scholarly journals LGG-11. INSTITUTIONAL EXPERIENCE OF BRAF TARGETING THERAPY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii368-iii368
Author(s):  
Gino Bardi Lola ◽  
Mariko Sato
Keyword(s):  
Targeted Therapy ◽  
Adverse Events ◽  
Retrospective Chart Review ◽  
Mek Inhibitor ◽  
Common Side Effect ◽  
Low Grade ◽  
Targeting Therapy ◽  
Common Diagnosis ◽  
Institutional Experience ◽  
Severe Adverse Events

Abstract BACKGROUND The use of BRAF inhibitors is widely accepted in adult oncology as treatment for BRAF mutated cancers. BRAF alterations are frequently found in both pediatric low grade and high-grade gliomas, which has opened a new door to targeted therapies for pediatric gliomas. Targeted therapy drugs are associated with predictable patterns of adverse events. However treating in children may potentiate unique challenges. We present our institutional experience of targeted therapy with a focus on adverse events. METHODS We conducted a retrospective chart review of patients treated with BRAF and/or MEK inhibitors between 2015–2019. RESULTS There are nine patients treated with either MEK inhibitor(n=) or the combination therapy(n=). The most common diagnosis was Pilocytic astrocytoma. Targeted therapy was chosen as salvage therapy in all patients. The most common side effect was a pruritic erythematous rash, observed in 8 out of 9 patients. Cardiac toxicity (Grade 2, n=1) and GI toxicity (Grade 3, n=1) were found in patients treated with MEK inhibitor. Both cases resulted in cessation of therapy or significant decreased dose respectively. While two patients died due to progression of disease and two other continued to progress, 5 patients have demonstrated stable disease while on therapy. CONCLUSIONS Our study revealed the incidence of severe adverse events in two patients with BRAF targeted therapy. Due to the potential life-long use of targeted therapy, it is important to follow guidelines of adverse event monitoring and to develop a prevention and management strategy for severe adverse events.

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 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-16. TO BE PRECISE - KNOW YOUR TARGETS: INSTITUTIONAL EXPERIENCE WITH TUMOR TARGETED THERAPY FOR RECURRENT/PROGRESSIVE PEDIATRIC LOW-GRADE GLIOMA AND PLEXIFORM NEUROFIBROMA

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i35-i35
Author(s):  
Mackenzie Silverman ◽  
Joseph Piatt ◽  
Andrew Walter ◽  
Rahul Nikam ◽  
Gurcharanjeet Kaur
Keyword(s):  
Targeted Therapy ◽  
Targeted Therapies ◽  
Progressive Disease ◽  
Plexiform Neurofibroma ◽  
Cns Tumors ◽  
Low Grade ◽  
Therapy Initiation ◽  
Community Oncology ◽  
Institutional Experience ◽  
Pediatric Cns Tumors

Abstract Introduction The oncogenic drivers of pediatric CNS tumors are rapidly being identified with the implementation of high throughput genetic screening. Precision medicine approaches to treatment have shown promising results, but data remains limited in the community oncology setting. We aim to describe our institutional experience using targeted therapies for plexiform neurofibroma and recurrent/progressive pediatric low-grade glioma (pLGG). Methods We performed a retrospective chart review of all patients treated with tumor targeted therapies for recurrent/progressive pLGG and plexiform neurofibroma over the past 5 years. Results Ten patients treated with tumor targeted therapies were identified. Regimens included combination Dabrafenib and Trametinib (n=3), Trametinib monotherapy (n=2), Selumetinib (n=3), Vemurafenib (n=1), and Larotrectinib (n=1). Median age at therapy initiation was 11.5 years (range 1.1 - 18 years). Tumor molecular status included BRAFV600E mutation (n=4), NF1 mutation (n=2), KIAA1549-BRAF fusion (n=1), NACC-NTRK fusion (n=1), and FGFR1 mutation (n=1). Patients trialed an average of 2 treatment regimens prior to targeted therapy initiation (range 0–5). Mean duration of therapy was 14.5 months (range .5–33 months) with 8 patients remaining on treatment. Based on modified RANO criteria, responses included partial (n=1), stable disease (n=8), and progressive disease (n=1). Progressive disease was noted after 4 months of treatment with Dabrafenib and Trametinib combination therapy, but rate of tumor growth was decreased. Subjective functional improvement was seen in 50% of patients. The most common toxicities included rash (n=5) and pyrexia (n=2). Trametinib was discontinued in one patient due to intra-tumoral hemorrhage of unclear etiology. Conclusion Treatment of pediatric CNS tumors with targeted agents appears to be feasible and efficacious in the community oncology setting. Multi-institutional clinical trials are currently ongoing for each of these therapies. There remains a need for community oncology institutional data regarding their use.

