Title: Hepatic Arterial Infusion Chemotherapy plus Regorafenib in Advanced Colorectal
Cancer: A Real-World Retrospective Study
Version: 2 Date: 03 Jan 2022
Reviewer:  Hironaga Satake
Reviewer's report:
Thank you for submitting your paper.
Cao et al. reported retrospective research of real-world data of HAIC plus REG in advanced
CRC.
Following aspects are missing that might improve the value of this article.
Major
P2-L44 to L46
Abstract-Conclusions
The authors described ‘Regorafenib combined with Hepatic arterial infusion chemotherapy is an
effective second-line treatment option for treating colorectal cancer patients with liver metastasis
refractory to standard systemic therapy.’, but
- As this is a retrospective study with a small number of patients, uneven patient backgrounds,
and insufficient observation period, it is not possible to go into detail, so please change the
description of the conclusion.
- Since more than 78% of patients have already received at least a second line regimen, it is
appropriate to position it as a 'second line or later treatment option'.
P5- L119 to L120
Materials and Methods – Study design and Setting
- Is it a multi-center study or single-center study? Please describe.
P6- L137 to L139
Materials and Methods – Participants
- Since the inclusion criterion is that “the patient must have received at least one systemic
chemotherapy”, exclude the previously untreated patients from the analysis.
P7- L163 to L165
Materials and Methods – Procedures and Treatment
- How did you determine the starting dose of REG? Is it at doctor's discretion? Please describe.
P11- L248 to L250
Discussion
- Please change the description since the previous context does not lead to the conclusion that
‘HAIC plus REG is a good prognosis’.
P16- L367
Discussion
- Please describe in the "RESULTS” section the data that support the benefit of this strategy in
patients without extrahepatic disease.
Table1
- Describe the patient backgrounds enrolled in the study, including ECOG PS, clinical stage,
primary tumor site, number of elevated tumor markers (CEA), median or mean number and
distribution of heterogeneous/coincidental liver metastases, number and maximum diameter
(single or multiple, bilobed or unilobed) of liver metastses, median number of distant metastatic
organs, and distant metastatic sites.
- For “Previous Treatment Regimens”, please indicate the number and percentage of patients
receiving prior treatment with ‘oxaliplatin’ and ‘irinotecan’, ‘FP’, respectively.
Minor
P4- L78 to L79
Introduction
- Since CORRECT (Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/
S0140-6736(12)61900-X. Epub 2012 Nov 22.) is an international Phase3 trial that evaluated the
efficacy of REG before CONCUR, cite CORRECT in the background section.
P8- L167 to L168
Materials and Methods – Outcome measures
- Please describe the difference between PFS and TTP.
P8- L172 to L173
Materials and Methods – Outcome measures
- It is strange that endpoint is written as CR, PR, SD, PD. Is it the percentage of each?
P8- L188
Results – Baseline characteristics
- What does it mean that REG is ‘missing’? The inclusion criteria of the study stated that patients
with HAIC who received REG were eligible for the study, so I think they are not eligible for
the study.
P9- L198
Results – Treatment profile of HAIC combined with REG
- There are too many cases of REG termination due to reasons other than PD or intolerance, so
please explain the reasons.
P10- L215
Results – Univariable analyses
- Are these “PR” and “SD” assessments for “intrahepatic” lesions or “extrahepatic” lesions?
Please describe.
P10- L217
Results – Univariable analyses
- What is the rationale for setting the cutoff for CEA at 100 ng/ml? Please describe.
P10- L235
Results – Toxicity
- What is the abbreviation for “ADRs”? Please describe.
P12- L261 to L284
Discussion
-  This paragraph only describes a previously reported reviews, so please either delete it or
change it to describe the relevance to this study.
-
P13- L285 to L298
Discussion
- This paragraph is also not something that can be mentioned from this study, so please consider
deleting or changing it.
P13 L308 to L338
Discussion
- This part is redundant and only describes a previously reported reviews. Please delete or change
it if you do not want to relate or contrast it with this study.
Table1
- In the Total of “Pre-Reg Treatment Line”, “n=57” is listed, but why does the percentage not
add up to “100%”?
Table 2
- Are you sure you want to list the highest grade for LYM, WBC, and ALB?
Table 3&4
- Sort by the frequency of occurrence in either “Any Grade” or “Gr3/4”.
