Prevalence and Quality of Life in Patients with Lymphoedema following Axillary Clearance for Breast and Cutaneous Malignancies

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

1.       The study deals with LE monitoring and diagnosis after ALND, and its impact on QoL, a topic that is very important and affecting many BC survivors. Please see my notes:

2.       Methods are completely missing in the manuscript that was sent-

a.       How were the arm measurements done and what was defined as an abnormal test?

b.       How were the patients selected?

c.       The patients that were ‘previously diagnoses’ with LE- based on what was that diagnosis done? Was there ant tool used anytime to prove it, even in the time preceded this study?

3.      2cm identifying criterion for LE is widely used in many other studies, so it does not solely explain the very high rate of LE in this study. Perhaps more data about the patients would help, such as- number of LN’s involved and removed, BMI, how many received radiation therapy to the axilla itself?

4.       Table 1 should compare the 3 groups in regard to other confounders that might influence the results- age, comorbidities, time since surgery, extent of surgery and other treatments, stage and subtype of disease, BMI etc…

5.       Comparing breast cancer survivors QoL to that of a healthy individual does not necessarily  indicate that reduced QoL is directly related to LE, as it can be related to many other side effects of the treatments of cancer. The correct comparison would be BC survivors who underwent the same treatment except for the fact that they developed LE, and here the LYMQOL didn’t show statistically significant difference, as shown in figure 1 and 2. Hence the conclusion at the end of the manuscript in inaccurate.

6.       I suggest adding to the limitations the relatively small number of pts, and the fact that the measurements were done in different times from surgery and only one time, rather that a periodic follow up.

7.       In the Discussion section- I find lines 142-176 completely not relevant, the study deals with established LE, the way to diagnose and define it, and the effects it has on QoL- so the discussion should focus on the current literature about LE measurements, monitoring and diagnosis, rather than treatment methods.

8.       “our findings emphasise the importance of preventive interventions such as ILR”- this study did not examine this association and therefore cannot have this sentence as a conclusion.

 

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

Many methodical choices were incorrect:

-       “Materials and methods” session should be before the “results” session

-       The timing from ALND to the completion of the questionnaire and the arms’ measurements should be specified

-       When you mentioned the 40 patients without a significant difference in arm circumference, you wrote that 9 of them had reported an already established diagnosis of lymphedema, you should mention how they were diagnosed with lymphedema

-       The control group you started mentioning at some point in the “results” has not appeared before, you should have mentioned it at the beginning of your “materials and methods” session, anyway the control group has not the same amount of patients as the “lymphedema” and “no lymphedema” group, therefore their comparison is not accurate

In the "discussion" mentioning the methods adopted to prevent the onset of lymphedema, you are excluding lots of them. I would suggest to dedicate more space to this topic since the interest of the scientific community on this subject is increasing. In alternative you might mention some recent systematic reviews on this topic.

A "conclusion" section is entirely missing.

Comments on the Quality of English Language

English quality is average.

 

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

1. Introduction:

The last paragraph of the introduction is mixed:

-          This part belongs to the methods section-

In this cohort study, we recruited 73 patients who underwent ALND for breast cancer

or cutaneous malignancies of the upper limb from 2011 to 2021 at a tertiary oncology 

centre in Melbourne, Australia. Participants completed a questionnaire survey about their 

medical and surgical history, andthat included the lymphoedema quality of life 

(LYMQOL) questionnaire, a validated lymphoedema-specific HRQoL tool [98]. We then 55

measured the patients’ bilateral arm circumferences as a screening tool for the presence of

lymphoedema.

-          This part can stay in the introduction-

The primary objectives of this study were to (i) identify the prevalence of 57

upper limb lymphoedema following ALND and (ii) assess the impact of lymphoedema 58

on patient HRQoL.

-          And this part belongs to the conclusion or discussion-

The findings of this study provide an overview of the disease burden 59

in our catchment area and support evaluate the need to provide screening and prevention 

strategies.

2. Methods-please specify how were the patients contacted? Via phone? Mail? During clinic visit?

- The score of the LYMQOL in each domain- does it get better or worse as it goes high? There is only referral to the overall score but not to each domain.

116- the authors should specify in the methods that the time from surgery to  filling out the Q was random and not uniform btw the groups.

123- what is the control group? It has not been mentioned so far in the text. How were they selected? What do we know about them? There is nothing in the results to describe them, so how can the comparison being done?

124- ‘Participants without subjective symptoms of lymphoedema, were instructed to score 1 (not at all) where relevant and answer mood and quality of life questionnaires independent of their symptoms.’ – this sentence is not clear- why only subjective diagnosis and not objective? What does it mean independent of their symptoms? Consider rephrasing

3. Results-

196-199- it is suggested not to start a sentence with a number, and I suggest adding the absolute number next to the percentage.

231-238-what does F stands for?

Table 2 is not presented clearly- the lines are displaced.

Table 4- I suggest adding the percentage next to the numbers.

level of ALND- should be categorized as a ordinal and NOT  continuous variable. Hence, there is no point in presenting it as an average. The optimal way to appreciate the extent of surgery would be to compare number of nodes removed, because even in full ALND sometimes the number of nodes removed is relatively low. Number of nodes can be presented as a continuous variable.

Same comment for grade of tumor- NOT A CONTINOUS VARIABLE

Missing important data are stage of disease btw the groups.

-In regard to radiation fields- Does the authors have data of nodal radiation?

Discussion-

The most critical limitation of this study is it’s design- the fact that the time from surgery to the clinical evaluation was not uniform btw the groups, and the comparison to controls that are completely healthy population.

The treatment itself adds another major bias as there is no standardization in the type of treatment received or its duration, we do not know if the treatment itself is a factor that improves QoL or indicates a worse condition from the first place (e.g. perhaps only the more advanced LE got Tx). The purpose of the study was to merely appreciate the prevalence of LE after ALND and its impact on QoL, therefore adding the impact of treatment effect, which is so broad in its nature and can lead to opposite directions, eventually makes it impossible to reach any conclusion. (and the evidence to that is that the treated group had a worse QoL)

Conclusions- line 575- ‘in patients after ALND’

 

 

 

 

 

 

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

In the Abstract abbreviations shouldn't be included.

In the Materials and Methods you clearly write that patients with a previous diagnosis of lymphedema were not included in the syudy. However, later in the Results you mention patients with a prior diagnosis of lymphedema not having received any previous treatment. This is very confusing. Moreover you should specifiy the incidence of lymphedema between patients receiving radiotherapy and not since radiotherapy is strictly linked with higher rates of lymphedema. The diferrent rates of lymphedema between patients undergoing treatment for melanoma or breast cancer should also be specified.

In the Discussion you say that there is no clear evidence that lymphedema has a bad impact on quality of life. This is hard to believe considered the wide literature saying the opposite. You should prove your assumptions with more evidence.

Comments on the Quality of English Language

English is understandable though of average quality

Author Response

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Author Response File: Author Response.docx

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

The paper is well conceived and structured.