Personalizing the Treatment of Women with Ductal Carcinoma In Situ (DCIS) Using the DCIS Score: A Qualitative Study on Score Use

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The reviewer commends family medicine for playing a crucial role in overseeing the personalized treatment of women with DCIS.  Impacts to surgeons, radiation oncologists, pathologists, nurse navigators and research nurses are vital to having consolidated approaches to care. However, there is potential for improvement in interdisciplinary communication and coordination. The authors point out reasons of challenges, but it would be even more exciting to consider options for improving the situation as a plan. 

Some more references/comments on why DCIS is targeted for this study should be expanded upon.

Line 30: 

THere are possible other companies. Oncotype is only one . Oncotype is not the only company that offers genomic tests for breast cancer. There are other options, such as Sophia, Ambry, Agendia (MammaPrint), Myriad, and more. These tests can help determine the risk of recurrence and the benefit of chemotherapy/radiation therapy for certain patients. 

Number of genes, types, companies etc etc cost etc (you could check these costs, I have an old list I try to keep track of) 

Oncotype Oncotype DX 21 FFPE ~$4k 

Sophia EndoPredict 12 FFPE ~ $3,5k 

Ambry BreastNext 17 Blood or saliva ~$2,5k (this wouldn’t work as a biopsy) 

Agendia MammaPrint 70 Fresh or FFPE ~$4,2k  

Myriad EndoPredict 8 FFPE ~$3,5k  

How much sample is needed for each? (cores and samples?) 

Line 30: Is the use of oncotype or any similar tools considered a standard practice? Are there randomized controlled trial (RCT) results supporting their efficacy that can be referenced? An additional challenge may arise from the multitude of companies providing such tools, making it unclear which one is optimal. Have your oncologists, surgeons, or radiation oncologists expressed preferences or criteria for selecting a particular tool? 

What is the role of oncologists in this. THe authors mentioned radoncs and surgeons but the role of oncologists are not as strongly mentioned. Did the authors consider more investigation in that area? 

Line 58: If the specific understanding of two groupings, radiation oncologists/breast cancer surgeons is used, why/how was this chosen. Are compared to cancer policy decision makers. More justification or reasoning on the exact members of each group and why they are chosen.  

Line 75: CCO is Cancer Care Ontario (didn’t it change to be part of Ontario Health?), an agency created by the Government of Ontario provides outstanding materials in regards to diagnostic and treatment responses. It would be very interesting to see the authors perspectives on how their guidelines compare/complement and serve providers and patients as compared to NCCN. 

106: The central theme could revolve around the 'barriers' hindering adoption. The evidence may delve into this concept, explicitly outlining the authors' perspectives on potential methods to overcome these challenges, to be further discussed in the discussion sections.  

116: The elements could be regarded as 'clinical pearls' (see Table 1). Who served as the adjudicators for the identified 'themes'? Was it solely the author who synthesized them? Is there a quantitative aspect involved, such as counting? If so, how many reviewers were involved, and how many code cards were generated in the process? Some discussion of the use of ‘counting’ 

Line 6: table 1. Is it possible to assign a ‘person responsible’ to serve as the arbiters of the oncotype process. Would this be pathology or perhaps even genetics. In your institutions do you know which ones would be the ones to be responsible over the responsibility purely on radonc and surgery? 

Line 7 – table 1 : Is it possible a new certificate and/or training could be given to family medicine in the role or ‘person’ responsible for managing the test. Perhaps even a PA? This sort of decision could be made by someone with more internal medicine training with special experience perhaps working alongside pathology/genetics. 

Line 8- table: seems[small point missing a number 8. ] Who are the decision makers. Are they financial officers? What are their roles. What is their process of swaying their opinion for adoption. 

Is there a period of acceptance for the test with some outcomes that could be proposed. For example, how would you know if patients are being overtreated

Line 44: stronger monetary analysis should be done to provide base analysis. One can look that up and provide some example numbers for those in US and those in Canada. 

Line 238: It seems someone on the team, should be assigned to have the responsibility of keeping up to date on clinical trials. Who would that person be on that team. Is this something to be discussed also at a tumor board. How can tumor boards be integrated into your decision tool 

Line 278: We thank the authors for their candor on the ability to get RadOncs and Surgeons to respond in this study. It is often hard to get their attention. That could be that additional responsibility from outside these two groups is needed.  Does that suggest that this problem needs more outside guidance from other providers willing to take the time and Management.  

What kind of sequalae for overtreatment are the worst for patients. Lymph edema? Potential for secondary cancers? It would be nice to state these and the order of management and concern. What about CDK inhibitors.  