Title: Hepatic Arterial Infusion Chemotherapy plus Regorafenib in Advanced Colorectal
Cancer: A Real-World Retrospective Study
Version: 2 Date: 03 Jan 2022
Reviewer:  Hironaga Satake
Reviewer's report:
Thank you for submitting your paper.
Cao et al. reported retrospective research of real-world data of HAIC plus REG in advanced
CRC.
Following aspects are missing that might improve the value of this article.
Major
P2-L44 to L46
Abstract-Conclusions
The authors described ‘Regorafenib combined with Hepatic arterial infusion chemotherapy is an
effective second-line treatment option for treating colorectal cancer patients with liver metastasis
refractory to standard systemic therapy.’, but
- As this is a retrospective study with a small number of patients, uneven patient backgrounds,
and insufficient observation period, it is not possible to go into detail, so please change the
description of the conclusion.
- Since more than 78% of patients have already received at least a second line regimen, it is
appropriate to position it as a 'second line or later treatment option'.
P5- L119 to L120
Materials and Methods – Study design and Setting
- Is it a multi-center study or single-center study? Please describe.
P6- L137 to L139
Materials and Methods – Participants
- Since the inclusion criterion is that “the patient must have received at least one systemic
chemotherapy”, exclude the previously untreated patients from the analysis.
P7- L163 to L165
Materials and Methods – Procedures and Treatment
- How did you determine the starting dose of REG? Is it at doctor's discretion? Please describe.
P11- L248 to L250
Discussion
- Please change the description since the previous context does not lead to the conclusion that
‘HAIC plus REG is a good prognosis’.
P16- L367
Discussion
- Please describe in the "RESULTS” section the data that support the benefit of this strategy in
patients without extrahepatic disease.
Table1
- Describe the patient backgrounds enrolled in the study, including ECOG PS, clinical stage,
primary tumor site, number of elevated tumor markers (CEA), median or mean number and
distribution of heterogeneous/coincidental liver metastases, number and maximum diameter
(single or multiple, bilobed or unilobed) of liver metastses, median number of distant metastatic
organs, and distant metastatic sites.
- For “Previous Treatment Regimens”, please indicate the number and percentage of patients
receiving prior treatment with ‘oxaliplatin’ and ‘irinotecan’, ‘FP’, respectively.
Minor
P4- L78 to L79
Introduction
- Since CORRECT (Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/
S0140-6736(12)61900-X. Epub 2012 Nov 22.) is an international Phase3 trial that evaluated the
efficacy of REG before CONCUR, cite CORRECT in the background section.
P8- L167 to L168
Materials and Methods – Outcome measures
- Please describe the difference between PFS and TTP.
P8- L172 to L173
Materials and Methods – Outcome measures
- It is strange that endpoint is written as CR, PR, SD, PD. Is it the percentage of each?
P8- L188
Results – Baseline characteristics
- What does it mean that REG is ‘missing’? The inclusion criteria of the study stated that patients
with HAIC who received REG were eligible for the study, so I think they are not eligible for
the study.
P9- L198
Results – Treatment profile of HAIC combined with REG
- There are too many cases of REG termination due to reasons other than PD or intolerance, so
please explain the reasons.
P10- L215
Results – Univariable analyses
- Are these “PR” and “SD” assessments for “intrahepatic” lesions or “extrahepatic” lesions?
Please describe.
P10- L217
Results – Univariable analyses
- What is the rationale for setting the cutoff for CEA at 100 ng/ml? Please describe.
P10- L235
Results – Toxicity
- What is the abbreviation for “ADRs”? Please describe.
P12- L261 to L284
Discussion
-  This paragraph only describes a previously reported reviews, so please either delete it or
change it to describe the relevance to this study.
-
P13- L285 to L298
Discussion
- This paragraph is also not something that can be mentioned from this study, so please consider
deleting or changing it.
P13 L308 to L338
Discussion
- This part is redundant and only describes a previously reported reviews. Please delete or change
it if you do not want to relate or contrast it with this study.
Table1
- In the Total of “Pre-Reg Treatment Line”, “n=57” is listed, but why does the percentage not
add up to “100%”?
Table 2
- Are you sure you want to list the highest grade for LYM, WBC, and ALB?
Table 3&4
- Sort by the frequency of occurrence in either “Any Grade” or “Gr3/4”.
