Secondary Malignancy in Giant Cell Tumor: A Single-Center Study

Round 1

Reviewer 1 Report

The manuscript by Joo et al titled "Secondary Malignancy in Giant Cell Tumor: A Single-Center Study" gives an overview of the experience at the authors' center with respect to the occurrence of secondary malignancy in patients previously diagnosed with giant cell tumor.  However, I believe that several aspects of this study raise questions on its relevance. Among them, the paucity of patients included in this study on a rare tumor (12 patients over the course of 23 years) makes it difficult to draw any conclusions that can be of any clinical relevance. 

Author Response

Thank you for your comprehensive review. Our response to your advice is as follows.

 

The manuscript by Joo et al titled "Secondary Malignancy in Giant Cell Tumor: A Single-Center Study" gives an overview of the experience at the authors' center with respect to the occurrence of secondary malignancy in patients previously diagnosed with giant cell tumor.  However, I believe that several aspects of this study raise questions on its relevance. Among them, the paucity of patients included in this study on a rare tumor (12 patients over the course of 23 years) makes it difficult to draw any conclusions that can be of any clinical relevance.

à It is agreed that you can raise questions because of the paucity of cases in this study. You pointed out one of the fundamental issues in researching rare diseases. Secondary malignancy in giant cell tumor is very rare as you know and it is difficult to collect massive quality data for a short period of time. As another reviewer commented, the current study could be worthwhile because the patients in this study did not receive radiation treatment and all cases were the extremity lesions.

 

If you give us another piece of advice, we will happily consider the next revision. We look forward to your generous reply.

 

Thank you for your time and consideration.

Reviewer 2 Report

Authors described clinico-pathological features of secondary malignancy in giant cell tumor (MGCT) that did not occur after radiotherapy. While twelve patients were analyzed, they have found initial metastasis was a predictive factor for overall survival. Additionally, they have found that benign local recurrence of GCTB was a negative factor for metastasis-free survival of MGCT patients. I am thinking this article provides novel clinical information into the treatment of MGCT. However, there some minor concerns.

Minor)

1. Authors should add "Case No (identification No)" in Table 1 and 2 to clarify each case.
2. Authors should add the number of recurrences regarding benign GCTB period in the Tables.
3. This cohort excluded trunk cases and included only extremities. Therefore, I think that authors should emphasize this cohort is consisting of both non-radiation and extremity cases. This modification would provide aciculate information for readers.
4. Authors should provide immunohistochemistry data regarding anti-H3F3 in both their primary GCTBs and secondary MGCTs.
5. Authors should discuss roles of denosumab in MGCTs.

Author Response

Thank you for your thoughful review. We revised the paper to reflect your comments and the details are as follows.

 

1. Authors should add "Case No (identification No)" in Table 1 and 2 to clarify each case.

à Thank you for the advice. You can see the “Patient No.” in the middle column of Table 1 and the first column of Table 2.

2. Authors should add the number of recurrences regarding benign GCTB period in the Tables.

à Thank you for the suggestion. You can see the number of recurrences in the column of Local recurrence of Primary benign giant cell tumor in the Table 1.

3. This cohort excluded trunk cases and included only extremities. Therefore, I think that authors should emphasize this cohort is consisting of both non-radiation and extremity cases. This modification would provide aciculate information for readers.

à You must have suggested a good point. We added it in the Results and Discussion sections.

4.Authors should provide immunohistochemistry data regarding anti-H3F3 in both their primary GCTBs and secondary MGCTs.

à Since the histone mutation in giant cell tumor of bone is described in the WHO classification published in 2020, we believe that the data should be helpful to provide more relevant information. We mentioned the views of most existing studies in the pre-revision version of manuscript. In this country, clinical use of various ancillary tests such as immunohistochemistry that are not very essential for diagnosing some diseases is officially not permitted by the national authorities.

5. Authors should discuss roles of denosumab in MGCTs.

à As you suggested, we reviewed the papers regarding the relationship of denosumab and secondary malignant transformation of giant cell tumor of bone in the Discussion section.

 

If our responses are not enough to convince you, Please let us know the issues. We will happily prepare additional steps. We look forward to your affirmative reply.

 

Thank you for your time and consideration.

Round 2

Reviewer 1 Report

The overall quality of the study by Joo et al has definitely improved in the revised version of the manuscript. However, other issues should be addressed before its publication on Current Oncology.

As the presented data relies on a very small number of patients and the overall conclusions over survival being correlated with the presence of metastasis, the overall relevance of this work is quite mild. We suggest putting more emphasis on the lack of cases in this study that were associated with radiation treatment, as reported by the authors.   Abstract: line 26, "respectively" is missing.  Table 1: Follow-up period is not specified that it is in months 

Author Response

Thank you for your concise review. We revised the paper to reflect your advice and the details are as follows.

 

As the presented data relies on a very small number of patients and the overall conclusions over survival being correlated with the presence of metastasis, the overall relevance of this work is quite mild. We suggest putting more emphasis on the lack of cases in this study that were associated with radiation treatment, as reported by the authors.

à We totally agree with you. To highlight the reason that this study is worthwhile despite a small number of cases, we presented current background on the relationship between secondary malignant transformation of benign giant cell tumor of bone and radiation treatment in the Introduction and Discussion sections, described that our patient did not received radiotherapy for benign giant cell tumor of bone before malignant changes in the Results section, repeated the characteristics of our study cohort in the Discussion and Conclusions sections.

 

Abstract: line 26, "respectively" is missing.

à Thank you for your pointing out. The term was added.

 

Table 1: Follow-up period is not specified that it is in months

à Thank you for your precise advice. Latency period in Table 1 is expressed in months. In Table 2, we added “months” considering a unit of the follow-up period. 

 

If you send us another piece of advice, we will happily consider the next revision. We look forward to your positive response.

 

Thank you for your time and consideration.