Complications of Head Immobilization Devices in Children: Contact Mechanics, and Analysis of a Single Institutional Experience

Neurosurgery ◽  
2017 ◽  
Vol 82 (5) ◽  
pp. 678-685 ◽  
Author(s):  
Mohamed A Zaazoue ◽  
Mostafa Bedewy ◽  
Liliana C Goumnerova
Keyword(s):  
Adverse Events ◽  
Obstructive Hydrocephalus ◽  
Skull Fracture ◽  
Retrospective Chart Review ◽  
Neurological Deficits ◽  
Neurosurgical Procedures ◽  
Age At Surgery ◽  
Risk Patients ◽  
Institutional Experience ◽  
Precautionary Measures

Abstract BACKGROUND Head immobilization devices (HIDs) are a staple of neurosurgical procedures, including in the intraoperative magnetic resonance imaging (iMRI) operating rooms (ORs) where material modifications were necessary for compatibility with the magnets utilized. OBJECTIVE To present the experience in this OR environment and discuss the multifactorial nature of the observed adverse events. METHODS A retrospective chart review was performed, utilizing the Department of Neurosurgery and iMRI OR databases to identify patients who suffered complications related to HIDs between November 2007 and March 2016. A literature review was also done to identify the magnitude of the problem and the availability of safety guidelines. RESULTS Nine hundred and forty patients underwent surgery in the iMRI OR requiring head immobilization. Seven (0.7%) suffered complications related to the HID—depressed skull fractures (n = 7) and epidural hematomas (n = 6). Age at surgery ranged from 1.6 to 10.3 yr. All patients had posterior fossa neoplasms and associated obstructive hydrocephalus. Four patients (57%) suffered permanent neurological deficits. Six patients (86%) underwent a surgical procedure to evacuate the epidural hematomas and repair the depressed skull fracture. In contrast, 1 out of 445 patient (0.2%) suffered HID-related adverse events in the conventional ORs, aged 10.2 yr. CONCLUSION HIDs are important to provide stability and support during neurosurgical procedures. Modifications in the material or the shape of the pins can significantly change the pressure exerted. Most of these complications are preventable if certain precautionary measures are taken especially in certain high-risk patients, and the overall benefits of HIDs continue to outweigh the risks. There is a need for consensus on guidelines for the safe use of these devices.

scholarly journals LGG-23. EXCELLENT CLINICAL / RADIOLOGICAL RESPONSE TO BRAF INHIBITION IN A YOUNG CHILD WITH IN-OPERABLE SUPRA-SELLAR PILOCYTIC ASTROCYTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii370-iii371
Author(s):  
Stacy Chapman ◽  
Demitre Serletis ◽  
Colin Kazina ◽  
Mubeen Rafay ◽  
Sherry Krawitz ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Pilocytic Astrocytoma ◽  
Clinical Symptoms ◽  
Obstructive Hydrocephalus ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Low Grade ◽  
Dramatic Improvement ◽  
Chemotherapeutic Regimen ◽  
Response To Chemotherapy

Abstract In-operable low grade gliomas (LGG) in the pediatric population continue to present a treatment dilemma. Due to the low-grade nature of these tumors, and variable response to chemotherapy / radiation, the choice of adjuvant treatment is difficult. Overall survival is directly related to the degree of surgical resection, adding complexity to these inoperable tumors. Current chemotherapeutic regimen for these inoperable tumors includes vincristine (VCR) and carboplatin (Carbo). With advancements in the molecular characterization of gliomas, the role of targeted therapy has come into question. We present a 2-year-old female with biopsy proven Pilocytic Astrocytoma (positive BRAF-V600E mutation) involving the hypothalamic/optic chiasm region. She presented with ataxic gait, bi-temporal hemianopia, obstructive hydrocephalus and central hypothyroidism, which progressed to altered consciousness, and right hemiparesis due to location/mass effect of the tumor. She was initially treated with chemotherapy (VCR/Carbo) but her tumor progressed at 6 weeks of treatment. As her tumor was positive for BRAF-V600E mutation, she was started on Dabrafenib monotherapy, resulting in dramatic improvement in her clinical symptoms (able to stand, improved vision), and a 60% reduction in tumor size at 3-months. At 6-months, follow up MRI showed slight increase in the solid portion of the tumor, with no clinical symptoms. We plan to add MEK inhibitor (Trametinib) and continue with Dabrafenib. Our experience and literature review suggests that LGG with BRAF-V600E mutations may benefit from upfront targeted therapy. Prospective clinical trials comparing the efficacy of BRAF inhibitors versus standard chemotherapy in LGG with BRAF mutations are urgently needed.

scholarly journals Development of a Multidisciplinary Aerodigestive Program: An Institutional Experience

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 535
Author(s):  
Seung Kim ◽  
Mireu Park ◽  
Eunyoung Kim ◽  
Ga Eun Kim ◽  
Jae Hwa Jung ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chart Review ◽  
Retrospective Chart Review ◽  
Multidisciplinary Management ◽  
Neurologic Disease ◽  
Institutional Experience ◽  
Swallowing Difficulty ◽  
The Common ◽  
Chronic Comorbidities

We share our experience on the implementation of a multidisciplinary aerodigestive program comprising an aerodigestive team (ADT) so as to evaluate its feasibility. We performed a retrospective chart review of the patients discussed at the monthly ADT meetings and analyzed the data. A total of 98 children were referred to the ADT during the study period. The number of cases increased steadily from 3.5 cases per month in 2019 to 8.5 cases per month in 2020. The median age of patients was 34.5 months, and 55% were male. Among the chronic comorbidities, neurologic disease was the most common (85%), followed by respiratory (36%) and cardiac (13%) disorders. The common reasons for consultation were suspected aspiration (56%), respiratory difficulty (44%), drooling/stertor (30%), regurgitation/vomiting (18%), and feeding/swallowing difficulty (17%). Following discussions, 58 patients received active interventions, including fundoplication, gastrostomy, laryngomicrosurgery, tracheostomy, and primary dilatation of the airway. According to the questionnaire of the caregiver, the majority agreed that the main symptoms and quality of life of patients had improved (88%), reducing the burden on caregivers (77%). Aerodigestive programs may provide comprehensive and multidisciplinary management for children with complex airway and digestive tract disorders.

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