scholarly journals A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1–associated pediatric low-grade glioma: a Neurofibromatosis Clinical Trials Consortium study

2020 ◽  
Vol 22 (10) ◽  
pp. 1527-1535 ◽  
Author(s):  
Nicole J Ullrich ◽  
Sanjay P Prabhu ◽  
Alyssa T Reddy ◽  
Michael J Fisher ◽  
Roger Packer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Neurofibromatosis Type 1 ◽  
Mtor Inhibitor ◽  
Neurofibromatosis Type ◽  
Mtor Pathway ◽  
Pharmacokinetic Parameters ◽  
Low Grade ◽  
Nerve Sheath Tumor ◽  
Pathway Inhibition

Abstract Background Activation of the mammalian target of rapamycin (mTOR) pathway is observed in neurofibromatosis type 1 (NF1) associated low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied in this population. We evaluate the efficacy of the orally administered mTOR inhibitor everolimus for radiographically progressive NF1-associated pediatric LGGs. Methods Children with radiologic-progressive, NF1-associated LGG and prior treatment with a carboplatin-containing chemotherapy were prospectively enrolled on this phase II clinical trial to receive daily everolimus. Whole blood was analyzed for everolimus and markers of phosphatidylinositol-3 kinase (PI3K)/mTOR pathway inhibition. Serial MRIs were obtained during treatment. The primary endpoint was progression-free survival at 48 weeks. Results Twenty-three participants (median age, 9.4 y; range, 3.2–21.6 y) were enrolled. All participants were initially evaluable for response; 1 patient was removed from study after development of a malignant peripheral nerve sheath tumor. Fifteen of 22 participants (68%) demonstrated a response, defined as either shrinkage (1 complete response, 2 partial response) or arrest of tumor growth (12 stable disease). Of these, 10/15 remained free of progression (median follow-up, 33 mo). All remaining 22 participants were alive at completion of therapy. Treatment was well tolerated; no patient discontinued therapy due to toxicity. Pharmacokinetic parameters and pre-dose concentrations showed substantial between-subject variability. PI3K/mTOR pathway inhibition markers demonstrating blood mononuclear cell mTOR pathway inactivation was achieved in most participants. Conclusion Individuals with recurrent/progressive NF1-associated LGG demonstrate significant disease stability/shrinkage during treatment with oral everolimus with a well-tolerated toxicity profile. Everolimus is well suited for future consideration as upfront or combination therapy in this patient population.

Malignant Peripheral Nerve Sheath Tumor Arising from a Solitary Neurofibroma in a Patient without Neurofibromatosis Type 1

2016 ◽  
Vol 78 (5) ◽  
pp. 516-521
Author(s):  
Fumihisa SAWADA ◽  
Eiichi MAKINO ◽  
Takenobu YAMAMOTO ◽  
Ryo TANAKA ◽  
Yutaka FUJIWARA ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumor ◽  
Nerve Sheath ◽  
Solitary Neurofibroma

scholarly journals Malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1

2017 ◽  
Vol 75 (6) ◽  
pp. 366-371 ◽  
Author(s):  
Roberto André Torres de Vasconcelos ◽  
Pedro Guimarães Coscarelli ◽  
Regina Papais Alvarenga ◽  
Marcus André Acioly
Keyword(s):  
Overall Survival ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Tumor Size ◽  
Retrospective Chart Review ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

ABSTRACT Objective In this study, we review the institution’s experience in treating malignant peripheral nerve sheath tumors (MPNSTs). A secondary aim was to compare outcomes between MPNSTs with and without neurofibromatosis type 1 (NF1). Methods Ninety-two patients with MPNSTs, over a period of 20 years, were reviewed. A retrospective chart review was performed. The median age was 43.5 years (range, 3–84 years) and 55.4% were female; 41 patients (44.6%) had NF1-associated tumors. Results Mean tumor sizes were 15.8 ± 8.2 cm and 10.8 ± 6.3 cm for patients with and without NF1, respectively. Combined two- and five-year overall survival was 48.5% and 29%. Multivariate analysis confirmed the association of tumor size greater than 10 cm (hazard ratio (HR) 2.99; 95% confidence interval (CI) 1.14–7.85; p = 0.0258) and presence of NF1 (HR 3.41; 95%CI 1.88–6.19; p < 0.001) with a decreased overall survival. Conclusion Tumor size and NF1 status were the most important predictors of overall survival in our population.

Primary malignant peripheral nerve sheath tumor of the lung in a young child without neurofibromatosis type 1

2006 ◽  
Vol 47 (5) ◽  
pp. 636-638 ◽  
Author(s):  
Samar A. Muwakkit ◽  
Carlos Rodriguez-Galindo ◽  
Ahmad I. EL Samra ◽  
Ruby Khoury ◽  
Samir R. Akel ◽  
...  
Keyword(s):  
Young Child ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumor ◽  
Nerve Sheath

scholarly journals Lung parenchima changes in neurofibromatosis type 1

2016 ◽  
Vol 73 (2) ◽  
pp. 202-204
Author(s):  
Aleksandra Ilic ◽  
Snezana Raljevic ◽  
Tatjana Adzic ◽  
Vesna Skodric-Trifunovic ◽  
Jelena Stanimirovic
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Case Report ◽  
Neurofibromatosis Type 1 ◽  
Single Gene ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
X Rays ◽  
Neurogenic Tumors

