Title: Effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes
in patients with locally advanced GIST
Version: 3 Date: 18 Jul 2022
Reviewer:  Jan Peter Marquardt
Reviewer's report:
SUMMARY
The authors have revised their manuscript in a way that tries to address all points. They have
managed to address all minor points mostly to satisfaction. The major points regarding severe
limitations in the statistical analysis seem to be points that the authors will not be able to address
through change in methodology. Modifying the reporting to accurately reflect the extent of
limitations remains crucial to not misguide the scientific community into false confidence in
these findings.
Major points
- The definition of an "optimal cutoff" that is then used in a traditional hypothesis-testing
approach based on the same data set still remains the biggest limitation of statistical power in
the analysis. I would advise not calculating a p-value for significance of the ROC curves being
>0.5 as the assumptions for such a test are not met. At the very least this warrants explicit
mention of severe limitations in interpreting the results in the discussion. Nobody should be
able to mistakenly take these p-values at face value. Along the same vein, the all but guaranteed
overfitting in the multivariable models should be explicitly listed as a severe limitation of the
resulting p-values or better the multivariable analysis be reported without a p-value altogether.
Minor points
- Introduction, third paragraph: The intention of the comments was to rephrase the statements,
not have the comment inserted. In case of the first comment the paragraph now includes two
contradictory statements, please rework into a single statement in line with the comment rather
than including it verbatim.
- Materials and Methods, section Measurement and Definition:  While the used software and
procedures are now more clear, the description seems to imply that all voxels with an HU ranged
-29 to 150 were labelled skeletal muscle.  Given that the figures disprove this, the authors should
include a short statement about the segmentation (who did it, and in what software? manual vs.
machine-assisted?)
Title: Effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes
in patients with locally advanced GIST
Version: 3 Date: 18 Jul 2022
Reviewer:  Jan Peter Marquardt
Reviewer's report:
SUMMARY
The authors have revised their manuscript in a way that tries to address all points. They have
managed to address all minor points mostly to satisfaction. The major points regarding severe
limitations in the statistical analysis seem to be points that the authors will not be able to address
through change in methodology. Modifying the reporting to accurately reflect the extent of
limitations remains crucial to not misguide the scientific community into false confidence in
these findings.
Major points
- The definition of an "optimal cutoff" that is then used in a traditional hypothesis-testing
approach based on the same data set still remains the biggest limitation of statistical power in
the analysis. I would advise not calculating a p-value for significance of the ROC curves being
>0.5 as the assumptions for such a test are not met. At the very least this warrants explicit
mention of severe limitations in interpreting the results in the discussion. Nobody should be
able to mistakenly take these p-values at face value. Along the same vein, the all but guaranteed
overfitting in the multivariable models should be explicitly listed as a severe limitation of the
resulting p-values or better the multivariable analysis be reported without a p-value altogether.
Minor points
- Introduction, third paragraph: The intention of the comments was to rephrase the statements,
not have the comment inserted. In case of the first comment the paragraph now includes two
contradictory statements, please rework into a single statement in line with the comment rather
than including it verbatim.
- Materials and Methods, section Measurement and Definition:  While the used software and
procedures are now more clear, the description seems to imply that all voxels with an HU ranged
-29 to 150 were labelled skeletal muscle.  Given that the figures disprove this, the authors should
include a short statement about the segmentation (who did it, and in what software? manual vs.
machine-assisted?)
Please review this paper.
user
Title: Effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes
in patients with locally advanced GIST
Version: 3 Date: 18 Jul 2022
Reviewer:  Jan Peter Marquardt
Reviewer's report:
SUMMARY
The authors have revised their manuscript in a way that tries to address all points. They have
managed to address all minor points mostly to satisfaction. The major points regarding severe
limitations in the statistical analysis seem to be points that the authors will not be able to address
through change in methodology. Modifying the reporting to accurately reflect the extent of
limitations remains crucial to not misguide the scientific community into false confidence in
these findings.
Major points
- The definition of an "optimal cutoff" that is then used in a traditional hypothesis-testing
approach based on the same data set still remains the biggest limitation of statistical power in
the analysis. I would advise not calculating a p-value for significance of the ROC curves being
>0.5 as the assumptions for such a test are not met. At the very least this warrants explicit
mention of severe limitations in interpreting the results in the discussion. Nobody should be
able to mistakenly take these p-values at face value. Along the same vein, the all but guaranteed
overfitting in the multivariable models should be explicitly listed as a severe limitation of the
resulting p-values or better the multivariable analysis be reported without a p-value altogether.
Minor points
- Introduction, third paragraph: The intention of the comments was to rephrase the statements,
not have the comment inserted. In case of the first comment the paragraph now includes two
contradictory statements, please rework into a single statement in line with the comment rather
than including it verbatim.
- Materials and Methods, section Measurement and Definition:  While the used software and
procedures are now more clear, the description seems to imply that all voxels with an HU ranged
-29 to 150 were labelled skeletal muscle.  Given that the figures disprove this, the authors should
include a short statement about the segmentation (who did it, and in what software? manual vs.
machine-assisted?)
assistant