Upper-Limb Disability and the Severity of Lymphedema Reduce the Quality of Life of Patients with Breast Cancer-Related Lymphedema

Round 1

Reviewer 1 Report

Thank you for the authors. Some clarifications are asked:

-Is there any literature about the incidence of BCRL after both of the common causes, that is irradiation and axillary dissection? Please tell this in the paper.

-Do you have any preventive or early diagnosis strategies in your hospital? Please describe these in the paper.

-How specific was the information about the radiotherapy? If there is information about post-ablative/after resection and axillary fossa as a target, please add this information.

-Is the DASH validated questionnaire?

-Table 1: Please provide for "scores" the scale of the score. Are the dynamometry values age-dependent or does it matter in this case? Quite many stage IV patients are listed in the study, did they have primarily metastatic disease? Usually from "partial mastectomy" is used term resection and from "total mastectomy" ablation, please correct. Does the hormonal receptors mean antiestrogen/aromatase inhibitor therapy? Please describe what means the stage of lymphedema. Please add the information of patients who got both radiotherapy and axillary dissection. There were no more information about BMI, although it was mentioned in the previous text. Do you have information about the interval of the treatment and the beginning of the lymphedema and the interval of the treatment and the study procedures described here? Please add.

-Lines 118-119: no need to repeat Fig 1a-c. Please remove the latter one.

-Figure 1: Please clarify. The text says that figure 1E has an association, but the figure does not tell this.

Author Response

Reviewer #1:

Thank you for the authors. Some clarifications are asked:

 

1-Is there any literature about the incidence of BCRL after both of the common causes, that is irradiation and axillary dissection? Please tell this in the paper.

 

R: We thank the reviewer for the request, as it made us realize we had not been including the literature in that paragraph. We include the references: 6,9-13 (lines 49,50) in this new revised version.

 

2-Do you have any preventive or early diagnosis strategies in your hospital? Please describe these in the paper.

 

R: We appreciate your interest in our preventive or early diagnosis strategies. We have added a paragraph on this at the end of the discussion section including references (lines 267-269).

 

3-How specific was the information about the radiotherapy? If there is information about post-ablative/after resection and axillary fossa as a target, please add this information.

 

R: Thanks for the comment. We have included this information in the new revised version of Table 1.

 

4-Is the DASH validated questionnaire?

 

R: We thank the reviewer for this question. We realize that had not been including this important point in that paragraph. We include it in the new version (lines 120-122).  

 

5-Table 1: Please provide for "scores" the scale of the score. Are the dynamometry values age-dependent or does it matter in this case? Quite many stage IV patients are listed in the study, did they have primarily metastatic disease? Usually from "partial mastectomy" is used term resection and from "total mastectomy" ablation, please correct. Does the hormonal receptors mean antiestrogen/aromatase inhibitor therapy? Please describe what means the stage of lymphedema. Please add the information of patients who got both radiotherapy and axillary dissection. There were no more information about BMI, although it was mentioned in the previous text. Do you have information about the interval of the treatment and the beginning of the lymphedema and the interval of the treatment and the study procedures described here? Please add.

 

R: We thank the reviewer for the request, as it made us realize we had not been accurate enough in reporting our findings. Modifications were included in the “Upper-limb disability and QoL assessment” sub-section of the Materials and Methods and at the table 1.

 

6-Lines 118-119: no need to repeat Fig 1a-c. Please remove the latter one.

 

R: Ok we have removed Fig 1a-c as requested.

 

7-Figure 1: Please clarify. The text says that figure 1E has an association, but the figure does not tell this.

 

R: Of course, figure 1E shows a “borderline” significance (p=0.05) for the association. We have made this more explicit throughout the revised manuscript and this is why Fig1E does not have a solid line.

Reviewer 2 Report

Dear Authors

I have carefully reviewed the manuscript titled "Upper-limb disability and the severity of lymphedema reduce the quality of life of patients with breast cancer-related lymphedema." The study addresses an important and clinically relevant topic regarding the impact of breast cancer-related lymphedema (BCRL) on the quality of life (QoL) of female patients. The authors investigated the association between BCRL severity, upper-limb disability, and various dimensions of QoL.

