Carlos E. Prada, Robert B. Hufnagel , Trent R. Hummel, Anne M. Lovell, Robert J. Hopkin, Howard M.
Saal, Elizabeth K. Schorry. The Use of
Magnetic Resonance Imaging Screening for Optic Pathway Gliomas in Children with
Neurofibromatosis Type 1. Journal of
Pediatrics. Published Online: July 29,
2015.
Abstract
Objective
To evaluate the utility of screening brain/orbital magnetic
resonance imaging (MRI) in a large population of children with
neurofibromatosis type 1 (NF1) over a 20-year period.
Study design
A retrospective analysis of clinical and imaging data from
children with NF1 seen at a single center between 1990 and 2010 was performed.
Results
During the 20-year study period, 826 individuals with NF1
(402 females, 424 males) ages 1-9 years were screened for optic pathway gliomas
(OPGs) using brain/orbital MRI; 18% were identified with OPGs with a median age
at detection of 3 years. Fifteen percent of patients with OPGs had radiologic
or clinical progression requiring therapy. Children with chiasmatic and
postchiasmatic tumors were more likely to require therapy compared with
patients with prechiasmatic OPGs ( P < .0001). Patients with visual deficits
at the time of diagnosis were more likely to experience visual decline despite
therapy when compared with patients treated based on radiologic progression ( P
< .012).
Conclusions
Our findings confirm that chiasmatic and postchiasmatic OPG
in children with NF1 have the highest risk for progression and vision loss.
Early identification of OPG by screening MRI prior to the development of vision
loss may lead to improved visual outcomes. Children with negative brain and
orbital MRI screening at age 15 months or later did not develop symptomatic
OPGs.
From the article:
Prior to therapy, 12 children had vision abnormalities and
10 children had normal ophthalmologic evaluations. Patients with postchiasmatic
tumors (3/4) and chiasmatic tumors (8/15) were more likely to develop vision
abnormalities compared with patients with isolated prechiasmatic OPGs (1/3) ( P
< .01). The most common ophthalmologic findings were decreased visual acuity
(11/22), abnormal/atrophic optic disc (8/22), visual field defects (6/22), and
unilateral abnormal pupillary response (1/22). The majority of children with
OPGs received chemotherapy before 6 years of age (median 5 years; range 1.5-12
years). All patients initially received a regimen of vincristine and
carboplatin, with the exception of 1 patient who subsequently received
vincristine and dactinomycin after experiencing an allergic reaction to
carboplatin. Seven patients relapsed after therapy (median 3 years; range 1-8
years). Surgical resections were performed in 2 patients who had progressive
tumors despite chemotherapy, with severe vision abnormalities. Indications for
OPG surgery were hydrocephalus (n = 1) and mass effect (n = 1)…
Children with OPGs with visual findings prior to therapy
were more likely to experience visual decline (10/12) when compared with
children treated based on radiologic progression of OPGs (2/10) ( P < .012).
Fifty percent (50%) of patients with visual findings at diagnosis (6/12)
progressed to vision loss (final vision of 20/200 or worse) in 1 or both eyes
(5 unilateral, 1 bilateral). None of the patients treated based on radiologic
progression had visual acuities of 20/200 or worse…
In prior decades, many children with NF1 and asymptomatic
optic gliomas received unnecessary treatment for what is often a very indolent
lesion. Listernick et al were among the
first to assert that OPGs in asymptomatic children with NF1 infrequently
progress. In 1997, the OPG Task Force concluded early detection of tumors would
not reduce the rate of loss of vision, and there was no compelling evidence to
support OPG screening with neuroimaging. Blazo et al reported their results of brain
MRI screening of 84 children with NF1, where 13 children were found to have
OPG. They reported that 3 asymptomatic children with enlarging chiasmal lesions
were treated with chemotherapy and had preservation of vision, whereas 5
children ascertained outside of screening guidelines had substantial vision
loss, and suggested that routine surveillance for OPG could improve outcomes.
Listernik and Charrow responded to the
Blazo article, noting that 4 of the 5 tumors in the symptomatic patients were
associated with proptosis and represented a biologically different group of
tumors; they upheld their principle of screening only with ophthalmologic
examinations in young asymptomatic children.
Our study suggests that MRI screening has the potential to
improve and maintain visual outcome in young children with OPG. Supporting this
assertion is that none of the children who were identified only with MRI (no
visual symptoms) with progressive OPG, progressed to vision loss. However, 50%
of children who presented with visual symptoms at the time of diagnosis of a
progressive OPG demonstrated eventual vision loss in 1 or both eyes. This
suggests that screening MRIs in patients with NF1 may identify aggressive
lesions sooner and that this will lead to early treatment and, subsequently,
better visual outcomes…
A potentially negative consequence of brain/orbital MRI
screening is detection of lesions that would never progress or could resolve
spontaneously. This could lead to unnecessary parental anxiety and high costs
associated with frequent imaging. Our study suggests that the location of the
OPGs is an important marker for tumor progression and need for therapy given
that isolated prechiasmatic tumors are more likely to regress (25%) and to be
indolent than chiasmatic and postchiasmatic OPGs (10%). It is also important to
consider that chiasmatic and postchiasmatic OPGs are most likely to lead to
visual symptoms, supporting consideration of therapy for this group if tumor
growth is documented. Future studies will help to validate if frequency of
neuroimaging surveillance could be modified based on glioma location…
Our study also found an increased risk for need for therapy
in females with NF1 and OPG, confirming recent studies suggesting that sex
plays a role in the development of gliomas and neuronal dysfunction in patients
with NF1.
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