scholarly journals NFB-13. TRAMETINIB FOR PLEXIFORM NEUROFIBROMA AND RECURRENT LOW-GRADE GLIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii420-iii420
Author(s):  
Aimee Sato ◽  
Nathan Millard ◽  
Francisco Perez ◽  
Nicholas Vitanza ◽  
Sarah Leary
Keyword(s):  
Plexiform Neurofibroma ◽  
Retrospective Chart Review ◽  
Neurofibromatosis Type ◽  
Mek Inhibitor ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Inhibitor Therapy ◽  
Driver Mutations ◽  
Low Grade ◽  
Standard Clinical Practice

Abstract BACKGROUND Based on early clinical efficacy data, Seattle Children’s established a standard clinical practice for MEK inhibitor therapy for children with plexiform neurofibroma (PN) or recurrent low-grade glioma (LGG). METHODS Data were collected under an IRB-approved retrospective chart review. Trametinib was prescribed off-label at 0.025 mg/kg daily for up to two years. Physical exam and laboratory monitoring were monthly for 3 months, then every 3 months. Retinal examination, ECHO/ECG were every 3 months. Tumor response was evaluated by MRI every 3 months for LGG; imaging for PN was dependent on tumor location. RESULTS 30 patients received trametinib; 17 LGG, 16 PN (3 both); 22 with Neurofibromatosis, Type-1 (NF1); 16 female/15 male; median age 11 (range 4.1–22.6). Most common tumor location was optic pathway (n=11) and face/neck (n=10). Most common adverse events (AE) were dermatologic and gastrointestinal. Ten had dose interruption/reduction, only one discontinued therapy for AE. Six received dermatology specialty care for AE. With median follow-up of 12 months, only 3 patients had progression, one with NF1. One-year EFS was 100% for PN and 88%+7 for LGG. Driver mutations were identified in 9 of 10 tumors tested (5 BRAF fusion, 1 BRAFV600E, 1 FGFR1+NF1, 1 FGFR1+PTPN11, 1 NF1). Radiology review of response will be presented. CONCLUSIONS This real-world pediatric cohort supports efficacy and tolerability of MEK inhibitor therapy for short-term control of plexiform neurofibroma and low-grade glioma with and without NF1. Further studies are warranted to evaluate comparative efficacy, combination therapy and duration of therapy.

scholarly journals LGG-27. TARGETED THERAPY FOR PEDIATRIC LOW-GRADE GLIOMAS AND PLEXIFORM NEUROFIBROMAS WITH TRAMETINIB

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii371-iii371
Author(s):  
Tiffany Nguyen ◽  
Kathleen McMahon ◽  
Molly Hemenway ◽  
Jean Mulcahy Levy ◽  
Nicholas Foreman ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Retrospective Chart Review ◽  
Neurofibromatosis Type ◽  
Mek Inhibitor ◽  
Low Grade ◽  
Plexiform Neurofibromas ◽  
Low Grade Gliomas ◽  
Common Location ◽  
Best Response ◽  
The Face

Abstract BACKGROUND Targeted therapy aimed at modulating the RAS/RAF/MEK/ERK pathway is of increasing interest for patients with plexiform neurofibromas and low-grade gliomas. Trametinib is an FDA-approved MEK inhibitor that has little published pediatric experience to date. METHODS A retrospective chart review of patients treated with trametinib for low-grade gliomas (LGG) and/or plexiform neurofibromas (PN) between 2015–2018 was conducted at Children’s Hospital Colorado. Data collected included patient demographics, lesion location, Neurofibromatosis type 1 (NF1) status, best response of PN/LGG to trametinib, duration of trametinib therapy, and reported toxicities at least possibly attributed to trametinib. RESULTS Thirty (57% male; 73% NF1) patients were identified. Sixteen (53%) patients had PN only, 12 (40%) had LGG only, and two (7%) patients had both PN and LGG. The most common LGG location was the optic pathway/hypothalamus (72%). The most common location of PN was the face (63%). Two-thirds (8/12) of patients with LGG had a BRAF alteration or NF1 mutation. The median age at start of trametinib therapy was 9.9 years (range, 2.0 – 18.8 years). The median duration of trametinib therapy was 0.8 years (range 0.1 – 2.9 years). The most commonly reported adverse event was rash. No patients developed retinal toxicity or cardiotoxicity. Only two (7%) patients discontinued for toxicity and one (3%) for progressive disease. CONCLUSIONS Trametinib can be administered without significant toxicity to children with PN or LGG. Clinical benefit is noted in this cohort; however, prospective clinical trials are necessary to characterize efficacy formally.

scholarly journals Profound hearing loss following surgery in pediatric patients with posterior fossa low-grade glioma

