Thymoma and Thymic Carcinoma: Surgical Resection and Multidisciplinary Treatment

Round 1

Reviewer 1 Report

The authors present a comprehensive review of Thymoma and Thymic carcinoma.

Author Response

Thank you very much for reading this review and approving the article. We appreciate it!

Reviewer 2 Report

The manuscript summarized current surgical-orientated treatments for thymic tumors, and underscored the importance of multidisciplinary approach and surgeon’s expertise towards this disease.

Overall the manuscript is well written, and did impact and expand the knowledge pool of its field.

Major concern is that a review of this put much emphasis on surgeon's experience and skill would divert other key points that are also important and more feasible to generalize.

Other than language, the figures also need modification, i.e., images of fig 2 were labeled in Chinese. Fig 3 patient’s CT prior to the surgery should have been included. Fig 4, tissues and structures described in the fig legend should have been properly labeled in the corresponding images.

Author Response

We would like to begin with our sincere appreciation for all the valuable comments, insightful suggestions and thoughtful corrections offered our manuscript (cancers-2234842). The comments and suggestions definitely helped us to improve the quality of the manuscript. We have revised the manuscript in which all revisions have been marked up using the “Track Changes”

Point 1: Major concern is that a review of this put much emphasis on surgeon's experience and skill would divert other key points that are also important and more feasible to generalize.

Response 1: Thank you for your suggestion. We agree with your viewpoint. The review focuses on thymic tumor surgery and the surgeons' surgical experience needs to be shared. There is still a lack of high-quality research in the field of thymic tumors, and we hope to combine our center's experience to present a referable perspective to draw the attention of researchers in related fields.

 

Point 2: Other than language, the figures also need modification, i.e., images of fig 2 were labeled in Chinese. Fig 3 patient’s CT prior to the surgery should have been included. Fig 4, tissues and structures described in the fig legend should have been properly labeled in the corresponding images.

Response 2: We appreciate your suggestion. We have revised it as your suggestion. We have rechecked the grammar and expressions to enhance the readability of the article. The structure in Figure 2 has been added in English. Figure 3 was misunderstood due to poor description of the annotation. abcd images are all preoperative CTs to show the relationship between the tumor and major vessels. In Figure 4, we have re-labeled the structures in the images.

 

Reviewer 3 Report

The review introduces some surgical treatment and neoadjuvant therapy for thymic tumors in addition to their experience about how to manage debatable issues. I suggest a major revision.

1.         Some grammar, editing and typing errors must be corrected.

2.         The content is sometimes confused and not immediate to understand. And there are some unintelligible long sentences in this manuscript, consider rephrasing.

3.         When VATs and TETs first appear in INTRODUCTION, they should be marked with full names.

4.         “Surgical resection is the mainstay of the treatment for thymoma and thymic carcinoma; a multimodal approach is useful for many patients.” According to the REFERENCES, these two sentences lack the appropriate conjunctions.

5.         The cited references need to be significantly improved. Currently, there are several citations are too old, such as published in 2003 or 2004. Those references should be deleted or substituted.

6.         “The pathological stage and the radicality of the surgical resections are factors which predict patient survival.” The word “parent” in this sentence should be “parent’s”.

7.         Tumor staging should be one of the main factors affecting the selection of surgical treatment.

8.         There is something wrong with the notes in Figure2. “Increased retrosternal space is created by our sternum-lifting system, the relevant anatomy easily identified, and more complex dissection can be achieved of a.” The word “of a” in this sentence needs to be cut out.

9.         A Methods section should be inserted to exlain the methodology used for literature searching. I know that it is a narrative review but adding this paragraph can increase the scientific soundness of the work.

10.      In part 3 “Debatable issues about surgery for thymic tumors”, 3.2-3.6 does not present the main points of the dispute but merely enumerates them.

11.      There is a very weak connection between the topics, they were randomly distributed around the text.

Author Response

We would like to begin with our sincere appreciation for all the valuable comments, insightful suggestions and thoughtful corrections offered our manuscript (cancers-2234842). The comments and suggestions definitely helped us to improve the quality of the manuscript. We have revised the manuscript in which all revisions have been marked up using the “Track Changes”.

