Response to Reviewers
MS: 5790191321126825
Risks of Postoperative Paresis in Motor Eloquently and Non-Eloquently Located
Brain Metastases
Thomas Obermueller, Michael Schaeffner, Julia Gerhardt, Bernhard Meyer, Florian
Ringel and Sandro M Krieg
REVIEWER COMMENTS TO AUTHOR:
Reviewer #1
Dear Professor Schaller,
Thank you for your important comments. We carefully revised our manuscript
according to your input.
Concerns:
Concern 1:
It is not clear from the manuscript, if their patient series included patients with single
cerebral metastases only - and if so, of which size. The presence of multiple
metastases may have influenced the outcome, and the inclusion of small single
metastases should have triggered a reflex toward radiosurgical treatment as an
option as well.
Answer:
As outlined in table 1, 57% and 56.7% of all patients suffered from single brain
metastases (page 27). Unfortunately, we do not have data on tumor size. In our
hospital all patients with cerebral metastases are discussed in an interdisciplinary
tumor board (neurosurgeons, medical oncologists, radiation oncologists) and surgery
is only indicated in consent with this board (page 5).
Concern 2:
The term "eloquent" doesn't apply to motor function only. They use this term as
synonymous with lesions located in motor regions only.
Answer:
You are right. We therefore changed this term to „motor eloquent“ throughout the
manuscript as already mentioned in the title.
Concern 3:
How come that the rate of new motor deficits in patients with non-eloquently located
metastases is similarly high as in those located in motor regions. They should try to
explain - maybe on the basis of the postoperative MRI studies in their patients. What
is the meaning of coining a term "eloquent" for motor location if there is no difference
to the non-eloquently located lesions?
Answer:
You are right. But as shown in Fig. 4, there is a trend towards a higher deficit rate in
motor eloquently located metastases (page 25). We evaluated all postoperative MRI
scans in our patients. On page 14 and 15 we tried to explain the similar deficit rates
with these data and wrote: „In the motor eloquent group, four patients suffered
secondary hemorrhages causing permanent motor deficits. Ischemia only occurred in
one case. When operating especially near or within the rolandic cortex, our
department rarely uses the bipolar cautery, to avoid consecutive ischemia.
Even in the non-motor-eloquent group, we had two cases of new permanent motor
deficits (1.3%) after surgery due to ischemia and secondary hemorrhage. This tells
us that even such tumors carry the risk of postoperative paresis, and we have to bear
this fact in mind when we counsel our patients.“
Concern 4:
How do they explain the high rate of residual tumor? This is a very surprising finding.
Don't they adhere to the principle that resection of metastases should include
aspiration of surrounding tissue whenever possible (as "supramarginal resection" in
gliomas)? Are they changing their habits now? Could intraoperative fluorescence
help to improve? Would they propose their patients to be taken back to the OR, as
one does in case of residual tumor following glioma surgery, because extent of
resection translates in survival clearly?
Answer:
We do not perform routine supramarginal resections of metastases. On page 13 we
provide an explanation for our high rate of residual tumor. One explanation could be
the two cited recent studies, which provided some data that metastases might have
an infiltrative growth pattern (Kamp MA, Dibue M, Santacroce A, Zella SM, Niemann
L, Steiger HJ, Rapp M, Sabel M: The tumour is not enough or is it? Problems and
new concepts in the surgery of cerebral metastases. Ecancermedicalscience 2013,
7:306; Baumert BG, Rutten I, Dehing-Oberije C, Twijnstra A, Dirx MJ, DebougnouxHuppertz RM, Lambin P, Kubat B: A pathology-based substrate for target definition in
radiosurgery of brain metastases. Int J Radiat Oncol Biol Phys 2006, 66(1):187-194).
On the other hand, residual tumor in this study was defined as any case of contrast
enhancement, which can therefore result in considerable overestimation of real
residual tumor due to reactive postoperative changes. But you are right:
intraoperative imaging or repeated resection have to be discussed and we added this
important issue to the discussion section (page 14).
Concern 5:
On p14 "small lung cancer" should become "small cell lung cancer".
Answer:
This was changed on page 14.
Reviewer #2
Dear Professor Duffau,
Thank your for your review. We think that your comment increased the value of our
manuscript significantly.
Minor essential revisions
However, the authors should be cautious by speaking about "non-eloquent areas".
Indeed, they did not take into consideration language or visual functions: how many
metastasis involved the left dominant hemisphere? It seems that 15.3% of tumors
were located in the occipital lobe, but the rate of visual filed deficit was not given,
etc...
Answer:
You are right. As mentioned in the title we strictly analyzed motor function. However,
this was not clearly mentioned in the manuscript. We therefore changed „eloquent“ to
„motor eloquent“ throughout the manuscript.