Development of Inclined Applicators for Flattened Beam Intraoperative Radiotherapy
, Kwangwoo Park 5,*,†, Rena Lee 6 and Jin Sung Kim 1,2,3Round 1
Reviewer 1 Report
General comments:
The authors developed inclined applicators for flattened beam intraoperative radiotherapy. The add-on shielding device was created using 3D printing. The developed applicator was used to treat four patients in a clinical setting. The study is of potential interest to the reader of applied sciences. I would like to ask the authors to consider following specific comments.
Specific comments:
Figure 1
Figures are of poor quality.
I cannot identify what are shown.
Figure 2
Figures are of poor quality.
The authors should indicate which parts were created using 3D printing.
Figure 3,4 and 5
Photographs are of poor quality. Experimental setup cannot be grasped.
I would like ask authors to consider drawing figures of experimental setup.
Page 4 Line 135
“[22-23]”
There is a concern about the way the authors cite the studies performed by other researchers. Although the authors should refer 22 and 23 as previous studies, because these were performed by other researchers, the authors should explain experimental setup of this study more in detail.
Page 4 Line 135
“figure 5 (a) and (b)” should be “figure 3 (a) and (b).
Page 4 Line 137
“figure 5 (c)” should be “figure 3 (c).
Page 4 Line 146
Put “(figure 4)” after “at depths of 2, 5, and 15 mm”
Page 5 Line 157
Put “(figure 5)” after “dose measurements”
Figure 6
Caption for figure 6 is too much omitted. I cannot identify what is shown in each figure. More specific description is needed.
Table 1
0 degree FFF is appeared twice at first and third line. I cannot identify which is for with a flattening filter and which is for without a flattening filter.
“*Schneider et al, 2014” should be “*Schneider et al, 2014 [22]”
Page 6 Line 183
“The equipment was set to a dose rate of 48.36 cGy/min for a 3-minute period, a dose rate of 145 cGy/min for a 3-minutes @period,”
This part should be written in “2. Materials and Methods”.
Page 6 Line 186
“while the difference between the two models without a flattening filter was 1.0 cGy”
I cannot understand how the value of 1.0 cGy was obtained from values in table 2.
Page 6 Line 186
“Figure 7 show the calibration curve obtained for dose calibration.”
If it is for the calibration of EBT3 film, this can be
“Figure 7 shows the calibration curve for EBT3 film.”
Page7 Line 203
“in figure 3 (c) [24]”
There is a concern about the way the authors cite the studies performed by other researchers. Although the authors should refer 24 as previous studies, because these were performed by other researchers, the authors should explain experimental setup of this study more in detail.
Page 7 Line 206
“measured by Schneider et al.” should be “measured by Schneider et al. [22]”
Page 7 Line 212
“the same level of uniformity [25]”
There is a concern about the way the authors cite the studies performed by other researchers. Although the authors should refer 25 as previous studies, because these were performed by other researchers, the authors should explain experimental setup of this study more in detail.
Figure 8
Because photographs are of poor quality, green arrows cannot be identified.
Author Response
Comments for the Author:
Reviewer #1: The authors developed inclined applicators for flattened beam intraoperative radiotherapy. The add-on shielding device was created using 3D printing. The developed applicator was used to treat four patients in a clinical setting. The study is of potential interest to the reader of applied sciences. I would like to ask the authors to consider following specific comments.
Specific comments:
- Figure 1
Figures are of poor quality.
I cannot identify what are shown.
(Answer) we increased the size of the figures to enhance their visibility. And we made modifications to the description of Figure 1 in the manuscript.
Figure 1. (Left) Flat and (Right) surface applicators
L 92 - 95: Figure 1 illustrates the flat and surface applicators provided by the manufacturer. The flat applicators offer a uniform dose distribution at a specific depth, while the surface applicators deliver a uniform dose distribution at the surface.
- Figure 2
Figures are of poor quality.
The authors should indicate which parts were created using 3D printing.
(Answer) We have enlarged the figure to enhance visibility, ensuring better visualization of the 3D printed components. Additionally, we have included an explanation of the 3D printing process in the figure's caption.
Figure 2. Design Diagram and Types of Developed Applicators: (a) The location and actual picture of each part of the add-on shielding device. The blue part represents 3D printed PLA, within which Cerrobend (yellow) is inserted; (b) the conceptual design of the four types of developed applicators.