2017 ◽  
Vol 5 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Yahya Ghazwani ◽  
Ibrahim Qaddoumi ◽  
Johnnie K Bass ◽  
Shengjie Wu ◽  
Jason Chiang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Posterior Fossa ◽  
Extent Of Resection ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Low Grade ◽  
Total Resection ◽  
Profound Hearing Loss

Abstract Background Hearing loss may occur in patients with posterior fossa low-grade glioma who undergo surgery. Methods We retrospectively reviewed 217 patients with posterior fossa low-grade glioma, including 115 for whom results of hearing tests performed after surgery and before chemotherapy or radiation therapy were available. We explored the association of UHL with age at diagnosis, sex, race, tumor location, extent of resection, posterior fossa syndrome, ventriculoperitoneal shunt placement, and histology. Results Of the 115 patients, 15 (13.0%: 11 male, 6 black, 8 white, 1 multiracial; median age 7 years [range, 1.3–17.2 years]) had profound UHL after surgery alone or before receiving ototoxic therapy. Median age at tumor diagnosis was 6.8 years (range, 0.7–14.1 years), and median age at surgery was 6.8 years (range, 0.7–14.1 years). Patients with UHL had pathology characteristic of pilocytic astrocytoma (n = 10), ganglioglioma (n = 4), or low-grade astrocytoma (n = 1). Of these 15 patients, 4 underwent biopsy, 1 underwent gross total resection, 1 underwent near-total resection, and 9 underwent subtotal resection. UHL was more frequent in black patients than in white patients (OR 7.3, P = .007) and less frequent in patients who underwent gross total resection or near-total resection than in those who underwent subtotal resection (OR 0.11, P = .02). Conclusions Children undergoing surgery for posterior fossa low-grade glioma are at risk for UHL, which may be related to race or extent of resection. These patients should receive postoperative audiologic testing, as earlier intervention may improve outcomes.

scholarly journals Neurologic impairments from pediatric low-grade glioma by tumor location and timing of diagnosis

2018 ◽  
Vol 65 (8) ◽  
pp. e27063 ◽  
Author(s):  
Zsila S. Sadighi ◽  
Elizabeth Curtis ◽  
Jennifer Zabrowksi ◽  
Catherine Billups ◽  
Amar Gajjar ◽  
...  
Keyword(s):  
Tumor Location ◽  
Low Grade Glioma ◽  
Low Grade

scholarly journals PEDT-02 DIAGNOSIS, TREATMENT AND CLINICAL OUTCOME OF ATYPICAL BRAINSTEM TUMOUR IN CHILDHOOD

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii16-ii16
Author(s):  
Takaaki Yanagisawa ◽  
Takaya Honda ◽  
Masatada Yamaoka ◽  
Masaharu Akiyama ◽  
Kohei Fukuoka ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Survival Data ◽  
Treatment Strategy ◽  
Retrospective Chart Review ◽  
Malignant Tumour ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Clinical Findings ◽  
Low Grade Glioma ◽  
Pathological Diagnosis ◽  
Low Grade

Abstract BACKGROUND Brainstem tumours account for 10–15% of brain tumors in childhood. Diffuse intrinsic pontine glioma (DIPG) accounts for 60–80% of them and are diagnosed based on clinical findings and radiologic features. All the rest of tumours excluding DIPG are very rare, heterogeneous group of tumours including low-grade glioma and malignant embryonal tumors. It is often difficult to diagnose and decide treatment strategy for their rarity. METHODS To present our experience with atypical brainstem tumours, a retrospective chart review was conducted to identify eligible cases treated over a ten-year period. All tumors involving brainstem, felt not to be DIPGs for absence of clinical/neuroimaging features were included. Demographic information, pathological findings, neuroimaging characteristics, surgical and nonsurgical management plans, and survival data were collected for analysis. RESULTS Between April 2007 and March 2017, 16 patients (14 initial and 2 recurrent) aged from 3 to 20 years were identified. 14 of them were symptomatic and 4 of them were asymptomatic at reference. Of 10 symptomatic cases, 10 were biopsied and pathological diagnosis was low-grade glioma in 8, glioblastoma in 2 cases. They had treatment depending on the pathological diagnosis. Of 4 asymptomatic cases, one with small focal tumour, with no findings suggesting malignant tumour with 11C-methioninePET or MRS, progressed to show typical clinical and image findings of DIPG in a year. For other three, they remain asymptomatic without progression with no treatment for 25months, 60months, and 65 months respectively. Malignant transformation was observed in one with biopsy-conformed oligoastrocytoma with no K27M-H3 mutations treated with chemotherapy and another with pilocytic astrocytoma treated with chemotherapy and radiotherapy. CONCLUSIONS Though molecular findings such as K27M-H3 mutations can predict clinical outcome in some cases, it still remains difficult to diagnose and find treatment strategy of atypical brainstem tumours. The need and usefulness of nationwide registry study is warranted.

