Title: Predictors of pathological complete response after total neoadjuvant treatment using short
course radiotherapy for locally advanced rectal cancer
Version: 2 Date: 25 Jan 2025
Reviewer:  Ramakrishnan Ayloor Seshadri
Reviewer's report:
The authors have responded to some of the comments but the changes stated by them have not
been made in the revised highlighted manuscript provided. For example- The title still mentions
chemoradiation which is not an appropriate term to describe the type of radiation used in this
study as pointed out in my comments earlier. This needs to be changed and similar descriptions
(NCRT) used throughout the text also need to be changed
The revised manuscript still does not mention the definition of chemotherapy interruption- was
it a delay of more than 1 wees, 2 weeks, 3 weeks etc? Since this is an important prognostic
factor for pCR it is important to clearly define what is chemotherapy interruption according to
the authors.
While mentioning about the two pathologists and interobserver consistency, could the authors
also mention if both pathologists reviewed every patients and concurred the findings of
pathological complete response?
It is indeed surprising that induction chemotherapy resulted in higher pCR rates than
consolidation chemo. A longer interval between radiation and surgery has been associated with
a higher pCR rates in multiple studies since radiation effect is time dependent. Even the OPRA
trial showed a higher complete response rates in the consolidation chemo arm. In this study the
time interval between RT and surgery was 9 weeks for induction chemo and at least 20 weeks
for consolidation chemo so one would expect higher response in the consolidation arm. Could
the authors discuss why the results are different in this study?
Title: Predictors of pathological complete response after total neoadjuvant treatment using short
course radiotherapy for locally advanced rectal cancer
Version: 2 Date: 25 Jan 2025
Reviewer:  Ramakrishnan Ayloor Seshadri
Reviewer's report:
The authors have responded to some of the comments but the changes stated by them have not
been made in the revised highlighted manuscript provided. For example- The title still mentions
chemoradiation which is not an appropriate term to describe the type of radiation used in this
study as pointed out in my comments earlier. This needs to be changed and similar descriptions
(NCRT) used throughout the text also need to be changed
The revised manuscript still does not mention the definition of chemotherapy interruption- was
it a delay of more than 1 wees, 2 weeks, 3 weeks etc? Since this is an important prognostic
factor for pCR it is important to clearly define what is chemotherapy interruption according to
the authors.
While mentioning about the two pathologists and interobserver consistency, could the authors
also mention if both pathologists reviewed every patients and concurred the findings of
pathological complete response?
It is indeed surprising that induction chemotherapy resulted in higher pCR rates than
consolidation chemo. A longer interval between radiation and surgery has been associated with
a higher pCR rates in multiple studies since radiation effect is time dependent. Even the OPRA
trial showed a higher complete response rates in the consolidation chemo arm. In this study the
time interval between RT and surgery was 9 weeks for induction chemo and at least 20 weeks
for consolidation chemo so one would expect higher response in the consolidation arm. Could
the authors discuss why the results are different in this study?
Please review this paper.
user
Title: Predictors of pathological complete response after total neoadjuvant treatment using short
course radiotherapy for locally advanced rectal cancer
Version: 2 Date: 25 Jan 2025
Reviewer:  Ramakrishnan Ayloor Seshadri
Reviewer's report:
The authors have responded to some of the comments but the changes stated by them have not
been made in the revised highlighted manuscript provided. For example- The title still mentions
chemoradiation which is not an appropriate term to describe the type of radiation used in this
study as pointed out in my comments earlier. This needs to be changed and similar descriptions
(NCRT) used throughout the text also need to be changed
The revised manuscript still does not mention the definition of chemotherapy interruption- was
it a delay of more than 1 wees, 2 weeks, 3 weeks etc? Since this is an important prognostic
factor for pCR it is important to clearly define what is chemotherapy interruption according to
the authors.
While mentioning about the two pathologists and interobserver consistency, could the authors
also mention if both pathologists reviewed every patients and concurred the findings of
pathological complete response?
It is indeed surprising that induction chemotherapy resulted in higher pCR rates than
consolidation chemo. A longer interval between radiation and surgery has been associated with
a higher pCR rates in multiple studies since radiation effect is time dependent. Even the OPRA
trial showed a higher complete response rates in the consolidation chemo arm. In this study the
time interval between RT and surgery was 9 weeks for induction chemo and at least 20 weeks
for consolidation chemo so one would expect higher response in the consolidation arm. Could
the authors discuss why the results are different in this study?
assistant