Please review this paper.
user
Title: Hepatic Arterial Infusion Chemotherapy plus Regorafenib in Advanced Colorectal
Cancer: A Real-World Retrospective Study
Version: 2 Date: 03 Jan 2022
Reviewer:  Hironaga Satake
Reviewer's report:
Thank you for submitting your paper.
Cao et al. reported retrospective research of real-world data of HAIC plus REG in advanced
CRC.
Following aspects are missing that might improve the value of this article.
Major
P2-L44 to L46
Abstract-Conclusions
The authors described ‘Regorafenib combined with Hepatic arterial infusion chemotherapy is an
effective second-line treatment option for treating colorectal cancer patients with liver metastasis
refractory to standard systemic therapy.’, but
- As this is a retrospective study with a small number of patients, uneven patient backgrounds,
and insufficient observation period, it is not possible to go into detail, so please change the
description of the conclusion.
- Since more than 78% of patients have already received at least a second line regimen, it is
appropriate to position it as a 'second line or later treatment option'.
P5- L119 to L120
Materials and Methods – Study design and Setting
- Is it a multi-center study or single-center study? Please describe.
P6- L137 to L139
Materials and Methods – Participants
- Since the inclusion criterion is that “the patient must have received at least one systemic
chemotherapy”, exclude the previously untreated patients from the analysis.
P7- L163 to L165
Materials and Methods – Procedures and Treatment
- How did you determine the starting dose of REG? Is it at doctor's discretion? Please describe.
P11- L248 to L250
Discussion
- Please change the description since the previous context does not lead to the conclusion that
‘HAIC plus REG is a good prognosis’.
P16- L367
Discussion
- Please describe in the "RESULTS” section the data that support the benefit of this strategy in
patients without extrahepatic disease.
Table1
- Describe the patient backgrounds enrolled in the study, including ECOG PS, clinical stage,
primary tumor site, number of elevated tumor markers (CEA), median or mean number and
distribution of heterogeneous/coincidental liver metastases, number and maximum diameter
(single or multiple, bilobed or unilobed) of liver metastses, median number of distant metastatic
organs, and distant metastatic sites.
- For “Previous Treatment Regimens”, please indicate the number and percentage of patients
receiving prior treatment with ‘oxaliplatin’ and ‘irinotecan’, ‘FP’, respectively.
Minor
P4- L78 to L79
Introduction
- Since CORRECT (Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/
S0140-6736(12)61900-X. Epub 2012 Nov 22.) is an international Phase3 trial that evaluated the
efficacy of REG before CONCUR, cite CORRECT in the background section.
P8- L167 to L168
Materials and Methods – Outcome measures
- Please describe the difference between PFS and TTP.
P8- L172 to L173
Materials and Methods – Outcome measures
- It is strange that endpoint is written as CR, PR, SD, PD. Is it the percentage of each?
P8- L188
Results – Baseline characteristics
- What does it mean that REG is ‘missing’? The inclusion criteria of the study stated that patients
with HAIC who received REG were eligible for the study, so I think they are not eligible for
the study.
P9- L198
Results – Treatment profile of HAIC combined with REG
- There are too many cases of REG termination due to reasons other than PD or intolerance, so
please explain the reasons.
P10- L215
Results – Univariable analyses
- Are these “PR” and “SD” assessments for “intrahepatic” lesions or “extrahepatic” lesions?
Please describe.
P10- L217
Results – Univariable analyses
- What is the rationale for setting the cutoff for CEA at 100 ng/ml? Please describe.
P10- L235
Results – Toxicity
- What is the abbreviation for “ADRs”? Please describe.
P12- L261 to L284
Discussion
-  This paragraph only describes a previously reported reviews, so please either delete it or
change it to describe the relevance to this study.
-
P13- L285 to L298
Discussion
- This paragraph is also not something that can be mentioned from this study, so please consider
deleting or changing it.
P13 L308 to L338
Discussion
- This part is redundant and only describes a previously reported reviews. Please delete or change
it if you do not want to relate or contrast it with this study.
Table1
- In the Total of “Pre-Reg Treatment Line”, “n=57” is listed, but why does the percentage not
add up to “100%”?
Table 2
- Are you sure you want to list the highest grade for LYM, WBC, and ALB?
Table 3&4
- Sort by the frequency of occurrence in either “Any Grade” or “Gr3/4”.
assistant