Effect of 5-Aminolevulinic Acid and Sodium Fluorescein on the Extent of Resection in High-Grade Gliomas and Brain Metastasis
and Anders Rosendal Korshoej 1,3,*Round 1
Reviewer 1 Report
Cramer Ahrens at el have elaborated a review in which they have summarized the information of the main studies in the literature about fluorescence guided neurosurgery, focussing in the use of 5-ALA and SF on HGG and brain metastasis. The article is clear and well-constructed, but I question its originality because similar reviews that include most of the studies mentioned in the present article, have been published recently (Ghandi et al 2019, Schipmann et al 2019, Schupper et al 2021) , although the current review adds a direct comparison between 5-ALA and SF which havent been published before and can be relevant to the field.
I miss in the introduction an explanation of why the 5-ALA only fluoresces in tumoral cells.
The cited references are current and the conclusion coherent: “Additional comparative studies are needed”.
As a minor coment:
the authors say that 5-ALA is “selectively taken up by HGG” (line 88-89), what is inexact as it is also taken up by other tumoral cells.
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Reviewer 2 Report
The authors provide a well written review on flourescence-guided surgery in high-grade glioma patients. No further comments.
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Reviewer 3 Report
This is a very important review, as to my knowledge this is the first scientific compilation of this emerging intraoperative guidance tracer comparing to the “gold standard”. Few points may be added to the paper to make it more complete.
The financial aspects of surgery is important. How do the two labeling agents improve operation time /recovery time of the patients etc.. The authors state about the prices of the agents. Its some sort of one sided, usually hospital generate 5ALA itself and are not required to open market. Please provide comparison of open market price (with references9, in house production cost. Certainly one needs references for prices also for SF to support their arguments.
Personalized medicine: 5ALA and SF have a preference to any molecular sub-identity of HGG / brain mets? Does the field look into this? This can help to develop intraoperative decision to infuse target therapies (such as targeted drug loaded wafers similar as with Gliadel wafers ) directly in the resection cavity (where the tumors usually recur due to residual cells upon resection).
AI is emerging in surgery, especially in robotic surgery. Can intervention-guided fluorescence imaging techniques benefit from AI, and if, what are the current approaches to do so (I am aware that this may relate to other surgeries more than neurosurgery)
Minor:
Cellular level: Retention times of 5ALA /SF … are there studies available=?
A short description of mechanism of both 5-ALA and SF can give the readers some insight
Check English again.
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