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  • 1.  Clinical case

    Posted 7 days ago

    ID: 30M presenting with headaches and new-onset seizure

    PMHx: None

    Exam: Neurologically intact

    Course: MRI reviewed a large frontotemporal enhancing mass suspicious for high grade glioma. Underwent maximal safe resection. Pathology consistent with epithelioid glioblastoma, IDH-wildtype. MGMT promoter methylated. NGS identified a BRAF V600E mutation.

    Question: Would you favour standard Stupp chemoradiation and reserve BRAF/MEK inhibition for recurrence, or incorporate targeted therapy upfront in the adjuvant setting? Would you consider concurrent BRAF/MEK inhibition with radiation, or only after completion of radiation?



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    Kevin Wang
    Princess Margaret Cancer Centre
    Toronto ON
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  • 2.  RE: Clinical case

    Posted 6 days ago

    Kevin, very interesting case. BRAF mutant gliomas in adults (even young ones) unfortunately have poor prognosis in general despite the BRAF/MEK inhibitors. Starting BRAF/MEK inhibitor upfront is likely going to induce resistance quickly.


    These patients tend to develop leptomeningeal disease, and quick resistance to targeted therapy. Was the tumor (contrast enhancing portion) removed completely? My prediction is (but I may be wrong) is that it was well encapsulated and likely did not appear as diffuse as usual GBMs in the operating room; was it stuck on the dura or close to CSF cisterns/ventricles? 
    If so, has the patient received a pan spine MRI? Do you have access to liquid biopsy assays in the CSF? I have had patients with GBM and PXA grade III with BRAF V600E that did worse than standard GBM in young individuals. In the case of PXA Grade III, after a GTR of the mass and standard Supp protocol, I run BRAF V600E ddPCR assay in her CSF before she developed imaging concerning for leptomeningeal disease and at the time of symptom onset (headaches and neck pain) and she had BRAF mutation present in her CSF. Was the tumor completely removed here? If there is any concern for leptomeningeal disease argument could be made for pan spine and brain radiation. Interested to hear other people's thoughts that have treated tumors like these.

    Dimitrios Mathios 

    Washington University in St Louis

    Siteman Cancer Center



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    Dimitrios Mathios
    Washington University in St. Louis
    St Louis MO
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  • 3.  RE: Clinical case

    Posted 3 days ago
    Dear Dr. Wang, thank you for sharing this case. Given the presence of MGMT promoter methylation, consider proceeding with the standard concurrent radiotherapy and temozolomide regimen, followed by adjuvant temozolomide. In the setting of recurrence, or potentially as maintenance therapy after completion of the standard chemotherapy protocol, consideration could be given to BRAF/MEK inhibitors. In general, concurrent administration of BRAF/MEK inhibitors with radiation therapy is preferably avoided.


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    Sonikpreet Aulakh
    Associate Professor
    West Virginia University
    Morgantown WV
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