Tumor growth delay by adjuvant alternating electric fields which appears non-thermally mediated

• TTFields did not have a significant impact on tumor growth as single treatment.
• TTFields combined with chemotherapeutic drug show a 47% of tumor growth reduction.
• Mild hyperthermia did not have an impact on tumor growth as single treatment.
• Mild hyperthermia did not have an impact on tumor growth as adjuvant.
• TTFields effect appears to be non-related with the induced temperature increase.

Delivery of the so-called Tumor Treatment Fields (TTFields) has been proposed as a cancer therapy. These are low magnitude alternating electric fields at frequencies from 100 to 300 kHz which are applied continuously in a non-invasive manner. Electric field delivery may produce an increase in temperature which cannot be neglected. We hypothesized that the reported results obtained by applying TTFields in vivo could be due to heat rather than to electrical forces as previously suggested. Here, an in vivo study is presented in which pancreatic tumors subcutaneously implanted in nude mice were treated for a week either with mild hyperthermia (41 °C) or with TTFields (6 V/cm, 150 kHz) and tumor growth was assessed. Although the TTFields applied singly did not produce any significant effect, the combination with chemotherapy did show a delay in tumor growth in comparison to animals treated only with chemotherapy (median relative reduction = 47%). We conclude that concomitant chemotherapy and TTFields delivery show a beneficial impact on pancreatic tumor growth. Contrary to our hypothesis, this impact is non-related with the induced temperature increase.