Point 1: Some grammar, editing and typing errors must be corrected.

Response 1: Thank you for pointing out the mistakes. We have corrected the mistakes.

Point 2: The content is sometimes confused and not immediate to understand. And there are some unintelligible long sentences in this manuscript, consider rephrasing.

Response 2: Thank you for your valuable comments. We have rechecked the grammar and expressions to enhance the readability of the article.

Point 3: When VATs and TETs first appear in INTRODUCTION, they should be marked with full names.

Response 3: Thank you for pointing out the mistake. We have replaced the first occurrence of these two terms with the full name.

Comment 4:“Surgical resection is the mainstay of the treatment for thymoma and thymic carcinoma; a multimodal approach is useful for many patients.” According to the REFERENCES, these two sentences lack the appropriate conjunctions.

Response 4: Thank you for your suggestion. We rechecked the reference and changed the sentence to “Surgical resection is the mainstay of the treatment for thymoma and thymic carcinoma; while a multimodal approach is proved to be useful for many patients.”

Point 5: The cited references need to be significantly improved. Currently, there are several citations are too old, such as published in 2003 or 2004. Those references should be deleted or substituted.

Response 5: Thank you for your suggestion. We removed two papers published in 2003 and 2004. The reason for citing them at that time was that there were some consensus conclusions in them.

Point 6:“The pathological stage and the radicality of the surgical resections are factors which predict patient survival.” The word “parent” in this sentence should be “parent’s”.

Response 6: Thank you for pointing out the mistake. We correct the“patient”to “patient’s”.

Point 7: Tumor staging should be one of the main factors affecting the selection of surgical treatment.

Response 7: Thank you for your advice. Tumor staging is indeed important for the choice of surgical treatment. We have added this point to 2.2.

Point 8: There is something wrong with the notes in Figure2. “Increased retrosternal space is created by our sternum-lifting system, the relevant anatomy easily identified, and more complex dissection can be achieved of a.” The word “of a” in this sentence needs to be cut out.

Response 8: Thank you for pointing out the mistake. We cut out the word “of a”.

Point 9: A Methods section should be inserted to explain the methodology used for literature searching. I know that it is a narrative review but adding this paragraph can increase the scientific soundness of the work.

Response 9: Thanks for your suggestions. We have added search and filtering methods to the “Methods” section.

Point 10: In part 3 “Debatable issues about surgery for thymic tumors”, 3.2-3.6 does not present the main points of the dispute but merely enumerates them.

Response 10: Thank you for your suggestion. For each topic in 3.2-3.6, we have summarized the main ideas based on the center's experience.

 

Point 11: There is a very weak connection between the topics, they were randomly distributed around the text.

Response 11: Thank you for your suggestion. We have reordered some sections to make the text flow better. We try to present a comprehensive overview of the multidisciplinary treatment of TETs, with a focus on surgical approaches.

 

Reviewer 4 Report

Dear Authors and Editors,

 I read with interest the manuscript entitled” Thymoma and Thymic Carcinoma: Surgical Resection and Multidisciplinary Treatment” by Zhang et colleagues.

 Author provided a brief report of the main debated issued in the TET management.

The text is really interesting with a lot of explanatory pictures.

However, there are some issued and concerns that should solved.

1)      The text should be extensively reviewed by an English mother-tongue specialist.

2)      In the introduction, authors reported that median OS is 18.9 years for thymoma. This sentence should be removed since it is incorrect. In most cases OS is not affected at all by thymoma due to the indolent behavior of thymoma (in most cases).

3)      Introduction provided a long summary of all the main thymoma features (from the epidemiology to the multimodality treatment) that could be cut because they are not related to the aim of the text and make the introduction too long and poorly readable.

4)      In 2.1.1 chapter is not clear which center is referred to; moreover, each reported point should be discussed.

