Three-Dimensional Printed Silicone Bite Blocks for Radiotherapy of Head and Neck Cancer—A Preliminary Study
, Jehn-Chuan Lee 2,4, Chien-Ming Chu 5, Hung-Chi Tai 1,3, Tien-Chi Hou 1, Fred Yi-Shueh Chen 1, Chih-Wen Chi 6 and Yu-Jen Chen 1,2,6,7,8,*Round 1
Reviewer 1 Report
The authors have described the use of silicon 3D printed bite blocks. Due to their 3D printable nature, they can be easily customised for different patients, and the use of silicon 3D printing as opposed to MED610 is encouraging.
However, the authors have failed to confirm most of the claims made in the manuscript. Most importantly, the manuscript lacks any quantitative evaluation. Most if not all of the results have been described using subjective words, such as good, adequate, great, superior, etc. (Lines 98-100). Even the result and discussion of the key figure of the paper (Figure 4) lacks any quantitative evaluation and is limited to the usage of words like better, higher, lower, etc. Moreover, the whole study has been based on only two patients, which is too small to make any conclusion, more so when no significant difference was reported in one of them (Line 232-233).
The manuscript should also describe the silicon 3D printing procedure in more detail to allow its reproduction rather than just listing the name of the 3D printer.
Author Response
Point 1: The authors have failed to confirm most of the claims made in the manuscript. Most importantly, the manuscript lacks any quantitative evaluation. Most if not all of the results have been described using subjective words, such as good, adequate, great, superior, etc. (Lines 98-100). Even the result and discussion of the key figure of the paper (Figure 4) lacks any quantitative evaluation and is limited to the usage of words like better, higher, lower, etc. Moreover, the whole study has been based on only two patients, which is too small to make any conclusion, more so when no significant difference was reported in one of them (Line 232-233).
Response 1: We appreciate this helpful comment to make our contents more comprehensive. We have added on the quantitative evaluation as “the volume with minimum dose received by 100% of prescribed dose (PTV D100%)”, “maximum dose in the PTV (PTVmax)”, “minimum dose in the PTV (PTVmin) “, “conformity index (CI)“, and “homogeneity index (HI)” in the part of “2.8. Dosimetric comparison”, “3.2. Dosimetric comparison”. We have added 2 additional tables to summarize the dosimetry of the patients as follows:
|
Patient 1 |
3D printed bite blocks |
Conventional oral corks |
|
PTV D100% |
95% |
95% |
|
PTVmax |
107% |
106.2% |
|
PTVmin |
82.7% |
76.8% |
|
CI |
0.96 |
0.94 |
|
HI |
1.13 |
1.12 |
|
Median dose of oral cavity |
45.7 Gy |
48.6 Gy |
Table 1. Dosimetry of Patient 1.
|
Patient 2 |
3D printed bite blocks |
Conventional oral corks |
|
PTV D100% |
98% |
97% |
|
PTVmax |
103% |
106.1% |
|
PTVmin |
90.3% |
89.3% |
|
CI |
0.99 |
1.00 |
|
HI |
1.08 |
1.12 |
|
V26 of right parotid gland |
38% |
70% |
|
V26 of left parotid gland |
34% |
68% |
Table 2. Dosimetry of Patient 2.
In Discussion, the following paragraph has been added:
“In this investigation, we mainly aimed to establish the technique and processing procedures with optimization of intraoral materials for 3D printing. It is our understanding that preliminary results of clinical test from too few patients are not convinced to draw conclusion that 3D printed silicone bite blocks are better than conventional oral corks. However, the preliminary study shows a trend of better PTV coverage, dose homogeneity, and lower scattered dose to healthy tissue in these 2 patients. Further investigation is warranted for validation.”
Point 2: The manuscript should also describe the silicone 3D printing procedure in more detail to allow its reproduction rather than just listing the name of the 3D printer.
Response 2: For this issue, we have inserted additional description into “2.2. Materials of 3D printed bite blocks” & “2.5. 3D printing process” to elaborate it. Please refer to the revised text as below:
Revised text –
“2.2. Materials of 3D printed bite blocks
Initially, the 3D printed bite blocks were laid out with MED610, a biocompatible material widely used in medical treatment, surgical guides, orthopaedic procedures, and dental implants. However, patients with HNC often complained of pain and discomfort when 3D printed bite blocks fabricated from the rigid MED610 were used for oral wounds, mucositis, or xerostomia during RT. Therefore, we fabricated the 3D printed bite blocks with silicone, an elastic but firm, strong, durable, and safe material. These 3D printed bite blocks were manufactured by the silicone 3D printer (S100, San Draw Inc., Taiwan), and the material of bite blocks was SIL 28 (San Draw Inc., Taiwan), which was one part of Room Temperature Vulcanization (RTV) silicone specially designed for 3D printing, has passed biocompatibility testing of ISO 10993-5 (Figure 2). The hardness (ASTM D2240) of SIL 28 was 28, Shore A, and the tensile strength was 270psi. The tear strength was 5 kgf/cm, and the elongation was 300%. The silicone bite blocks had superior mechanical and physical properties, such as good elasticity, adequate rigidity, heat and cold resistance, and great biocompatibility. The hardness of the unique silicone 3D printed bite blocks was adjustable by varying their internal structures and silicone components. The silicone bite blocks lost their smell after being left to stand in air. Their dosimetry was examined and showed no interference in RT planning. All patients tolerated the blocks well in intraoral placement.”
