Title: Long-Term Outcomes of S-1 and Oxaliplatin Neoadjuvant Chemotherapy with Total
Mesorectal Excision and Lateral Lymph Node Dissection for Rectal Cancer
Version: 3 Date: 02 Jun 2024
Reviewer:  Shigeo Toda
Reviewer's report:
Dear authors,
This study investigated the feasibility of neoadjuvant chemotherapy followed by total mesorectal
excision and lateral lymph node dissection for rectal cancer. The data presented is valuable and of
great interest to readers. However, I believe some revisions should be made before publication.
I have some comments as follows:
First, I do not think it is appropriate to include local recurrence and distant recurrence in the
analysis of risk factors for survival because we cannot know the recurrence status at the time
of therapeutic intervention.
Second, you should include information about adjuvant chemotherapy in the methods section.
On page 6, line 11, it appears that all patients underwent adjuvant chemotherapy. It would be
better to describe the detailed conditions in the methods section.
Third, the authors suggested multivisceral resection, particularly total pelvic exenteration
(TPE), to further reduce the local recurrence rate. However, I believe a 5.8% local recurrence
rate is already reasonable. Organ function would be better maintained with selective
chemoradiotherapy (CRT) rather than TPE. Selective CRT (for example, for patients with
threatened circumferential resection margin) would be more effective in improving local control
while preserving organ function as much as possible.
Finally, some revisions in the abstract would be helpful for clarity. The inclusion criteria should
be specified in the methods section, such as “stage II or III rectal cancer located within 10 cm
from the anal verge.” The phrase “one of four study hospitals” is unnecessary and should be
omitted, as it is impossible to mention that original study in the abstract. Additionally, there are
too many “primary endpoints.” Typically, there is only one primary endpoint, with the others
being secondary endpoints. Was this distinction defined in the original study?
There are a few small mistakes or points that I found difficult to understand, as follows:
On page 2, line 5, "pelvis recurrence" should be changed to "pelvic recurrence."
On page 2, line 7, and page 5, line 5, the phrase "ineligibility for R0 resection" is rather difficult
to understand. I suggest using "R1 or R2 resection" or "positive resection margin" instead.
On page 3, under "Background," line 8, "Deeper than cT3" usually does not include cT3.
Therefore, "cT3 or cT4" is preferable.
On page 3, "Background," line 24, before using the abbreviation "SOX" for the first time in the
manuscript, it is better to spell it out. In the methods section, it would be helpful to explain the
SOX regimen in detail, as it is not performed worldwide. On page 6, line 20, the SOX regimen
consists of S-1, an oral drug, and oxaliplatin, an infusional drug; therefore, it is not an oral
regimen. The logic that “SOX is best because it is an oral regimen” is unclear and needs further
explanation.
Instead of the phrase “risk factor of ~,” usually “risk factor for ~” is commonly used. This
appears frequently in the manuscript.
On page 4, line 15, the author states that vessels were resected en-bloc in cases of lateral lymph
node metastasis. It is difficult to determine metastasis during surgery. Please add an explanation
about how metastasis is defined during surgery.
On page 5, lines 4-5 and 25, mucinous carcinoma is a subtype of adenocarcinoma. Therefore,
expressions such as “mucinous carcinoma not adenocarcinoma” and “pathology other than
adenocarcinoma” are difficult to understand. Please provide some explanation.
On page 6, line 6, “oral treatment” should be “medical treatment” or “medication.”
On page 6, line 8, “specular” should be “endoscopic” if you want to describe “laparoscopic and
robotic.”
On page 7, lines 4-7, the statement about MRI being useful for predicting LPLN metastasis but
not adequate for LPLN is unclear. Please explain this in more detail.
On page 7, line 8, specify what type of image is the object of “machine learning” (e.g., CT,
MRI, or others).
On page 7, line 18, “consolidation chemotherapy” is more often used instead of “intensified
chemotherapy.”