The observational, cross-sectional study design is appropriate for investigating the associations between BCRL severity, upper-limb disability, and QoL. The methods for assessing BCRL severity, upper-limb disability, and QoL dimensions are well-described and appear to be robust.

statistical analysis is well-executed, providing insights into the relationships between BCRL severity, upper-limb disability, and QoL dimensions. The use of stepwise multiple linear regression to identify predictors for different QoL dimensions is appropriate.

However, the small sample and the monocentric design represent the major concern of the paper.

I suggest the following changes to improve the manuscript:

Major revisions

-          Introduction Clarity: While the introduction provides a general overview of the context, it could benefit from more explicit statements about the research gap and the specific aims of the study. In accordance, you should cite the following references:

- Thompson B, Gaitatzis K, Janse de Jonge X, Blackwell R, Koelmeyer LA. Manual lymphatic drainage treatment for lymphedema: a systematic review of the literature. J Cancer Surviv. 2021 Apr;15(2):244-258. doi: 10.1007/s11764-020-00928-1

- de Sire A, Losco L, Lippi L, Spadoni D, Kaciulyte J, Sert G, Ciamarra P, Marcasciano M, Cuomo R, Bolletta A, Invernizzi M, Cigna E. Surgical Treatment and Rehabilitation Strategies for Upper and Lower Extremity Lymphedema: A Comprehensive Review. Medicina (Kaunas). 2022 Jul 19;58(7):954. doi: 10.3390/medicina58070954.

-  Ivanauskiene R, Kregzdyte R, Padaiga Z. Evaluation of health-related quality of life in patients with breast cancer. Medicina (Kaunas). 2010;46(5):351-9. PMID: 20679752.

-          Ethical Considerations: It is mentioned that the study was conducted in compliance with the Declaration of Helsinki and approved by the Ethical Board, but no specific details about the ethical considerations, patient consent process, and potential conflicts of interest are provided.

-          Sample size calculation should be characterized

-          The author should characterize who performed the assessments and the data analysis and eventually if was blinded.

-          Sample Size and Generalizability: The study's sample size is relatively small (n = 30), which might limit the generalizability of the findings. I should be discussed the potential implications of the sample size on the study's conclusions and how it might influence the interpretation of the results.

-          Discussion Expansion: In the discussion section, further elaborate on the clinical implications of the study's findings. In particular, emphasize the role of lymphedema management in a comprehensive rehabilitation treatment for breast cancer, addressing the multicomponent disability of breast cancer patients. In accordance, you should cite the following references:

- Den J, Sisti A. Recent Advances in Breast Cancer Diagnosis, Treatment, Psychology, Management, and Reconstruction. Medicina (Kaunas). 2023 Jan 22;59(2):212. doi: 10.3390/medicina59020212. PMID: 36837414; PMCID: PMC9965058.

- Dalzell MA, Smirnow N, Sateren W, Sintharaphone A, Ibrahim M, Mastroianni L, Vales Zambrano LD, O'Brien S. Rehabilitation and exercise oncology program: translating research into a model of care. Curr Oncol. 2017 Jun;24(3):e191-e198. doi: 10.3747/co.24.3498.

Minor revisions

1.      The whole manuscript should be adapted to Journal guidelines.

 

2.      An extensive English revision is necessary because some periods are difficult to be read.  

 An extensive English revision is necessary because some periods are difficult to be read. 

Author Response

Reviewer #2:

 

Dear Authors

I have carefully reviewed the manuscript titled "Upper-limb disability and the severity of lymphedema reduce the quality of life of patients with breast cancer-related lymphedema." The study addresses an important and clinically relevant topic regarding the impact of breast cancer-related lymphedema (BCRL) on the quality of life (QoL) of female patients. The authors investigated the association between BCRL severity, upper-limb disability, and various dimensions of QoL.