“2.5. 3D printing process
CT images were converted into uncompressed digital imaging and communications in medicine (DICOM) images, and the occlusal surfaces were contoured. Tongue depressors were also contoured for tongue fixation. All data was saved as standard tessellation language (STL) files and imported into the 3D modeling software (Tinkercad, v. 2017, Autodesk Inc., USA). The 3D printing process was performed after the blueprint was checked by the radiation oncologists. The blueprint was shown in Figure 3. The STL files of the final digitalized 3D printed bite blocks were imported into the silicone 3D printer (S100, San Draw Inc., Taiwan) for 3D printing. A 3D printing system (FAMTM, San Draw Inc., Taiwan) was introduced for the process. FAMTM, which stood for Full-colour, Adjustable hardness, and Multi-material 3D printing, was specially designed to create multi-colour models out of RTV silicone, a flexible and tactile material. The 3D printed bite blocks were created with 3 mm of uniform thickness. The time required for 3D printing was approximate 2 hours. After the 3D bite blocks were printed, patients underwent a secondary CT simulation without contrast with the customized oral devices for RT planning.”
Author Response File: 
Author Response.docx
Reviewer 2 Report
Line 43 – add comma - 650,000
Line 59 – remove double full stop
Line 88 – What specific silicone material was used?
Author Response
Point 1: Line 43 – add comma - 650,000
Response 1: We appreciate this helpful comment for proofreading. We have added comma in line 43.
Point 2: Line 59 – remove double full stop
Response 2: We appreciate this helpful comment for proofreading. We have removed double full stop from line 59.
Point 3: Line 88 – What specific silicone material was used?
Response 3: For this issue, we have inserted additional description to elaborate it. Please refer to the revised text in “2.2. Materials of 3D printed bite blocks” as below:
Revised text –
“2.2. Materials of 3D printed bite blocks
Initially, the 3D printed bite blocks were laid out with MED610, a biocompatible material widely used in medical treatment, surgical guides, orthopaedic procedures, and dental implants. However, patients with HNC often complained of pain and discomfort when 3D printed bite blocks fabricated from the rigid MED610 were used for oral wounds, mucositis, or xerostomia during RT. Therefore, we fabricated the 3D printed bite blocks with silicone, an elastic but firm, strong, durable, and safe material. These 3D printed bite blocks were manufactured by the silicone 3D printer (S100, San Draw Inc., Taiwan), and the material of bite blocks was SIL 28 (San Draw Inc., Taiwan), which was one part of Room Temperature Vulcanization (RTV) silicone specially designed for 3D printing, has passed biocompatibility testing of ISO 10993-5 (Figure 2). The hardness (ASTM D2240) of SIL 28 was 28, Shore A, and the tensile strength was 270psi. The tear strength was 5 kgf/cm, and the elongation was 300%. The silicone bite blocks had superior mechanical and physical properties, such as good elasticity, adequate rigidity, heat and cold resistance, and great biocompatibility. The hardness of the unique silicone 3D printed bite blocks was adjustable by varying their internal structures and silicone components. The silicone bite blocks lost their smell after being left to stand in air. Their dosimetry was examined and showed no interference in RT planning. All patients tolerated the blocks well in intraoral placement.”
Author Response File: Author Response.docx
Reviewer 3 Report
The authors show the results of a research aimed at fabricating 3D customizable, silicone bite blocks so as to immobilize mouth and tongue for radiotherapy.
The paper sounds technically good. However, I have some concerns that authors should take into account so as to improve the paper:
- Figure 4 is too long. Because of its complexity, I suggest dividing it into other figures so that they can be analyzed separately. On the other hand, the figure is not clear, especially the relative dose part, so I suggest improving the resolution. The explanation (figure caption) of this figure is too long; I suggest that this explanation be part of the text itself.
- The conclusion part is too short. I suggest that the authors should set out in full detail the improvements achieved as well as future work.
Author Response
Point 1: Figure 4 is too long. Because of its complexity, I suggest dividing it into other figures so that they can be analyzed separately. On the other hand, the figure is not clear, especially the relative dose part, so I suggest improving the resolution. The explanation (figure caption) of this figure is too long; I suggest that this explanation be part of the text itself.
Response 1: We appreciate this helpful comment to make our contents more comprehensive. We have divided the Figure 4 into two parts (Figure 4 & Figure 5). To improve the visual quality, we have provided revised Figure 4 & Figure 5 of higher resolution in the attachment. For comparison of Figure 4a and 4b, we inserted new Figures in the manuscript with arrowhead indicated. Please see the attachment.
