An Effective Primary Treatment Using Radiotherapy in Patients with Eyelid Merkel Cell Carcinoma

Round 1

Reviewer 1 Report

This paper is dealing with radiotherapy as primary therapy of MCC located at the eyelid. None of the patients (n = 11) relapsed during follow-up (median 62 months).

The paper is done properly. It is clinically interesting despite the relatively small patient cohort.

There are only some minor points of criticism:

1.  3.2 Treatment, Table 2:

In the chapter Treatment three patients were mentioned who underwent “surgery with insufficient margins of 0.1 cm”, but in Table 2 it is stated that surgical margins were > 5 mm. What is correct?

2.  3.3 Irradiation, Table 2:

Hypofracting was used in three patients (Table 2). However, in the text five patients are mentioned. This discrepance should be clarified.

3. Introduction:  Line 18: Eyelid is written twice; lines 26 and 29 include spelling errors.

Author Response

We thank the reviewer for their comments and suggestions for improvement.

comment 1 : Treatment, Table 2:

In the chapter Treatment three patients were mentioned who underwent “surgery with insufficient margins of 0.1 cm”, but in Table 2 it is stated that surgical margins were > 5 mm. What is correct?

Response 1 : The three patient indewen surgical biopsy. The excision is made without margins. surgery in these  in the smalest leasions was not performed to ensure adequate carcinological margins, but rather to identify the lesion.

Comment 2 : 3.3 Irradiation, Table 2:

Hypofracting was used in three patients (Table 2). However, in the text five patients are mentioned. This discrepance should be clarified.

Response 2 : I thank the reviewer for having noticed this error. After verification, the correct number of patients with hypofractionation is 3/11. 

Comment 3 : Introduction: Line 18: Eyelid is written twice; lines 26 and 29 include spelling errors.

Response 3 : Sorry for this mistake, the spelling errors and double words were corrected.

Reviewer 2 Report

The authors report clinical cases of eyelid MCC and suggest radiotherapy (eyelid irradiation) as an effective primary treatment. I have a few minor comments.

- The title could be changed to something like "An effective primary treatment using radiotherapy in patients with eyelid Merkel cell carcinoma". It's a little strange to say the "role" of radiotherapy.

-Abstract Background: Change "Merkel's carcinoma" to "Merkel cell carcinoma (MCC)"

-Abstract conclusion: "Our data suggest that curative radiotherapy is an effective and safe treatment for MCC in the eyelid and periocular region."

-Page 2~, MCC does not need to be spelled out throughout the rest of the manuscript after introducing the abbreviation.

-Table 2, Linked to MC? or MCC?

-Table 3 needs a title.

-Concluions: MMC to MCC

-If the authors will not explain what the MCPyV is, it will be better to delete the MCPyV part in the discussion. It's distracting to suddenly mention it in the discussion since the authors did not have any data on it from the listed patients.

Author Response

Thank you for the interest to our work. We thank the reviewer for his comments and suggestions for improvement.

comment 1 : The title could be changed to something like "An effective primary treatment using radiotherapy in patients with eyelid Merkel cell carcinoma". It's a little strange to say the "role" of radiotherapy.

Response 1  :Thank you for the suggestion. The title has been changed.

Comment 2 : Abstract Background: Change "Merkel's carcinoma" to "Merkel cell carcinoma (MCC)"

Response 2  :Thank you for the correction. The name has been changed.

Comment 3 : Abstract conclusion: "Our data suggest that curative radiotherapy is an effective and safe treatment for MCC in the eyelid and periocular region."

Response 3  :Thank you for the correction, the change has been made

Comment 4 : Page 2~, MCC does not need to be spelled out throughout the rest of the manuscript after introducing the abbreviation.

Response 4  :Thank you for the correction, the change has been made

Comment 5 Table 2, Linked to MC? or MCC?

Response 5  : Sorry for this mistake, the change has been made

Comment 6 : Table 3 needs a title.

Response 6: the title "Review of the literature of eyelid MCC treated with curative radiotherapy" has been added.

Comment 7: Concluions: MMC to MCC

Response 7  : Sorry for this mistake, the change has been made

Comment 8: If the authors will not explain what the MCPyV is, it will be better to delete the MCPyV part in the discussion. It's distracting to suddenly mention it in the discussion since the authors did not have any data on it from the listed patients.

Response 8  : As the same comment has been done by other reviewer, this part as been removed.

Best regard,

Marie Boileau

Reviewer 3 Report

The article by Boileau, M. et al. about the role of radiotherapy in Merkel cell carcinoma is simple but well conducted. Probably there could be obtained more information from this nice case series, but it is still relevant as is.

There are some major issues:

-   I miss information in Materials and Methods. I guess no chemotherapy was applied, but you can state it. May be you can include a table with all the MCC cases you found in the database, the cases excluded and the cases included. You include in results some data that might be located in materials, but I can accept it that way.

-   I miss a table explaining the deaths of the patients.

There are some minor issues as well:

-    Introduction, page 2. Please, check the sentence “Most of the previously re- ported eyelid and eyelid MCCs”.

-    Introduction, page 2. The sentence “This has led to the use of the 8th-edition American Joint Committee” should be revised. Please include the criteria you refer.

