Canadian Consensus Recommendations for the Management of Operable Stage II/III Non-Small-Cell Lung Cancer: Results of a Modified Delphi Process
, Quincy Chu 2, Pierre Olivier Fiset 3, Biniam Kidane 4, Natasha B. Leighl 5, Philippe Joubert 6, Donna Maziak 7, David Palma 8, Anna McGuire 9, Barbara Melosky 10, Stephanie Snow 11, Houda Bahig 12 and Normand Blais 13,*
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
Thank you for the opportunity to analyze your very interesting article on a burden and evolving topic.
In this article, authors have generated new recommendations for the treatments of patients with stage II and III NSCLC.
Concerning the introduction:
The introduction is well written, highlighting all the complexity to treat patients with stage II and III NSCLC guided by new knowledges leading to new targeted therapies including multimodality treatment. No major concerns
Concerning the methodology:
Consensus Panel:
Maybe just a little comment, about the “expert status” of your thoracic surgery fellow. Maybe a little bit young? Nevertheless, I know the high-quality training and education program in thoracic surgery in Canada.
Litterature review and data synthesis:
No major concerns.
Concerning the results
Results are well reported and clearly presented in tables. The statement selection provide a good overview of “all” lung cancer conditions.
Concerning the discussion:
It’s a well written discussion and well documented with all statements discussed
4.1: No major concerns.
As mention the IV CT scan is mandatory for pre operative analysis of the patient’s anatomy.
Nice synthesis about the indication of the brain images and it’s conflicting reports.
Also nice synthesis about the pre therapeutic biomarker testing which now will be performed in routine.
4.2: No major concerns, good references with recent data dealing with neo adjuvant immunotherapy. Need to highlight the importance of a multidisciplinary meeting with expert surgeons and expert oncologists also.
4.3: No major concerns
Re-staging is still debated, good references in your article.
Dealing with the operative lymph node assessment, a lymph node dissection is preferred rather than a sampling. Nevertheless, it’s a burden subject, moreover with the immunotherapy, and some practitioners advocated to only sample lymph node in order to have lymphatic tissue in the lung to enhance the immune response! But it’s very debated.
Concerning the lung resection, an anatomical lung resection is preferred and indicated rather than a sublobar or for selected frailty patient for example. As mention, the goal is to provide a R0 resection and the best nodal stagging.
4.4: No major concerns.
Concerning the conclusion:
It’s a well written, and easy reading consensus recommendations dealing with difficult lung cancer stages II and III due to a lack of consensus and data.
This nice work is very helpful.
As you have mentioned, many of your statement are debated due to a lack of strong evidence, and this will be more difficult again with new systemic treatments. The multidisciplinary board is one of the most important things that need to be highlighted in order to provide best cares to our patients.
Congratulations to authors for this difficult work.
Author Response
Reviewer 1
In this article, authors have generated new recommendations for the treatments of patients with stage II and III NSCLC.
Concerning the introduction:
The introduction is well written, highlighting all the complexity to treat patients with stage II and III NSCLC guided by new knowledges leading to new targeted therapies including multimodality treatment. No major concerns
Concerning the methodology:
Consensus Panel:
Maybe just a little comment, about the “expert status” of your thoracic surgery fellow. Maybe a little bit young? Nevertheless, I know the high-quality training and education program in thoracic surgery in Canada.
We thank the reviewer for this comment and have updated the manuscript so that it now reads:
“…a working group of 3 experts was assembled which including an attending thoracic, medical oncologist and radiation oncologist (JS, NB, HB) and a thoracic surgery fellow (JT).”
Literature review and data synthesis:
No major concerns.
Concerning the results
Results are well reported and clearly presented in tables. The statement selection provide a good overview of “all” lung cancer conditions.
Concerning the discussion:
It’s a well written discussion and well documented with all statements discussed.
4.1: No major concerns.
As mentioned, the IV CT scan is mandatory for pre-operative analysis of the patient’s anatomy.
Nice synthesis about the indication of the brain images and it’s conflicting reports.
Also nice synthesis about the pre therapeutic biomarker testing which now will be performed in routine.
4.2: No major concerns, good references with recent data dealing with neo adjuvant immunotherapy. Need to highlight the importance of a multidisciplinary meeting with expert surgeons and expert oncologists also.
The reviewer raises another important point regarding the central role of the MDT in formulating treatment options. The following sentence has been added to highlight this:
“This again emphasizes the central role of the MDT helping form consensus on the patient’s therapeutic options.”
4.3: No major concerns
Re-staging is still debated, good references in your article.
Dealing with the operative lymph node assessment, a lymph node dissection is preferred rather than a sampling. Nevertheless, it’s a burden subject, moreover with the immunotherapy, and some practitioners advocated to only sample lymph node in order to have lymphatic tissue in the lung to enhance the immune response! But it’s very debated.
