Dramatic clinical and radiographic response to BRAF inhibition in a patient with progressive disseminated optic pathway glioma refractory to MEK inhibition

Bavle, Abhishek; Jones, Jeremy; Lin, Frank; Malphrus, Amy D.; Adesina, Adekunle M.; Su, Jack

doi:10.1080/08880018.2017.1360971

Cited by 20 publications

(16 citation statements)

References 20 publications

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“…BRAF inhibitors, including vemurafenib and dabrafenib, have proved successful either alone or in conjunction with trametinib, an inhibitor of another MAPK member MEK, to treat adults with papillary craniopharyngioma, resulting in tumor shrinkage with good tolerability [2,5,24,25]. In addition, increasing pediatric data is emerging for BRAF and MEK inhibitors in the treatment of surgically inaccessible gliomas that express BRAF V600E mutations, with an acceptable side effect profile in this age group [1,3,4,16,18,29]. While initial results are promising, long-term safety data is lacking as is knowledge on the longevity of therapy required.…”

Section: Discussionmentioning

confidence: 99%

Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature

et al. 2018

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Introduction Craniopharyngiomas are one of the most frequently diagnosed hypothalamo-pituitary tumors in childhood. The adamantinomatous histological subtype accounts for most pediatric cases, while the papillary variant is almost exclusively diagnosed in adults. Here, we report a case of papillary craniopharyngioma in a very young child, confirmed by molecular tissue analysis. Case report A 4-year-old girl was being investigated for symptomatic central hypothyroidism. Brain MR imaging revealed a large solid/cystic suprasellar mass, splaying the optic chiasm and measuring 3 × 1.9 × 2.3 cm. The patient underwent a transsphenoidal near total resection of the lesion, which was encased within a tumor capsule. Post-operatively, the patient developed transient diabetes insipidus but otherwise recovered well. The pathology of the lesion was consistent with a papillary craniopharyngioma with regions of stratified squamous epithelium accompanied by superficial goblet cells and ciliated cells. Subsequent next-generation sequencing analysis of the lesion confirmed the presence of a BRAF V600E mutation (BRAFc.1799T>A p. (Val600Glu). To date, she remains free from progression 1 year following surgery. Conclusion This is the youngest case published to date of papillary craniopharyngioma with a confirmed BRAF V600E mutation. The case encourages discussion about the most appropriate adjuvant therapy for tumor progression in such cases, given the risks of radiotherapy to the developing brain and the increasing availability of oral BRAF inhibitor therapy.

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Section: Discussionmentioning

confidence: 99%

Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature

et al. 2018

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“…Both dabrafenib and vemurafenib are FDA-approved in the treatment of BFAF V600E/K -mutated melanoma. Case reports describing dramatic responses to dabrafenib in infants and children with recurrent LGG that harbor BRAF V600E mutations(42, 43) led to an ongoing multi-institutional phase I/IIa trial (NCT01677741) of dabrafenib in children with recurrent BRAF V600 mutated solid tumors. Thirty-two children with pLGG have been enrolled.…”

Section: Targeted Treatments For Pediatric Lggmentioning

confidence: 99%

Management of pediatric low-grade glioma

Blank

Bandopadhayay

Haas‐Kogan

et al. 2019

Current Opinion in Pediatrics

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Purpose of review: Pediatric low-grade gliomas have been treated with similar therapies for the last 30 years. Recent biological insights have allowed a new generation of targeted therapies to be developed for these diverse tumors. At the same time, technological advances may redefine the late toxicities associated with radiation therapy. Understanding recent developments in pediatric low-grade glioma therapy is essential to the management of these common pediatric tumors. Recent findings: It is now well understood that aberrations of the MAPK pathway are key to oncogenesis in low-grade gliomas. This understanding, along with the development of available targeted agents, have heralded a new era of understanding and treatment for these patients. Promising, sustained responses are now being seen in early phase trials among patients with multiply recurrent/progressive disease. Also, newer and highly conformal radiation approaches such as proton beam radiotherapy maintain efficacy of radiation but limit radiation-associated toxicities. Summary: Novel therapies offer the potential for tumor control with greatly reduced toxicities. However, late effects of these therapies are just now being explored. Improved radiation approaches and targeted agents have the potential to redefine traditional therapy for pediatric low-grade glioma.

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“…Loss of function of PTEN (phosphatase and tensin homolog) which is the main negative PI3K regulator or PI3K overactivation can lead to malignant tumor behavior (11). The aforementioned pathways present the basis for tailoring of a more targeted molecular treatment with MAPK pathway being commonly targeted with BRAF or MEK inhibitors (16). EGFR pathway is also a very popular molecular treatment pathway usually through monoclonal antibodies that disrupt EGFR ligand binding (17).…”

Section: Molecular Biologymentioning

confidence: 99%

Paediatric gliomas: diagnosis, molecular biology and management

Blionas¹,

Giakoumettis²,

Klonou³

et al. 2018

Ann. Transl. Med.

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Paediatric gliomas represent the most common brain tumour in children. Early diagnosis and treatment greatly improve survival. Histological grade is the most significant classification system affecting treatment planning and prognosis. Paediatric gliomas depend on pathways and genes responsible for mitotic activity and cell proliferation as well as angiogenesis (MAPK, VEGF, EFGR pathways). Symptoms such as focal neurologic deficit or seizures can facilitate diagnosis, but they are not always present and therefore diagnosis is occasionally delayed. Imaging has adequate diagnostic accuracy (surpassing 90%), and novel imaging techniques such as MR spectroscopy and PET increase only slightly this percentage. Low grade gliomas (LGG) can be approached conservatively but most authors suggest surgical excision. High grade gliomas (HGG) are always operated with exception of specific contradictions including butterfly or extensive dominant hemisphere gliomas. Surgical excision is universally followed by radiotherapy and chemotherapy, which slightly increase survival. Inoperable cases can be managed with or without radiosurgery depending on location and size, with adjunctive use of radiotherapy and chemotherapy. Surgical excision must be aggressive and gross total resection (GTR) should be attempted, if possible, since it can triple survival. Radiosurgery is effective on smaller tumours of <2 cm. Surgical excision is always the treatment of choice, but glioma recurrences, and residual tumours in non-critical locations are candidates for radiosurgery especially if tumour volume is low. Management of recurrences includes surgery, radiosurgery and chemoradiotherapy and it should be individualized according to location and size. In combination with molecular targeted therapeutic schemes, glioma management will be immensely improved in the next years.

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Dramatic clinical and radiographic response to BRAF inhibition in a patient with progressive disseminated optic pathway glioma refractory to MEK inhibition

Cited by 20 publications

References 20 publications

Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature

Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature

Management of pediatric low-grade glioma

Paediatric gliomas: diagnosis, molecular biology and management

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