-    Introduction, page 2. “duE to the age of patientS”. The next sentence also begins with “Due to”…

-    Introduction, page 2. The sentence beginning with “The standard care is wide local excision” has no logic. Please check.

-    Introduction, page 2. “conSidered”

-    Introduction, page 2. “reasonable” is a subjective word. It may be a valid treatment.  You should properly cite your article.

-    Introduction, page 2. “Both studIES”

-    Introduction, page 2. You should also properly cite here the work of Dubois et al.

-    Materials, page 3, section 2.1. Which medical records did you search? Pathology database for example?

-    Materials, page 3, section 2.1. Merkel cell carcinoma is generally positive with CK20 and Enolase, and negative with CK7.

-    Materials, page 3, section 2.1. Did you include patients with localized disease in other places different from the eyelid?

-    Discussion, page 5. “Carcinologic”? May be you are thinking in “oncologic”. I never heard or read that word.

-    Discussion, page 7. I think it’s good to include some references about MCPyV status and chemotherapy. May be you can include a pair of extra sentences in this respect with future perspectives. 

English is decent in some sentences, but great attention should be put on grammar / style, as there are too many minor flaws and, in some points, a confusing style. I included some errors as minor issues, but a rigorous revision is mandatory regarding this aspect. Please note that I only included a minor portion of these gramatical issues.

Author Response

We comment 1 : The article by Boileau, M. et al. about the role of radiotherapy in Merkel cell carcinoma is simple but well conducted. Probably there could be obtained more information from this nice case series, but it is still relevant as is.

Response 1: We thank the reviewer for the interest to the present work and his comments and suggestions for it's improvement. The english as been reviewed.

comment 2 :   I miss information in Materials and Methods. I guess no chemotherapy was applied, but you can state it. May be you can include a table with all the MCC cases you found in the database, the cases excluded and the cases included. You include in results some data that might be located in materials, but I can accept it that way.

Response 2 :  We added the precision  in material and methods "No chemotherapy or immunotherapy were performed."  We can not had the information of all th MCC cas foud in our data base.

Comment 3 :  I miss a table explaining the deaths of the patients.

Response 3 : We added the precision on the text. " Causes of death were cardiac, infectious or related to advanced age. "

Comment  4 :    Introduction, page 2. Please, check the sentence “Most of the previously re- ported eyelid and eyelid MCCs”.

Response 4 : We  made the correction  "eyelid and periocular region"

Comment 5 :  Introduction, page 2. The sentence “This has led to the use of the 8th-edition American Joint Committee” should be revised. Please include the criteria you refer.

Response 5 : the referece has been added. The sentence has also been precised "This led to the use of the 8th edition of the American Joint Committee on Cancer classification criteria for eyelid carcinoma rather than the MCC criteria to achieve a more consistent T-category designation"  and the related article cited.

Comment 6 :    Introduction, page 2. “duE to the age of patientS”. The next sentence also begins with “Due to”…

Response 6 :  The second sentence cas change from "due to ..." to "Because of early and rapid discomfort, eyelid lesions are diagnosed earlier and have a better prognosis."

Comment 7 :  Introduction, page 2. The sentence beginning with “The standard care is wide local excision” has no logic. Please check.

Response 7 : the sentence hase been changed to "The standard care of MCC is wide local excision of the lesion with a negative lateral margin of 20 mm. An adjuvant radiation therapy to the primary tumor site is also recommended."

Comment 8 :  Introduction, page 2. “conSidered”

Response 8 : The correction has been made.

Comment 9:    Introduction, page 2. “reasonable” is a subjective word. It may be a valid treatment.  You should properly cite your article.

Response 9 : it has been changed for : "Indeed, our team previously reported that curative external beam radiotherapy (EBRT) leads to a similar oncological outcome as combined treatment, with fewer aesthetic sequelae for early Merkel cell carcinoma" quoting Dubois et al.

Comment 10 :  Introduction, page 2. “Both studIES”

Response 10 : the correction has been made

Comment 11 :  Introduction, page 2. You should also properly cite here the work of Dubois et al.

Response 11 : the citation has been added.

Comment 12 :   Materials, page 3, section 2.1. Which medical records did you search? Pathology database for example?

Response 12 : We have examined all MCC cases discussed in our tumor bord between 1999 and 2019. It is a clinical data base. Among them we selected only eyelid lesions.

Comment 13 :   Materials, page 3, section 2.1. Merkel cell carcinoma is generally positive with CK20 and Enolase, and negative with CK7.

Response 13 : the precision has been made

Comment 14 :   Materials, page 3, section 2.1. Did you include patients with localized disease in other places different from the eyelid?

Response 14 : we excluded patients with localized disease in other places different from the eyelid. The precision was made.

Comment 15 :   Discussion, page 5. “Carcinologic”? May be you are thinking in “oncologic”. I never heard or read that word

Response 15 : Yes it is a mistake of translation that was not corrected by our english editing, thank you for th correction. The change as been made in all th sentences where we could find this word.

Comment 16 : Discussion, page 7. I think it’s good to include some references about MCPyV status and chemotherapy. May be you can include a pair of extra sentences in this respect with future perspectives. 

Response 16 : this part has been removed at the request of the other 2 reviewers to not  confuse and distract the reader from the main message.