scholarly journals P14.27 The significance of multicentric noncontrast-enhancing lesions distant from surgically resected glioblastoma: Case series of 3 patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii72-iii73
Author(s):  
J Hwang ◽  
H An ◽  
S Yoon ◽  
K Park
Keyword(s):  
Temporal Lobe ◽  
Multidisciplinary Treatment ◽  
Case Series ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Post Contrast ◽  
Poor Prognostic Factor ◽  
Prognostic Features ◽  
18Fdg Pet

Abstract BACKGROUND Glioblastoma is the most malignant primary brain tumor. The tumor location and multiplicity plays an important role in surgical and further treatment. The incidence of multiple lesions at the time of diagnosis was known as 1–20%, which showed a poor prognostic factor. Most researches has focused on multiple contrast-enhancing lesions, however, multicentric non-enhancing lesions distant from glioblastoma has been rarely evaluated. The authors reported the case series of the patient who showed multicentric non contrast-enhancing lesions without connection to histologically-proven glioblastoma. MATERIAL AND METHODS Multicentric non contrast-enhancing lesions were defined as areas of FLAIR hyperintensity and mass effect without post-contrast enhancement, separated from the histologically-proven glioblastoma in a newly diagnosed disease. Three patients who showed distant non-enhancing lesions with appearance of a multicentric low-grade glioma were included in this study. The typical enhancing lesions were surgically resected and standard chemo-radiotherapy was followed in all patients. RESULTS All patients were male and their age was 38, 60 and 65 years old respectively. Multicentric tumor location was as follows: Case 1, left frontal lobe with non-enhancing lesion in left parahippocampal gyrus; Case 2, left parietal with non-enhancing lesion in left anteromedial temporal lobe; Case 3, left thalamus with non-enhancing lesions in both basal frontal and right temporal lobe. Pathologically, the resected enhancing tumor revealed glioblastoma in 2 patients and diffuse midline glioma in 1. All tumors were IDH-wild type. The resected enhanced lesion showed no progression but all non-enhancing lesions developed contrast-enhancing tumors at 3, 13 and 17 months after initial treatment, with high tracer uptake on 18FDG-PET or 18FDOPA-PET. Despite multidisciplinary treatment, two patients died from disease progression at 30 and 32 months after diagnosis and one patient is still alive with overall survival of 15 months. CONCLUSION The appearance of multicentric non-enhancing lesions distant from a typically enhancing tumor showed an uncommon finding in glioblastoma and poor prognostic features. These lesions progress faster than expected for a low-grade glioma. These lesions should be distinguished from typical low-grade glioma and should be considered more advanced lesions than their appearances suggest.

Trametinib Induces Neurofibroma Shrinkage and Enables Surgery

2019 ◽  
Vol 50 (05) ◽  
pp. 300-303 ◽  
Author(s):  
Pia Vaassen ◽  
Nikola Dürr ◽  
Andreas Röhrig ◽  
Rainer Willing ◽  
Thorsten Rosenbaum
Keyword(s):  
Vertebral Column ◽  
Plexiform Neurofibroma ◽  
Neurofibromatosis Type ◽  
Mek Inhibitor ◽  
Suppressor Gene ◽  
Complete Disappearance ◽  
Therapeutic Success ◽  
Mek Inhibitors ◽  
Plexiform Neurofibromas ◽  
Peripheral Nerve Sheath Tumors

AbstractPlexiform neurofibromas are congenital peripheral nerve sheath tumors characteristic of neurofibromatosis type 1 (NF1)—a frequent neurocutaneous disorder caused by mutations of the NF1 tumor suppressor gene. Since plexiform neurofibromas are a major cause of the burden of disease and may also progress to malignancy, many efforts have been undertaken to find a cure for these tumors. However, neither surgery nor medication has so far produced a breakthrough therapeutic success. Recently, a clinical phase I study reported significant shrinkage of plexiform neurofibromas following treatment with the MEK inhibitor selumetinib. Here, we report an 11-year-old NF1 patient with a large plexiform neurofibroma of the neck that had led to a sharp-angled kinking of the cervical spine and subsequent myelopathy. Although surgical stabilization of the cervical vertebral column was urgently recommended, the vertebral column was inaccessible due to extensive tumor growth. In this situation, treatment with the MEK inhibitor trametinib was initiated which resulted in a 22% reduction in tumor volume after 6 months of therapy and finally enabled surgery. These data show that MEK inhibitors may not lead to complete disappearance of NF1-associated plexiform neurofibromas but can be an essential step in a multimodal therapeutic approach for these tumors. The course of our patient suggests that MEK inhibitors are likely to play a significant role in providing a cure for one of the most devastating manifestations of NF1.

