Tumor-Treating Fields in Glioblastomas: Past, Present, and Future

SIMPLE SUMMARY: Glioblastoma (GBM) is the most common malignant primary brain tumor. Although the standard of care, including maximal resection, concurrent radiotherapy with temozolomide (TMZ), and adjuvant TMZ, has largely improved the prognosis of these patients, the 5-year survival rate is still < 10%. Tumor-treating fields (TTFields), a noninvasive anticancer therapeutic modality, has been rising as a fourth treatment option for GBMs, as confirmed by recent milestone large-scale phase 3 randomized trials and subsequent real-world data, elongating patient overall survival from 16 months to 21 months. However, the mechanisms of antitumor efficacy, its clinical safety, and potential benefits when combined with other treatment modalities are far from completely elucidated. As an increasing number of studies have recently been published on this topic, we conducted this updated, comprehensive review to establish an objective understanding of the mechanism of action, efficacy, safety, clinical concerns, and future perspectives of TTFields. ABSTRACT: Tumor-treating fields (TTFields), a noninvasive and innovative therapeutic approach, has emerged as the fourth most effective treatment option for the management of glioblastomas (GBMs), the most deadly primary brain cancer. According to on recent milestone randomized trials and subsequent observational data, TTFields therapy leads to substantially prolonged patient survival and acceptable adverse events. Clinical trials are ongoing to further evaluate the safety and efficacy of TTFields in treating GBMs and its biological and radiological correlations. TTFields is administered by delivering low-intensity, intermediate-frequency, alternating electric fields to human GBM function through different mechanisms of action, including by disturbing cell mitosis, delaying DNA repair, enhancing autophagy, inhibiting cell metabolism and angiogenesis, and limiting cancer cell migration. The abilities of TTFields to strengthen intratumoral antitumor immunity, increase the permeability of the cell membrane and the blood–brain barrier, and disrupt DNA-damage-repair processes make it a promising therapy when combined with conventional treatment modalities. However, the overall acceptance of TTFields in real-world clinical practice is still low. Given that increasing studies on this promising topic have been published recently, we conducted this updated review on the past, present, and future of TTFields in GBMs.