**8. Tumor treating fields**

In 2015, Optune™ became the first FDA-approved therapy for newly diagnosed glioblasto‐ mas in over a decade to demonstrate statistically significant extension of progression free and overall survival. Optune™ is the brand name for the NovoTTF™ 100A system manufac‐ tured by the commercial stage oncology company Novocure™.

Optune™ is a portable, noninvasive device delivering low-intensity, intermediate frequency, alternating bidirectional electric fields referred to as Tumor Treating Fields (TTF). The electric fields are delivered locoregionally via transducer arrays through the shaved scalp. The mechanism of action is the antimitotic action of the tumor treating fields interfering with cell division and organelle assembly within the rapidly replicating tumor cells. While micropho‐ tography has shown examples of prolonged mitoses and proliferation arrest, the specificity of the tumor treating fields for tumor cells only in the absence of an exact mechanism has raised skepticism within the Neuro-Oncology and Oncology clinician community [40].

What is undeniable, however, is the two-year survival rate among patients treated with Optune™ in combination with temozolomide was 48% higher than in patients compared with patients treated with temozolomide alone [41]. In 2014, the multinational, randomized Phase III EF-14 trial was halted after successful demonstration of superior progression-free and overall survivals in patients receiving Optune™ in combination with temozolomide, com‐ pared with temozolomide alone. Patients treated with Optune™, in combination with temozolomide, demonstrated a statistically significant increase in progression-free survival compared with temozolomide alone (median progression-free survival of 7.2 months compared with 4.0 months, hazard ratio = 0.62, *p* = 0.001. There was also a statistically significant increase in overall survival compared with temozolomide alone (median overall survival of 20.5 months compared with 15.6 months, hazard ratio = 0.66, *p* = 0.004) [40–42]. It is noted that patients in the control arm received a median of four cycles of temozolamide, whereas patients in the Optune™ arm received six cycles of temozolamide, which is an additional confounding factor (patients lived longer therefore they got more temo).

The bottom line here is the availability of Optune™ as a viable option for all patients with newly diagnosed glioblastoma after successful chemoradiation and stable disease at poten‐ tial initiation of treatment with tumor treating fields [42]. We look forward to the incorpora‐ tion of Optune™ in future trials as a standard arm and with permutations of other combinatorial therapies.
