HG-MRS may be useful diagnostic modality for evaluating molecular status and prognosis in brainstem glioma noninvasively.

Prognostic factors in adult brainstem glioma: a tertiary care center analysis and review of the literature

IntroductionAdult brainstem gliomas (BSGs) are rare central nervous system tumours characterized by a highly heterogeneous clinical course. Median survival times range from 11 to 84 months. Beyond surgery, no treatment standard has been established. We investigated clinical and radiological data to assess prognostic features providing support for treatment decisions.Methods34 BSG patients treated between 2000 and 2019 and aged ≥ 18 years at the time of diagnosis were retrospectively identified from the databases of the two largest Austrian Neuro-Oncology centres. Clinical data including baseline characteristics, clinical disease course, applied therapies, the outcome as well as neuroradiological and neuropathological findings were gathered and analysed. The tumour apparent diffusion coefficient (ADC), volumetry of contrast-enhancing and non-contrast-enhancing lesions were determined on magnetic resonance imaging scans performed at diagnosis.ResultsThe median age at diagnosis was 38.5 years (range 18–71 years). Tumour progression occurred in 26/34 (76.5%) patients after a median follow up time of 19 months (range 0.9–236.2). Median overall survival (OS) and progression-free survival (PFS) was 24.1 months (range 0.9–236.2; 95% CI 18.1–30.1) and 14.5 months (range 0.7–178.5; 95% CI 5.1–23.9), respectively. Low-performance status, high body mass index (BMI) at diagnosis and WHO grading were associated with shorter PFS and OS at univariate analysis (p < 0.05, log rank test, respectively). ADC values below the median were significantly associated with shorter OS (14.9 vs 44.2 months, p = 0.018).ConclusionECOG, BMI, WHO grade and ADC values were associated with the survival prognosis of BSG patients and should be included in the prognostic assessment.

Adult brainstem glioma presenting with isolated persistent hemifacial spasm or facial nerve palsy

ObjectAdult brainstem gliomas are a rare group of heterogeneous brain tumors. Classical clinical presentation includes progressive impairment of cranial nerves associated with long tract signs. The prognosis and response to treatment are poor; nevertheless, some patients do have a long survival. The objective of this study was to describe a series of patients with an isolated persistent hemifacial spasm and/or facial nerve palsy as the presenting symptom of a brainstem glioma. MethodsFourteen patients from 3 French hospitals (Paris, Caen, Lille) were included. Clinical and radiological features and overall survival were retrospectively analyzed. A review of the literature of similar cases was performed. ResultsMean age at diagnosis was 35 years (range 19–57 years). Mean duration of facial nerve involvement before diagnosis was 17 months (range 1–48 months). Tumors were characterized on MRI by a lateralized location in the pons, a T1-weighted hyposignal, a T2-weighted hypersignal and no contrast enhancement after Gadolinium injection except for 2 cases. Biopsies were performed in 10 cases and showed 8 low-grade and 2 high-grade gliomas. All the patients were initially treated with radiotherapy and 6 patients with chemotherapy after progression. Eleven patients died from tumor progression. Median survival time was 90 months. ConclusionsAdult brainstem gliomas revealed by a progressive isolated involvement of the facial nerve seem to have particular clinico-radiological features of slow progressive tumors and may be associated with long patient survival.

Clinical and Genetic Features of Brainstem Glioma in Adults: A Report of 50 Cases in a Single Center.

Background and PurposeBrainstem gliomas (BSGs) in adults are rare brain tumors with dismal outcomes. The aim of this study was to determine the clinical and genetic features in a series of BSGs and their association with the prognosis.MethodsFifty patients who underwent a stereotactic biopsy between January 2016 and April 2018 at a single institution were collected. Data on clinicopathological characteristics were analyzed and factors associated with patient survival were identified using a Cox regression model.ResultsThe median age at diagnosis was 55.5 years, and 62% of the patients were male. Glioblastoma (44%) accounted for the largest proportion of BSGs, and oligodendroglioma (2 of 50) was rarely encountered. The IDH mutation (6 of 44) occurred infrequently in astrocytomas, and IDH-mutant tumors harbored both ATRX loss and MGMT promoter methylation at a relatively low level. Wild-type IDH astrocytomas were identified as having high rates of 1p/19q codeletion (5 of 38) and loss of heterozygosity 1p (8 of 38) or 19q (8 of 38) only. In diffuse midline glioma H3K27M mutant, MGMT promoter methylation occurred in three of four cases. Patients were offered radiotherapy and/or concurrent/adjuvant temozolomide chemotherapy, and their median survival time was 13 months. Multivariate analysis revealed that a low tumor grade, absence of tumor enhancement, duration of symptoms ≥3 months, Karnofsky performance status ≥70, and ATRX loss conferred a survival advantage.ConclusionsAdult BSGs showed different molecular genetic characteristics, but also resembled supratentorial gliomas in their clinical features associated with oncological outcomes.

Adult brainstem glioma: a multicentre retrospective analysis of 47 Italian patients.

