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Review
Peer-Review Record

Tumor-Treating Fields Therapy for Pediatric Brain Tumors

Neurol. Int. 2021, 13(2), 151-165; https://doi.org/10.3390/neurolint13020015
by Atsushi Makimoto 1,2,*, Ryo Nishikawa 3, Keita Terashima 4, Jun Kurihara 5, Hiroyuki Fujisaki 6, Satoshi Ihara 7, Yoshihiko Morikawa 2 and Yuki Yuza 1
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Neurol. Int. 2021, 13(2), 151-165; https://doi.org/10.3390/neurolint13020015
Submission received: 10 February 2021 / Revised: 10 March 2021 / Accepted: 15 March 2021 / Published: 8 April 2021

Round 1

Reviewer 1 Report

This paper is an ambitious review of a patented device, Optune, which delivers TTF technology in hopes of providing a low-toxicity treatment option which may help patients with incurable GBM tumors. The authors provide an overview of the field in general, some hypotheses in terms of how the technology may work at the cellular level, and describe their intention of carrying out a pediatric clinical trial. They present a very reasonable outline for the trial, along with a good sense of the trials and tribulations therein. 

The article includes an extensive review of adult experience, safety data, and some technical aspects as well.  Readers who are interested in new emerging technologies may find this work inspiring and learn a significant amount of new information. 

Author Response

Thank you for your review of our article. I made several minor corrections of the English as suggested. Discussion of drawbacks of the treatment was added according to the comments from another reviewer.

Reviewer 2 Report

Makimoto et al. present a very rosy picture of TTF when in reality there is still much skepticism regarding its use and benefit.

No where are the issues of concerns mentioned in this manuscript.

Wick; TTFields: where does all the skepticism come from? PMID:26917587

Lassman; Current usage of tumor treating fields for glioblastoma PMID 32666048

Additionally, it is very expensive and multiple cost benefit analysis have failed to show benefit even if it is thought to be effective.

Bernard-Arnoux; The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma PMID:2717757

Connock;  Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma: an updated evaluation using a partitioned survival model. PMID: 31127507 

Furthermore, it requires shaving the head and wearing over 18 hours a day. The Qol analysis may not accurately reflect the same concerns in quality of life as in children having to wear it all day.

All of these issues should be included and discussed.

Author Response

Thank you for your valuable comments. I noticed that the original version was biased toward the positive aspects of TTFields therapy. I added one additional section entitled, “Reliability and feasibility of TTFields therapy as a standard of care” on page 8 (lines 300 – 345) and discussed the issues which you pointed out. I also added several sentences in other places to maintain the coherence of the article (lines 262-265 and 279-281 on page 7, and lines 520-522 on page 12). I also made several minor corrections of the English as suggested.

Round 2

Reviewer 2 Report

Paper is more fairly balanced regarding potential pros/cons of TTF and appropriately discusses skepticism for some neuro-oncologists and reasons behind it.

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