The observational, cross-sectional study design is appropriate for investigating the associations between BCRL severity, upper-limb disability, and QoL. The methods for assessing BCRL severity, upper-limb disability, and QoL dimensions are well-described and appear to be robust.

statistical analysis is well-executed, providing insights into the relationships between BCRL severity, upper-limb disability, and QoL dimensions. The use of stepwise multiple linear regression to identify predictors for different QoL dimensions is appropriate. However, the small sample and the monocentric design represent the major concern of the paper. I suggest the following changes to improve the manuscript:

 

Major revisions

 

1-Introduction Clarity: While the introduction provides a general overview of the context, it could benefit from more explicit statements about the research gap and the specific aims of the study. In accordance, you should cite the following references:

 

- Thompson B, Gaitatzis K, Janse de Jonge X, Blackwell R, Koelmeyer LA. Manual lymphatic drainage treatment for lymphedema: a systematic review of the literature. J Cancer Surviv. 2021 Apr;15(2):244-258. doi: 10.1007/s11764-020-00928-1

- de Sire A, Losco L, Lippi L, Spadoni D, Kaciulyte J, Sert G, Ciamarra P, Marcasciano M, Cuomo R, Bolletta A, Invernizzi M, Cigna E. Surgical Treatment and Rehabilitation Strategies for Upper and Lower Extremity Lymphedema: A Comprehensive Review. Medicina (Kaunas). 2022 Jul 19;58(7):954. doi: 10.3390/medicina58070954.

-  Ivanauskiene R, Kregzdyte R, Padaiga Z. Evaluation of health-related quality of life in patients with breast cancer. Medicina (Kaunas). 2010;46(5):351-9. PMID: 20679752.

 

1. Thank you for your comments and suggestions. We have incorporated these references into the introduction of our revised manuscript.

 

2- Ethical Considerations: It is mentioned that the study was conducted in compliance with the Declaration of Helsinki and approved by the Ethical Board, but no specific details about the ethical considerations, patient consent process, and potential conflicts of interest are provided.

 

1. As described in the text, our research was approved by the Ethics committee at the participating institutions. All participants signed a written consent form. A copy of both the ethics approval and a blank informed consent form were provided along with the original submission to the editorial office. Also, a conflict-of-interest declaration can be found at the end of the manuscript as requested.

 

3- Sample size calculation should be characterized

 

1. OK. We have added that this was a convenience sample in the revised methods

 

4- The author should characterize who performed the assessments and the data analysis and eventually if was blinded.

 

1. as indicated in our manuscript; assessments were performed by the first author (K. R.-P.). Regarding data, these were blindly analyzed by a statistician. This has been added to the methods section of the revised manuscript.

 

5- Sample Size and Generalizability: The study’s sample size is relatively small (n = 30), which might limit the generalizability of the findings. I should be discussed the potential implications of the sample size on the study’s conclusions and how it might influence the interpretation of the results.

 

1. Agreed. This is actually mentioned at the end of the discussion section and it is included as a limitation of our study.

 

6- Discussion Expansion: In the discussion section, further elaborate on the clinical implications of the study's findings. In particular, emphasize the role of lymphedema management in a comprehensive rehabilitation treatment for breast cancer, addressing the multicomponent disability of breast cancer patients. In accordance, you should cite the following references:

- Den J, Sisti A. Recent Advances in Breast Cancer Diagnosis, Treatment, Psychology, Management, and Reconstruction. Medicina (Kaunas). 2023 Jan 22;59(2):212. doi: 10.3390/medicina59020212. PMID: 36837414; PMCID: PMC9965058.

- Dalzell MA, Smirnow N, Sateren W, Sintharaphone A, Ibrahim M, Mastroianni L, Vales Zambrano LD, O'Brien S. Rehabilitation and exercise oncology program: translating research into a model of care. Curr Oncol. 2017 Jun;24(3):e191-e198. doi: 10.3747/co.24.3498.

 

R, Thank you for your suggestions. As requested, we have expanded our discussion incorporating a short paragraph on the role of rehabilitation programs in the context of lymphedema adding the reference by Dalzell et al. and another article by Stein et al. that we found more appropriate (new references #40 and #41). We hope this is acceptable for the reviewer.

 

Minor revisions

1-The whole manuscript should be adapted to Journal guidelines.

 

R.1. We have adapted the manuscript to the template provided by the journal and have formatted reference to the journal style as requested.

 

2-An extensive English revision is necessary because some periods are difficult to be read.  

 

R.2. We have spellchecked the entire manuscript and revised English grammar.

 

Round 2

Reviewer 2 Report

Dear Authors,

in my opinion, the manuscript is interesting, and the results are intriguing.

You have significantly improved the paper during the revision process.

Best regards