We thank the reviewer for this comment, and apologize that the illustration of the timeline was accidentally missing from the submission (we have now added it). The limiting factor for study duration was the well being of the animals. The tumors in the control group were very large, causing stress and weight loss of the animals. The arrays placed on the animals, together with the individual housing needed to prevent wire entanglement, adds even more stress and increases animal weight loss. Overall, it was non-ethical to continue the study further. We have now added this explanation to the discussion section to clarify this limitation of the study: “In the HCC animal model, the acute effects of TTFields and sorafenib were examined. Due to the large tumors developed in the control group and the stress experienced by the animals as a result of the individual housing and motility limitations imposed by the sham and TTFields arrays, longer treatment durations were not feasible.” Point 4: There is no explanation why the most effective dose was 150 kHz and higher does actually decreases the killing.
Another puzzling experiment is the schedule for the in vivo work. Since the authors missed to add Figure 4A for timeline, based on Methods section the rats were treated for 5 days with TTFields and or sorafenib and a day later the rays were sacrificed. While a short “acute” follow-up is welcome the most important experiment should allow the follow-up for much more days to indeed observe the effect of TTFields added to sorafenib. I could not find an explanation for not including a long term follow-up. In my opinion, this is a key therapeutically experiment which must be done and included in the study.