Rare Case of Mosaicism in a Glioblastoma Harboring NTRK Fusion and PDGFRA Amplification
Posted: Tuesday, August 17, 2021
Daniel J. Shepherd, MD, PhD, of Massachusetts General Hospital, Boston, and colleagues presented reportedly the first case of mosaicism in glioblastoma harboring both an NTRK2 fusion and platelet-derived growth factor receptor alpha (PDGFRA) amplification. Published in The Oncologist, this case highlights the possible effectiveness of NTRK-targeted therapy (larotrectinib and entrectinib) for cancers involving NTRK fusions.
A 26-year-old man presented with worsening right extremity weakness, fatigue, difficulty with expressive language, and loss of coordination. He was right-hand dominant and had an unremarkable medical history. An MRI displayed a heterogeneously enhancing 3.5-cm mass in the left frontal lobe with T2 signal abnormality.
Biopsy revealed a densely cellular tumor made up of epithelioid cells with large pleomorphic nuclei and microvascular proliferation, indicative of glioblastoma. Molecular testing identified copy number loss of CDKN2A, two variants in TP53, and a KANK1-NTRK2 gene fusion. The patient was administered levetiracetam and corticosteroids for seizure prophylaxis and underwent subsequent bulky tumor resection; the tumor was found to be unresectable, and he was discharged to inpatient rehabilitation 3 days after surgery.
The patient was administered temozolomide and concurrent radiotherapy for 6 weeks. A post-treatment MRI displayed residual enhancement of the tumor without evidence of significant disease progression. The TKR receptor larotrectinib was administered shortly thereafter. An MRI on day 49 showed a response to treatment, with the residual enhancing mass lesion decreasing from 25 to 10 mm. In addition, the patient experienced a slight improvement in motor weakness.
An MRI performed on day 106 displayed disease progression, and the patient was experiencing seizures. Biopsy confirmed recurrent/residual glioblastoma, and the TRK inhibitor entrectinib was administered. Surprisingly, a solid fusion assay no longer identified a KANK1-NTRK2 fusion, although new amplifications in PDGFRA and MYCN were revealed. The patient was taken off entrectinib and began treatment with nivolumab plus bevacizumab. However, the disease was aggressive and refractory to treatment, and the patient died 380 days after diagnosis.
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