Title: Clinical value of systemic immunoinflammatory index in predicting recurrence and
metastasis in patients with primary liver cancer
Version: 3 Date: 15 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the role of SII as an inflammation-based biomarker is well outlined, a more
detailed explanation of the biological mechanisms behind how neutrophils, platelets, and
lymphocytes contribute to tumor progression could provide additional depth. Specifically, how
the inflammatory microenvironment in liver cancer affects metastasis and recurrence could be
discussed further.
-While the introduction discusses SII as a prognostic factor for various cancers, it would benefit
from a clearer link to primary liver cancer. The introduction could mention more explicitly the
lack of studies on SII's role in liver cancer recurrence and metastasis to justify the need for this
study.
-The formula for SII is given as (platelet count × neutrophil count) / lymphocyte count, but this
is inconsistent with the formula mentioned in the abstract (platelet count - neutrophil count) /
lymphocyte count. The methodology section should clarify the correct formula and ensure
consistency with the abstract and results. Additionally, some explanation of why this specific
combination of biomarkers (platelets, neutrophils, and lymphocytes) is used in SII, in terms of
cancer progression, would be helpful.
-The inclusion criteria specify that preoperative imaging should show no distant metastasis or
lymph node metastasis. This is important for the study's focus on recurrence and metastasis after
TACE. However, more detail on the imaging techniques used (e.g., MRI, CT) would help clarify
how metastasis was assessed. Including details on the resolution and sensitivity of the imaging
methods used would also strengthen this aspect.
-The follow-up period of 3 years is robust, but the methodology could benefit from clarification
regarding how recurrence and metastasis were monitored. Specifically, were patients routinely
screened with imaging (e.g., MRI, CT) during follow-up? Were there specific intervals at which
imaging was performed, and were there any other criteria (clinical symptoms, biochemical
markers) used to assess recurrence or metastasis besides imaging?
-The results section mentions that the average SII index and AFP levels for each patient
were used for follow-up statistical analysis. However, the methodology for calculating these
averages (e.g., how often blood samples were taken, whether this was a single post-treatment
measurement or an average over multiple follow-up visits) should be clarified. This is
particularly important for the SII index, which may fluctuate over time due to various factors
(e.g., inflammation, infection, or treatment-related effects).
-The results mention both intrahepatic recurrence and extrahepatic metastasis but do not specify
the relative frequency or significance of these two types of recurrence/metastasis in terms of
patient outcomes. It might be useful to discuss whether patients with extrahepatic metastasis had
poorer outcomes than those with intrahepatic recurrence, or whether these types of recurrence
respond differently to further treatment.
-The limitations of SII as a predictor are briefly mentioned, such as its potential variability due
to external factors like infection or inflammation. It would be helpful to further explore these
limitations in the context of clinical practice. For example, could fluctuations in SII due to non-
cancer-related inflammation lead to false positives or negatively impact its clinical utility?
-While the discussion includes some references to the role of SII in other cancers, it would
be beneficial to further elaborate on its specific role in liver cancer. Are there any unique
characteristics of the liver tumor microenvironment that might make SII a particularly useful
predictor in this type of cancer?
Title: Clinical value of systemic immunoinflammatory index in predicting recurrence and
metastasis in patients with primary liver cancer
Version: 3 Date: 15 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the role of SII as an inflammation-based biomarker is well outlined, a more
detailed explanation of the biological mechanisms behind how neutrophils, platelets, and
lymphocytes contribute to tumor progression could provide additional depth. Specifically, how
the inflammatory microenvironment in liver cancer affects metastasis and recurrence could be
discussed further.
-While the introduction discusses SII as a prognostic factor for various cancers, it would benefit
from a clearer link to primary liver cancer. The introduction could mention more explicitly the
lack of studies on SII's role in liver cancer recurrence and metastasis to justify the need for this
study.
-The formula for SII is given as (platelet count × neutrophil count) / lymphocyte count, but this
is inconsistent with the formula mentioned in the abstract (platelet count - neutrophil count) /
lymphocyte count. The methodology section should clarify the correct formula and ensure
consistency with the abstract and results. Additionally, some explanation of why this specific
combination of biomarkers (platelets, neutrophils, and lymphocytes) is used in SII, in terms of
cancer progression, would be helpful.
-The inclusion criteria specify that preoperative imaging should show no distant metastasis or
lymph node metastasis. This is important for the study's focus on recurrence and metastasis after
TACE. However, more detail on the imaging techniques used (e.g., MRI, CT) would help clarify
how metastasis was assessed. Including details on the resolution and sensitivity of the imaging
methods used would also strengthen this aspect.