Regards,
Title: Long-Term Outcomes of S-1 and Oxaliplatin Neoadjuvant Chemotherapy with Total
Mesorectal Excision and Lateral Lymph Node Dissection for Rectal Cancer
Version: 3 Date: 02 Jun 2024
Reviewer:  Shigeo Toda
Reviewer's report:
Dear authors,
This study investigated the feasibility of neoadjuvant chemotherapy followed by total mesorectal
excision and lateral lymph node dissection for rectal cancer. The data presented is valuable and of
great interest to readers. However, I believe some revisions should be made before publication.
I have some comments as follows:
First, I do not think it is appropriate to include local recurrence and distant recurrence in the
analysis of risk factors for survival because we cannot know the recurrence status at the time
of therapeutic intervention.
Second, you should include information about adjuvant chemotherapy in the methods section.
On page 6, line 11, it appears that all patients underwent adjuvant chemotherapy. It would be
better to describe the detailed conditions in the methods section.
Third, the authors suggested multivisceral resection, particularly total pelvic exenteration
(TPE), to further reduce the local recurrence rate. However, I believe a 5.8% local recurrence
rate is already reasonable. Organ function would be better maintained with selective
chemoradiotherapy (CRT) rather than TPE. Selective CRT (for example, for patients with
threatened circumferential resection margin) would be more effective in improving local control
while preserving organ function as much as possible.
Finally, some revisions in the abstract would be helpful for clarity. The inclusion criteria should
be specified in the methods section, such as “stage II or III rectal cancer located within 10 cm
from the anal verge.” The phrase “one of four study hospitals” is unnecessary and should be
omitted, as it is impossible to mention that original study in the abstract. Additionally, there are
too many “primary endpoints.” Typically, there is only one primary endpoint, with the others
being secondary endpoints. Was this distinction defined in the original study?
There are a few small mistakes or points that I found difficult to understand, as follows:
On page 2, line 5, "pelvis recurrence" should be changed to "pelvic recurrence."
On page 2, line 7, and page 5, line 5, the phrase "ineligibility for R0 resection" is rather difficult
to understand. I suggest using "R1 or R2 resection" or "positive resection margin" instead.
On page 3, under "Background," line 8, "Deeper than cT3" usually does not include cT3.
Therefore, "cT3 or cT4" is preferable.
On page 3, "Background," line 24, before using the abbreviation "SOX" for the first time in the
manuscript, it is better to spell it out. In the methods section, it would be helpful to explain the
SOX regimen in detail, as it is not performed worldwide. On page 6, line 20, the SOX regimen
consists of S-1, an oral drug, and oxaliplatin, an infusional drug; therefore, it is not an oral
regimen. The logic that “SOX is best because it is an oral regimen” is unclear and needs further
explanation.
Instead of the phrase “risk factor of ~,” usually “risk factor for ~” is commonly used. This
appears frequently in the manuscript.
On page 4, line 15, the author states that vessels were resected en-bloc in cases of lateral lymph
node metastasis. It is difficult to determine metastasis during surgery. Please add an explanation
about how metastasis is defined during surgery.
On page 5, lines 4-5 and 25, mucinous carcinoma is a subtype of adenocarcinoma. Therefore,
expressions such as “mucinous carcinoma not adenocarcinoma” and “pathology other than
adenocarcinoma” are difficult to understand. Please provide some explanation.
On page 6, line 6, “oral treatment” should be “medical treatment” or “medication.”
On page 6, line 8, “specular” should be “endoscopic” if you want to describe “laparoscopic and
robotic.”
On page 7, lines 4-7, the statement about MRI being useful for predicting LPLN metastasis but
not adequate for LPLN is unclear. Please explain this in more detail.
On page 7, line 8, specify what type of image is the object of “machine learning” (e.g., CT,
MRI, or others).
On page 7, line 18, “consolidation chemotherapy” is more often used instead of “intensified
chemotherapy.”