scholarly journals LGG-17. CLINICAL OUTCOME OF PEDIATRIC LOW GRADE GLIOMA WITH POSITIVE BRAF-FUSION TREATED WITH MEK INHIBITOR

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i35-i35
Author(s):  
T L Ku Dennis ◽  
Anthony P Y Liu ◽  
Eric Fu ◽  
Chung-Wing Luk ◽  
Jeffrey P W Yau ◽  
...  
Keyword(s):  
Partial Response ◽  
Skin Reaction ◽  
Treatment Option ◽  
Clinical Symptoms ◽  
Mek Inhibitor ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Conventional Chemotherapy ◽  
Unresectable Tumor ◽  
Braf Fusion

Abstract Background Low grade glioma (LGG) is the most common central nervous system (CNS) tumor in children. Some are treated with surgery alone, while chemotherapy is given for unresectable tumor with clinical symptoms or progression. Conventional chemotherapy is effective but 30–40% patients may have reactivation of disease requiring re-treatment throughout lifetime. MEK inhibitor for BRAF-fusion positive LGG is a new treatment option for refractory cases. Methods Retrospective search in territory-wide pediatric oncology registry for children diagnosed with LGG from 2010–2020 in Hong Kong. To identify patients with molecular confirmed BRAF-fusion positive LGG and any treatment with MEK inhibitor. Results Twelve patients (N=12) were identified with BRAF-fusion positive LGG, male:female was 1:2, age 0.3–15.1yr (median 5.0yr) at presentation. The median follow up duration was 1.8yr. Five patients (42%) had surgical resection only. Seven patients (58%) were given chemotherapy with Carboplatin / Vincristine. Five out of seven (n=7) treated patients (71%) have partial response at their initial treatment. Two patients (29%) had progressive disease during treatment and switched to second-line chemotherapy, vinblastine however without improvement. Three patients required re-treatment as disease reactivation. Total five patients had refractory diseases were treated with MEK inhibitor, Trametinib including one diagnosed NF-1. All of them have adverse skin reaction and raised transaminase with one required dose reduction. They have been taking the MEK inhibitor for 0.1–3.3 yr with sustainable partial response. Conclusion Pediatric LGG has overall favourable prognosis. Some of them treated with surgery alone while conventional chemotherapy could also achieve satisfactory disease control. For refractory disease with BRAF-fusion positive, MEK inhibitor is a well tolerated treatment option showing sustainable partial response. However, prolonged medication and disturbing skin reaction are still a major concern for this group of patients. On-going clinical trials to compare conventional chemotherapy versus MEK inhibitor could give us more insight about the clinical benefit, patient selection and treatment duration.

JS01.4.A The neurocognitive function changes with awake craniotomy for low-grade glioma in the left hemispheric eloquent regions

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii5-ii5
Author(s):  
Y Wang ◽  
P Ji ◽  
S Guo ◽  
J Liu ◽  
Y Zhai ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Brain Mapping ◽  
Treatment Strategy ◽  
Cognitive Assessment ◽  
Tumor Resection ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Awake Craniotomy ◽  
Low Grade ◽  
Eloquent Area

Abstract BACKGROUND Cognitive deficit was frequently observed in glioma patients, especially for those on the eloquent area. Considering the increased life expectancy, brain mapping during awake craniotomy was preferentially applied to exacerbate neurocognitive deficits. The aim of the current study was to evaluate the neurocognitive changes during the perioperative period of resection of low-grade glioma (LGG) in the left side eloquent area with awake craniotomy in a major neurosurgical center in China for 5 years. MATERIAL AND METHODS We retrospectively analyzed patients with left-sided glioma in eloquent areas, who received awake craniotomy during 2016–2020. Montreal Cognitive Assessment Scale, BN-20, and EORTC-QLQ-C30 questionnaire were applied for neurological cognitive assessment. We performed a correlation analysis between changes in cognitive performance and tumor characteristics, including tumor location, pathological grade. Treatment-related factors were also analyzed, such as the extent of resection (EOR), preoperative and postoperative Karnofsky Performance Score (KPS), postoperative treatment strategy (chemo- and radiotherapy), progression-free survival (PFS), overall survival (OS). RESULTS 68 patients were included in our current study. For the language domain, memory domain, and executive functions, 7.4% (5/68) patients presented mild postoperative cognitive performance deterioration compared to preoperative. Tumor location was the only factor that greatly influenced the postoperative cognitive performance, while other features (EOR, KPS, pathological grades) and treatment strategy were found no effect on cognitive change. The extent of tumor resection ranged from 81% to 100%. CONCLUSION Our study underlines the importance of the application of brain mapping during awake craniotomy, which helps to maximize extent of tumor resection while preserving cognitive function in individuals with LGG in eloquent regions.

Sign in / Sign up

Export Citation Format

Share Document