From Diagnosis Delay to Targeted Therapy: A Retrospective Study of Pediatric DLGNT with a Comprehensive Literature Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript presents a retrospective multicenter cohort of pediatric patients with diffuse leptomeningeal glioneuronal tumors (DLGNT), complemented by an extensive and well-structured narrative review of the literature. Given the rarity of DLGNT and the absence of standardized management guidelines, the topic is timely and highly relevant. The manuscript is logically organized, and figures/tables effectively support the text.

The manuscript is suitable for publication after minor revisions:

• DNA methylation profiling was available for only two patients. This limitation is mentioned, but the authors may consider emphasizing more clearly how this impacts subgroup interpretation and prognostic conclusions.
• In a few instances, percentages slightly differ between sections (e.g., MAPK alterations, leptomeningeal enhancement). A careful consistency check throughout the manuscript is recommended.
• The promising results observed with tovorafenib should be interpreted cautiously. A brief statement explicitly highlighting the small sample size and relatively short follow-up would further balance the discussion.
• While the limitations of RAPNO criteria in DLGNT are acknowledged, it would be helpful to more explicitly describe how progression or response was adjudicated in cases with predominant leptomeningeal disease, to improve reproducibility.

Author Response

We thank the reviewers for the time devoted to reviewing our manuscript and for their valuable and constructive suggestions. Please note that the line numbering differs from the previous version, as the manuscript has been adapted to the Cancers format; therefore, the line numbers cited by the reviewers may not correspond to those in the revised version.

The English text has been revised as requested by the reviewer.

Below are our responses to their comments.

 

1 : DNA methylation profiling was available for only two patients. This limitation is mentioned, but the authors may consider emphasizing more clearly how this impacts subgroup interpretation and prognostic conclusions.

• This limitation has been added in the discussion, lines 440-442

 

2 : In a few instances, percentages slightly differ between sections (e.g., MAPK alterations, leptomeningeal enhancement). A careful consistency check throughout the manuscript is recommended

• Percentages have been checked and modifications highlighted

 

3 : The promising results observed with tovorafenib should be interpreted cautiously. A brief statement explicitly highlighting the small sample size and relatively short follow-up would further balance the discussion.

• This limitation has been added in the discussion, lines 439-440

 

4 : While the limitations of RAPNO criteria in DLGNT are acknowledged, it would be helpful to more explicitly describe how progression or response was adjudicated in cases with predominant leptomeningeal disease, to improve reproducibility

• This part has been added and the paragraph adjusted, lines 211-217

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

Although diffuse leptomeningeal glioneuronal tumor is very rare, this is a relatively large cohort study (11 cases), and I believe this information about the cohort is important.

Unfortunately, there are no case images in this report. I would appreciate it if you could present a few cases in which typical meningeal enhancement was observed, or in which meningeal enhancement was not initially observed but was revealed during follow-up.

 

P2 line 78, radiological findings

If this tumor is suspected, the authors would do well to briefly explain what radiological methods are required and whether advanced techniques are required for diagnosis and the follow-up study after treatment.

 

P2, line 83

Yes, this finding is so important that the authors should emphasize it with additional references such as AJNR Am J Neuroradiol. 2020 Nov;41(11):2155-2159, Child's Nervous System (2024) 40:2359–2366, Pediatric Radiology (2025) 55:2861. If the current study found this finding, please clarify it under the results.

 

P3 line 95 phakomatoses

Please be specific about what the illness is.

 

Page5 line 188

Please clearly state what kind of MR imaging was used in the primary site evaluation. Was contrast-enhanced MRI used in all cases?

Author Response

We thank both reviewers for the time devoted to reviewing our manuscript and for their valuable and constructive suggestions. Please note that the line numbering differs from the previous version, as the manuscript has been adapted to the Cancers format; therefore, the line numbers cited by the reviewers may not correspond to those in the revised version.

The tables have been improved as requested by the reviewer.

Below are our responses to their comments.

1: Unfortunately, there are no case images in this report. I would appreciate it if you could present a few cases in which typical meningeal enhancement was observed, or in which meningeal enhancement was not initially observed but was revealed during follow-up.

• Figures 2 has been added to illustrate two of our cases

 

 2: P2 line 78, radiological findings.

If this tumor is suspected, the authors would do well to briefly explain what radiological methods are required and whether advanced techniques are required for diagnosis and the follow-up study after treatment.

• A phrase has been added, lines 95-96

 

3 : P2, line 83.

Yes, this finding is so important that the authors should emphasize it with additional references such as AJNR Am J Neuroradiol. 2020 Nov;41(11):2155-2159, Child's Nervous System (2024) 40:2359–2366, Pediatric Radiology (2025) 55:2861. If the current study found this finding, please clarify it under the results.

• The three citations have been added. The first was already present in the text as citation 13. The second and third have been added as citations 29 and 30 (line 102). In line 248, we clarify how many patients presented this finding.

 

4 : P3 line 95 phakomatoses

Please be specific about what the illness is.

• The term has been changed with neurocutaneous syndromes (line 113).

 5 : Page5 line 188

Please clearly state what kind of MR imaging was used in the primary site evaluation. Was contrast-enhanced MRI used in all cases?

• All cases were contrast-enhanced MRI and it has been specified in line 244

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your appropriate response.