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Peer-Review Record

Longitudinal Measurements of Inflammatory Indices During Treatment for Locally Advanced Rectal Cancer and Associations with Smoking, Ethnicity and Pathological Response

by Nancy Huang 1,*, Joseph Descallar 2,3, Wei Chua 2,4,5, Weng Ng 2,4,5, Emilia Ip 4,5, Christopher Henderson 3,6,7, Tara L. Roberts 2,7 and Stephanie Hui-Su Lim 1,2,7
Reviewer 1: Anonymous
Reviewer 2:
Submission received: 24 March 2025 / Revised: 24 April 2025 / Accepted: 25 April 2025 / Published: 7 May 2025

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

line 94-97: It would enhance the flow if you could move the confounding variable disclaimer to the beginning of the paragraph, before you discuss the association between ethnicity and inflammation/treatment response

line 155-156: The full name of ypT and ypN is found in Table 1, but since that table only comes up later in the article, it is advisable to include the full name in the text where it was first mentioned

line 166: To check for potential selection bias, it would help to compare the gender and age distribution of your patient population to larger samples from epidemiology studies.

Author Response

Comment 1 : line 94-97: It would enhance the flow if you could move the confounding variable disclaimer to the beginning of the paragraph, before you discuss the association between ethnicity and inflammation/treatment response

Response 1 : Thank you for this suggestion. We have rectified this in lines 85-88, 96-97.

 

Comment 2 : line 155-156: The full name of ypT and ypN is found in Table 1, but since that table only comes up later in the article, it is advisable to include the full name in the text where it was first mentioned

Response 2 : Thank you for pointing this out, it has now been corrected in line 156.

 

Comment 3 : line 166: To check for potential selection bias, it would help to compare the gender and age distribution of your patient population to larger samples from epidemiology studies.

Response 3 : We thank the reviewer for this suggestion. Data from the NSW Cancer Registry showed that the average age of rectal cancer diagnosis for people born in Australia is 66 years with the majority (59%) being male (Feletto et al. 2019). Our study had a slightly higher proportion of males (73%) and lower median age of 58 years. We acknowledge that there is a possible element of selection bias and this small cohort of patients may not be representative of the general population. However, this is consistent with the younger age of trial populations.  We have acknowledged this in lines 357 – 360.

 

Feletto, E., Yu, X. Q., Lew, J. B., St John, D. J. B., Jenkins, M. A., Macrae, F. A., Mahady, S. E., & Canfell, K. (2019). Trends in Colon and Rectal Cancer Incidence in Australia from 1982 to 2014: Analysis of Data on Over 375,000 Cases. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 28(1), 83–90. https://doi.org/10.1158/1055-9965.EPI-18-0523

 

Reviewer 2 Report

Comments and Suggestions for Authors

Longitudinal measurements of inflammatory indices during 2 treatment for locally advanced rectal cancer and associations 3 with smoking, ethnicity and pathological response

This is a complex longitudinal multicentre study of 29 patients with locally advanced rectal cancer who received adjuvant and neoadjuvent chaemoradiation and chaemotherapy and in whom the authors studied CEA levels, various inflammatory markers plus various haematological cellular trends in six pre designed time stations. The data included multiple BMI, smoking habits, ethnic origin and radiation regression grades. This paper is saturated with data that makes it difficult to identify which are the relevant ones from one reading and certainly necessitates several attempts but thankfully the conclusions are succinate and statements like ‘patients with a pN0 status reflecting good responses,  had a higher NLR and PLR at all time-points’ are useful indicators.

The paper is well written and presented, but on the long side and heavily referenced .The relative small numbers makes it difficult to draw large scale conclusions never the less it is an important contribution.

It may be useful to add if their data were used to decide on treatment regimes

Author Response

Comments 1: This is a complex longitudinal multicentre study of 29 patients with locally advanced rectal cancer who received adjuvant and neoadjuvent chaemoradiation and chaemotherapy and in whom the authors studied CEA levels, various inflammatory markers plus various haematological cellular trends in six pre designed time stations. The data included multiple BMI, smoking habits, ethnic origin and radiation regression grades. This paper is saturated with data that makes it difficult to identify which are the relevant ones from one reading and certainly necessitates several attempts but thankfully the conclusions are succinate and statements like ‘patients with a pN0 status reflecting good responses,  had a higher NLR and PLR at all time-points’ are useful indicators.

The paper is well written and presented, but on the long side and heavily referenced .The relative small numbers makes it difficult to draw large scale conclusions never the less it is an important contribution.

It may be useful to add if their data were used to decide on treatment regimes

Response 1 : Thank you for the review and comments. We acknowledge that this paper is long and heavily referenced as it reflects the complexity in the field of cancer-related inflammation. The small numbers in our study make us cautious to draw firm conclusions. The results generated in this study have not been used to decide on treatment regimens, however are important factors that can potentially be used to stratify patient groups in future clinical trials.

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