Title: Clinical Characteristics and Treatment Outcomes of Primary Malignant Melanoma of
Esophagus: A Single Center Experience
Version: 1 Date: 27 Dec 2021
Reviewer's report:
This study performed a superficial analysis on a small set of primary malignant melanoma of
esophagus (PMME) and no conclusive statement was given. However, PMME was a rare disease
with aggressive disease course and poor outcomes. Based on this, this summary about PMME
as work done by the authors in the current study could also help the clinicians to judge and treat
such a disease. But there were still many revisions that should be made.
Major revision:
1. Immunotherapy alone showed limited efficacy in mucosal melanoma while the bi-
immunotherapy was proved to achieve progress in the outcomes of the mucosal melanoma by the
results of CheckMate 067. This background should be added to the Introduction section of this
manuscript. Moreover, much less study focus on the PMME, so more details about the so-called
evidence of “immune-checkpoint inhibitor for metastatic PMME have shown promising results
[8-10]” (1st paragraph of the Background) by authors should also be stated in the Background.
2. As the main purpose of the current study focused on the impact of the surgery on the outcomes
of the PMME, the current global surgical outcomes needed to be clearly described, so as to
compare with the final results of the current study.
3. It’s quite questionable that the differences of the OS between the Mass forming group and
the diffusely infiltrative group were significant (P = 0.048) ‘cause the latter had only 2 patients.
So, I recommend that Figure 2D could be deleted.
4. Also, we should conclude with cautions when we said, ”Having a diffusely infiltrative tumor
morphology was significantly associated with better overall survival than mass-forming tumor
morphology.”
Minor revisions:
1. More about the statistical analyses were needed in the Methods of the Abstract. The details
about the follow-up time should be clarified.
2. What does the reference date mean? Is that referring to the cutoff date of the follow-up?
3. Could all the lost follow-up patients’ survival data be supplemented by the National Health
Insurance System Database? How to deal with the lost follow-up data if they could not be
followed in the National Health Insurance System Database?
4. Why was there such a large male predominance in this study (88.2% vs. 11.8%, ratio of almost
8:1)? Even when looking into the data from Ref. 10, the same ethnic of PMME cohort from
eastern Asia just showed a male/female ratio of 2.17:1.
5. I’m just curious about the symptoms of the diffusely infiltrative PMME. How about are they?
No symptom? ‘Cause, we saw the number of these two groups were the same (n=2, 11.8%).
6. There’s one patient with Upper PMME but still received the surgery. Why?
Radiochemotherapy may be a better choice for this patient. And also, were there any patients
who underwent neoadjuvant treatment?
7. Did the patients with post-operative complications include the Upper PMME, or not?
8. For patients without surgery but who underwent immunotherapy as the 1st-line treatment,
the factors that influence the OS could not only be the immunotherapy, the subsequential
therapy such as the Trastuzumab + Deruxtecan, that is DS-8201 (we can speculate that the
DS-8201 brought about 8 months of PFS for this patient who received Nivolumab as his 1st-
line treatment), could also impact on the final survival data. Similar evidence was the second
patient who received Pembrolizumab as his 1st-line treatment only obtained 2 months of PFS.
I think the author should draw more discussion about this.
9. The authors discussed that: “In the present study, whether or not the patient underwent surgery
was not associated with overall survival (Figure 2B). We assume that this is because of the
extremely aggressive biology of PMME.” Is there any other consideration about the reason?
10. The features of diffusely infiltrative melanoma may not be equal to those of SSM in
cutaneous. The latter shows neoplastic melanocytes Paget's-like spread between squamous
epithelium. These parts of the discussion need revision. If necessary, the author needs a
consultation with the pathologist.
11. As a supplement, the gene mutation, as well as the PD-L1 expression level detection, may
help to provide a general acknowledgment of this disease. If they could be provided.
Title: Clinical Characteristics and Treatment Outcomes of Primary Malignant Melanoma of
Esophagus: A Single Center Experience
Version: 1 Date: 27 Dec 2021
Reviewer's report:
This study performed a superficial analysis on a small set of primary malignant melanoma of
esophagus (PMME) and no conclusive statement was given. However, PMME was a rare disease
with aggressive disease course and poor outcomes. Based on this, this summary about PMME
as work done by the authors in the current study could also help the clinicians to judge and treat
such a disease. But there were still many revisions that should be made.
Major revision:
1. Immunotherapy alone showed limited efficacy in mucosal melanoma while the bi-
immunotherapy was proved to achieve progress in the outcomes of the mucosal melanoma by the
results of CheckMate 067. This background should be added to the Introduction section of this
manuscript. Moreover, much less study focus on the PMME, so more details about the so-called
evidence of “immune-checkpoint inhibitor for metastatic PMME have shown promising results
[8-10]” (1st paragraph of the Background) by authors should also be stated in the Background.
2. As the main purpose of the current study focused on the impact of the surgery on the outcomes
of the PMME, the current global surgical outcomes needed to be clearly described, so as to
compare with the final results of the current study.
3. It’s quite questionable that the differences of the OS between the Mass forming group and
the diffusely infiltrative group were significant (P = 0.048) ‘cause the latter had only 2 patients.
So, I recommend that Figure 2D could be deleted.
4. Also, we should conclude with cautions when we said, ”Having a diffusely infiltrative tumor
morphology was significantly associated with better overall survival than mass-forming tumor
morphology.”
Minor revisions:
1. More about the statistical analyses were needed in the Methods of the Abstract. The details
about the follow-up time should be clarified.
2. What does the reference date mean? Is that referring to the cutoff date of the follow-up?
3. Could all the lost follow-up patients’ survival data be supplemented by the National Health
Insurance System Database? How to deal with the lost follow-up data if they could not be
followed in the National Health Insurance System Database?
