Three-Dimension-Printed Custom-Made Prosthetic Reconstructions in Bone Tumors: A Single Center Experience

Round 1

Reviewer 1 Report

The review is quite vague, the topic is addressed in generic terms.

The approach is too much “clinical”, which is weird when in discussion there is novel technology. Antibiotic and farmacologic procedures, pre-/post- op are relevant, but the surgical issues here seem to be more of interest for the readers. Superficial porosity of the protheses for osteointegration is ok, but what about the contact with the other tissues.

1. What is the main question addressed by the research?
   It is simply a report of a number of cases of custom implants
   
   2. Do you consider the topic original or relevant in the field, and if so, why?
   Not very original; many centre have done this similar exercise, and many more will do soon
   
   3. What does it add to the subject area compared with other published material?
   A little, just a few more cases for general considerations
   
   4. What specific improvements could the authors consider regarding the methodology?
   Entering into details on design and technology related issues
   
   5. Are the conclusions consistent with the evidence and arguments presented and do they address the main question posed?
   In part
   
   6. Are the references appropriate?
   Yes; though many more can be added
   
   7. Please include any additional comments on the tables and figures.
   Tables are ok. Figures are poor (two Xray and one picture from the operating theathre); more modelling and technical aspects should be shown

Author Response

Dear Editor,

We are pleased to submit our R1 version of the manuscript entitled “Three-dimension-printed custom-made prosthetic reconstruc-tions in bone tumors: a single center experience”.  The reviewers’ comments have been very appreciated. Therefore, an itemized response, structured as a point-by-point answer, is provided below in the attached files.

The review is quite vague, the topic is addressed in generic terms.

The approach is too much “clinical”, which is weird when in discussion there is novel technology. Antibiotic and farmacologic procedures, pre-/post- op are relevant, but the surgical issues here seem to be more of interest for the readers. Superficial porosity of the protheses for osteointegration is ok, but what about the contact with the other tissues.

Authors’ response: Dear Reviewer,  we are really pleased with your valuable observations on our work. We indicated in materials and methods section soft tissue reconstruction by trevira tube.

 

What is the main question addressed by the research?
Authors’ response:

It is simply a report of a number of cases of custom implants

Not very original; many centre have done this similar exercise, and many more will do soon
Authors’ response:

Thanks for the comment. We would like to specify that this type of surgery is quite rare and the papers in the literature rarely exceed 20 patients treated. Furthermore, in our work we introduce the use of silver as an infection prevention, an innovation not present in other paper.

 

Please include any additional comments on the tables and figures.
Tables are ok. Figures are poor (two Xray and one picture from the operating theathre); more modelling and technical aspects should be shown.

Authors’ response:

Dear reviewer, as kindly suggested we added more imaging regarding the preoperative planning and the prosthesis model.

Reviewer 2 Report

Vitiello et al. reported the single center experience of 3D printed customized prosthetic reconstructions in bone tumors. The study is satisfactory described although briefly discussed, and is anyway intersting in the pesonalized medicine landscape. Some points must be improved:

 

Major comments:

1.       Abstract: please add a line including the 3D printed material and the method the scaffold shape was custom-made.

2.       Introduction: Add some specifications about the 3D printed materials used for this and similar applications, including a description of the customization process, from CT to 3D printing and sterilization methods.

3.       Please indicate the number of cases that were retrospectively analyzed in the given period.

4.       Lines 156-160: Satisfaction assessment of patients should be better described and given as a separate section in the Methods, not inside “Clinical and radiological follow up”

1.       Discuss your study by including additional considerations about the befits of using personalized versus non-personalized prosthetic reconstruction. Please mention other studies that reported on personalized bone reconstruction with biomaterials, e.g., for dental or maxillofacial applications, and give a general comment on the advancement in thi field.

Minor comments:

·         Lines 82 and 85: Remove extra blank spaces after “[17]” and in/after “Helsinki .”

·         Line 87: Do you have a protocol number?

·         Line 113: Is “(GM)” the name/last name initials of the expert in oncologic orthopedic surgery? If so, please write “G.M.”. Otherwise explain the acronym.

