Fiber-Optic Based Laser Wakefield Accelerated Electron Beams and Potential Applications in Radiotherapy Cancer Treatments

Round 1

Reviewer 1 Report

The manuscript entitled by “Fiber-Optic Based Laser Wake-field Accelerated Electron Beams and Potential Applications in Radiotherapy Cancer Treatments” by D. Roa et al. presents a possible application of laser accelerated electron beams to cancer treatments. This perspective paper describes well the way of applying laser accelerated electron beams in a high density regime to high dose rate brachytheraphy. And also, this paper shows an interesting approach of using laser accelerated electron beam to cancer therapy. So, I would like to recommend publications of this paper in Photonics.

Followings are suggestions to improve the manuscript before the publications.

1. Usually, the high power laser pulses for electron acceleration can not propagate through optical fiber because of the damage threshold of the optical fiber. It would be better to describe the way to deliver the high intensity laser pulse thorugh optical fiber channels in the manuscript.
2. The figure caption and description for figure 3 is too brief. Dimensions and scales are not clearly visible in the upper of figure 3, and also it is not clear what means absorbed dose calculations in this figure. The caption and description on this part would be better to be elaborated.
3. The description for figure 4 (e) ~ (i) are very shallow. It is not easy to be understood what these figures means. It would be better to elaborate these figures in the text, too.
4. And also, I would like to suggest that the below paper is added to the references between 3 ~ 5 :

"Stable generation of GeV-class electron beams from self-guided laser-plasma channels", Nasr A. M. Hafz, et al., Nature Photonics, vol.2(9), 571-577 (Sep. 2008)

Author Response

Thank you for your valuable comments, please find detailed response in the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comment on “Fiber-optic based Laser Wake-field accelerated Electron beams …”, by D. Roa et al.,

This manuscript explores the use of fiber lasers for applications to brachytherapy via acceleration of electrons with laser wakefield acceleration in high density plasmas.  This is a very attractive application of laser-driven acceleration of charged particles to radiotherapy that relies on recent rapid progress of ultrafast laser technology.

In general the perspective article is well written, informative and interesting. I would recommend publication provided the following issues are properly addressed.

• In the introduction the brief review of LWFA results to date is not clear and partially confusing. The results on monoenergetic electrons cited [7-9] in the third paragraph “Subsequent experiments …” were reported in 2004, before the results cited [4-5] in the preceding paragraph which are among the most advanced results to date, so they are not “subsequent”. The authors should rewrite the introduction to fix these inconsistencies.
• In the second paragraph “Experimental verification …”, the reference to electron beam current should be specified. Peak currents in laser driven electron accelerators are quite high and higher than most RF accelerators due to the very short pulse duration and comparable charge. Average currents are mainly due to pulse repetition rate which for RF accelerators can be quite high. The authors should specify what they mean with electron beam current.
• In the following paragraph, when discussing low energy electrons accelerated by lasers, previous work in the laser intensity and electron energy range of interest here was carried earlier e.g. Journal of Physics D: Applied Physics 49, 275401 (2016). The authors should run a check and cite relevant literature, especially if related to experimental work that is key for the validation of the proposed concept.
• In Section 2 “Rationale”, in paragraph 3 “In these interactions … ”, the authors refer to “… electron density approaching unity” without specifying the units. From the following text it is evident that they refer to the density in units of the critical density (at the laser wavelength). But this should be properly defined before calling the density in the text, possibly providing also a value of the critical density used here.
• In the following paragraph “For this application …” the authors should explain better the role of the lens. Is it used to do simultaneously temporal compression and focusing? More quantitative details on this would be useful.
• In Paragraph c. Potential for FLASH Brachytherapy, the authors state that “ … FLASH treatments are more effective in eradicating cancerous tumors …”. Is this confirmed by literature? Based on existing results, evidence is mainly on the sparing effect of healthy tissue, with similar effect on tumor tissue. This is a very important point and the authors should substantiate their statement with references or remove it.