4. Why was there such a large male predominance in this study (88.2% vs. 11.8%, ratio of almost
8:1)? Even when looking into the data from Ref. 10, the same ethnic of PMME cohort from
eastern Asia just showed a male/female ratio of 2.17:1.
5. I’m just curious about the symptoms of the diffusely infiltrative PMME. How about are they?
No symptom? ‘Cause, we saw the number of these two groups were the same (n=2, 11.8%).
6. There’s one patient with Upper PMME but still received the surgery. Why?
Radiochemotherapy may be a better choice for this patient. And also, were there any patients
who underwent neoadjuvant treatment?
7. Did the patients with post-operative complications include the Upper PMME, or not?
8. For patients without surgery but who underwent immunotherapy as the 1st-line treatment,
the factors that influence the OS could not only be the immunotherapy, the subsequential
therapy such as the Trastuzumab + Deruxtecan, that is DS-8201 (we can speculate that the
DS-8201 brought about 8 months of PFS for this patient who received Nivolumab as his 1st-
line treatment), could also impact on the final survival data. Similar evidence was the second
patient who received Pembrolizumab as his 1st-line treatment only obtained 2 months of PFS.
I think the author should draw more discussion about this.
9. The authors discussed that: “In the present study, whether or not the patient underwent surgery
was not associated with overall survival (Figure 2B). We assume that this is because of the
extremely aggressive biology of PMME.” Is there any other consideration about the reason?
10. The features of diffusely infiltrative melanoma may not be equal to those of SSM in
cutaneous. The latter shows neoplastic melanocytes Paget's-like spread between squamous
epithelium. These parts of the discussion need revision. If necessary, the author needs a
consultation with the pathologist.
11. As a supplement, the gene mutation, as well as the PD-L1 expression level detection, may
help to provide a general acknowledgment of this disease. If they could be provided.
Please review this paper.
user
Title: Clinical Characteristics and Treatment Outcomes of Primary Malignant Melanoma of
Esophagus: A Single Center Experience
Version: 1 Date: 27 Dec 2021
Reviewer's report:
This study performed a superficial analysis on a small set of primary malignant melanoma of
esophagus (PMME) and no conclusive statement was given. However, PMME was a rare disease
with aggressive disease course and poor outcomes. Based on this, this summary about PMME
as work done by the authors in the current study could also help the clinicians to judge and treat
such a disease. But there were still many revisions that should be made.
Major revision:
1. Immunotherapy alone showed limited efficacy in mucosal melanoma while the bi-
immunotherapy was proved to achieve progress in the outcomes of the mucosal melanoma by the
results of CheckMate 067. This background should be added to the Introduction section of this
manuscript. Moreover, much less study focus on the PMME, so more details about the so-called
evidence of “immune-checkpoint inhibitor for metastatic PMME have shown promising results
[8-10]” (1st paragraph of the Background) by authors should also be stated in the Background.
2. As the main purpose of the current study focused on the impact of the surgery on the outcomes
of the PMME, the current global surgical outcomes needed to be clearly described, so as to
compare with the final results of the current study.
3. It’s quite questionable that the differences of the OS between the Mass forming group and
the diffusely infiltrative group were significant (P = 0.048) ‘cause the latter had only 2 patients.
So, I recommend that Figure 2D could be deleted.
4. Also, we should conclude with cautions when we said, ”Having a diffusely infiltrative tumor
morphology was significantly associated with better overall survival than mass-forming tumor
morphology.”
Minor revisions:
1. More about the statistical analyses were needed in the Methods of the Abstract. The details
about the follow-up time should be clarified.
2. What does the reference date mean? Is that referring to the cutoff date of the follow-up?
3. Could all the lost follow-up patients’ survival data be supplemented by the National Health
Insurance System Database? How to deal with the lost follow-up data if they could not be
followed in the National Health Insurance System Database?
4. Why was there such a large male predominance in this study (88.2% vs. 11.8%, ratio of almost
8:1)? Even when looking into the data from Ref. 10, the same ethnic of PMME cohort from
eastern Asia just showed a male/female ratio of 2.17:1.
5. I’m just curious about the symptoms of the diffusely infiltrative PMME. How about are they?
No symptom? ‘Cause, we saw the number of these two groups were the same (n=2, 11.8%).
6. There’s one patient with Upper PMME but still received the surgery. Why?
Radiochemotherapy may be a better choice for this patient. And also, were there any patients
who underwent neoadjuvant treatment?
7. Did the patients with post-operative complications include the Upper PMME, or not?
8. For patients without surgery but who underwent immunotherapy as the 1st-line treatment,
the factors that influence the OS could not only be the immunotherapy, the subsequential
therapy such as the Trastuzumab + Deruxtecan, that is DS-8201 (we can speculate that the
DS-8201 brought about 8 months of PFS for this patient who received Nivolumab as his 1st-
line treatment), could also impact on the final survival data. Similar evidence was the second
patient who received Pembrolizumab as his 1st-line treatment only obtained 2 months of PFS.
I think the author should draw more discussion about this.
9. The authors discussed that: “In the present study, whether or not the patient underwent surgery
was not associated with overall survival (Figure 2B). We assume that this is because of the
extremely aggressive biology of PMME.” Is there any other consideration about the reason?
10. The features of diffusely infiltrative melanoma may not be equal to those of SSM in
cutaneous. The latter shows neoplastic melanocytes Paget's-like spread between squamous
epithelium. These parts of the discussion need revision. If necessary, the author needs a
consultation with the pathologist.
11. As a supplement, the gene mutation, as well as the PD-L1 expression level detection, may
help to provide a general acknowledgment of this disease. If they could be provided.
assistant