Line-Field Confocal Optical Coherence Tomography for the Diagnosis of Skin Carcinomas: Real-Life Data over Three Years

Round 1

Reviewer 1 Report

In my opinion, resolution of the images on LC-OCT (I am one of the users of it) is not sufficient to see individual keratinocytes clearly and to appreciate palisading as seen in Basal Cell Carcinomas. I recommend that this should be included in somewhere or in the discussion of the paper. 

Author Response

REVIEWER 1

In my opinion, resolution of the images on LC-OCT (I am one of the users of it) is not sufficient to see individual keratinocytes clearly and to appreciate palisading as seen in Basal Cell Carcinomas. I recommend that this should be included in somewhere or in the discussion of the paper. 

Single keratinocytes inside the epidermis are well visible and can be clearly identified by the presence of their nuclei which are seen as central roundish hypo-reflective areas with the surrounding medium-reflective cytoplasm. In normal skin, the peripheral contours of keratinocytes are visible on horizontal sections and not on vertical sections. As pointed out single cells of basal cell carcinoma are not always visible because they can be crowded and form the so-called millefeuille pattern that corresponds to linear horizontal lines determined by the medium reflection of the cytoplasm of the cells separated by dark holes corresponding to cell nuclei. Although peripheral palisading is less visible than in histopathology and RCM, with LC-OCT we can appreciate cells piled one on the other at the periphery of the tumor islands with flat dark overlapped nuclei that have the same orientation.

Reviewer 2 Report

In this manuscript for an original article, the performance of line-field confocal optical coherence tomography (LC-OCT) for the diagnosis of skin carcinomas was investigated based on real-life data of three years. The study is reports on an important topic, the text of the manuscript is clear and the conclusions are supported by the data. However, there are some major and minor issues to be clarified by the authors. In conclusion, this manuscript should be subjected to a major revision to be deemed for publication in Current Oncology.

 

Major remarks:

1.                   In the Introduction, the technical background of LC-OCT should be further elucidated, for those readers that are not familiar with this novel technique

2.                   AKs should be placed to the “malignant” group, as they require intervention. Classifying them as benign lesions is rather misleading. Even if they do not require surgical treatment, cryosurgery is often performed, that is used in malignant conditions such as superficial BCC and in situ SCC.

3.                   Positive and negative predictive value outcomes should be reported in addition to sensitivity and specificity

4.                   Graphic 1-4 can be omitted, it does not make any sense to report sensitivity and specificity data in a graph

5.                   Clinical images should be displayed in the Results, not in the Discussion

6.                   A paragraphs of the discussion reads as follows “The majority of the cases of our study were included in a similar work of our group that evaluated the diagnostic accuracy of LC-OCT for the diagnosis of skin carcinomas in one year of clinical activity”. Is it possible that the performance improved since LC-OCT has been used since a longer period?

7.                   Limitations of the study should be discussed in detail such as retrospective nature

Minor remarks:

1.       In the abstract, instead of the term “useless biopsies”, it should be “unnecessary biopsies”

2.       Tables appears more like a figures, the guidelines for table preparation of the journal should be followed

3.       The column of “MELANOM A” in Table 1 should be rearranged

4.       The used dermoscope device should be described

 

 

 

The manuscript should be revised by a native speaker

Author Response

REVIEWER 2

In this manuscript for an original article, the performance of line-field confocal optical coherence tomography (LC-OCT) for the diagnosis of skin carcinomas was investigated based on real-life data of three years. The study is reports on an important topic, the text of the manuscript is clear and the conclusions are supported by the data. However, there are some major and minor issues to be clarified by the authors. In conclusion, this manuscript should be subjected to a major revision to be deemed for publication in Current Oncology.

Major remarks:

1. In the Introduction, the technical background of LC-OCT should be further elucidated, for those readers that are not familiar with this novel technique

We added in the introduction a part on the technical background of LC-OCT.

2. AKs should be placed to the “malignant” group, as they require intervention. Classifying them as benign lesions is rather misleading. Even if they do not require surgical treatment, cryosurgery is often performed, that is used in malignant conditions such as superficial BCC and in situ SCC.

As suggested, we classified AK in the malignant group and we adjusted the statistical analysis consequently.

3. Positive and negative predictive value outcomes should be reported in addition to sensitivity and specificity

As suggested, we added positive predictive value and negative predictive value to the statistics and reported the outcomes in the manuscript.

4. Graphic 1-4 can be omitted, it does not make any sense to report sensitivity and specificity data in a graph

We agreed with the removal of Graphics 1-4 from the manuscript because they don’t provide any additional information other than an immediate overview of the differences between dermoscopy and LC-OCT.