Regards,
Please review this paper.
user
Title: Long-Term Outcomes of S-1 and Oxaliplatin Neoadjuvant Chemotherapy with Total
Mesorectal Excision and Lateral Lymph Node Dissection for Rectal Cancer
Version: 3 Date: 02 Jun 2024
Reviewer:  Shigeo Toda
Reviewer's report:
Dear authors,
This study investigated the feasibility of neoadjuvant chemotherapy followed by total mesorectal
excision and lateral lymph node dissection for rectal cancer. The data presented is valuable and of
great interest to readers. However, I believe some revisions should be made before publication.
I have some comments as follows:
First, I do not think it is appropriate to include local recurrence and distant recurrence in the
analysis of risk factors for survival because we cannot know the recurrence status at the time
of therapeutic intervention.
Second, you should include information about adjuvant chemotherapy in the methods section.
On page 6, line 11, it appears that all patients underwent adjuvant chemotherapy. It would be
better to describe the detailed conditions in the methods section.
Third, the authors suggested multivisceral resection, particularly total pelvic exenteration
(TPE), to further reduce the local recurrence rate. However, I believe a 5.8% local recurrence
rate is already reasonable. Organ function would be better maintained with selective
chemoradiotherapy (CRT) rather than TPE. Selective CRT (for example, for patients with
threatened circumferential resection margin) would be more effective in improving local control
while preserving organ function as much as possible.
Finally, some revisions in the abstract would be helpful for clarity. The inclusion criteria should
be specified in the methods section, such as “stage II or III rectal cancer located within 10 cm
from the anal verge.” The phrase “one of four study hospitals” is unnecessary and should be
omitted, as it is impossible to mention that original study in the abstract. Additionally, there are
too many “primary endpoints.” Typically, there is only one primary endpoint, with the others
being secondary endpoints. Was this distinction defined in the original study?
There are a few small mistakes or points that I found difficult to understand, as follows:
On page 2, line 5, "pelvis recurrence" should be changed to "pelvic recurrence."
On page 2, line 7, and page 5, line 5, the phrase "ineligibility for R0 resection" is rather difficult
to understand. I suggest using "R1 or R2 resection" or "positive resection margin" instead.
On page 3, under "Background," line 8, "Deeper than cT3" usually does not include cT3.
Therefore, "cT3 or cT4" is preferable.
On page 3, "Background," line 24, before using the abbreviation "SOX" for the first time in the
manuscript, it is better to spell it out. In the methods section, it would be helpful to explain the
SOX regimen in detail, as it is not performed worldwide. On page 6, line 20, the SOX regimen
consists of S-1, an oral drug, and oxaliplatin, an infusional drug; therefore, it is not an oral
regimen. The logic that “SOX is best because it is an oral regimen” is unclear and needs further
explanation.
Instead of the phrase “risk factor of ~,” usually “risk factor for ~” is commonly used. This
appears frequently in the manuscript.
On page 4, line 15, the author states that vessels were resected en-bloc in cases of lateral lymph
node metastasis. It is difficult to determine metastasis during surgery. Please add an explanation
about how metastasis is defined during surgery.
On page 5, lines 4-5 and 25, mucinous carcinoma is a subtype of adenocarcinoma. Therefore,
expressions such as “mucinous carcinoma not adenocarcinoma” and “pathology other than
adenocarcinoma” are difficult to understand. Please provide some explanation.
On page 6, line 6, “oral treatment” should be “medical treatment” or “medication.”
On page 6, line 8, “specular” should be “endoscopic” if you want to describe “laparoscopic and
robotic.”
On page 7, lines 4-7, the statement about MRI being useful for predicting LPLN metastasis but
not adequate for LPLN is unclear. Please explain this in more detail.
On page 7, line 8, specify what type of image is the object of “machine learning” (e.g., CT,
MRI, or others).
On page 7, line 18, “consolidation chemotherapy” is more often used instead of “intensified
chemotherapy.”
Regards,
assistant