Adult brainstem gliomas are rare primary brain tumours with heterogeneous clinical course. The low frequency of these tumours makes it difficult to achieve high-quality evidence regarding prognostic factors, adequate therapeutic approach and outcome in such patients. In this retrospective study, we analysed clinical, radiological, molecular, prognostic and therapeutic factors in a series of 47 histologically proven adult brainstem gliomas recruited over a 20-year period (1998-2018). Twenty-two patients were male, 25 female with median age of 39 years. The tumour involved one brainstem segment in 20 cases and 2 or more segments in 27. Contrast enhancement was reported in 28 cases. Surgical procedures included biopsy in 26 cases and partial/total resection in the remaining 21. Histological diagnosis was of low-grade glioma in 23 patients, high-grade glioma in 22 and non-diagnostic in 2 cases. Data regarding molecular biology were available for 22 patients. Median overall survival was 35 months, in particular 16 months in high-grade glioma and 84 months in low-grade glioma. At univariate analysis, tumour grade was the only factor with a statistically significant impact on survival time (p = 0,003), whereas younger age, better performance status and total/subtotal resection showed a trend to more prolonged survival. This study also confirms safety of biopsy/surgery in adult brainstem glioma patients and shows a clear trend to a more frequent assessment of molecular biology data. Further prospective multicentre efforts, and hopefully clinical trials, are necessary to improve outcome in this neglected glioma patient population.

381P Adult brainstem gliomas: Clinicopathological profile and outcomes of a single center 10-year cohort

381P Adult brainstem gliomas: Clinicopathological profile and outcomes of a single center 10-year cohort

P14.33 Adult brainstem gliomas in neurofibromatosis type 1 (NF1)

Abstract BACKGROUND The brainstem is the second location of brain tumors after optic pathways in NF1. In NF1 children, brainstem gliomas are usually indolent and have a better prognosis than their counterparts in non NF1 children. In contrast, the natural history and prognosis of adult brainstem gliomas in NF1 are nearly unknown. MATERIAL AND METHODS We conducted a retrospective analysis of medical records and MRI of adult NF1 patients followed for a brainstem glioma in 8 centers over a 17 years period (2000–2017). Clinical and imaging characteristics, management and outcome were analyzed. RESULTS Twenty five patients were included in the study (13 males and 12 females) with a median age of 32 (range 17–58). The epicenter of the tumor was located into the pons n=13 (52%), the mesencephalon n=7 (28%), the medulla oblongata n=5 (20%). On MRI, contrast enhancement was seen in 19 tumors (76%). Pathological examination was available in 13 tumors (52%) and showed a high grade astrocytoma (III or IV) in 9 tumors. Five patients were asymptomatic, 3 remained asymptomatic during the follow-up (median follow-up: 86 months, range 22–124). Twenty patients were symptomatic with a median duration of symptom of 2.5 months (range 1–10) before diagnosis. Among these symptomatic patients, 15 died from tumor progression despite treatment with radiation therapy and or chemotherapy. The median overall survival of symptomatic patients was 36 months. CONCLUSION Brainstem gliomas are rare tumors in adults with NF1. Unlike children, adult brainstem gliomas seem to have an unexpected poor prognosis, suggesting the disease may be different in adulthood.

First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression

First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression

Clinical Efficacy of CyberKnife Radiosurgery for Adult Brainstem Glioma: 10 Years Experience at Tianjin CyberKnife Center and Review of the Literature.

Background: Brainstem glioma is a rare brain tumor with poor prognosis and difficulty for surgical resection. We sought to retrospectively analyze and evaluate the clinical efficacy of CyberKnife for brainstem gliomas.Methods: From 2006 to 2015, a total of 21 brainstem gliomas patients who received CyberKnife radiosurgery treatment enrolled in this study and 18 patients with follow up. CyberKnife image-guided radiosurgical system were applied consecutively with the median prescribed total dose of 26 Gy (14–33 Gy) at two to six fractions on days utilizing CyberKnife system, and the median biological equivalent doses of 59.8 Gy (33.6–76.56 Gy). The clinic pathlogical features, survival were analyzed to explore the efficacy of CyberKnife radiosurgery in treatment of brainstem glioma.Results: With median follow-up of 54.5 months, patients with brainstem gliomas had median overall survival of 19 months, five patients still alive. The primary endpoints of the 1- and 2-year overall survival rates were 87.5 and 52.4%, respectively. During the treatment course, six patients were observed to have pseudoprogression with mass effect on MRI. Four patients developed radiation complications. Grade 2 radiation-related toxicity were observed in three patients and one patient with grade 3.Conclusion: The efficacy of brainstem gliomas—treated with CyberKnife is efficacious with mild toxicity.

Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and Prognosis.

Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.

Value of 18F-FET PET in adult brainstem glioma

PurposeTo investigate 18F-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) imaging characteristics of adult brainstem glioma (BSG). Materials and methodsFET-PET imaging and progression-free survival (PFS) of 16 adult patients with BSG was analyzed (9 high-grade gliomas, 7 low-grade gliomas). SUVmax, TBR, and time activity curves of FET-PET were calculated. ResultsProgressive gliomas had higher SUVmax (3.57 ± 1.47 vs. 1.60 ± 0.51; p = 0.003) and TBRmax (3.00 ± 1.12 vs. 1.36 ± 0.33; p = 0.001) than stable gliomas. Kaplan-Meier analysis showed longer PFS of tumors with TBRmax < 2.0 compared to tumors with TBRmax > 2.0 (665 ± 32 days versus 220 ± 39 days; p < 0.001). ConclusionFET-PET uptake might be associated with disease progression in adult BSG.