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Cancers Nov 2021Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their... (Review)
Review
Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their spontaneous counterparts. Focus has shifted to therapy aimed at minimizing symptoms given the risks of persistent, multiple tumors and new tumor growth. In this review, we will highlight the translation of preclinical data to therapeutic trials for patients with neurofibromatosis, particularly neurofibromatosis type 1 and neurofibromatosis type 2. Successful inhibition of MEK for patients with neurofibromatosis type 1 and progressive optic pathway gliomas or plexiform neurofibromas has been a significant advancement in patient care. Similar success for the malignant NF1 tumors, such as high-grade gliomas and malignant peripheral nerve sheath tumors, has not yet been achieved; nor has significant progress been made for patients with either neurofibromatosis type 2 or schwannomatosis, although efforts are ongoing.
PubMed: 34885143
DOI: 10.3390/cancers13236032 -
No Shinkei Geka. Neurological Surgery May 2021Pediatric gliomas include various types of glioma broadly categorized as low- or hi-grade based on histopathological features. Clinically significant types include...
Pediatric gliomas include various types of glioma broadly categorized as low- or hi-grade based on histopathological features. Clinically significant types include cerebellar astrocytomas, optic pathway / hypothalamic pilocytic astrocytomas, and brainstem gliomas. Neurosurgical roles vary for different kinds of pediatric gliomas. Since these representative tumors remain rare, the patients should be directed toward facilities with experienced neurosurgeons. Radiotherapy and chemotherapy are very important as either adjuvant or primary treatment modalities. Recent advancements in molecular biology have revealed unique genetic aberrations in different types of pediatric gliomas. The RAS/MAPK pathway anomalies, including fusion and V600E mutation, are present in most low-grade gliomas. BRAF/MEK-inhibitors have yielded promising clinical study results. Diffuse midline gliomas, including diffuse intrinsic pontine gliomas, often harbor mutations such as H3K27M. Agents that target these molecular aberrations are unavailable. Because gliomas in infants are sub-categorized by their genetic abnormalities, novel agents targeting , , or fusions are promising treatments.
Topics: Astrocytoma; Brain Neoplasms; Child; Glioma; Humans; Infant; Protein-Tyrosine Kinases; Proto-Oncogene Proteins
PubMed: 34092570
DOI: 10.11477/mf.1436204438 -
Neurology India 2021The prevalence of hydrocephalus among patients with neurofibromatosis type I (NF1) is estimated to be between 1 and 13%. Aqueductal webs, chiasmatic-hypothalamic tumors,... (Review)
Review
The prevalence of hydrocephalus among patients with neurofibromatosis type I (NF1) is estimated to be between 1 and 13%. Aqueductal webs, chiasmatic-hypothalamic tumors, and thalamic mass effect related to NF changes are the common causes of NF1-related hydrocephalus. Brain tumors and moyamoya syndrome may mimic the clinical presentation of hydrocephalus in children with NF1, and should be ruled out while evaluating children with headaches. Treatment of NF1-related hydrocephalus should be personally tailored, including shunts, endoscopic procedures such as septostomy and third ventriculostomy, and tumor resection or debulking. Despite these personalized treatments, many of the primary treatments (including shunts and endoscopic procedures) fail, and patients should be screened and followed accordingly. In the current manuscript, we review the causes of NF1-related hydrocephalus, as well as treatment options.
Topics: Brain Neoplasms; Cerebral Aqueduct; Child; Humans; Hydrocephalus; Neurofibromatosis 1; Ventriculostomy
PubMed: 35102991
DOI: 10.4103/0028-3886.332254 -
Cells Sep 2023Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas,... (Review)
Review
Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.
Topics: Adult; Humans; Child; Neurofibromatosis 1; Optic Nerve Glioma; Brain Neoplasms; Hyperthermia, Induced; Immunotherapy; Tumor Microenvironment
PubMed: 37830595
DOI: 10.3390/cells12192380 -
World Neurosurgery Jun 2021Surgical management of gliomas is predicated on "safe maximal resection" across all histopathologic grades because progression-free survival and overall survival are... (Review)
Review
BACKGROUND
Surgical management of gliomas is predicated on "safe maximal resection" across all histopathologic grades because progression-free survival and overall survival are positively affected by the increasing extent of resection. Administration of the prodrug 5-aminolevulinic acid (5-ALA) induces tumor fluorescence with high specificity and sensitivity for malignant high-grade glioma (HGG). Fluorescence-guided surgery (FGS) using 5-ALA improves the extent of resection in the contrast-enhancing and nonenhancing tumor components in HGG. It has also shown preliminary usefulness in other central nervous system tumors, but with certain limitations.