·         Line 152: Extra blank space in “[21].”

·         Line 156: Change “12 months follow up visit” into “12 month follow up visit”. Month is an adjective thus non-plural.

·         Table 2: What does “N pt” stand for? Please state in footnotes all acronyms even if already given in the text. The table must be self explanatory. Use dot and not comma for decimal numbers as from scientific english best parctice. In BMI, please insert values with same accuracy: 26 must be 26.00.

·         Lines 183 and 184: Use “dL” for deciliters.

·         Lines 184-87: Remove extra blank spaces.

·         Tables 3 and 4: Same type of corrections as in Table 2.

·         Line 213: Be consistent with “3D” or “3-D” through the text.

·         Line 229, 238, 244, 246, 250, 266, 286, 300: Remove extra blank spaces. Punctuation is before references, please change.

·         Line 254: Address this typo “[RV14]”

·         Line 255: Change comma into dot in “3,6 g/dL”

Author Response

Dear Editor,

We are pleased to submit our R1 version of the manuscript entitled “Three-dimension-printed custom-made prosthetic reconstruc-tions in bone tumors: a single center experience”.  The reviewers’ comments have been very appreciated. Therefore, an itemized response, structured as a point-by-point answer, is provided below in the attached files.

Vitiello et al. reported the single center experience of 3D printed customized prosthetic reconstructions in bone tumors. The study is satisfactory described although briefly discussed, and is anyway intersting in the pesonalized medicine landscape. Some points must be improved:

 

Major comments:

1. Abstract: please add a line including the 3D printed material and the method the scaffold shape was custom-made.

Authors’ response:

Dear reviwer, we would like to thank you for the time spent in reviewing our investigation and for the valuable comments you provided us.  As you kindly suggested we added in the abstract a line including the method and the scaffold shape was custom-made

 

2. Introduction: Add some specifications about the 3D printed materials used for this and similar applications, including a description of the customization process, from CT to 3D printing and sterilization methods.

Authors’ response:

As you suggested we added some more information about the prostheses manufacturing process, from the DICOM images acquisition to preoperative sterilization.

3. Please indicate the number of cases that were retrospectively analyzed in the given period.

Authors’ response: We indicated in the following version the total number of patient we analyzed from March 2016 and March 2021

4. Lines 156-160: Satisfaction assessment of patients should be better described and given as a separate section in the Methods, not inside “Clinical and radiological follow up”

Authors’ response: we made an additional chapter for the patients’ satisfaction assessment

1. Discuss your study by including additional considerations about the befits of using personalized versus non-personalized prosthetic reconstruction. Please mention other studies that reported on personalized bone reconstruction with biomaterials, e.g., for dental or maxillofacial applications, and give a general comment on the advancement in thi field.

Authors’ response: We included some more consideration of 3d prostheses reconstruction benefits and we mentioned other studies as you kindly suggested.

 

Minor comments:

• Lines 82 and 85: Remove extra blank spaces after “[17]” and in/after “Helsinki .”
• Line 87: Do you have a protocol number?
• Line 113: Is “(GM)” the name/last name initials of the expert in oncologic orthopedic surgery? If so, please write “G.M.”. Otherwise explain the acronym.
• Line 152: Extra blank space in “[21].”
• Line 156: Change “12 months follow up visit” into “12 month follow up visit”. Month is an adjective thus non-plural.
• Table 2: What does “N pt” stand for? Please state in footnotes all acronyms even if already given in the text. The table must be self explanatory. Use dot and not comma for decimal numbers as from scientific english best parctice. In BMI, please insert values with same accuracy: 26 must be 26.00.
• Lines 183 and 184: Use “dL” for deciliters.
• Lines 184-87: Remove extra blank spaces.
• Tables 3 and 4: Same type of corrections as in Table 2.
• Line 213: Be consistent with “3D” or “3-D” through the text.

 

Authors’ response: Dear reviewer, we are thankful for your valuable observation. We correct all the typo and errors you pointed-out.

