Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Interesting study looking at ILR in IBC patients.

Major issues:
1. As mentioned in the discussions section, the trimodal therapy is the common treatment regimen in many centers.
However, the actual treatment (chemo and/or radiotherapy) protocols (CTx/RTx type and dose) for IBC can vary greatly between institutions.
While, the narrative/literature review is interesting, it seems to add little value in terms of actualy statistical comparison.
Also, direct comparison is difficult since historical rates 47~50.6% had different lymphedema diagnosis criteria/follow-up period, etc.

If possible, analysis between other IBC patients within your instutition (if the sample size is too small, perhaps a historical cohort) would be more valuable.

2. Diagnosis criteria of lymphedema (lines 66~68) should be clarified: >=10% voluem change, BIS, etc.?

Minor issues:
1. Follow-up error: abstract (mean 24.4 months; 12.5-33.9) / limitations (mean 48 months)

2. Line 61: explanation on the surgical techniques of ILR used would be great. (either in this section or elsewhere).
Mapping methods (ICG, fluorescien, etc. / dual vs. single injection) and anastomoses details (lymphatic size, vein size, etc.) of the 18 patients would be valuable.

3. IRB approval, consent, etc.?

4. Table footnotes w/ abbreviations explained.

Author Response

Comments 1: As mentioned in the discussions section, the trimodal therapy is the common treatment regimen in many centers. However, the actual treatment (chemo and/or radiotherapy) protocols (CTx/RTx type and dose) for IBC can vary greatly between institutions. While, the narrative/literature review is interesting, it seems to add little value in terms of actual statistical comparison. Also, direct comparison is difficult since historical rates 47~50.6% had different lymphedema diagnosis criteria/follow-up period, etc. If possible, analysis between other IBC patients within your institution (if the sample size is too small, perhaps a historical cohort) would be more valuable.

Response 1: Thank you for your comments. Our intent with the study was to report preliminary data on lymphedema outcomes for IBC patients with the lymphedema multipronged preventative approach at our institution. Our institutional historical average was 47% as reported in Copeland-Halperin et al. 2024 (citation 3 of the paper). In our study, the definition of lymphedema was more inclusive (only needed symptoms to be considered positive) compared to the historical definition of >10% limb volume difference, which is likely the definition used to measure ~47-50% incidence for IBC patients. While we agree that no direct statistical comparison can be made between our results and our institutional historical rates of lymphedema, that was also not our intent in publishing this preliminary data. Our study is a retrospective review consisting of 18 patients due to the relative rare presentation of inflammatory breast cancer. More involved statistical analysis of the data would not be statistically significant given our small sample size. Larger subject populations would be more appropriate to statistically assess any difference in lymphedema incidence; however, this may always be challenging with studying inflammatory breast cancer given its rare presentation.

 

Comments 2: Diagnosis criteria of lymphedema (lines 66~68) should be clarified: >=10% volume change, BIS, etc.?

Response 2: Thank you for your comment. A diagnosis of lymphedema was made based on the presence or symptoms of lymphedema including heaviness of the posterior arm (present in 2 patients) and edema of the forearm (present in 1 patient). We have clarified this in the most recent version of the manuscript. Patients did not  meet the traditional cutoff of a limb volume difference of >10% to receive a diagnosis of lymphedema, as we wanted to be more inclusive and descriptive of patient symptoms.

 

Comments 3: Follow-up error: abstract (mean 24.4 months; 12.5-33.9) / limitations (mean 48 months).

Response 3: Thank you for your comment. We have corrected the error in the limitations section to state the mean follow-up of 24.4 months.

 

Comments 4: Line 61: explanation on the surgical techniques of ILR used would be great. (either in this section or elsewhere). Mapping methods (ICG, fluorescein, etc. / dual vs. single injection) and anastomoses details (lymphatic size, vein size, etc.) of the 18 patients would be valuable.

Response 4: Thank you for your comment. Our standard was to inject ICG in the 1^st and 3^rd webspaces of the hand, volar wrist, and proximal arm in 0.1ml aliquots. We do not have recorded data on lymphatic channel or vein size for the data set. We have added this information to line 63 of the manuscript.

 

Comments 5: IRB approval, consent, etc.?

Response 5: Institutional IRB approval was obtained (IRB Protocol #2025P003250). Informed consent was waived due to the retrospective nature of the study.

 

Comments 6: Table footnotes w/ abbreviations explained.

Response 6: The abbreviations of ID, BMI, and LVB have been removed from the table.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for sharing your experience with this patient population!  

1) I am curious to know your own center's lymphedema rate for patients with inflammatory breast cancer who have not had immediate lymphatic reconstruction.  I think it would be meaningful data to add to the published literature and would would strengthen the paper especially being from a leading cancer center.

2) You site taxane chemotherapy as a risk factor for BCRL but did not report in the outcomes. 

3) I am also interested in each of the patients experience with lymphedema - diagnosis, related complications and therapy.  It is mentioned in the results "developed symptoms" but it is not clear how each patient was diagnosed or not diagnosed with lymphedema (patient reported, bioimpedance, volume, measurements).  Given the smaller number of patients, it would be useful to better understand each of the patients diagnosis pathway, infections and compliance/noncompliance with therapy, as best known.

Thank you.

Author Response

Comments 1: I am curious to know your own center's lymphedema rate for patients with inflammatory breast cancer who have not had immediate lymphatic reconstruction. I think it would be meaningful data to add to the published literature and would strengthen the paper especially being from a leading cancer center.

Response 1: Thank you for your comment. The historical rate of lymphedema for patients with IBC at our institution has been previously reported by Copeland-Halperin et al. 2024 (citation 3) to be 47%. This study included 356 patients with IBC dating back to 1997. None of the patients in this study underwent immediate lymphatic reconstruction. We are hesitant to make any direct comparison between our current cohort’s rate of lymphedema and our institution’s historical rate as the methodology of each study differs significantly and would not be a statistically valid comparison to make.

 

Comments 2: You site taxane chemotherapy as a risk factor for BCRL but did not report in the outcomes.

Response 2: Thank you for your comment. All patients in this study received taxane-based chemotherapy. This has been clarified in the most recent draft at the end of the results section (line 97).

 

Comments 3: I am also interested in each of the patient’s experience with lymphedema - diagnosis, related complications and therapy.  It is mentioned in the results "developed symptoms" but it is not clear how each patient was diagnosed or not diagnosed with lymphedema (patient reported, bioimpedance, volume, measurements).  Given the smaller number of patients, it would be useful to better understand each of the patient’s diagnosis pathway, infections and compliance/noncompliance with therapy, as best known.

Response 3: Thank you for your comments. A diagnosis of lymphedema was made based on the presence or symptoms of lymphedema including heaviness of the posterior arm (present in 2 patients) and edema of the forearm (present in 1 patient). We have clarified this in the most recent version of the manuscript. Although patients above had these symptoms, these patients did not meet the traditional cutoff of a limb volume difference of >10% for diagnosis of lymphedema.. All patients with symptoms of lymphedema were considered to be positive for lymphedema for the purpose of the study but had limb volume differences of <10% measured via the LymphaTech device.