Prospective Evaluation of Kidney Function in Long-Term Survivors of Pediatric CNS Tumors
, Amedeo A. Azizi 1, Lisa Mayr 1, Chryssa Grylli 3, Daniela Schwarz 1, Monika Chocholous 1, Irene Slavc 1, Michael Boehm 4 and Andreas Peyrl 1,*
Round 1
Reviewer 1 Report
To editors and authors
Prospective evaluation of kidney function in long-term survivors of pediatric CNS tumors
This is a very detailed and effective manuscript with clear content which is fitted with aims and scope of Current Oncology.
I suggested this manuscript for publication after some revisions below
1) Add IRB date and number.
2) The citations format is precise but the reference format is totally wrong as MDPI guideline. Please read author's discipline or recent published papers from Current Oncology
3) In discussion please mention about the diagnostic CNS neoplasms in children, need to check, discuss and refer recent updated documents (PMID: 33137983) and (PMID: 32366451)
4) In limitation, add further direction research.
5) Other content is quite effective without reviewer concerns.
Best
Author Response
1)Add IRB date and number.
We highlighted the IRB number already mentioned in line 114-116: (EK 520/2009)
2)The citations format is precise but the reference format is totally wrong as MDPI guideline. Please read author's discipline or recent published papers from Current Oncology
We changed the reference format to comply with the MDPI guideline.
3) In discussion please mention about the diagnostic CNS neoplasms in children, need to check, discuss and refer recent updated documents (PMID: 33137983) and (PMID: 32366451)
We included the above-mentioned citations in the introduction.
4) In limitation, add further direction research.
We summarized possible further research directions by including the following sentence:
“Further research should focus on risk stratification and prevention methods, thereby focusing on diagnosis and treatment of hypertension.”
Reviewer 2 Report
In the article “Prospective evaluation of kidney function in long-term survivors of pediatric CNS tumors”, Natalia Stepien and group investigate the effects of chemotherapeutic intervention for pediatric CNS tumors on long-term kidney function. Overall, the authors should be applauded for their work. The introduction adequately discusses the necessity of this study, and Stepien et al. wrote an excellent discussion that clearly compares their findings to the current literature as well as the pitfalls to their studies. With this, there are some concerns that need to be addressed prior to publication:
Major Concerns:
- The introduction should include further background information on CNS tumors for readers that might not be knowledgeable (e.g., what classifies as a CNS tumor, what is the current occurrence and survival rate, etc.)
- If possible, the authors should note the location of the CNS tumor. This is particularly important as epithelioid sarcoma does not always occur in the CNS.
- As the authors note, chemotherapy for CNS tumors is given in combination with others and thus, in table two, it would be beneficial for authors to discern out the correlation values for the chemotherapy protocols highlighted in Supplementary Table 2 instead of lumping them under one statistic. Additionally, would the authors benefit from showing the data in graphical format to help with visualization?
- When the authors note the patients who did have decreased kidney function in Supplementary Table 3, they fail to consider/acknowledge potential comorbidities or a past medical history that could be a factor in their poor kidney function or susceptibility to decreased kidney function from chemotherapies.
Minor Concerns
- In line 108, please cite the “previous studies”.
- In table two, the Mann-Whitney test is used but was not discussed in the methods.
- In Supplementary Figure 1, please make it clear that the 41 patients did not choose to participate in the study.
- For all Supplementary Figures/Tables, the font in the legend is too small and will pose difficulties for individuals with visual impairment.
Author Response
Major Concerns:
- The introduction should include further background information on CNS tumors for readers that might not be knowledgeable (e.g., what classifies as a CNS tumor, what is the current occurrence and survival rate, etc.)
We have modified the introduction to provide more general information (line 1-5)
- If possible, the authors should note the location of the CNS tumor. This is particularly important as epithelioid sarcoma does not always occur in the CNS.
We added a supplementary figure where tumor localization was classified into supratentorial, infratentorial, spinal or disseminated. Supplementary Figure 2
- As the authors note, chemotherapy for CNS tumors is given in combination with others and thus, in table two, it would be beneficial for authors to discern out the correlation values for the chemotherapy protocols highlighted in Supplementary Table 2 instead of lumping them under one statistic. Additionally, would the authors benefit from showing the data in graphical format to help with visualization?
We added supplementary figure 3 to visualize the correlation of chemotherapy protocols in a graphical format.
- When the authors note the patients who did have decreased kidney function in Supplementary Table 3, they fail to consider/acknowledge potential comorbidities or a past medical history that could be a factor in their poor kidney function or susceptibility to decreased kidney function from chemotherapies.
All pre-treatment co-morbidities are listed and now highlighted in supplementary table 3 in the column “diagnosis”, see “patient 2” with stenosis of the renal arteries and NF1. Since the study included pediatric patients only most patients had no co-morbidities or relevant risk factors in their past medical history.
Minor Concerns
- In line 108, please cite the “previous studies”.
We have cited the requested studies.
- In table two, the Mann-Whitney test is used but was not discussed in the methods.
We added the application of the Mann-Whitney-U test to the methods section and explained the reasons for using the different tests.
- In Supplementary Figure 1, please make it clear that the 41 patients did not choose to participate in the study.
We added an explanation on the 41 potentially eligible patients not included in the study in the caption.
- For all Supplementary Figures/Tables, the font in the legend is too small and will pose difficulties for individuals with visual impairment.
Thank you for this important suggestion, we adjusted the font size in our figures/tables/supplementary material.
Reviewer 3 Report
Thank you very much for allowing me to review this manuscript.
The paper is certainly well written and addresses a very important issue.
Minor revisions requested from my side:
- In the results part, I think it would be useful to investigate if there is a multivariate relationship between the reduction in renal function between different types of chemotherapy used, nephrotoxic antibiotics, and craniospinal radiotherapy.
- Is there a correlation between patients who presented hypertension and reduced renal function? Or was hypertension an isolated, transient finding?
- It should be emphasized that the retrospective design is a limitation of the study.
Author Response
Minor revisions requested from my side:
- In the results part, I think it would be useful to investigate if there is a multivariate relationship between the reduction in renal function between different types of chemotherapy used, nephrotoxic antibiotics, and craniospinal radiotherapy.
None of the patients showed a reduction in renal function, we have correlated each chemotherapeutic agent as well as nephrotoxic medications with eGFR using univariate analyses, nonetheless for a multivariate analysis our numbers were too small. We added this limitation to the discussion.
- Is there a correlation between patients who presented hypertension and reduced renal function? Or was hypertension an isolated, transient finding?
Only one patient had hypertension and mild tubular function impairment with sustained eGFR.
- It should be emphasized that the retrospective design is a limitation of the study.
As mentioned in the title and in the methods section (line 74 & 89) the patients were prospectively evaluated for their kidney function.
