Tailoring the Evidence for Exercise Oncology within Breast Cancer Care

Round 1

Reviewer 1 Report

 

General comments:

The aim of this article was to better identify how to implement exercise in breast cancer from diagnosis to the end of the treatment. The authors started by showing the usefulness of exercise throughout cancer treatment, and then showed how to tailor exercise in the face of impairment such as metastasis, fatigue, or pain. The effects of exercise in breast cancer treatment have been widely studied and much information is actually available. These information focus on the types of exercises (aerobic or resistance), which are beneficial according to treatments side effects or the moment in the treatment; the usefulness of behavior change techniques; adherence; physiological improvement and so on. In view of this literature, the authors could have made perhaps more obvious choices or more in-depth analyses. The authors wrote “Finally, discerning how exercise can be tailored to address breast cancer-related impairments so that individuals are able to participate safely and effectively, has also not been studied extensively”, which shows that more work is needed. In this regard, some tailoring considerations lack evidence-based proposals.

The article is interesting but I have some reservations about its content. Three major points seem important to develop.

1) The main reservation concerns the redundancies between the different parts of the manu-script. For example, cardiorespiratory fitness, body composition and mental health are ad-dressed both in the section on exercise in the breast cancer continuum, but also in the section focusing on adapting exercise to deficiencies or side effects with almost the same conclusions in each part. These redundancies could be avoided by focusing on information that is currently missing. For example, there are a few literature reviews and meta-analyses that have looked at the effectiveness of behavior change techniques on engaging patients in regular exercise or physical activity programs; or the effect of aerobic exercise versus resistance exercise on decreasing cancer-related fatigue.

2) Helping patients to better adhere to exercise or physical activity requires a better under-standing of the mechanisms involved. A part could be dedicated to the description of some mechanisms that explain the reluctance to engage in exercise. Tailoring exercise is possible if the mechanism is identified. For instance, the tailored considerations made by the authors on cancer-related fatigue are insufficient to be sure that they will be engaged in long-term physical activity. Mechanisms can be psychosocial, neurophysiological, biological,… and should be integrated in the manuscript.

3) A methodological part must be included to explain how the literature was found to answer the question of better adherence to exercise or physical activity in breast cancer patients (because some references are missing). It could be useful to focus on either the moments (diagnosis, during treatment and post-treatment) or on the symptoms or functional impairments.

Specific comments:

Table 2, first question to correct.

Figure 1 should be described a bit more to understand the algorithm.

Overall, the article has good proposals but there are lots of redundancies. Moreover, some mechanisms should be integrated in order to better understand the tailored considerations made by the authors. At least, A methodological part is needed to understand the search of the literature.

Author Response

General Comments:

The aim of this article was to better identify how to implement exercise in breast cancer from diagnosis to the end of the treatment. The authors started by showing the usefulness of exercise throughout cancer treatment, and then showed how to tailor exercise in the face of impairment such as metastasis, fatigue, or pain. The effects of exercise in breast cancer treatment have been widely studied and much information is actually available. These information focus on the types of exercises (aerobic or resistance), which are beneficial according to treatments side effects or the moment in the treatment; the usefulness of behavior change techniques; adherence; physiological improvement and so on. In view of this literature, the authors could have made perhaps more obvious choices or more in-depth analyses. The authors wrote “Finally, discerning how exercise can be tailored to address breast cancer-related impairments so that individuals are able to participate safely and effectively, has also not been studied extensively”, which shows that more work is needed. In this regard, some tailoring considerations lack evidence-based proposals. The article is interesting but I have some reservations about its content. Three major points seem important to develop.

• Thank you for your time and effort in reviewing our manuscript! Below we have responded to each comment regarding changes made in the document and to provide our own perspective regarding certain points. We feel that with your suggestions and our edits made to the document, the manuscript is now stronger in its overall message.

1) The main reservation concerns the redundancies between the different parts of the manu-script. For example, cardiorespiratory fitness, body composition and mental health are ad-dressed both in the section on exercise in the breast cancer continuum, but also in the section focusing on adapting exercise to deficiencies or side effects with almost the same conclusions in each part. These redundancies could be avoided by focusing on information that is currently missing. For example, there are a few literature reviews and meta-analyses that have looked at the effectiveness of behavior change techniques on engaging patients in regular exercise or physical activity programs; or the effect of aerobic exercise versus resistance exercise on decreasing cancer-related fatigue. 

