Outcome of Reoperation for Local Recurrence Following En Bloc Resection for Bone Giant Cell Tumor of the Extremity

Round 1

Reviewer 1 Report

The Authors performed an observational retrospective study reporting on the clinical outcomes of patients affected with giant cell tumor of the bone, experiencing local relapse, and salvaged with en bloc resection. This is a multicentric study performed in 3 Institution in Italy, Greece, and Japan. The manuscript is of interest. Hereby few comments:

 

Introduction

 

-        I would suggest defining what is meant by ‘en bloc’ resection and what are the challenges and advantages of this approach, considering the different anatomical sites of disease presentation.

 

Material and methods

-        Lines 64-65. This information is already included in Figure 1. Please eliminate this sentence.

-        Line 66-69. Again, this is already there in Figure 1.

-        A) Denosumab administration before the first en bloc resection; B) denosumab administration before surgery for local recurrence. I think these 2 sentences can be combined: Denosumab administration before the first en bloc resection and before salvage surgery (or similarly upon author’s choice).

-        Line 78: what do you mean by ‘oncological outcome’?

-        Table 2: I think it is a bit confusing the way you display the so defined ‘oncological outcome’ in Table 2. What is NED (local recurrence) and NED (metastasis)? Do you mean patients free from local recurrence: meaning either with no evidence of recurrence at any site or with a recurrence in sites other than local? And free from distant metastasis: no evidence of relapse or with a local recurrence and no metastasis? Please clarify.

Author Response

Reviewer 1

Comment

The Authors performed an observational retrospective study reporting on the clinical outcomes of patients affected with giant cell tumor of the bone, experiencing local relapse, and salvaged with en bloc resection. This is a multicentric study performed in 3 Institution in Italy, Greece, and Japan. The manuscript is of interest. Hereby few comments:

 

Introduction

I would suggest defining what is meant by ‘en bloc’ resection and what are the challenges and advantages of this approach, considering the different anatomical sites of disease presentation.

 

Response

We have replaced the original sentences with the following sentences. (the “Introduction” section in the revised manuscript): “En bloc resection (resection of a large bulky tumor virtually without dissection) should be considered in cases of extensive cortical destruction with extensive soft tissue involvement [15,16]. GCTB often extends close to the joints, necessitating resection of the joints and reconstruction with prosthesis or allografts in extremities other than the proximal fibula and distal ulna [15,16]. En bloc re-section and reconstruction with a prosthesis or allograft can reduce local recurrence rates (2–13%) compared to curettage; however, postoperative function is poor, leading to more frequent complications, such as loosening of the pros-thesis, fracture of the allograft, and joint subluxation [16–18]. Because tourniquets cannot be used for GCTB in the proximal femur or proximal humerus, the amount of bleeding is greater than that at other extremity sites. Hence, pre-operative embolization is required [16,17]."

 

Comment

Material and methods

Lines 64-65. This information is already included in Figure 1. Please eliminate this sentence.

 

Response

We deleted the sentence as you suggested.

 

Comment

Line 66-69. Again, this is already there in Figure 1.

 

Response

We deleted the sentence as you suggested.

 

Comment

1. A) Denosumab administration before the first en bloc resection; B) denosumab administration before surgery for local recurrence. I think these 2 sentences can be combined: Denosumab administration before the first en bloc resection and before salvage surgery (or similarly upon author’s choice).

 

Response

We have replaced the original sentences with the following sentences. (the “Materials and Methods” section in the revised manuscript): “denosumab administration before the first en bloc resection and before surgery for local recurrence,”

 

Comment

Line 78: what do you mean by ‘oncological outcome’?

 

Response

We added the following sentences into the “Materials and Methods” section: “oncological outcome (whether or not the tumor was observed at the final fol-low-up, whether or not the patient died of the tumor),”

 

Comment

Table 2: I think it is a bit confusing the way you display the so defined ‘oncological outcome’ in Table 2. What is NED (local recurrence) and NED (metastasis)? Do you mean patients free from local recurrence: meaning either with no evidence of recurrence at any site or with a recurrence in sites other than local? And free from distant metastasis: no evidence of relapse or with a local recurrence and no metastasis? Please clarify.

