Planning TTFields treatment using the NovoTAL system-clinical case series beyond the use of MRI contrast enhancement

Jennifer Connelly, Adília Hormigo, Nimish Mohilie, Jethro Hu, Aafia Chaudhry, Nicholas Blondin

Gliomas are the most common primary brain tumors in adults and invariably carry a poor prognosis. Recent clinical studies have demonstrated the safety and compelling survival benefit when tumor treating fields (TTFields) are added to temozolomide for patients with newly diagnosed glioblastoma. TTFields are low-intensity, intermediate frequency (200 kHz) alternating electric fields, delivered directly to a patient's brain through the local application of non-invasive transducer arrays. Experimental simulations have demonstrated that TTFields distribute in a non-uniform manner within the brain. To ensure patients receive the maximal therapeutic level of TTFields at the site of their tumor, tumor burden is mapped and an optimal array layout is personalized using the NovoTAL software. The NovoTAL software utilizes magnetic resonance imaging (MRI) measurements for head size and tumor location obtained from axial and coronal T1 postcontrast sequences to determine the optimal paired transducer array configuration that will deliver the maximal field intensity at the site of the tumor. In clinical practice, physicians planning treatment with TTFields may determine that disease activity is more accurately represented in noncontrast-enhancing sequences. Here we present and discuss a series of 8 cases where a treating physician has utilized non-contrast enhancement and advanced imaging to inform TTFields treatment planning based on a clinical evaluation of where a patient is believed to have active tumor. This case series is, to our knowledge, the first report of this kind in the literature. All patients presented with gliomas (grades 2-4) and ranged in age from 49 to 65 years; 5 were male and 3, female. Each patient had previously received standard therapy including surgery, radiation therapy and/or chemotherapy prior to initiation of TTFields. The majority had progressed on prior therapy. A standard pre- and postcontrast MRI scan was acquired and used for TTFields treatment planning. This paper details important approaches for integrating clinical considerations, nonmeasurable disease and advanced imaging into the treatment planning workflow for TTFields. As TTFields become integrated into standard care pathways for glioblastoma, this case series demonstrates that treatment planning beyond the extent of contrast enhancement is clinically feasible and should be prospectively compared to standard treatment planning in a clinical trial setting, in order to determine the impact on patient outcomes.