• We agree with the Reviewer’s comment that there are redundancies between both the literature section (formerly section 2) and the tailoring section (formerly section 3). We also agree with providing more information on behaviour change within Exercise Oncology (and examples of its potential use in real-world settings). As such, we have made significant edits to the overall document. The “Supporting Evidence” section (formerly section 2) has been removed and condensed into the edited “Background” section. We have also added a section dedicated to “Behaviour Change” (now section 3).

2) Helping patients to better adhere to exercise or physical activity requires a better under-standing of the mechanisms involved. A part could be dedicated to the description of some mechanisms that explain the reluctance to engage in exercise. Tailoring exercise is possible if the mechanism is identified. For instance, the tailored considerations made by the authors on cancer-related fatigue are insufficient to be sure that they will be engaged in long-term physical activity. Mechanisms can be psychosocial, neurophysiological, biological,… and should be integrated in the manuscript. 

• Thank you for your insight on this important topic. To the Reviewer’s point about identifying mechanisms, inherently this is not a feasible approach in real-world settings. To take the Reviewer’s own example (fatigue), indeed there are mechanisms involved but it is unclear what primarily drives cancer-related fatigue. As such, in this paper we have focused on screening. For example, if a patient presents with fatigue, it is not possible for practitioners (i.e., Clinical Exercise Physiologists, Physiatrist) to diagnose how that fatigue is manifesting in real-time, particularly with fatigue and its multi-factorial nature. Rather, the fatigue is noted, and the most up-to-date recommendations and strategies (i.e., visual analog scales) are used in the exercise prescription so that each exercise session considers the degree of fatigue that patient is experiencing in real-time. Future work in identifying mechanisms of cancer-related impairments (e.g., fatigue) is certainly important, but primarily is best addressed within RCTs. This information can then be used to update exercise prescriptions (i.e., modality, volume) and tailoring in real-world settings.  

3) A methodological part must be included to explain how the literature was found to answer the question of better adherence to exercise or physical activity in breast cancer patients (because some references are missing). It could be useful to focus on either the moments (diagnosis, during treatment and post-treatment) or on the symptoms or functional impairments.

• With the removal of the “Supporting Evidence” Section, we believe this has been addressed. As this was not a formal systematic review, references within the tailoring section are the most appropriate references to make recommendations at this time, while also knowing that there is certainly more work to be done in this area.

Specific comments: 

Table 2, first question to correct.

• Upon review, it is not clear to us what needs to be corrected. We please ask the reviewer if they would clarify their comment as to what needs to be corrected in Question 1 on this table (NOTE: This is now Table 3 in the revised version).

Figure 1 should be described a bit more to understand the algorithm.

• We have made edits within the “Standard Breast Cancer Care” section to provide more clarity on Figure 1.

Author Response File: Author Response.docx

Reviewer 2 Report

Overall, authors attempted to address potential strategies on screening, triage, and referral pathways across the breast cancer continuum. Although the fundamental concept of submitted manuscript is highly important, quality of manuscript can be improved by providing more specific information and evidence.

- Authors may seem highly selective in citing previous studies (e.g. OptiTrain or Dieli-Conwright et al) only, although there are numerous other studies that can be used to support the evidence. It would be helpful if authors can state upfront about their selection of articles, based on what criteria? e.g. recent 10 years? Or only RCT? and etc..

-Tailoring considerations for each subsection: it is strongly recommended to present or suggest more methods on screening and identifying patients at risk of each functional impairment could be used, i.e. CIPN, lymphedema, bone metastasis, cardiotoxicity.. For cardiotoxicity as an example, authors could suggest prescribing a certain type of exercise to patients at ejection fraction of xx or VO2peak at <xx ml/kg/min? For tailoring exercise for bone metastatic patients, can Fracture Risk Assessment Tool (FRAX) be used to identify at risk of individuals first to screen and identify? Although no specific studies have been conducted in the breast cancer populations, authors would need to suggest currently available tools from other field for screening and identification of patients, which is what authors were aiming for in the background, and this is the main focus of manuscript, but insufficient information.