Line 289: Finally, it would interesting if the authors were to consider providing guidance to CCO what exactly would they say. Is that something that the authors considered. It would also be interesting to see if there was a response from CCO.  

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The title of the work: Personalizing the Treatment of Women with Ductal Carcinoma in Situ (DCIS) Using the DCIS Score: A Qualitative Study on Score Use.

It is a very interesting paper about the concerns of radiation oncologists, surgeons, and decision makers about the real advantages of using predictive scores to estimate the necessity/possible avoidance of radiotherapy in case of low risk in situ ductal carcinoma patients. The interviews elaborate the uncertainty of the radiation oncologists, the opinion and responsibilities of the surgeons, the feelings and fears of the patients, and the aspects of decision makers etc. It is really an interesting debate with some very special psychological, philosophical, and financial consideration; however, it is mainly a great discussion and not a scientific/medical paper and the reader also feels a kind of a pressure on decision makers as well.  This kind of mixed feelings and ambivalence aggravates to judge the real value of the work. Nevertheless, in case of acceptance, I recommend the modification of the title (and the abstract) to inform the readers that this is a kind of psychological/philosophical approach to support the decision making in the health care system.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The presented manuscript reports on personalizing the treatment of women with DCIS using the Oncotype DCIS Score: A Qualitative Study on Score Use.

The manuscript was written by native speakers and it is professionally presented. It reports on interviews with radiation oncologists, surgeons and decision-makers on the use of this special risk analysis in order to get an idea of the role and clinical use of the predictive test.

The results are statements of a low number of professionals (n=28) that are at least in my understanding not reperesentative. When starting to read the article I expected the rating of the test correlated with clinical endpoints of DCIS patients to evaluate its predictive potential. I was disappointed to read statements of individuals and some summary of the authors. All in all the results are of limited interest to an international audience and the methods are not leading to representative results.

I am sorry, but I cannot suport this manuscript for publication.    

Comments on the Quality of English Language

Avoid double spaces at the beginning of a sentence.

Author Response

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Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Appreciate authors attempt. One of the major limitation of the study is the limited sample size amongst the various subsets to make any valid conclusion on a topic with very little evidence. 

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

There are several things I  would suggest to improve the article:

1) I think the readership should  also have a list  of other  approved companies that are possible for their purposes (not everyone has access to the same tests) - this could be in the supplementary materials.  [this is for response 1.)

2. response 8: (I think the below is informative to readership and should be added in methods and/or discussion  ) - the cut and paste did not go well in below but it is what authors said in response: (they can edit shorten and add the references to match) 

We did not explicitly count the various codes during the analysis; however, for transparency all codes were captured in the data management software. We used the constant comparative method (Glaser and Strauss 1967; Boeije 2002) and principles of grounded theory (Glaser and Strauss 1967; Charmaz 2006) to check that the themes were supported by quotations across different types of participants (radiation oncologists, breast cancer surgeons and policy decision-makers when appropriate). We checked and

contribute to knowledge about future test implementation in actual practice.

Breast cancer surgeons

were included because they are the clinicians who decide whether to

refer patients with DCIS post breast

conserving surgery to radiation oncologists for consideration of radiation therapy. We believed that breast

cancer surgeons were important to include because of treatment planning discussions they would have

had with patients that might influence patient’s expectations regarding subsequent radiation treatment.

were knowledgeable about how the provincial government makes funding decisions about molecular

We included this group because they

biomarker assays. The input by cancer policy decision-makers could help inform future implementation of

such assays for DCIS.

[this is useful information and should be added).

3

reported instances when a quotation was not supportive of the theme. We are not certain that counting the codes would have helped us develop the major themes.) 

2. 

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

No further comments

Author Response

Response: Thank you for reviewing our responses to the original Reviewer comments.

Reviewer 4 Report

Comments and Suggestions for Authors

thank you for your responses. I appreciate that the authors have made it clear that the study is a qualitative study in their title. However, it would be prudent to include that information in the conclusion section as well to be clear to our readers. 

Comments on the Quality of English Language

minor revisions

Author Response

Response Round 2 Reviewer 4

Comments and Suggestions for Authors

thank you for your responses. I appreciate that the authors have made it clear that the study is a qualitative study in their title. However, it would be prudent to include that information in the conclusion section as well to be clear to our readers. 

Response: We thank the Reviewer for reviewing our responses and for making this suggestion. We have revised the first sentence in the Conclusions section on page 10, lines 337 to address the Reviewer’s comment. We now say, “Radiation oncologists in this qualitative research study had concerns about over-treatment of women with DCIS but lacked tools to reliably predict which women could safely avoid radiation.”