5)      In 2.2 paragraph, authors should report the standard of care with the main guidelines before reporting the single center experience (the paragraph 3.2 should be advanced). Authors may provide a table with all pros and con of all the approaches.

6)      Authors should better explain what they mean for complete thymectomy (i.e. extended thymectomy according to Masaoka or Jaretsky?, including or not the peri-aortic fat?)

7)      The discussion of unresectable and/or advanced thymoma should be better defined (PMID: 34252198)

8)      Authors should check all the references (i.e Francesco and colleagues at line 359 should be an error)

9)      The chemo-immunotherapy paragraph is relay interesting, authors should extend this section with one o more table with the standard of care and the new proposals for unresectable or R1/2 and M+ thymoma and thymic carcinoma.  

10)   4.2 should be modified in radiation therapy (not radiologists)

11)   The main contentious issues (as reported by authors) are not exhaustively discussed in the text. I suggest reducing their number and provide a better analysis of the selected topic as the role of the MIS. Other topic as the salvage surgery and debulking surgery have been only briefly reported, and they could be removed.

12)   All the discussion on the IVa Thymoma is lack. I really believe that the role of the multidisciplinary team is better appreciated in these cases. Author should consider also the role of intracavitary therapies (PMID: 32170942).

13)   Also the role of MG should be better analyzed (PMID: 33358889).

Author Response

We would like to begin with our sincere appreciation for all the valuable comments, insightful suggestions and thoughtful corrections offered our manuscript (cancers-2234842). The comments and suggestions definitely helped us to improve the quality of the manuscript. We have revised the manuscript in which all revisions have been marked up using the “Track Changes”

Point 1: The text should be extensively reviewed by an English mother-tongue specialist.

Response 1: Thank you for your suggestion. We have rechecked the grammar and expressions to enhance the readability of the review. The structure in Figure 2 has been added in English.

Point 2: In the introduction, authors reported that median OS is 18.9 years for thymoma. This sentence should be removed since it is incorrect. In most cases OS is not affected at all by thymoma due to the indolent behavior of thymoma (in most cases).

Response 2: Thank you for your suggestion, we reconsidered this data and decided to delete the data of OS for thymoma.

Point 3: Introduction provided a long summary of all the main thymoma features (from the epidemiology to the multimodality treatment) that could be cut because they are not related to the aim of the text and make the introduction too long and poorly readable.

Response 3: Thank you for your suggestion. We have reduced the length of the introduction section and changed some paragraphs.

Point 4: In 2.1.1 chapter is not clear which center is referred to; moreover, each reported point should be discussed.

Response 4: Thank you for your advice. 2.1.1 is to clarify, which cases we would consider for open incisions and procedures assisted by large vessel replacement or CPB etc., which often require adequate space due to the operation's complexity and the tumor's aggressiveness, based on Shanghai General hospital experience.

Point 5: In 2.2 paragraph, authors should report the standard of care with the main guidelines before reporting the single center experience (the paragraph 3.2 should be advanced). Authors may provide a table with all pros and con of all the approaches.

Response 5: Thanks for your suggestion. The recommendations in the currently available guidelines are: “Minimally invasive procedures are not routinely recommended due to the lack of long-term data. However, minimally invasive procedures may be considered for clinical stage I-II if all oncologic goals can be met as in standard procedures, and if performed in specialized centers by surgeons with experience in these techniques.” We have added a brief description of the guide to the review and a table for the surgical approaches.

Point 6: Authors should better explain what they mean for complete thymectomy (i.e. extended thymectomy according to Masaoka or Jaretsky?, including or not the peri-aortic fat?)

Response 6: Thank you for your suggestion. Complete thymectomy is defined as the removal of the entire thymus including the thymoma.

Point 7: The discussion of unresectable and/or advanced thymoma should be better defined (PMID: 34252198)

Response 7: Thank you for your suggestion. We have added the definition of advanced thymoma and cited this literature.

Point 8: Authors should check all the references (i.e Francesco and colleagues at line 359 should be an error)

Response 8: Thank you for your suggestion. We rechecked all references. The reference itself is fine, we corrected the name of the author.

