Review for 10.1186/s12876-025-03635-2 (2025)

Title: The Prognostic Value of Systemic Inflammation Response Index in Digestive System
Carcinomas: A Systematic Review and Meta-Analysis
Version: 3 Date: 14 Nov 2024
Reviewer's report:
The systematic review and meta-analysis titled "The Prognostic Value of Systemic Inflammation
Response Index in Digestive System Carcinomas" addresses an important topic in oncology –
the prognostic value of the Systemic Inflammation Response Index (SIRI) in GI malignancies. I
had the chance to evaluate the first revision provided by the authors in response to the previous
reviewers. However, some concerns remain. Prognostication is a very serious issue and can
impact not only treatment management but also patients' understanding of their disease. I believe
this work is valuable as a systematic review, but I am not comfortable with the meta-analysis
performed, as heterogeneity is very high, and tumor type, cancer staging, and the role of surgery
were not properly addressed.
Major
Abstract line 24: “…studies published up to May 30, 2023…”. Authors should disclose a specific
time range for the search.
Methods line 140: “…The search concluded on May 30, 2023.” Same comment as above.
Inclusion and Exclusion Criteria line 157: “…(2) studies investigating the association between
pre-treatment SIRI and tumor outcomes; (3) studies evaluating the prognostic impact of SIRI,
including OS, progression-free survival (PFS), disease-free survival (DFS), TTP, or disease
specific survival (DSS)”.
I don’t believe there is a difference between item 2 and item 3, as the association between
a biomarker not related to treatment selection and treatment outcomes is the definition of a
prognostic marker. These two items could be condensed into one. Additionally, it is not clear
what the term “tumor outcomes” refers to – does this mean response rate? Please clarify.
Inclusion and Exclusion Criteria line 157: “The following exclusion criteria were used: (1)
articles not- original articles, such as reviews, abstracts, conference papers and case reports”.
The type of article included (cohort studies) should be reflected in the inclusion criteria.
Results line 231: “These 40 articles, published between 2016-2023, encompassed a total of 1366
participants and included 49 cohort studies were included. Notably, seven articles [13, 14, 19,
26-29] contained two cohort studies each, while one article [12] included three cohort studies.”
This sentence seems a little bit confuse. I would state something simpler like “A total of 1366
patients from 49 cohorts from 40 studies were included.” Also is important to state that these
studies were included on the systematic review part of the work as only 26 articles were included
in the meta-analysis part.
Results line 253: “Additional characteristics of all enrolled cohort studies, such as patient age,
gender, tumor staging, treatment modalities, SIRI cut-off selection, and follow-up duration, are
summarized in Tables 1 and 2.” I believe the major issue with this manuscript, which makes
me think a meta-analysis is not appropriate in this case, is hidden in this statement. Cancer
staging and histology are key to prognosis. This meta-analysis included stage I colorectal cancer
(Cao, 2023) and stage IV pancreatic cancer (Pacheco-Barcia, 2020), and you cannot assume that
systemic inflammation will have the same prognostic effect in these scenarios.
Results line 267: “To investigate potential sources of heterogeneity, univariable random-
effects meta-regression was performed.” Meta-regression is usually performed with continuous
variables, which is not the case for localized versus metastatic disease. Also, the effect of surgery
was not considered. Many trials were included in the "mixed" group, which could minimize the
difference between the non-metastatic and metastatic groups.
Minor
Introduction line 121: “…changes in SIRI…”. The authors should clarify what types of changes
they are referring to. I believe they are referring to changes in SIRI levels after systemic treatment
compared to baseline.
Methods line 146: “Gray literature was not included, as it is often challenging to retrieve and
lacks peer-reviewed.” I agree that gray literature is challenging to retrieve. However, lacking
peer review is not a sufficient reason to exclude gray literature from systematic reviews and
meta-analyses. This is a well-known limitation of a validated strategy used to increase the
number of observations in this context.