- Figure 3,4 and 5
Photographs are of poor quality. Experimental setup cannot be grasped.
I would like ask authors to consider drawing figures of experimental setup.
(Answer) We created a diagram to effectively convey the experimental procedure we conducted, and I have included it in the figure for better presentation.
Figure 3. Experimental setup for measuring the vertical leakage dose and PDD for (a) 0° and (b) 45°, and that for measuring the (c) horizontal leakage dose for 0°
Figure 4. Experimental setup used to measure the beam profile of the developed applicators. The measurements were conducted on the surface and at depths of 2, 5, and 15 mm of the solid water phantom.
- Page 4 Line 135
“[22-23]”
There is a concern about the way the authors cite the studies performed by other researchers. Although the authors should refer 22 and 23 as previous studies, because these were performed by other researchers, the authors should explain experimental setup of this study more in detail.
(Answer) Thank you for your insightful comments and suggestions. We appreciate your feedback regarding the citation and explanation of the studies performed by other researchers, specifically referenced as [22] and [23] in our manuscript.
To address your concern, we would like to add the following revisions in our manuscript to better clarify the experimental setup.
L 133 - 137: To assess the leakage dose and percent depth dose (PDD), we employed the EBT3 film and a human equivalent phantom and conducted vertical and horizontal measurements for all four applicators, in accordance with the methodology detailed by Schneider et al. [22-23]. The setup for the measurements can be seen in figure 3 (a) and (b), which were adapted from the guidelines provided in Schneider et al.'s study.
- Page 4 Line 135
“figure 5 (a) and (b)” should be “figure 3 (a) and (b).
(Answer) we modified the sentence in the manuscript.
- Page 4 Line 137
“figure 5 (c)” should be “figure 3 (c).
(Answer) we modified the sentence in the manuscript.
- Page 4 Line 146
Put “(figure 4)” after “at depths of 2, 5, and 15 mm”
(Answer) we modified the sentence in the manuscript.
- Page 5 Line 157
Put “(figure 5)” after “dose measurements”
(Answer) we modified the sentence in the manuscript.
- Figure 6
Caption for figure 6 is too much omitted. I cannot identify what is shown in each figure. More specific description is needed.
(Answer) We acknowledge the feedback that the caption for Figure 6 was overly abbreviated, which made it difficult to clearly understand what each subfigure was illustrating. To address this, We have revised the caption and added specific descriptions for each subfigure. The revised description is as follow:
Figure 6. Measured horizontal and vertical leakage dose, PDD for a 0° applicator with and without a flattening filter: (a) Horizontal leakage dose for 0° applicator; (b) Vertical leakage dose for 0° applicator; (c) PDD for 0° applicator with a flattening filter; (d) PDD for 0° applicator without a flattening filter; (e) Horizontal leakage dose for 45° applicator; (f) Vertical leakage dose for 45° applicator; (g) PDD for 45° applicator with a flattening filter; (h) PDD for 45° applicator without a flattening filter.
- Table 1
0 degree FFF is appeared twice at first and third line. I cannot identify which is for with a flattening filter and which is for without a flattening filter.
“*Schneider et al, 2014” should be “*Schneider et al, 2014 [22]”
(Answer) We have revised the table according to your suggestion and added explanations for FF and FFF abbreviations in the table.
Table 1. Measured uniformity of the developed applicators at surface and depths of 2, 5, and 15 mm
|
|
Uniformity |
|||
|
|
Surface |
2 mm depth |
5 mm depth |
15 mm depth |
|
0° FF |
1.23 |
1.28 |
1.30 |
1.22 |
|
Flat appl. * |
1.31 |
- |
1.13 |
- |
|
0° FFF |
1.29 |
1.32 |
1.27 |
1.25 |
|
Surface appl.* |
1.28 |
- |
1.47 |
- |
* Schneider et al, 2014 [22]
Abbreviations: FF, flattening filter; FFF, flattening filter-free
- Page 6 Line 183
“The equipment was set to a dose rate of 48.36 cGy/min for a 3-minute period, a dose rate of 145 cGy/min for a 3-minutes @period,”
This part should be written in “2. Materials and Methods”.
(Answer) we modified the sentence in the manuscript.