Point 9: The chemo-immunotherapy paragraph is relay interesting, authors should extend this section with one more table with the standard of care and the new proposals for unresectable or R1/2 and M+ thymoma and thymic carcinoma. 

Response 9: Thank you for your suggestion. About the chemo-immunotherapy and the comparison of treatment methods, we will continue to study and show in our future work. In this review, because of the limited space, we mainly introduce surgical treatment and give a brief introduction to chemotherapy and immunotherapy, and we hope that further research in this part will be carried out in the future to enrich the multidisciplinary treatment.

Point 10: 4.2 should be modified in radiation therapy (not radiologists)

Response 10: Thank you for pointing out the mistake. We have corrected it as your advice.

Point 11: The main contentious issues (as reported by authors) are not exhaustively discussed in the text. I suggest reducing their number and provide a better analysis of the selected topic as the role of the MIS. Other topic as the salvage surgery and debulking surgery have been only briefly reported, and they could be removed.

Response 11: Thank you for your suggestion. The research on this part is really limited and we would like to discuss it in the context of our experience in order to draw the attention of relevant scholars. Salvage surgery and debulking surgery are situations that are sometimes encountered in clinical work and are rarely reported, so we would like to share these experiences.

 

Point 12: All the discussion on the IVa Thymoma is lack. I really believe that the role of the multidisciplinary team is better appreciated in these cases. Author should consider also the role of intracavitary therapies (PMID: 32170942).

Response 12: Thanks for your suggestion. There are fewer studies on the treatment of stage IV tumors and multidisciplinary studies, and we hope that more relevant studies will be available in the future. Intracavitary therapy is indeed a novel modality, and we have added this to the review.

Point 13: Also the role of MG should be better analyzed (PMID: 33358889).

Response 13: Thank you for your suggestion. Myasthenia gravis is indeed an important symptom in thymic tumors, and in the introduction section we described patients with symptoms of myasthenia gravis can improve their symptoms with surgical treatment. This article presents valuable arguments for the function of surgical therapy for MG. We have added it to the references.

 

Reviewer 5 Report

the Authors present a comprehensive overview of the multidisciplinary treatment of TETs, with a focus on surgical approaches.

This review has undoubtely a good educational value and is well presented. I can offer a few comments/suggestions:

- I understand that this is a narrative review, but can the Authors provide some explanations on how literature was selected for consideration.

- The Introduction is a bit long: I suggest to provide a brief statement of the scopes of the paper, and then divide the current content into some more paragraphs.

- The Discussion can be extended.

Author Response

We would like to begin with our sincere appreciation for all the valuable comments, insightful suggestions and thoughtful corrections offered our manuscript (cancers-2234842). The comments and suggestions definitely helped us to improve the quality of the manuscript. We have revised the manuscript in which all revisions have been marked up using the “Track Changes”.

Point 1: I understand that this is a narrative review, but can the Authors provide some explanations on how literature was selected for consideration.

Response 1: Thanks for your suggestions. We have added search and filtering methods to the “Methods” section.

Point 2: The Introduction is a bit long: I suggest to provide a brief statement of the scopes of the paper, and then divide the current content into some more paragraphs.

Response 2: Thank you for your suggestion. We have reduced the length of the introduction section and changed some paragraphs.

Point 3: The Discussion can be extended.

Response 3: Thank you for your suggestion. The discussion section of the article is short because we have discussed various aspects of the main surgical treatment in the review. In essence, the review itself discusses many details, and the content in the discussion section focuses on the reasons why thymic tumors are currently less studied and what needs to be done in the future.

Round 2

Reviewer 4 Report

Dear Editors and Authors

 I really appreciated the effort made to change the manuscript according to the reviewers suggestions.

 I believe that article is suitable for pubblication.

 Best regards

Author Response

Dear reviewer,

Thank you for taking the time to read my review and for your insightful comments, which help to make it more thorough and readable.

Many thanks!

Best regards