Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors present an excellent systematic review on low-grade fibromyxoid sarcoma with a proper pooled analysis of a large number of patients. Some, mainly minor, comments are to be made.

In lines 102-103, I would suggest to change the order of the components conform the order they are noted below. So, first the institutional case series.

The data on MUC4 testing and positivity seems to me inconsistent in the table 2 (57% of 428 cases) and the results text (97% of 251 cases).

I would suggest not only to note the FUS-CREB3 fusion in table 2, but also the total of FUS gene alterations (263/318, 83%), since FUS gene fusions are so frequent.

Line 285, the fact that radiotherapy and chemotherapy “neither demonstrated a consistent benefit in local control or survival.” should be transferred to the “oncological outcomes and follow-up section. Where is the analysis to support their inconsistent benefit? This should be confirmed, to justify such a conclusion (Also in Conclusions and Abstract).

Similarly, the outcome of the institutional series (lines 291-292) should be transferred to the next section.

Lines 334-336, “Superficial tumors appear to have a more favorable prognosis, likely due to earlier recognition, smaller size, and facilitated excision, as demonstrated by Billing et al [61]”. Why is it not confirmed by analysis of the cases in the present study?

Lines 394-395, “The median follow-up of 3 years in the present review likely underestimates late recurrences and metastases, which can occur decades after surgery.” Here should be added that this underestimation is suggested especially by the present study’s median time to first, local, lung and other distant recurrence of 3.1, 2.8, 4.0 and 2.3 years, respectively.

Author Response

The authors present an excellent systematic review on low-grade fibromyxoid sarcoma with a proper pooled analysis of a large number of patients. Some, mainly minor, comments are to be made.

Comment 1: In lines 102-103, I would suggest to change the order of the components conform the order they are noted below. So, first the institutional case series.

Response 1: Following the comments of Reviewer 2, who indicated that the case descriptions did not add sufficient value to the manuscript, we have moved the institutional case series to the Appendix. As a result, the manuscript is no longer structured into two separate components, and the order referred to in lines 102–103 has been adjusted accordingly. The sentence in lines 102–103 is therefore now consistent with the revised structure of the manuscript.

Comment 2: The data on MUC4 testing and positivity seems to me inconsistent in the table 2 (57% of 428 cases) and the results text (97% of 251 cases).

Response 2: Table 2 is correct. The discrepancy was due to an error in the Results text, which has now been corrected to match the data reported in the table.

Comment 3: I would suggest not only to note the FUS-CREB3 fusion in table 2, but also the total of FUS gene alterations (263/318, 83%), since FUS gene fusions are so frequent.

Response 3: Thank you for this helpful suggestion. We have now added the total number and percentage of FUS gene alterations (263/318, 83%) to Table 2 (now table 1), in addition to the FUS–CREB3 fusion.

Comment 4: Line 285, the fact that radiotherapy and chemotherapy “neither demonstrated a consistent benefit in local control or survival.” should be transferred to the “oncological outcomes and follow-up section. Where is the analysis to support their inconsistent benefit? This should be confirmed, to justify such a conclusion (Also in Conclusions and Abstract).

Response 4: The statement regarding the inconsistent benefit of radiotherapy and chemotherapy has now been moved to the “Oncological outcomes and follow-up” section. We have also added a descriptive summary of the available outcome data to support this statement. In addition, we have clarified in the Limitations section that formal comparative statistical analyses could not be performed because of the small number of patients in these treatment subgroups.

Comment 5: Similarly, the outcome of the institutional series (lines 291-292) should be transferred to the next section.

Response 5: Thank you for this suggestion. We have moved the outcome of the institutional case series (previously reported in lines 291–292) to the subsequent section, as recommended.

Comment 6: Lines 334-336, “Superficial tumors appear to have a more favorable prognosis, likely due to earlier recognition, smaller size, and facilitated excision, as demonstrated by Billing et al [61]”. Why is it not confirmed by analysis of the cases in the present study?

Response 6: We have now addressed this point by adding data on no evidence of disease and death of disease for superficial versus deep tumors to the Oncological Outcomes and Follow-up section of the Results. These data show a more favorable oncological outcome for superficial tumors, consistent with the findings of Billing et al. However, formal statistical comparison between superficial and deep tumors could not be performed because of the small number of events in each subgroup. This limitation has now been explicitly acknowledged in the Limitations section.

Comment 7: Lines 394-395, “The median follow-up of 3 years in the present review likely underestimates late recurrences and metastases, which can occur decades after surgery.” Here should be added that this underestimation is suggested especially by the present study’s median time to first, local, lung and other distant recurrence of 3.1, 2.8, 4.0 and 2.3 years, respectively.

Response 7: We have now added the median times to first, local, lung, and other distant recurrence (3.1, 2.8, 4.0, and 2.3 years, respectively) to the sentence in lines 394–395 to better support the statement that late recurrences and metastases are likely underestimated.

   

Reviewer 2 Report

Comments and Suggestions for Authors In the present review article, the authors have done a systematic meta-analysis of the studies reporting on low-grade fibromyxoid sarcomas and their related subtypes. The manuscript is very-well written and I believe a significant contribution to the field, since the authors have succeeded in summarising and analysing the data in a manner that is useful for the physicians managing these rare entities.  I also  the presentation of the 4 institutional cases does not really add anything and should be omitted. This would mean that that Table 1 is left out. Figure 2 can be included, since it adds to the manuscript. SOme information from Figure 1 can be added top the legend of Figure 2. 

Author Response

Comment 1: In the present review article, the authors have done a systematic meta-analysis of the studies reporting on low-grade fibromyxoid sarcomas and their related subtypes. The manuscript is very-well written and I believe a significant contribution to the field, since the authors have succeeded in summarising and analysing the data in a manner that is useful for the physicians managing these rare entities.  I also  the presentation of the 4 institutional cases does not really add anything and should be omitted. This would mean that that Table 1 is left out. Figure 2 can be included, since it adds to the manuscript. SOme information from Figure 1 can be added top the legend of Figure 2. 

Response 1: We thank the reviewer for the positive and encouraging assessment of our work. In line with this comment, we have removed the institutional case descriptions from the main manuscript and relocated them to the Appendix, as they were felt not to add substantial value to the main analysis. Consequently, Table 1 has been omitted. Figure 2 has been retained. 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you, I do not have any further comments