L 159 - 160: We verified the dose rate as 48.36 cGy/min for a 3-minute period using OSLD absolute dose measurements (figure 5).
- Page 6 Line 186
“while the difference between the two models without a flattening filter was 1.0 cGy”
I cannot understand how the value of 1.0 cGy was obtained from values in table 2.
(Answer) we modified the sentence in the manuscript.
L 187 - 189: The difference between the 0° and 45° applicators with a flattening filter was 2.5 cGy, while the difference between the two models without a flattening filter was 1.9 cGy
- Page 6 Line 186
“Figure 7 show the calibration curve obtained for dose calibration.”
If it is for the calibration of EBT3 film, this can be
“Figure 7 shows the calibration curve for EBT3 film.”
(Answer) we modified the sentence in the manuscript.
- Page7 Line 203
“in figure 3 (c) [24]”
There is a concern about the way the authors cite the studies performed by other researchers. Although the authors should refer 24 as previous studies, because these were performed by other researchers, the authors should explain experimental setup of this study more in detail.
(Answer) Thank you for your thoughtful comments on our manuscript, and for pointing out the need for clarification in our citation of Reference 24.
In the section of the manuscript you mentioned, we cited Reference 24 to highlight a specific challenge inherent in EBT3 film dosimetry: the potential for dose measurement artifacts from bending or cutting the film surface. In the referenced study [24], the researchers, like us, had cut the EBT3 film for their experiments and regarded the edges as potential artifacts. As illustrated in our Figure 3(c), they therefore chose to exclude the first 0.7mm from the cutting edge when interpreting the dose, to minimize any impact these artifacts may have on the measurements.
In our experiment, we faced a similar challenge. As with the authors of Reference 24, we considered these artifacts during our dose measurement. To avoid any potential inaccuracies in dose readings due to such artifacts, we also chose to disregard the first 0.7mm from the cutting edge of the film when measuring dose.
- Page 7 Line 206
“measured by Schneider et al.” should be “measured by Schneider et al. [22]”
(Answer) we modified the sentence in the manuscript.
- Page 7 Line 212
“the same level of uniformity [25]”
There is a concern about the way the authors cite the studies performed by other researchers. Although the authors should refer 25 as previous studies, because these were performed by other researchers, the authors should explain experimental setup of this study more in detail.
(Answer) Thank you for your query. I understand your request to be a clarification about the surface applicator and its comparison with our newly developed applicator, based on the findings from the study [25] titled "Dosimetric characteristics of INTRABEAM® flat and surface applicators."
In the cited study [25], the dosimetric characteristics of the INTRABEAM® surface applicators were examined. The research was conducted using Gafchromic EBT 2 QD+ (GEBT) film in a solid water phantom, as well as an ionization chamber and a solid state detector in a scanning water phantom.
The key findings pertaining to the surface applicators were that they provided a uniform dosimetry at the surface without any hot spots at the perimeter of the field. This feature is particularly effective for delivering a uniform dose treatment for the first 2-3 millimeters. However, when considering treatments that require a deeper depth, the uniformity of dose distribution decreases with the surface applicators. This necessitates a larger margin for treatment volume to compensate for the dose tapering at the edge of the field.
Our newly developed applicator has been designed to improve upon these limitations. While the surface applicator performs excellently at the surface level, it lacks the required uniformity at depth. We designed our applicator to achieve a flat dose distribution at a depth of 5 mm, where the tumor bed typically shows the most uniform dose distribution. This is a significant improvement over the surface applicator in terms of maintaining dose uniformity at depth, which optimizes treatment for the tumor bed.
- Figure 8
Because photographs are of poor quality, green arrows cannot be identified.
(Answer) We made modifications to the green arrow to enhance visibility of the tumor location.
Figure 8. Intraoperative treatment using the developed applicator: (a, b) axial magnetic resonance images for the patient 1 and 2 respectively; (c, d) PET/CT image of patient 3 and 4 respectively; (e, f, g) applicator setup for patient 2, 3 and 4 respectively; green arrows represent the location of tumors.
Author Response File: 
Author Response.docx
Reviewer 2 Report
The research was very interesting and easy to understand.
I thought the picture in Figure 1 was too small and difficult to understand.
Page 3, lines 109-110
The order of the explanations in this text and the order of Figure2(b) seem to be different. I think it would be better to unify them.
Page 4, line 135
It says "Figure5," which I think is correct for Figure3.