5. Clinical images should be displayed in the Results, not in the Discussion

As you suggested, we moved the images to the results part.

6. A paragraphs of the discussion reads as follows “The majority of the cases of our study were included in a similar work of our group that evaluated the diagnostic accuracy of LC-OCT for the diagnosis of skin carcinomas in one year of clinical activity”. Is it possible that the performance improved since LC-OCT has been used since a longer period?

In our opinion, a longer period of use of the device can increase the diagnostic accuracy and we added in the manuscript that this trend is possibly explained by an increasing learning curve in the interpretation of LC-OCT images thanks to a longer period of use of the device.    

7. Limitations of the study should be discussed in detail such as retrospective nature.

The limitations of the study were better discussed (see discussion part). Diagnoses were prospectively given.

Minor remarks:

1. In the abstract, instead of the term “useless biopsies”, it should be “unnecessary biopsies”

We changed it, as suggested.

2. Tables appears more like a figures, the guidelines for table preparation of the journal should be followed

We modified the tables, conforming them to the journal style.

3. The column of “MELANOM A” in Table 1 should be rearranged

We rearranged the tables and the column “MELANOM A” is now adjusted.

4. The used dermoscope device should be described

As suggested, we specified the used dermatoscopes: VivaCam D200, (VivaScope GmbH, Munich, Germany) at 15x magnification to acquire images, and both this videodermoscope and the Dermlite DL200 Hybrid hand-held dermoscope (Dermlite, Aliso Viejo, California, USA) to make diagnoses.

Reviewer 3 Report

The authors present a paper about "Line-field confocal optical coherence tomography for the diagnosis of skin carcinomas: real-life data of three years".

The topic is innovative and it deserves attention both from a clinical and from a research point of view.

 

The sample is adequate from a statistical point of view because it includes 1481 skin lesions.

 

I believe it would an addition to integrate the following points as follows:

 

1) Are there any anatomical sites which the authors consider to be more challenging (for example the internal cantus of the eyelid) or do they believe that LC-OCT has no limitations? Please further explain this point

 

2) Since the authors addressed the topic of NMSC it would important to include as many entities as possible at least in the discussion section including also rarer entities like Extramammary Paget disease (see for example PMID: 36966472)

 

3) Why did the authors choose to focus particularly on BBC for their endpoints and not on SCC? Please provide additional explanation about this point

4) When dealing with the limitations of thei study the authors stated that "all diagnoses were performed by a single skin imaging expert": it would be impoartatn to define the concept of skin imaging expert (how many years of practice? additional specializations? spefic training courses perfomed?). Is there a learning curve and if so how long did it take for the expert to become so?

Author Response

REVIEWER 3

The authors present a paper about "Line-field confocal optical coherence tomography for the diagnosis of skin carcinomas: real-life data of three years".

The topic is innovative and it deserves attention both from a clinical and from a research point of view.

 

The sample is adequate from a statistical point of view because it includes 1481 skin lesions.

 

I believe it would an addition to integrate the following points as follows:

 

• Are there any anatomical sites which the authors consider to be more challenging (for example the internal cantus of the eyelid) or do they believe that LC-OCT has no limitations? Please further explain this point

Yes, there are. We specified in the manuscript that we excluded lesions of the eyelid margin, the internal cantus of the eye, and the upper eyelid because LC-OCT could damage the retina. 

• Since the authors addressed the topic of NMSC it would important to include as many entities as possible at least in the discussion section including also rarer entities like Extramammary Paget disease (see for example PMID: 36966472)

As suggested by the reviewer, we considered also PMID: 36966472 (we cited it in the manuscript as reference number 5) as an example of rarer NMSCs that we did not consider in the study. 

• Why did the authors choose to focus particularly on BBC for their endpoints and not on SCC? Please provide additional explanation about this point

NMSCs different from BCC, Bowen’s disease, and SCC were excluded due to the lack of established LC-OCT diagnostic criteria. We explained that point in the discussion part.

• When dealing with the limitations of thei study the authors stated that "all diagnoses were performed by a single skin imaging expert": it would be impoartatn to define the concept of skin imaging expert (how many years of practice? additional specializations? spefic training courses perfomed?). Is there a learning curve and if so how long did it take for the expert to become so?

As suggested, we provided a better definition of “skin imaging expert” both in the materials and methods part and in the discussion part.

Round 2

Reviewer 2 Report

The authors have thoroughly corrected all of the raised issues. I recommend acceptance of this revised manuscript in its present form.

Reviewer 3 Report

The authors have satisfactorily addressed my previous comments. I have no further suggestions