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Effect of radiotherapy in patients with low-grade gliomas.

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Effect of Radiotherapy in
Patients with Low-Grade
matched patients using a screening battery representative for
important functions of both hemispheres within comparable
time intervals after therapy. Otherwise, the main conclusion
of this study remains very interesting but unfortunately not
well substantiated.
F. W. Kreth, MD, M. Peper, PhD, W. Bini, MD,
and C. B. Ostertag, M D
Neurocbirurgiscbe Universitatsklinik
Abteilung Stereotaxie
Breisacher Str. 64
79106 FreiburglGemzany
We welcome the recommendations of Taphoorn and coworkers [11 for additional psychological investigations to
evaluate the effects of treatment on patients with low-grade
gliomas. The authors have compared neuropsychological investigations of patients after surgery alone (20 patients), after
surgery radiotherapy (2 1patients) and a control group with
extracerebral disease. Neuropsychological investigation revealed a similar pattern of cognitive and affective disturbances in both glioma groups, showing a greater deficit and
incidence compared with the control group. The failure to
detect significant differences between the surgery and the
radiotherapy groups suggested that radiotherapy had no negative impact on clinical and psychological status.
A major drawback of this study was that the patients were
not matched with regard to tumor size, location, and laterality. Emotional effects of tumor lesions, for example, have
been reported to be strongly influenced by the lesion site
and size [2}. Thus the assessment of the affective status seems
questionable in the Taphoorn study because these important
covariates were not considered.
If tumor locations were heterogeneous then the behavior
tests used should be representative of both hemispheres [3].
The tests presented, however, did not address important
functions of the right hemisphere, such as visual perception
and visual memory. Thus the more frequent detection of
cognitive deficits in patients with lesions of the so-called
dominant hemisphere appeared at least in part to be a result
of the method. Both the heterogeneity of the data and their
evaluation biased the results.
How did the authors distinguish between favorablelunfavorable treatment effects and those of the lesion itself in this
study? Which effects were caused by the tumor and which
by the therapy? The authors wished to investigate the risk
of radiotherapy, but did they weigh the risk of radiotherapy
against its benefit? Could better tumor control or tumor
shrinkage after radiotherapy improve psychological function
in the first 213 years after treatment preceding or masking
radiation toxicity? Psychological impairment after radiotherapy has been judged as a late complication and therefore
not necessarily detectable early after therapy. Thus the good
results after radiation therapy may indicate the efficacy of
radiation particularly in those patients with a shorter
follow-up. Unfavorable tumor-related effects may be major
in the surgery group. Most patients underwent partial resection. The authors could not exclude, although they stated
that the clinical status remained unchanged over time, that
the patients in the surgery group might have greater disability
due to ongoing tumor-related effects than those in the radiotherapy group. Thus a similar outcome in both groups might
be based on completely different causes, either treatment or
tumor related or both. It would have been better to have
performed longitudinal neuropsychological studies in well-
1. Taphoorn MJB, Klein Schiphorst A, Snoek FJ, e t al. Cognitive
functions and quality of life in patients with low-grade gliornas:
the impact of radiotherapy. Ann Neurol 1994;36:48-54
2. Irle E, Peper M, Wowra B, Kunze S . Mood changes after surgery
for tumors of the cerebral cortex. Arch Neurol 1994;51:164-174
3. Mesulam MM. Patterns in behavioral neuroanatorny. In: Mesulam MM, ed. Principles of behavioral neurology. Philadelphia:
FA Davis, 1985:l-70
M. J. B. Taphoorn, M D
Kreth and colleagues raise substantial criticisms with respect
to the methodology of our study. Clearly, our study was not
a prospective clinical trial, as we emphasized in the discussion. To reduce the risk of selection bias, we studied consecutive patients from hospitals with different therapeutic strategies: the exclusion of any of these patients for the sake of
matching was avoided. Both patient groups happened to be
well matched for age and interval from diagnosis to testing,
but not for tumor laterality. Although Kreth and colleagues
rightly state that we did not study the possible influence of
tumor laterality on the affective status, their argument is
weak, referring to a paper concluding that lesion laterality
does not influence the affective status [l]. Moreover, in the
same study it was demonstrated that lesions of the frontal and
parietal cortexes were responsible for the negative changes in
mood. In this respect, our patient groups were not so badly
matched: 13 of 20 patients of the radiotherapy group versus
12 of 2 1 patients of the nonradiotherapy group had parietal
or frontal tumors. Finally, in contrast to what Kreth and colleauges argue, lesion size in the study to which they refer,
did not appear to have a strong influence on the affective
status. W e miss the point made by Kreth and colleagues with
respect to the cognitive test battery applied, because in our
study two important tests were used, designed to detect
deficits in right hemisphere processes like pattern perception
and spatial thinking (Benton Facial Recognition and Judgement of Line Orientation test). Moreover, we analyzed and
described the results of the neuropsychological assessment
for subgroups of patients with left and right hemisphere tumors and found no significant differences.
The cause of treatment effects cannot be deduced from
our study as we already pointed out in the discussion. Kreth
and colleagues merely speculate on early positive effects of
radiotherapy on neuropsychological function, followed by a
negative impact that might in time result in the same degree
682 Copyright 0 1995 by the American Neurological Association
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effect, patients, radiotherapy, low, glioma, grade
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