Hemoglobin and Neutrophil Count as Prognostic Factors in Cholangiocarcinoma Patients in 2nd Line Treatment Setting: Results from a Small Monocentric Retrospective Study

Round 1

Reviewer 1 Report (Previous Reviewer 2)

I have no further comments.

 

Author Response

Thank you for having accepted our paper in its current form.

Reviewer 2 Report (Previous Reviewer 1)

In this round of revision, the authors expanded the abstract. However, the authors did not address the majority of my concerns. The manuscript is still hard to read for most journal readers in its current format. Moreover, the authors need to indicate in the introduction and the results section that the results are only suggestive due to the cohort size (Not only in the discussion). The title should also indicate that fact. Please note the following:

 

1- More details were requested regarding the Shapiro-Wilk Test. I didn't see it anywhere in the revised manuscript.

 

2- More explanation in the method section about the ROC test. What software was used? Provide the code if using R, python, or other coding languages. Please indicate the input that was used for the test. The only difference in the revised manuscript that I observed was the addition of more details about the hematological assays used.

 

3- I could not find any supplemental material which indicates the multivariate analysis.

 

4- Please tune down the reporting of the results to indicate that the dataset is limited in size. Indicate that in the introduction, methods, and, where applicable, in the results sections.

 

5- The treatments in the introduction still need a simple explanation. What are the mechanisms of these drugs? The introduction is still challenging for most journal readers in its current format.

Author Response

To the editorial office of Current Oncology and to reviewer 2,

Please find below the replies to reviewer 2 comments.

 

In this round of revision, the authors expanded the abstract. However, the authors did not address the majority of my concerns. The manuscript is still hard to read for most journal readers in its current format. Moreover, the authors need to indicate in the introduction and the results section that the results are only suggestive due to the cohort size (Not only in the discussion). The title should also indicate that fact. Please note the following:

REPLY: We have changed both the title, the abstract and the discussion as suggested. We have acknowledged the small sample size limitations of this analysis.

 

• More details were requested regarding the Shapiro-Wilk Test. I didn't see it anywhere in the revised manuscript.

REPY: Shapiro-Wilk test was only used in order to assess normality of distribution of lab-tests results. As we expected that distribution of lab-tests results would not adhere to standard gaussian distribution and since we expected that patients sample size would be rather small, we opted for Shapiro-Wilk instead of other tests that are used to assess normality (such as D’Agostino-Pearson or Kolmogorov-Smirnov) as it has best power to assess normality, particularly when the sample size is quite small. We added this to the methods section of the paper.

• More explanation in the method section about the ROC test. What software was used? Provide the code if using R, python, or other coding languages. Please indicate the input that was used for the test. The only difference in the revised manuscript that I observed was the addition of more details about the hematological assays used.

REPLY: We added the software that was used for statistical analysis (namely R software ver 4.1.2 and MedCalc® Statistical Software version 19.7.2. Packages that were used in R were survminer, MatchIt, ROCit and survival. As we stated already in the text, the classification variable (Medcalc, ROCit) was the fact of having achieved more than 6.2 months of overall survival (as it represents median overall survival of patients who were enrolled in ABC-06 trial). We added informations concerning which statistical programs and which R packages have been used in the test.

 

• I could not find any supplemental material which indicates the multivariate analysis.

REPLY: We did not include any supplemental material concerning multivariate analysis. The statement concerning the presence of supplemental material (that was contained in the article template that Current Oncology provided us) has been removed.

 

• Please tune down the reporting of the results to indicate that the dataset is limited in size. Indicate that in the introduction, methods, and, where applicable, in the results sections.

REPLY: We have added in several parts of the text that the dataset is limited in size and we have “tuned down” the discussion and conclusions.

 

• The treatments in the introduction still need a simple explanation. What are the mechanisms of these drugs? The introduction is still challenging for most journal readers in its current format.

