Innovations in the Management of Vaginal Cancer

Round 1

Reviewer 1 Report

A well written paper. In section 1.3 - I would mention that spread is also hemtogenous.1.4 - Although it is clinically staged I would emphasize the need for an MRI for XRT planning and also the need for PET/CT - data extrapolated from the management of cervix cancer.  Would you consider cisplatin single agent with XRT - again extrapolated from cervix data rather than a combination of 5FU/Cisplatin. Is there any role for Carboplatin as a radiosensitizer if there is CI to cisplatin. 

I would use simpler language with regards to the M1B index. MIB is is used to look at the expression of the Ki 67 antigen ( High Ki ag correlates to high mitotic activity).

With XRT mention image guided brachytherapy + role for interstitial XRT. Also add Ref Schmid et al, Recommendations from Gyn- GEC-ESTRO, Radiotherapy and Oncology, April 2020. 

 

Author Response

Revisions to “Innovations in the Management of Vaginal Cancer”: curroncol-1660831

 

Thank-you for reviewing our paper and for your comments. Attached is a tracked copy and a clean copy of the manuscript. Below are our responses.

 

Reviewer #1

A well written paper. In section 1.3 - I would mention that spread is also hemtogenous.1.4 - Although it is clinically staged I would emphasize the need for an MRI for XRT planning and also the need for PET/CT - data extrapolated from the management of cervix cancer.

• Thank-you for this comment. We have incorporated these changes in lines 132-137 in the manuscript.

Would you consider cisplatin single agent with XRT - again extrapolated from cervix data rather than a combination of 5FU/Cisplatin. Is there any role for Carboplatin as a radiosensitizer if there is CI to cisplatin.

• Thank-you for this comment. We have changed the wording of lines 240-241 to more specifically state that the most common forms of chemotherapy used for chemoradiation are cisplatin and 5-FU. There are case reports and series reporting the use of various other agents, including carboplatin.

I would use simpler language with regards to the M1B index. MIB is is used to look at the expression of the Ki 67 antigen (High Ki ag correlates to high mitotic activity).

• Thank-you for this suggestion. The wording of this has been changed in lines 95-99 of the manuscript.

Reviewer 2 Report

• (1)Please mention the correlation between VAIN (vaginal intraepithelial neoplasia) and vaginal cancer.
• (2)Please add a paragraph about vaginal melanoma.
• (3)Please add a paragraph about vaginal botryoid rhabdomyosarcoma.
• (4)Please mention the correlation between prenatal diethylstilbestrol (DES) exposure and vaginal clear cell carcinoma.
• (5)Lines 294-300: Please mention that in the CheckMate 358 trial, patients known to have human papillomavirus–negative tumors were ineligible.

Author Response

Revisions to “Innovations in the Management of Vaginal Cancer”: curroncol-1660831

 

Thank-you for reviewing our paper and for your comments. Attached is a tracked copy and a clean copy of the manuscript. Below are our responses.

Reviewer #2

(1)Please mention the correlation between VAIN (vaginal intraepithelial neoplasia) and vaginal cancer.

• Thank-you for this suggestion. This has been added into lines 63-70 of the manuscript.

(2)Please add a paragraph about vaginal melanoma.

• Thank-you for this suggestion. A new section has been added titled “7. Special Circumstances”. This addresses vaginal melanoma, as well as vaginal botryoid rhabdomyosarcoma.

(3)Please add a paragraph about vaginal botryoid rhabdomyosarcoma.

• Thank-you for this suggestion. A new section has been added titled “7. Special Circumstances”. This addresses vaginal melanoma, as well as vaginal botryoid rhabdomyosarcoma.

(4)Please mention the correlation between prenatal diethylstilbestrol (DES) exposure and vaginal clear cell carcinoma.

• Thank-you for this suggestion. This has been added to line 53 of the manuscript.

(5)Lines 294-300: Please mention that in the CheckMate 358 trial, patients known to have human papillomavirus–negative tumors were ineligible.

• Thank-you for this suggestion. A sentence was added in lines 302-304 to address the eligibility criteria according to HPV status.

Reviewer 3 Report

A well written review from a surgical perspective. As they correctly state that radiotherapy with or without chemotherapy is the standard treatment, it is interesting that all the authors seem to be surgeons so there is not much information on radiotherapy. 

MIB-1 is one method of measuring the Ki-67 index and the abbreviation Ki-67 is more commonly used to describe the mitotic rate.

The prohibition of modern imaging in the traditional FIGO system as  mentioned is a major problem compared to the TNM system used  elsewhere in the body and Stage 2 vaginal cancer can be an extensive lesion.

Table 1 lists some studies with very small numbers of limited value.

This review does not add much, but perhaps there is little to add! A nice short summary for the surgical trainee or non-oncologist

Author Response

Revisions to “Innovations in the Management of Vaginal Cancer”: curroncol-1660831

Thank-you for reviewing our paper and for your comments. Attached is a tracked copy and a clean copy of the manuscript. Below are our responses.

Reviewer #3

A well written review from a surgical perspective. As they correctly state that radiotherapy with or without chemotherapy is the standard treatment, it is interesting that all the authors seem to be surgeons so there is not much information on radiotherapy.

• Thank-you for this comment. As radiotherapy or chemoradiation is standard treatment, we felt that this has been well-addressed in the literature. To address the gap in the literature, we focused our review on surgical and systemic treatments for vaginal cancer.

MIB-1 is one method of measuring the Ki-67 index and the abbreviation Ki-67 is more commonly used to describe the mitotic rate.

• Thank-you for this comment. The wording of this has been changed in lines 95-99.

The prohibition of modern imaging in the traditional FIGO system as mentioned is a major problem compared to the TNM system used elsewhere in the body and Stage 2 vaginal cancer can be an extensive lesion.

• Thank-you for this comment. We have added a sentence to address this in line 132.

Table 1 lists some studies with very small numbers of limited value.

• Thank-you for this comment. The Table highlights what the current evidence is for the use of systemic chemotherapy in the treatment of recurrent or metastatic vaginal cancer. As indicated, the evidence is very sparse and one of the purposes of this table is to highlight this.

This review does not add much, but perhaps there is little to add! A nice short summary for the surgical trainee or non-oncologist.

• Thank-you for this comment. With this review, we hope to fill a gap in the literature in addressing surgical and systemic therapies for vaginal cancer. While radiation and chemoradiation are the standard treatments, there is a role for surgical and systemic therapies, which we addressed in this paper.