Ther-21. Targeting Lin28 With Dfmo in Patients With Etmr Suggests Clinical Benefit

Mitchell, Deanna; Durston, Mary; Nagulapally, Abhinav B.; Steinbrecher, Julie; Kraveka, Jacqueline M.; Ferguson, William S.; Eslin, Don; Brown, Valerie I.; Neville, Kathleen; Bergendahl, Genevieve; Sholler, Giselle L. Saulnier

doi:10.1093/neuonc/noz036.226

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“…Polyamines, regulated by ODC, modulate eIF-5A, which is a direct regulator of the LIN28/let-7 axis. 14 Case 2 received omburtamab, a murine IgG1 monoclonal antibody, in an attempt to deliver radioimmunotherapy through the CSF and avoid craniospinal irradiation, and Case 3 received intrathecal topotecan for CSF prophylaxis and everolimus as a targeted approach to downregulate mTOR signaling. 8 , 15 …”

Section: Discussionmentioning

confidence: 99%

A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes

Hanson

Hoffman

Nagabushan

et al. 2020

Neuro-Oncology Advances

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Background Embryonal tumor with multilayer rosettes (ETMR) is a rare CNS malignancy affecting young children that carries a very poor prognosis. Treatment with intensive surgical resection, radiotherapy, and high-dose chemotherapy is insufficient treatment in the vast majority of cases. Effective, biologically-based therapies for this tumor are therefore desperately needed. The Dana-Farber Cancer Institute modified IRS-III protocol incorporates pre-clinically active agents, such as doxorubicin and actinomycin D, into the treatment regimen for ETMR and may improve patient outcomes. Methods The authors present a case series of five children with ETMR treated with an IRS-III-based chemotherapy backbone. Results All five patients received a gross-total tumor resection. Patients received between 12-51 weeks of IRS-III therapy at the discretion of their treating physician. Four patients received focal radiation therapy, with the fifth patient instead receiving a cycle of high-dose chemotherapy with autologous stem cell rescue. Four patients have progression-free survival (PFS) of >18 months. Chemotherapy treatment was reasonably tolerated by all five patients with one case of mild sinusoidal obstructive syndrome and once case of Grade 3 peripheral neuropathy. Conclusions The patient outcomes in this small cohort are far better than would be expected based on the historical survival for this tumor. Given the tremendous need for effective therapy for ETMR, further investigation of this approach is warranted. An international consensus protocol based on the IRS-III regimen has been developed and will be available through a multi-center clinical trial and a global treatment registry.

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Section: Discussionmentioning

confidence: 99%