 

Reviewer 3 Report

In the manuscript entitled "Three-dimension-printed custom-made prosthetic reconstructions in bone tumors: a single center experience" are reporting in the outcome of 3D printed prosthesis used for bone reconstruction needed following bone tumors management.

Monitoring the patients following prosthetic implantation is important as well their evolution and response to the implantation.

The paper presents some potential, however some issues need to be addressed.

 The results are just summarily presented. Some more data should be reported. 

For example, in table 2 and 3 are detailed a series of information regarding the demographic information as well as blood values for all patients. However, when the data reporting the patients outcomes are reported, only the average are reported. Table 4 should report the data in a similar manner as the one reported in table 2 and 3.

 

Author Response

Dear Editor,

We are pleased to submit our R1 version of the manuscript entitled “Three-dimension-printed custom-made prosthetic reconstruc-tions in bone tumors: a single center experience”.  The reviewers’ comments have been very appreciated. Therefore, an itemized response, structured as a point-by-point answer, is provided below in the attached files.

 

In the manuscript entitled "Three-dimension-printed custom-made prosthetic reconstructions in bone tumors: a single center experience" are reporting in the outcome of 3D printed prosthesis used for bone reconstruction needed following bone tumors management. Monitoring the patients following prosthetic implantation is important as well their evolution and response to the implantation. The paper presents some potential, however some issues need to be addressed. The results are just summarily presented. Some more data should be reported. For example, in table 2 and 3 are detailed a series of information regarding the demographic information as well as blood values for all patients. However, when the data reporting the patients outcomes are reported, only the average are reported. Table 4 should report the data in a similar manner as the one reported in table 2 and 3.

 

Authors’ response:  Firstly we would like to thank you for the time spent in reviewing our investigation and for the valuable suggestions you provided us.

We modified the Table 4 as you suggested. The results were exposed deeply.

Reviewer 4 Report

The authors provided clinical results and discussions on implants fabricated using electron beam melting. While the manuscript is generally well executed, there are several issues that should be addressed before further consideration for publication.

1. There are several details lacking in the experiments. Suggest the authors to provide a more detailed description of electron beam melting and additive manufacturing (3D printing). There is also need to provide the scanning procedure (for example, what are the scanning parameters involved?)

2. What are the preliminary studies conducted for the implants fabricated? Any benchmarking done? There are quite a bit of work done on EBM produced implants.

3. Is there a control group for the implants and discussions?

Author Response

1. There are several details lacking in the experiments. Suggest the authors to provide a more detailed description of electron beam melting and additive manufacturing (3D printing). There is also need to provide the scanning procedure (for example, what are the scanning parameters involved?)

Authors’ response:  Firstly we would like to thank you for the time spent in reviewing our investigation and for the valuable suggestions you provided us. We have added the required details within the text (Materials and Methods)

 

2. What are the preliminary studies conducted for the implants fabricated? Any benchmarking done? There are quite a bit of work done on EBM produced implants.

Authors’ response:  We have added the required details about previous jobs that have already used a similar technology.

 

3. Is there a control group for the implants and discussions?

Authors’ response:  There is no control group. The alternative to using custom made prostheses are bone graft from a cadaveric donor. Any difference will be analyzed in an ad hoc paper.

Round 2

Reviewer 1 Report

The authors have addressed my issues, and manuscript has thus improved.

Author Response

Thank you very much for your appreciation and for the time you have dedicated to us.

Reviewer 3 Report

The authors have made the changes suggested and the manuscript improved. The manuscript can be accepted in the present form.

Author Response

Thank you very much for your appreciation and for the time you have dedicated to us.

Reviewer 4 Report

While the authors have addressed most of the concerns raised, there are still some minor clarifications needed before further consideration for publication.

1. For the electron beam melting process, is the powder sintered or fully melted? The following reference might be useful for description of the electron beam melting process.

- Sing et al. (2016), Laser and electron‐beam powder‐bed additive manufacturing of metallic implants: A review on processes, materials and designs, Journal of Orthopaedic Research 34 (3), 369-385

2. For the material, Ti6Al4V should be used instead of subscript for the numbers as it is an alloy, not a chemical compound

Author Response

Changed as required and suggested quotation added. Thank you.