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PONE-D-20-37225

Effects of time to chemoradiation on high-grade gliomas from Buenos Aires Metropolitan Area

PLOS ONE

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: The authors report their retrospective experience with high grade glioma in metropolitan Buenos Aires. in a series of 63 patients accumulated over six years, they note that among this cohort that a time greater than 8 weeks to the start of chemoirradiation from surgery as well as biopsy were two strong negative predictors of outcome. Both of these were more significant than whether patients were treated in public vs. private sectors.

There are several deficiencies in this analysis. First, the number of patients analyzed were accrued at a rate of only ten per year. It's hard to believe that this was a substantial fraction of the patients operated on at that time. No explanation is given for this and the low number of patients certainly opens up questions as to the robustness and generalizability of their results.

It's unclear why they excluded MGMT positive patients. While these patients may do better than ones that are unmethylated, it still would be useful to assess impact of delay and biopsy.

Time is not really a binary value, so it's unclear why they didn't assess delay as a continuous variable.

The lack of clinical data and retrospective nature of study is prone to bias. For instance, it could be that the time to RT resulted from prolonged Rehab hospitalizations due to physical deficits that by themselves would be negative prognostic factors.

The conclusion should be reworded. I’m sure they don’t mean to say that those are the only two bad prognostic factors for GBM.

While only one study may have reported the effects of wait time on outcome in Argentina, there are several in the literature, all favoring initiating treatment prior to 4-6 weeks. Likewise, there have been many studies that have pointed to the negative prognostic impact of biopsy.

Reviewer #2: The authors have provided an interesting description of the time from diagnosis to chemoirradiation from the Buenos Aires metropolitan area. Though it is already known that time to chemoirradiation significantly influences survival this study is important in order to develop better working protocols. To do so, one needs to understand the current situation, and this is achieved by this paper. Sadly, the authors show that only a minority of patients receives chemoirradiation at the proper time. Thus, the authors have much work to do to improve these times in the Buenos Aires Cosmopolitan Area, now that they provide an accurate diagnosis.

As the authors present a detailed analysis of the current situation, I would like to encourage them that, at the end of their manuscript they include a proposal on how to remedy the current defective situation. It will be important to read in a future report in a few years, how the time of chemoirradiation has been reduced for these patients.

This manuscript will benefit from a scientific english editor of the main manuscript's text.

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Reviewer #1: No

Reviewer #2: Yes: Pedro R. Lowenstein, MD, PhD

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Effects of time to chemoradiation on high-grade gliomas from the Buenos Aires Metropolitan Area

PONE-D-20-37225R1

Dear Dr. Prost,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Michael C Burger, M.D.

Academic Editor

PLOS ONE

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