CORRESPONDENCE
Letter: Commentary: Peritumoral
Edema/Tumor Volume Ratio: A Strong Survival
Predictor for Posterior Fossa Metastases
To the Editor:
We would like to thank Dr Chow and his collaborators for
their interest and observations, and for providing the critical and
excellent Commentary1 in response to our paper.2
A number of studies have supposed that the degree of edema
could be related to the volume of brain metastasis and survival, yet
prior our article,2 no systematic study had stated this relationship.
The commentary1 discusses the main result of our study.2
Chow et al1 describe the existence of very contradictory and
ambiguous data concerning the prognostic role of peritumoral
edema of brain tumors3 (by highlighting articles which deal with
metastases/gliomas). Moreover, they offer 3 arguments to explain
this heterogeneity: tumor location in the posterior fossa, imaging
limitations, and hitological heterogeneity.
Considering the first argument, Chow et al1 state that, given
the anatomic location of the tumors we studied (close to vital
structures such as the brainstem and the fourth ventricle), it is
logical to expect posterior fossa to play a pivotal role in deter-
mining the clinical relevance of peritumoral edema. We agree with
Chow et al1 but we also would like to put an emphasis on the
fact that our study was the first to focus on this location and
thus to have been able to confirm this “anatomic intuition.” Our
findings are interesting, especially since the data from Schneider
et al4 identified that metastases that exhibited edema were more
frequent in the infratentorial space. This finding was opposed to
the supratentorial location P < .0002.4
In a second instance, Chow et al1 raise the fact that it is
difficult to study peritumoral edema with T2 or fluid-attenuated
inversion-recovery (FLAIR) hyperintense regions using 1.5 or 3-T
magnetic resonance imaging (MRI) scans; indeed, they suggested
that these regions contain variable proportions of vasogenic,
cytotoxic edema, and tumor cell infiltration, which are impos-
sible to distinguish. Of course, this problem is mainly relevant
for highly infiltrating tumors, therefore gliomas, and is much less
if we consider the metastatic pathology. In addition to imaging
technique evolution, such as the application of machine learning
algorithms, as proposed by Chow et al1 we believe that the study
of the FLAIR peritumoral hypersignal, as we propose in our work,
has several interests:
i) In our experience it is sufficient for distinguishing edema
from metastasis;
ii) It is easy to use in clinical practice and volume measurements
are now facilitated with software, making the FLAIR/tumor
ratio a relevant factor to integrate into the graded prognostic
assessment classification.
Furthermore, our data corroborate the recent study of Wang
et al5 who focused on the Ktrans (volume transfer ratio calcu-
NEUROSURGERY
lated from perfusion parameters obtained by dynamic contrast-
enhanced MRI or DCE-MRI) in brain metastases. The Ktrans
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reflects vascular permeability, in order to evaluate tumor angio-
genis, and could then be used to monitor the damage of the
blood-brain barrier. In their study, Wang et al5 determined that
the Ktrans was highly correlated with the edema index, calculated
as Vtumor+edema /Vtumor , which could easily be applied to posterior
fossa.
In their third argument, Chow et al1 suggested the biais of
histological heterogeneity of metastases in our series to explain
our results concerning the prognostic value of peritumoral edema.
This point has been discussed in our article, and we agree with
Chow et al1 that a study of each histological type of metas-
tasis would obviously be of some interest but to a certain extent.
For example, Schneider et al4 demonstrated that breast brain
metastases resided rather in infratentorial space, whereas lung,
genitourinary, and melanoma preferred the supratentorial space.
However, we also think that, as the edema/tumor ratio is a very
significant prognostic factor despite the histological heterogeneity
of our series, on the contrary, it symbolizes the power of this radio-
logical criterion and should therefore be considered as a very inter-
esting feature in the decision algorithm for the management of a
priori surgical posterior fossa metastasis, regardless of the primary
neoplasia.
Finally, Chow et al1 regret that our study only included
operated posterior fossa metastases, while other therapeutics
(such as stereotactic irradiation) are validated for the first-line
management of these posterior fossa metastases.6 For our series,
we focused on the surgical metastases. This does not rule out other
treatments such as stereotactic irradiation which has been part of
the therapeutic arsenal in our institution since 2010. However,
from our experience as well as among the criteria defined by Wolf
et al6 perilesional edema is a contraindication to the treatment of
posterior fossa metastasis with stereotactic irradiation, the irradi-
ation being at risk of increasing this edema. It is therefore highly
likely that the measurement of the edema/tumor ratio is not
relevant for nonsurgical metastases.
Disclosure
The authors have no personal, financial, or institutional interest in any of the
drugs, materials, or devices described in this article.
Ilyess Zemmoura, MD, PhD∗ ‡
Bertrand Mathon, MD§ ¶
Aymeric Amelot, MD, PhD§ ¶
∗
CHRU de Tours
Department of Neurosurgery
Tours, France
‡
UMR 1253, iBrain
Université Tours, Inserm
Tours, France
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§ 3. Spanberger T, Berghoff AS, Dinhof C, et al. Extent of peritumoral brain edema

AP-HP, Department of Neurosurgery
correlates with prognosis, tumoral growth pattern, HIF1a expression and angiogenic
La Pitié-Salpêtrière University Hospital activity in patients with single brain metastases. Clin Exp Metastasis. 2013;30(4):357-
Paris, France 368.
¶
Sorbonne University, UPMC 4. Schneider T, Kuhne JF, Bittrich P, et al. Edema is not a reliable diagnostic sign to
University Paris 06 exclude small brain metastases. PLoS One. 2017;12(5):e0177217.

Downloaded from https://academic.oup.com/neurosurgery/advance-article-abstract/doi/10.1093/neuros/nyy573/5281545 by guest on 14 January 2019

5. Pfefferbaum A, Adalsteinsson E, Rohlfing T, Sullivan EV. MRI estimates of
Paris, France brain iron concentration in normal aging: comparison of field-dependent (FDRI)
and phase (SWI) methods. Neuroimage. 2009;47(2):493-500.
6. Wolf A, Kvint S, Chachoua A, et al. Toward the complete control of brain
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