Introduction. Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is one of the most common single-gene disorders (mutation on chromosome 17q) and usually associated with cutaneous, musculoskeletal and neurological disorders in humans. NF1 is generally complicated with one or more neurobehavioral disorders or tumors located in the peripheral nervous system such as neurofibromas, peripheral nerve sheath tumor, pheochromocytoma, etc. In the available medical literature, the thoracic manifestations of NF1 have been rarely described in these patients. There are few reports about intrathoracic neurogenic tumors, kyphoscoliosis, pneumonitis and pulmonary fibrosis in patients with NF1. Case report. A 65-year-old female was admitted to the Intensive Care Unit at the Lung Clinic of Belgrade University Clinical Center of Serbia. The patient?s general condition was poor with shortness of breath and present cyanosis. At the same time, the skin changes similar to NF1 were noticed, which were additionally documented by her medical history and diagnosed as NF1. After the application of noninvasive mechanical ventilation and other emergency respiratory medicine measures, the patient soon felt better. The parenchymal changes were viewed by subsequent X-rays and CT scanning of the thorax. Conclusion. This is a case report presenting the NF1 associated with the abnormality of lung parenchyma established during diagnostic procedures at the Intensive Care Unit, Clinic of Pulmonology.

Intracerebral malignant peripheral nerve sheath tumor in a child with neurofibromatosis Type 1 and middle cerebral artery aneurysm treated with endovascular coil embolization

2011 ◽  
Vol 8 (4) ◽  
pp. 346-352 ◽  
Author(s):  
Michael J. Ellis ◽  
Samuel Cheshier ◽  
Sunjay Sharma ◽  
Derek Armstrong ◽  
Cynthia Hawkins ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Neurofibromatosis Type 1 ◽  
Coil Embolization ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Nerve Sheath ◽  
Endovascular Coil Embolization

Among the neoplastic conditions that affect patients with neurofibromatosis Type 1 (NF1) are malignant peripheral nerve sheath tumors (MPNSTs), which typically arise from peripheral nerves of the limbs, trunk, and lumbar and brachial plexuses. Ionizing radiation is an established risk factor for MPNST development, especially in susceptible patients such as those with NF1. Patients with NF1 are also at risk for intracranial aneurysms, which are increasingly being successfully managed with endovascular therapies. The authors describe the case of a 9-year-old, previously healthy girl who presented in extremis with a right frontal intracerebral hemorrhage resulting from a ruptured right middle cerebral artery (MCA) trifurcation aneurysm. Following urgent decompressive craniectomy, the patient underwent endovascular coil embolization of the MCA aneurysm without complication. Given her mother's history of NF1, the child underwent genetic testing, which disclosed signs positive for NF1. The patient recovered well, but follow-up MR imaging and MR angiography performed at 14 months demonstrated a large frontotemporal mass encasing the right MCA trifurcation. The patient underwent frontotemporal craniotomy and subtotal resection of the mass, which was histologically found to be an intracranial MPNST. The patient received chemotherapy and focal radiation therapy and remains alive at 6 months postresection. To the authors' knowledge, this represents the only known case of intracranial neoplasm arising in the region of an intracranial aneurysm repaired by endovascular coil embolization. While patients with NF1 represent a population with genetic susceptibility to radiation-induced tumors, the pathogenesis of intracerebral MPNSTs remains poorly understood.

scholarly journals Brain tumors in neurofibromatosis type 1

2019 ◽  
Vol 2 (Supplement_1) ◽  
pp. i85-i97
Author(s):  
Amanda De Andrade Costa ◽  
David H Gutmann
Keyword(s):  
Tumor Growth ◽  
Neurofibromatosis Type 1 ◽  
Vision Loss ◽  
Critical Role ◽  
Neurofibromatosis Type ◽  
Therapeutic Drug ◽  
Low Grade ◽  
Increased Risk ◽  
Genetically Engineered Mice

Abstract AbstractAs a cancer predisposition syndrome, individuals with neurofibromatosis type 1 (NF1) are at increased risk for the development of both benign and malignant tumors. One of the most common locations for these cancers is the central nervous system, where low-grade gliomas predominate in children. During early childhood, gliomas affecting the optic pathway are most frequently encountered, whereas gliomas of the brainstem and other locations are observed in slightly older children. In contrast, the majority of gliomas arising in adults with NF1 are malignant cancers, typically glioblastoma, involving the cerebral hemispheres. Our understanding of the pathogenesis of NF1-associated gliomas has been significantly advanced through the use of genetically engineered mice, yielding new targets for therapeutic drug design and evaluation. In addition, Nf1 murine glioma models have served as instructive platforms for defining the cell of origin of these tumors, elucidating the critical role of the tumor microenvironment in determining tumor growth and vision loss, and determining how cancer risk factors (sex, germline NF1 mutation) impact on glioma formation and progression. Moreover, these preclinical models have permitted early phase analysis of promising drugs that reduce tumor growth and attenuate vision loss, as an initial step prior to translation to human clinical trials.

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