The explanation of Figure 4 & Figure 5 is too long. For this issue, we have incorporated the explanation into the main text (2.8. Dosimetric comparison & 3.2. Dosimetric comparison). Please refer to the revised text as below:
“2.8. Dosimetric comparison
Dosimetric parameters such as the PTV D100%, maximum dose in the PTV (PTVmax), minimum dose in the PTV (PTVmin), conformity index (CI), and homogeneity index (HI) of the PTV were calculated to analyse the quality of our RT planning. PTV D100% was the volume with minimum dose received by 100% of prescribed dose. PTVmax should not exceed 107% of the dose, and PTVmin should not be smaller than 95% of dose. The CI was defined as the ratio between the volume covered by the reference isodose, which according to the ICRU was 95% isodose and the target volume designated in this study was the PTVH. CI = VRI/TV, where VRI was reference isodose volume, and TV was target volume. The CI equal to 1 corresponded to the ideal dose coverage or high conformity. The CI greater than 1 indicated that irradiated volume exceeded the target volume and covered part of the healthy tissue. The CI less than 1 meant that the target volume was partially radiated. The HI was the ratio of the maximum dose in the target volume to the reference isodose. HI was Imax/RI, where Imax was maximum isodose in the target, and RI was reference isodose. The ideal value of HI was 1, and it increased as the plan became less homogeneous. The mean dose of the oral cavity was recorded for constraint concerning mucositis, and the V26 of bilateral parotid glands (the volume of the RT dose to 26 Gy in the parotid glands) was used for xerostomia consideration [14]. All dosimetric parameters were measured in comparison with conventional universal oral corks [15].”
“3.2. Dosimetric comparison
The dose distribution and dosimetry were reviewed as follows with the PTV D100%, PTVmax, PTVmin, CI, and HI of PTVH. The mean dose of the oral cavity and V26 of the bilateral parotid glands were also evaluated. For Patient 1, who was diagnosed with tongue cancer, cT2N0M0, stage II, he received composite resection for the primary tumour and neck lymph node dissection with pT2N0Mb, stage II. Adjuvant RT was arranged for perineural invasion. The PTVH was the surgical bed of the primary tumour with margins. The dosimetry when silicone 3D printed bite blocks were used exhibited better coverage of the PTVH and surface of the oral tongue than when conventional universal oral corks were used. The CIs of the PTVH of the plan with 3D printed bite blocks was 0.96, compared to the plan with conventional oral corks, 0.94. The HIs of the PTVH were 1.13 and 1.12. The median dose for the oral cavity was 45.7 Gy and 48.6 Gy (Table 1). The isodose line in 95% of the prescribed dose to the PTVH showed better coverage when silicone 3D printed bite blocks were used than conventional oral corks in the RT process (Figure 4a versus 4b with arrowhead indicated). The dose scattered to the oral cavity was lower when silicone 3D printed bite blocks were used than conventional oral corks. The radiation dose and hot spot of the oral tongue were higher with better constraints of adjacent normal tissues when silicone 3D printed bite blocks functioned as boluses (Figure 4).
For Patient 2, who was diagnosed as having left tonsil cancer. He received an operation, and a positive margin was noted in pathologic review. Adjuvant RT was arranged. The PTVH was the surgical bed of the primary tumour with margins. Dosimetry with the silicone 3D printing bite block showed similar distribution in PTVH to that with the conventional oral cork. In the DVH analysis, the RT dose that scattered to adjacent normal tissues such as bilateral parotid glands was lower when using the silicone 3D printing bite block than with conventional oral cork. The CIs of the PTVH of each plan were 0.99 and 1.00, and the HIs of the PTVH were 1.08 and 1.12. The HI was lower with 3D printed bite blocks, indicating a higher homogeneity. The V26 of the right parotid gland was 38% and 70%, and V26 of the left parotid gland was 34% and 68% (Table 2). The radiation dose to the bilateral parotid glands was lower with silicone 3D printing bite blocks (Figure 5).”
Point 2: The conclusion part is too short. I suggest that the authors should set out in full detail the improvements achieved as well as future work.
Response 2: For this issue, we have inserted additional description to elaborate it. Please refer to the revised text as below:
Original text –
“We fabricated silicone 3D printed bite blocks and used them in a clinical RT process. The material and shape of the oral devices were determined after taking into account the comfort of the patients and potential setup up errors. The 3D printed bite blocks with silicone might be a customizable, safe, and practical advanced technology for RT of head and neck cancer. Further clinical investigations for validation are warranted.”
Revised text –
“We fabricated silicone 3D printed bite blocks and used them in a clinical RT process. The material and shape of the oral devices were determined after taking into account the comfort of the patients and potential setup up errors. The tongue depressors helped to improve oral fixation during RT. A homogeneous dose may be obtained in the tumour bed with the 3D printed bite blocks when RT evaluation. The scattered dose to healthy tissue may decrease when uniform dose focused on the tumour bed. The 3D printed bite blocks with silicone might be a customizable, safe, and practical advanced technology for RT of head and neck cancer. However, considering the small case number, a large prospective study is needed, and SOPs should also be established for future work. Further clinical investigations for validation are warranted.”
Author Response File: Author Response.docx