-The follow-up period of 3 years is robust, but the methodology could benefit from clarification
regarding how recurrence and metastasis were monitored. Specifically, were patients routinely
screened with imaging (e.g., MRI, CT) during follow-up? Were there specific intervals at which
imaging was performed, and were there any other criteria (clinical symptoms, biochemical
markers) used to assess recurrence or metastasis besides imaging?
-The results section mentions that the average SII index and AFP levels for each patient
were used for follow-up statistical analysis. However, the methodology for calculating these
averages (e.g., how often blood samples were taken, whether this was a single post-treatment
measurement or an average over multiple follow-up visits) should be clarified. This is
particularly important for the SII index, which may fluctuate over time due to various factors
(e.g., inflammation, infection, or treatment-related effects).
-The results mention both intrahepatic recurrence and extrahepatic metastasis but do not specify
the relative frequency or significance of these two types of recurrence/metastasis in terms of
patient outcomes. It might be useful to discuss whether patients with extrahepatic metastasis had
poorer outcomes than those with intrahepatic recurrence, or whether these types of recurrence
respond differently to further treatment.
-The limitations of SII as a predictor are briefly mentioned, such as its potential variability due
to external factors like infection or inflammation. It would be helpful to further explore these
limitations in the context of clinical practice. For example, could fluctuations in SII due to non-
cancer-related inflammation lead to false positives or negatively impact its clinical utility?
-While the discussion includes some references to the role of SII in other cancers, it would
be beneficial to further elaborate on its specific role in liver cancer. Are there any unique
characteristics of the liver tumor microenvironment that might make SII a particularly useful
predictor in this type of cancer?
Please review this paper.
user
Title: Clinical value of systemic immunoinflammatory index in predicting recurrence and
metastasis in patients with primary liver cancer
Version: 3 Date: 15 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the role of SII as an inflammation-based biomarker is well outlined, a more
detailed explanation of the biological mechanisms behind how neutrophils, platelets, and
lymphocytes contribute to tumor progression could provide additional depth. Specifically, how
the inflammatory microenvironment in liver cancer affects metastasis and recurrence could be
discussed further.
-While the introduction discusses SII as a prognostic factor for various cancers, it would benefit
from a clearer link to primary liver cancer. The introduction could mention more explicitly the
lack of studies on SII's role in liver cancer recurrence and metastasis to justify the need for this
study.
-The formula for SII is given as (platelet count × neutrophil count) / lymphocyte count, but this
is inconsistent with the formula mentioned in the abstract (platelet count - neutrophil count) /
lymphocyte count. The methodology section should clarify the correct formula and ensure
consistency with the abstract and results. Additionally, some explanation of why this specific
combination of biomarkers (platelets, neutrophils, and lymphocytes) is used in SII, in terms of
cancer progression, would be helpful.
-The inclusion criteria specify that preoperative imaging should show no distant metastasis or
lymph node metastasis. This is important for the study's focus on recurrence and metastasis after
TACE. However, more detail on the imaging techniques used (e.g., MRI, CT) would help clarify
how metastasis was assessed. Including details on the resolution and sensitivity of the imaging
methods used would also strengthen this aspect.
-The follow-up period of 3 years is robust, but the methodology could benefit from clarification
regarding how recurrence and metastasis were monitored. Specifically, were patients routinely
screened with imaging (e.g., MRI, CT) during follow-up? Were there specific intervals at which
imaging was performed, and were there any other criteria (clinical symptoms, biochemical
markers) used to assess recurrence or metastasis besides imaging?
-The results section mentions that the average SII index and AFP levels for each patient
were used for follow-up statistical analysis. However, the methodology for calculating these
averages (e.g., how often blood samples were taken, whether this was a single post-treatment
measurement or an average over multiple follow-up visits) should be clarified. This is
particularly important for the SII index, which may fluctuate over time due to various factors
(e.g., inflammation, infection, or treatment-related effects).
-The results mention both intrahepatic recurrence and extrahepatic metastasis but do not specify
the relative frequency or significance of these two types of recurrence/metastasis in terms of
patient outcomes. It might be useful to discuss whether patients with extrahepatic metastasis had
poorer outcomes than those with intrahepatic recurrence, or whether these types of recurrence
respond differently to further treatment.
-The limitations of SII as a predictor are briefly mentioned, such as its potential variability due
to external factors like infection or inflammation. It would be helpful to further explore these
limitations in the context of clinical practice. For example, could fluctuations in SII due to non-
cancer-related inflammation lead to false positives or negatively impact its clinical utility?
-While the discussion includes some references to the role of SII in other cancers, it would
be beneficial to further elaborate on its specific role in liver cancer. Are there any unique
characteristics of the liver tumor microenvironment that might make SII a particularly useful
predictor in this type of cancer?
assistant