METHODS
We review and discuss the state of 5-ALA FGS for central nervous system tumors and identify the limitations in its use as a guide for future clinical optimization.
RESULTS
5-ALA FGS provides maximum clinical benefits in the treatment of newly diagnosed glioblastoma. 5-ALA fluorescence specificity is limited in low-grade glioma, recurrent HGG, and non-glial tumors. Several promising intraoperative adjuncts to 5-ALA FGS have been developed to expand its indications and improve the clinical efficacy and usefulness of 5-ALA FGS.
CONCLUSIONS
5-ALA FGS improves the clinical outcomes in HGG. However, further optimization of the diagnostic performance and clinical use of 5-ALA FGS is necessary for low-grade glioma and recurrent HGG tumors. Neurosurgical oncology will benefit from the novel use of advanced technologies and intraoperative visualization techniques outlined in this review, such as machine learning, hand-held fibe-optic probes, augmented reality, and three-dimensional exoscope assistance, to optimize the clinical usefulness and operative outcomes of 5-ALA FGS.
Topics: Brain Neoplasms; Glioblastoma; Humans; Image Enhancement; Levulinic Acids; Microscopy, Fluorescence; Neuronavigation; Neurosurgery; Optical Imaging; Aminolevulinic Acid
PubMed: 33684574
DOI: 10.1016/j.wneu.2021.02.118 -
Frontiers in Oncology 2023Diencephalic tumors tend to be low grade tumors located near several critical structures, including the optic nerves, optic chiasm, pituitary, hypothalamus, Circle of... (Review)
Review
Diencephalic tumors tend to be low grade tumors located near several critical structures, including the optic nerves, optic chiasm, pituitary, hypothalamus, Circle of Willis, and hippocampi. In children, damage to these structures can impact physical and cognitive development over time. Thus, the goal of radiotherapy is to maximize long term survival while minimizing late effects, including endocrine disruption leading to precocious puberty, height loss, hypogonadotropic hypogonadism, and primary amenorrhea; visual disruption including blindness; and vascular damage resulting in cerebral vasculopathy. Compared to photon therapy, proton therapy offers the potential to decrease unnecessary dose to these critical structures while maintaining adequate dose to the tumor. In this article, we review the acute and chronic toxicities associated with radiation for pediatric diencephalic tumors, focusing on the use of proton therapy to minimize treatment-related morbidity. Emerging strategies to further reduce radiation dose to critical structures will also be considered.
PubMed: 37213290
DOI: 10.3389/fonc.2023.1123082 -
Neuro-oncology Aug 2023People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of...
BACKGROUND
People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research.
METHODS
Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified. Retrospective data were collated, and pathology was reviewed centrally.
RESULTS
Forty-five patients, comprising 23 females (51%), met eligibility criteria, with a median of age 37 (18-68 years) and performance status of 80% (30%-100%). Tissue was available for 35 patients. Diagnoses included infiltrating (low-grade) astrocytoma (9), glioblastoma (7), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), high-grade astrocytoma (3), WHO diagnosis not reached (4) and one each of gliosarcoma, ganglioglioma, embryonal tumor, and diffuse midline glioma. Seventy-one percent of tumors were midline and underwent biopsy only. All 27 tumors evaluated were IDH1-wild-type, independent of histology. In the 10 cases with molecular testing, the most common genetic variants were NF1, EGFR, ATRX, CDKN2A/B, TP53, TERT, and MSH2/3 mutation. While the treatments provided varied, the median overall survival was 24 months [2-267 months] across all ages, and 38.5 [18-109] months in individuals with grade 1-2 gliomas.
CONCLUSIONS
Non-OPGs in adults with NF1, including low-grade tumors, often have an aggressive clinical course, indicating a need to better understand the pathobiology of these NF1-associated gliomas.
