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BRAF-Targeted Therapy in the Treatment of BRAF-Mutant High-Grade Gliomas in Adults

Tanner M. Johanns, George Ansstas, and Sonika Dahiya

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Successful Use of BRAF/MEK Inhibitors as a Neoadjuvant Approach in the Definitive Treatment of Papillary Craniopharyngioma

Karam Khaddour, Michael R. Chicoine, Jiayi Huang, Sonika Dahiya, and George Ansstas

Craniopharyngiomas are rare tumors that arise in the suprasellar region of the brain and are known for their aggressive nature despite their WHO grade I. This is due to the complex neuroanatomy of the sellar/suprasellar region and their proximity to the optic nerve apparatus, hypothalamic–pituitary tract, and other critical neuroanatomical structures. Definitive treatment is based on a multidisciplinary approach and often involves a combination of surgical, radiation, and medical therapy. However, there is high morbidity associated with surgery and RT due to the complex neuroanatomy of this region. Recently, BRAF V600E somatic mutation has been identified in most papillary craniopharyngiomas. This discovery has led to the novel use of RAF pathway inhibitors to treat these tumors. We report the successful use of dabrafenib (BRAF inhibitor) and trametinib (mitogen-activated protein kinase kinase inhibitor) in the neoadjuvant setting followed by definitive stereotactic radiosurgery. We propose an algorithm based on available literature on the integration of targeted therapy in the management of papillary craniopharyngiomas. Our observations, together with prior case reports, advocate the incorporation of targeted therapy for unresectable craniopharyngiomas and reinforce that treatment with dual-targeted therapy is safe and effective.

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Rapid Clinical and Radiographic Response With Combined Dabrafenib and Trametinib in Adults With BRAF-Mutated High-Grade Glioma

Tanner M. Johanns, Cole J. Ferguson, Patrick M. Grierson, Sonika Dahiya, and George Ansstas

BRAF V600E mutations have been successfully treated with targeted therapy in melanoma, non–small cell lung cancer, and thyroid cancer. Interestingly, these mutations have also been identified in a subset of pediatric and adult brain tumors, with several cases reportedly responding to targeted therapy. However, these reports have been limited to single-agent BRAF inhibitor therapy and recurrent disease. Herein, we report dramatic clinical and radiographic responses to combination dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) in 2 adults with high-grade gliomas (HGGs), with 1 patient treated in the first-line setting. These observations, together with prior case reports, advocate for routine screening of BRAF point mutations in adult HGGs, and suggest that treatment with dual-targeted therapy, even in newly diagnosed cases, is safe and effective.