Background Since the groundbreaking article from the University of Minnesota in 1961 by Drs. Galicich, French, and Melby describing the use of dexamethasone for peritumoral cerebral edema, the use of corticosteroids in patients with brain tumors has become routine. Unfortunately, little has been reported regarding the environment that fostered arguably the greatest translational research contribution in the history of neurosurgery. METHODS During a pilot study to assess corticosteroid uptake in brain tumors, Dr. Galicich observed that patients given a large dose of corticosteroids just before craniotomy had a relatively benign postoperative course. This led, in October 1959, to the administration of high-dose corticosteroids to a patient with a large recurrent glioblastoma who was semicomatose and severely hemiparetic. The results were dramatic, with almost complete resolution of neurological deficit during a period of several days and marked reduction of midline shift on repeat angiograms. This finding prompted the studies that confirmed the efficacy of high-dose corticosteroids in reducing peritumoral brain edema in humans reported in the 1961 article. RESULTS After publication, a revolution in brain tumor management occurred because corticosteroid therapy markedly reduced the morbidity and mortality associated with brain tumors both in the United States and worldwide. CONCLUSION The combination of astute clinical observation and follow up by rigorous clinical research at the University of Minnesota resulted in one of the greatest contributions in the history of neurosurgery, rivaled only by the operative microscope in its effect on morbidity, and unsurpassed in reduction of mortality.
Purpose/Objective(s): TTFields are FDA-approved for the treatment of recurrent and newly diagnosed Glioblastoma (GBM) in the supratentorial brain. The EF-14 trial showed that combining TTFields with adjuvant chemo-radiation leads to a significant increase in overall survival compared to adjuvant chemo-radiation alone. High-grade gliomas also occur in the infratentorium and brainstem of pediatric and adult patients. Brainstem gliomas have a median survival of 9 to 11 months, necessitating the exploration of novel treatment combinations, such as delivering TTFields to the infratentorial brain.We recently showed in a simulation-based study that TTFields can be successfully delivered to the infratentorium. Effective delivery was achieved by placement of the arrays on the vertex, bilateral posterolateral occiput, and superior-posterior neck; the array placement results in TTFields at therapeutic intensities throughout the brainstem and cerebellum of realistic computational head models.The previous simulation-based study was performed using realistic computational models of healthy individuals; it did not provide detailed insight into field distributions within tumor tissue located in the infratentorium. Here, we aim to expand the results of this previous study, by simulating the delivery of TTFields to the infratentorium of adult and pediatric patients with high-grade brainstem gliomas.Materials/Methods: A realistic computational model was created using MRI data of adult and pediatric patients with high-grade brainstem gliomas. Transducer arrays were placed on the model and the delivery of TTFields to the infratentorial brain was then simulated using a commercial numerical solver. The electric field distribution in the supratentorium, infratentorium, and within the tumor were derived from the simulations, and the dose in the tumor analyzed.Results: The distribution of calculated isofield lines demonstrates effective delivery of TTFields to infratentorial brain tumors.Conclusion: Our results provides rationale for clinically investigating the utility of TTFields in treating infratentorial high-grade gliomas.Citation Format: Marigdalia K. Ramirez-Fort, Brittany Cross, Ariel Naveh, Shearwood McClelland III, Melissa Mendez, Roberto Santiago, Sean S. Mahase, Jaime Matta, Ze'ev Bomzon, Christopher S. Lange. Simulating delivery of TTFields to the infratentorium in patients with brainstem gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4430.