Topics: Female; Humans; Adult; Neurofibromatosis 1; Retrospective Studies; Glioma; Astrocytoma; Brain Neoplasms; Disease Progression
PubMed: 36840626
DOI: 10.1093/neuonc/noad033 -
Frontiers in Oncology 2022The glioma-associated tumor microenvironment involves a multitude of different cells ranging from immune cells to endothelial, glial, and neuronal cells surrounding the... (Review)
Review
The glioma-associated tumor microenvironment involves a multitude of different cells ranging from immune cells to endothelial, glial, and neuronal cells surrounding the primary tumor. The interactions between these cells and glioblastoma (GBM) have been deeply investigated while very little data are available on patients with lower-grade gliomas. In these tumors, it has been demonstrated that the composition of the microenvironment differs according to the isocitrate dehydrogenase status (mutated/wild type), the presence/absence of codeletion, and the expression of specific alterations including H3K27 and/or other gene mutations. In addition, mechanisms by which the tumor microenvironment sustains the growth and proliferation of glioma cells are still partially unknown. Nonetheless, a better knowledge of the tumor-associated microenvironment can be a key issue in the optic of novel therapeutic drug development.
PubMed: 35875065
DOI: 10.3389/fonc.2022.891543 -
Pediatric Research Jan 2023Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to...
BACKGROUND
Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to tumor location and treatment modalities. We assessed the prevalence of endocrine dysfunction in children with OPGs and compared outcomes between those with and without NF1.
METHODS
We performed a retrospective medical record review of medical history, and clinical and laboratory data, of children diagnosed with OPGs (n = 59, 61% with NF1) during 1990-2020, followed at a tertiary endocrine clinic. Growth and puberty parameters and occurrence of endocrine dysfunction were evaluated.
RESULTS
Isolated optic nerve involvement was higher among patients with than without NF1. Patients without NF1 were younger at OPG diagnosis and more often treated with debulking surgery or chemotherapy. At the last endocrine evaluation, patients without NF1 had comparable height SDS, higher BMI SDS, and a higher rate of endocrine complications (78.3% vs. 41.7%, p = 0.006). Younger age at diagnosis, older age at last evaluation, and certain OPG locations were associated with increased endocrine disorder incidence.
CONCLUSIONS
Endocrine dysfunction was more common in patients without NF1; this may be related to younger age at presentation, tumor locations, a greater progressive rate, and more aggressive treatments.
IMPACT
The literature is sparse regarding sporadic OPGs, and the mean duration of follow-up is shorter than at our study. Our data show a higher rate of endocrine dysfunction in patients with OPGs than previously described. We also found a higher prevalence of endocrine dysfunctions among patients without compared to those with NF-1. A better understanding of the true prevalence of endocrine disabilities that may evolve along time can help in guiding physicians in the surveillance needed in patients with OPG.
Topics: Child; Humans; Neurofibromatosis 1; Retrospective Studies; Optic Nerve Glioma; Optic Nerve; Endocrine System Diseases
PubMed: 35538247
DOI: 10.1038/s41390-022-02098-5 -
Current Opinion in Oncology Nov 2019The current review summarizes recent advances on three important issues in neurofibromatosis type 1 (NF1) management: the identification of specific NF1 gene mutations... (Review)
Review
PURPOSE OF REVIEW
The current review summarizes recent advances on three important issues in neurofibromatosis type 1 (NF1) management: the identification of specific NF1 gene mutations predicting the risk for developing neurological malignancies; the molecular features of NF1-associated tumors and their differences from sporadic neoplasms; genetic, epigenetic, or microenviromental factors leading benign tumors to a malignant transformation in NF1.
RECENT FINDINGS
The association between the risk of developing optic pathway glioma and specific germiline NF1 mutations is still debated and further studies are needed with large, new cohorts of patients. The available evidences suggest that gliomas and malignant peripheral nerve sheath tumors (MPNSTs) in NF1 have a distinct genetic signatures, different from those observed in sporadic neoplasms. Some neoplasms, very rare in general population, such as subependymal giant cell astrocytoma, can be observed in NF1. A subgroup of low-grade NF1-gliomas, some MPNSTs and plexiform neurofibromas contain abundant T lymphocyte infiltrates suggesting that immunotherapy could be a potential therapeutic approach.
SUMMARY
These data support the notion that next-generation sequencing efforts are helpful in the genetic characterization of NF1-associated malignancies A better knowledge of those tumors at the genomic level, is essential for addressing new treatments and may contribute to a deeper comprehension of NF1/RAS signaling also in sporadic cancers.
Topics: Animals; Cell Transformation, Neoplastic; Germ-Line Mutation; Humans; Neurofibromatosis 1; Neurofibromin 1; Optic Nerve Glioma
PubMed: 31436563
DOI: 10.1097/CCO.0000000000000576