Author Response

Thank you for your valuable comments, please find detailed response in the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors of this manuscript discuss an interesting possible application of low-energy LWFA-electron beams for brachytherapy which may present advantages over the currently used brachytherapy based on radioactive stents.

While I do understand the scope of this special issue and despite the fact that there are well-known and esteemed co-authors in the list of authors, I am surprised by the rather low degree of scientific support given by the authors for their concept. I also want to mention that I know at least two other projects with exactly the same goal, but that is not mentioned in the manuscript (by the way: I am personally not involved in these other projects, I just happen to get to know that these two groups also pursue LWFA-based brachy therapy).

Let me give you my critique in detail in chronological order through the manuscript.

• lines 77 thru 84: although references are given, this central paragraph is hard to understand for readers from a broader scientific background (I assume that this special issue is not only meant for LWFA-insiders, but aims also at reaching out to those research groups who are interested in applications).
• Figure 1: the graphical quality is very poor, the plots in the original publication are much better readable.
• Figure 2, but also related main text blocks: my central critique about this manuscript is a surprising lack of supporting aspects and details - the following questions are not even touched through the entire manuscript:
  • what happens if the laser pointing is not stable?
  • where is the unused laser energy deposited?
  • what is the expected life-time of the nano target? How often must this be changed?
  • can the laser damage the target such that it must be replaced?
  • what is the expected life-time of the laser, or in other words, the maintenance efforts that need to be done?
•  Fig. 3: there is a reference given to a "slide 3" - it appears as if this figure has been taken from a presentation without adjustment. But, more crucial is that the list of questions above grows even longer:
  • what determines the spatial dose distribution?
  • how can this be adjusted, if at all?
• lines 123-125: here one needs concrete numbers and references. Just because treatment is longer is not a strong argument.
• line 161: how is the electron beam energy controlled to be tuneable?
• line 170: the fact that only one energy can be used, does not need to mean a disadvantage: in the end, what counts is the deposited dose (and dose rate) - so the authors need to support this statement.
• line 183: it remains completely unclear what "multi-energy electron beams" are supposed to be: what is meant here and how is this realised and why is this interesting?
• lines 188-195: while image-guidance sounds interesting, no details are given here: how would this work in detail, what are the conditions that need to be met for practical application?
• lines 207-211: here also numbers are needed, else it is pure speculation.
• table 1 also needs quantitative support (where do these numbers come from?), else it reads like a PR brochure as it appears quite optimistic (see the list of questions above).
• lines 266-268: here the authors are quite open about the scientific support - I strongly recommend to first run these in-depth studies - we all know that the "devil" is always in the details.

Summing up, when I have been asked to review this paper and have seen the list of co-auhtors, I was really happy to do so, because I was interested in reading what they will present. However, the very low degree of supporting material and more in-depth studies left me quite unsatisfied with this manuscript. I am sure that this idea (as also studied by other groups) is promising, but it needs much more in-depth insights, considerations, and numerical/experimental tests - even for a perspective special issue, because else it just appears as pure speculation.

I therefore do not recommend publication the manuscript in its present shape.

Author Response

Thank you for your valuable comments, please find detailed response in the attachment.

Author Response File: Author Response.pdf

Reviewer 4 Report

In this paper, the authors present a vision of what could be achievable with electron beams produced via LWFA and their use in cancer treatments with brachytherapy. Also, to describe the cost savings that an LWFA-HDR system could provide to a radiation oncology clinic since it eliminates the use of radioactive sources and radiation-shielded rooms for treatment. This article is clear, concise, and suitable for the scope of the journal. Several  small suggestions are supplied:
1. Suggest the authors improve the resolution of all graphs, also suggest rearranging fig.4.
2.  Suggest the authors give more detail about the information in the table.

Author Response

Thank you for your valuable comments, please find detailed response in the attachment.

Author Response File: Author Response.pdf