I think page 4, line 145-151 is an explanation of Figure 4 and page 5, line 157-162 is an explanation of Figure 5. I think it would be better to clearly state that in the text.
I think it would be better to crop the photo in Figure 4.
In Figure 8(a) and (b), it is difficult to identify the tumor in the MRI images. How about enlarging the pictures or using arrows to indicate the tumor? Also, if possible, I think it would be better to include the post-treatment examination images.
Author Response
Reviewer #2: The research was very interesting and easy to understand.
- I thought the picture in Figure 1 was too small and difficult to understand.
(Answer) we increased the size of the figures to enhance their visibility. And we made modifications to the description of Figure 1 in the manuscript.
Figure 1. (Left) Flat and (Right) surface applicators
L 92 – 95: Figure 1 illustrates the flat and surface applicators provided by the manufacturer. The flat applicators offer a uniform dose distribution at a specific depth, while the surface applicators deliver a uniform dose distribution at the surface.
- Page 3, lines 109-110
The order of the explanations in this text and the order of Figure2(b) seem to be different. I think it would be better to unify them.
(Answer) We revised the sentence in the manuscript to align with the sequence of Figure 2 (b).
L 108 - 110: Figure 2 (b) displays the types of add-on shielding devices designed, including: 1) an unflattened beam at 0°, 2) a flattened beam at 0°, 3) an unflattened beam at 45°, and 4) a flattened beam at 45°.
- Page 4, line 135
It says "Figure5," which I think is correct for Figure3.
(Answer) we modified the sentence in the manuscript.
- I think page 4, line 145-151 is an explanation of Figure 4 and page 5, line 157-162 is an explanation of Figure 5. I think it would be better to clearly state that in the text.
(Answer) We modified the sentence in the manuscript.
L 147 - 148: We measured the beam profile of four developed applicators by placing EBT3 film between solid water at depths of 2, 5, and 15 mm (figure 4).
L 159 - 160: We verified the dose rate as 48.36 cGy/min for a 3-minute period using OSLD absolute dose measurements (figure 5).
- I think it would be better to crop the photo in Figure 4.
(Answer) As you suggested, I cropped the picture of Figure 4 to better represent the experimental setup.
Figure 4. Experimental setup used to measure the beam profile of the developed applicators. The measurements were conducted on the surface and at depths of 2, 5, and 15 mm of the solid water phantom.
- In Figure 8(a) and (b), it is difficult to identify the tumor in the MRI images. How about enlarging the pictures or using arrows to indicate the tumor? Also, if possible, I think it would be better to include the post-treatment examination images.
(Answer) We made modifications to the green arrow to enhance visibility of the tumor location. And thank you for your suggestion to include post-treatment examination images in our study.
We understand that these images could provide further insights and enhance the comprehensibility of our research.
Regrettably, we did not obtain post-treatment examination images during the course of this research. The primary focus of our study was on the dosimetric measurements and the resulting data analysis, so our resources were directed accordingly.
We acknowledge the importance of visual data in interpreting and understanding research findings, and we will definitely take your feedback into consideration for future studies. We assure you that despite this omission, the absence of these images does not affect the validity or the integrity of our current results and conclusions.
Figure 8. Intraoperative treatment using the developed applicator: (a, b) axial magnetic resonance images for the patient 1 and 2 respectively; (c, d) PET/CT image of patient 3 and 4 respectively; (e, f, g) applicator setup for patient 2, 3 and 4 respectively; green arrows represent the location of tumors.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
Overall, I am satisfied with the revised version.
One minor comment:
Please explain “Cerrobend” because it is commercial or trade name.
Author Response
Comments for the Author:
Reviewer #1: Overall, I am satisfied with the revised version.
One minor comment:
Please explain “Cerrobend” because it is commercial or trade name.
(Answer) Thank you for your comment on the need to clarify the term "Cerrobend." Indeed, it is important for the readers to understand this commercial alloy and its relevance to our study. In response, we have provided an explanation in the revised manuscript:
L 102 – 105: Cerrobend, a commercial alloy composed mainly of bismuth, lead, tin, and cadmium that has a low melting point, was inserted into this PLA framework to finalize the construction of the add-on shielding device. This alloy is often used in medical applications where customized shaping of shields is required.
Author Response File: Author Response.docx