 

Response

We added the following sentences into the “Table 2” section: “*NED (local recurrence) indicates no tumor after treatment for local recurrence. NED (metastasis) indicates no tumor after treatment for distant metastases. Patients who were tumor-free after treatment for both local recurrence and distant metastasis were classified as having NED (metastasis). AWD (metastasis) refers to alive with distant metastasis.”

 

Responses to the Reviewer

Thank you for your detailed and thoughtful comments regarding our manuscript. Our article became better thanks to you.

Author Response File: Author Response.docx

Reviewer 2 Report

The theme is handled very well. I recommend improving the clarity of tables 1 and 2. Otherwise, I have no other comments on the article.

Author Response

Reviewer 2

Comment

The theme is handled very well. I recommend improving the clarity of tables 1 and 2. Otherwise, I have no other comments on the article.

 

Response

As you suggested, we deleted the content that overlaps with the text in Table 1.We added the following sentences into the “Table 2” section: “NED (local recurrence) indicates no tumor after treatment for local recurrence. NED (metastasis) indicates no tumor after treatment for distant metastases. Patients who were tumor-free after treatment for both local recurrence and distant metastasis were classified as having NED (metastasis). AWD (metastasis) refers to alive with distant metastasis.”

 

 

Responses to the Reviewer

Thank you for your detailed and thoughtful comments regarding our manuscript. Our article became better thanks to you.

Author Response File: Author Response.docx

Reviewer 3 Report

It was a pleasure to review this exciting manuscript on GCTB—generally few remarks rather than negative comments. With a total of 12 self-citations for the 1st and the last authors and 9 for 2nd, where other co-authors are also included in the self-cited articles, it all, unfortunately, looks like Tsukamoto, Mavrogenis & Errani & Co LTD rather than an innovative piece of work. Especially that other articles also analyse the same group of patients with similar scope starting from 1980. With 17% of all citation for the first author this is on the verge of accepted number of self-citations even though they are all within the scope of the article. Anyway, I can't see any information on H3F3A, especially with patients subject to malignant transformation. Despite the tumour, I would expect all malignant cases to have their initial diagnosis re-confirmed with H3F3A or need to be excluded. Not sure why the authors analyse patients from the period between Jan 1980 and Dec 2021 when they exclude a priori all patients with f/u shorter than 18 months. Otherwise, an interesting piece of work worth publication. Congratulation!

Author Response

Reviewer 3

Comment

It was a pleasure to review this exciting manuscript on GCTB—generally few remarks rather than negative comments. With a total of 12 self-citations for the 1st and the last authors and 9 for 2nd, where other co-authors are also included in the self-cited articles, it all, unfortunately, looks like Tsukamoto, Mavrogenis & Errani & Co LTD rather than an innovative piece of work. Especially that other articles also analyze the same group of patients with similar scope starting from 1980. With 17% of all citation for the first author this is on the verge of accepted number of self-citations even though they are all within the scope of the article.

 

Response

We have reduced self-citations as much as possible.

 

Comment

Anyway, I can't see any information on H3F3A, especially with patients subject to malignant transformation. Despite the tumour, I would expect all malignant cases to have their initial diagnosis re-confirmed with H3F3A or need to be excluded.

 

Response

Expression of H3F3A was confirmed only in 4 out of 29 cases. We added the following sentences as a limitation into the “Discussion” section: “Third, the presence of the H3F3A mutation could only be confirmed in 4 out of 29 patients. Two of the four patients experienced malignant transformation, and no H3F3A mutations were observed in the malignant lesions. Therefore, H3F3A mutation was not confirmed in the remaining 25 cases. These patients were diagnosed before evaluation. However, these patients were diagnosed by an experienced pathologist specializing in bone tumors.”.

 

Comment

Not sure why the authors analyse patients from the period between Jan 1980 and Dec 2021 when they exclude a priori all patients with f/u shorter than 18 months. Otherwise, an interesting piece of work worth publication. Congratulation!

 

Response

Patients with a follow-up period of less than 18 months were excluded, as the median time from en bloc resection to local recurrence for giant cell tumor of bone was 16 months.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

I do not have any other comment.