Author Response

Overall, authors attempted to address potential strategies on screening, triage, and referral pathways across the breast cancer continuum. Although the fundamental concept of submitted manuscript is highly important, quality of manuscript can be improved by providing more specific information and evidence.

• Thank you for your time and effort in reviewing our manuscript. Below we have responded to each comment regarding changes made in the document and to provide our own perspective regarding certain points. We feel that with your suggestions and our edits made to the document, the manuscript is now stronger in its overall message.

- Authors may seem highly selective in citing previous studies (e.g. OptiTrain or Dieli-Conwright et al) only, although there are numerous other studies that can be used to support the evidence. It would be helpful if authors can state upfront about their selection of articles, based on what criteria? e.g. recent 10 years? Or only RCT? and etc..

• We agree with the reviewer that this seemed highly selective. Based on this suggestion and comments from Reviewer 1, we have removed of the “Supporting Evidence” Section. We have focused more on the tailoring section and also included a behaviour change section (per Reviewer 1 suggestion) as well.

-Tailoring considerations for each subsection: it is strongly recommended to present or suggest more methods on screening and identifying patients at risk of each functional impairment could be used, i.e. CIPN, lymphedema, bone metastasis, cardiotoxicity.. For cardiotoxicity as an example, authors could suggest prescribing a certain type of exercise to patients at ejection fraction of xx or VO2peak at <xx ml/kg/min? For tailoring exercise for bone metastatic patients, can Fracture Risk Assessment Tool (FRAX) be used to identify at risk of individuals first to screen and identify? Although no specific studies have been conducted in the breast cancer populations, authors would need to suggest currently available tools from other field for screening and identification of patients, which is what authors were aiming for in the background, and this is the main focus of manuscript, but insufficient information.

• Thank you for providing your perspective as it relates to screening. Regarding specific screening criteria for each impairment in the tailoring section, we agree that this would be ideal. However, based on current evidence, we do not have the established criteria to do so. As such, we have opted for a more simplistic screening tool at the clinical level that then allows for further exercise screening and referral to the appropriate setting. We have chosen to focus on the practitioner’s (clinical exercise physiologist, physiatrist, pt/ot) own clinical judgement in identifying impairments and contraindications to exercise and referring to the proper setting to participate in exercise. In the reviewer’s example of cardiotoxicity, if a BC patient presents with a very low ejection fraction, the CEP would suggest supervised exercise, likely in clinical setting, as this individual would be classified as “high risk” if deemed safe for the patient. For the FRAX tool, this is designed to identify risk in the those with osteoporosis and, to our knowledge, has not yet been tested specifically within a bone mets population. Therefore, we feel we should not suggest using this type of tool as we are unsure of its sensitivity within this population to correctly identify those at risk.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Overall, the corrections made are relevant and make the manuscript very interesting. Nevertheless, the part on behavior change techniques remains incomplete. For instance, the stress and fatigue section have been studied by Finne et al. (2018) and Carey et al. (2019) who have identified several other techniques to cope with fatigue. Maybe the authors should improve this important section and make sure they haven't left anything out.

In the table 3, please remove the first "of the" in the first sentence: "To the best of your knowledge, do you currently meet any of the of the following exercise guidelines.

Author Response

Overall, the corrections made are relevant and make the manuscript very interesting. Nevertheless, the part on behavior change techniques remains incomplete. For instance, the stress and fatigue section have been studied by Finne et al. (2018) and Carey et al. (2019) who have identified several other techniques to cope with fatigue. Maybe the authors should improve this important section and make sure they haven't left anything out.

 

• Thank you for providing these references. We certainly agree that there are other techniques used to cope with factors like fatigue and stress. We would like to emphasize that Table 2, rather than being a review of all current techniques, is an actual example of what is currently being implemented in the EXCEL study (referred to in Section 3) as it relates to providing participant education and behaviour change technique information. We have made minor edits to the text in Section 3 to emphasize this point. We have also made additional edits to Section 3 recognizing that the Exercise and Educate model is both flexible and adaptable as it should follow the most up-to-date evidence for the respective tumour population in question, and importantly, be tailored to the individual.

In the table 3, please remove the first "of the" in the first sentence: "To the best of your knowledge, do you currently meet any of the of the following exercise guidelines.

 

• Addressed – thank you for bringing this to our attention!

Author Response File: Author Response.docx