REPLY: Considering that either FOLFOX and FOLFIRI chemotherapy regimens are standard chemotherapy that have been used in medical oncology for about 3 decades we had decided not to include mechanism of action of these drugs as we believe that they should already be well-known to the general “audience”. However, based on your comments we have added the explanation of the mechanism of action of chemotherapy that is commonly used in treatment of cholangiocarcinoma patients in second line setting in the introduction section.

 

We hope that with these changes our paper might be accepted for publication in Current Oncology.

Best regards

Riccardo Giampieri, MD, PhD, Associate Professor

On behalf of all co-authors.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report (Previous Reviewer 1)

In the revised manuscript, the authors addressed all my concerns. I appreciate that the authors added more info about the software used and more details about the statistical analysis for the general readers. The introduction is now more straightforward.

The manuscript has great value as it provides a data set that researchers could use to increase their cohort size. It also offers methodological details that researchers can use to reproduce the tests.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

In this manuscript, Liguori et al. describe statistical analyses in which Hemoglobin and Neutrophil counts were found to be significant prognostic markers for Biliary Tract Cancer (BTC) patients in 2nd line treatment. The development of diagnostic assays and the discovery of prognostic markers are of paramount importance for BTC patients. Hence,  this study is valuable even though it has a small cohort. Data obtained for this study can be combined later with other data in future studies. However, I have the following concerns that the authors need to address so that the study can be assessed more efficiently:  

1- Add notes to describe mFOLFOX, FOLFIRI, and other treatment options in the introduction. Adding notes is essential for treatments that were considered in the statistical tests.

2- The methods section could better describe the statistical analysis steps. More details are needed for the ROC test. More clarity is needed about the inputs for the ROC tests. How was the ROC used for determining cutoffs? Add more details about the 6.2-OS variable for ROC.

3- Similarly, more description is needed for the multivariate analyses. 

4- The effect of chemotherapy treatments (In the 1st line treatment) is not assessed in this study. I recommend a multivariate assay that demonstrates that what the patients received in their 1st line treatment does not affect the results of this study.

5- Describe to the readers why it is relevant to determine statistically whether the data is normally distributed (More details on the Shapiro-Wilk Test).

Reviewer 2 Report

Title: Hemoglobin and neutrophil count as prognostic factors in cholangiocarcinoma patients in 2^nd line treatment setting: results from a retrospective study

This study aimed to investigate the prognostic value of routine lab test indexes in biliary tract cancers patients treated with 2^nd-line chemotherapy. The authors concluded that serum hemoglobin and neutrophil count were able to reliably predict the prognosis of patients. The topic described in this manuscript seems interesting however the sample size (n=48) is too small to draw conclusions. I think further study is warranted to validate its clinical application. The novelty and scientific value of the findings are rather limited.

There are several concerns that the authors should address in current manuscript:

(1).     Please review and edit the English in your paper - prior to submission

(2).    Line 69-73: Only a single paragraph is used to describe the importance role of routine lab test indexes in human cancer. Please add more references and described in the text.

(3).    Line 89: A gene name should always be indicated in italics. IDH1, FGFR2, BRAF, etc.

(4).    Line 95: The instruments for the analysis of hemoglobin, neutrophil, lymphocyte, LDH, CEA, and etc are missing in the text.

(5).    Methods: Why C-reactive protein (CRP) is not included in routine blood test in order to estimate the status of inflammation in your study populations. 

(6).    2.1 Patients: It is highly recommended the authors to use a diagram to describe how to select your study population.

(7).    Line 183: Table3A: Their findings showed that monocyte count and serum albumin is significant using ROC curve analysis. However, the authors didn’t discuss their findings in the section of discussion. Serum album levels are important to predict the nutritional status in cancer patients. The authors did not describe the nutritional status of their study populations.

(8).    Line 256: Anemia is a very common side effect of cancer and cancer treatment. The authors did not discuss their findings in the section of discussion. This issue should be clearly discussed.