We thank the reviewer for raising this important point. Indeed, this is a contentious issue that has yet to be settled with good randomized data particularly in the setting of neoadjuvant (or peri-operative) immunotherapy. In order to reflect on this, we have added the following sentence to the discussion:
“Further high-quality research in this area is needed, particularly in the setting of neoadjuvant immunotherapy, in order to underpin the recommendation made here.”
Concerning the lung resection, an anatomical lung resection is preferred and indicated rather than a sublobar or for selected frailty patient for example. As mention, the goal is to provide a R0 resection and the best nodal stagging.
4.4: No major concerns.
Concerning the conclusion:
It’s a well written, and easy reading consensus recommendations dealing with difficult lung cancer stages II and III due to a lack of consensus and data.
This nice work is very helpful.
As you have mentioned, many of your statement are debated due to a lack of strong evidence, and this will be more difficult again with new systemic treatments. The multidisciplinary board is one of the most important things that need to be highlighted in order to provide best cares to our patients.
Congratulations to authors for this difficult work.
We thank the reviewer for their input and kind words.
Reviewer 2 Report
Comments and Suggestions for Authors
Dear Authors,
I would like to thank you for this outstanding contribution. This manuscript can be used as a document of SOP in MDTB or Divisions of Med Onc, Thoracic Surgery and Rad Onc.
Congratulations for producing this manuscript.
Author Response
We thank the reviewer for their kind remarks.
Reviewer 3 Report
Comments and Suggestions for Authors
This is an interesting review regarding the possible recommendations for the management of stage II and III NSCLC lung cancer. The main limitations is certainly the limited number of participants with a majority of medical oncologists as usual in this kind of study. Reading the paper I was initially a little confused which was solved by the end of your introduction: should you not added in your title management of operable stage II/III; this what you are telling us at the end of your introduction. Regarding the methods, I have always a problem with abstracts: could you tell us how many abstracts were still maintained in your review?
In your table 1 , you have a statement regarding PORT and I agree with your recommendations but there is no comments in your discussion on this issue.
Regarding the issue of MRI for brain mets, do you think we should make a difference between squamous cell ca and adenocarcinoma?
I fully agree with your comments to treat patient in a timely manner to avoid long delay in the start of the treatment
Making comments and decisions on immunotherapy in an adjuvant setting is not an easy task as studies and trials are on-going.
In general I am supporting your paper with the limitations above.
Author Response
Reviewer 2
This is an interesting review regarding the possible recommendations for the management of stage II and III NSCLC lung cancer. The main limitations is certainly the limited number of participants with a majority of medical oncologists as usual in this kind of study. Reading the paper I was initially a little confused which was solved by the end of your introduction: should you not added in your title management of operable stage II/III; this what you are telling us at the end of your introduction.
We thank the reviewer for this important reflection. Whilst the guidelines do include some reference to the management of non-operable disease, the predominant focus is with regards to those who have operable disease. We agree that the title should be clearer to reflect this and as such, have added the word ‘operable’ to the title.
Regarding the methods, I have always a problem with abstracts: could you tell us how many abstracts were still maintained in your review?
The reviewer also raises another important point. With the emergence of so much data regarding the management of stage II / III NSCLC, some of the reports invariably have only been presented at meetings. Ideally, we would include only those that have been formally published, however we felt that this would leave some specific gaps in the review. To the best of our knowledge, only 5 abstracts were included of which 2 were updates of data in already published trials.
In your table 1 , you have a statement regarding PORT and I agree with your recommendations but there is no comments in your discussion on this issue.
This is an important point that was missing from the original manuscript. We agree that some discussion regarding the role of PORT is required given the recommendation made. We are keen to keep this in the context of neoadjuvant therapy and as such, the following sentence has been added to the discussion:
“Evidence regarding the use of adjuvant radiotherapy following neoadjuvant immuno-chemotherapy is sparse and as such those with positive margins require discussion in the MDT setting.”
Regarding the issue of MRI for brain mets, do you think we should make a difference between squamous cell ca and adenocarcinoma?
This is an interesting point that was not discussed in the original manuscript and we agree that it warrants being mentioned. As such, the following sentence was added to the discussion:
“With regards to histological subtype, compared to squamous cell carcinoma, adenocarcinoma has been found to be more commonly associated with brain metastases when compared stage-by-stage in neurologically asymptomatic patients40. However, the diagnostic yield of MRI is similar between histological subtypes and therefore we cannot suggest different imaging modalities based on the type of NSCLC alone39.”
I fully agree with your comments to treat patient in a timely manner to avoid long delay in the start of the treatment.
Making comments and decisions on immunotherapy in an adjuvant setting is not an easy task as studies and trials are on-going.
We agree with the reviewer that this is a challenging issue and hope that these guidelines will support these complex decision making processes.
In general I am supporting your paper with the limitations above.
We thank the reviewer for their important insight and kind words.
