Copyright © 2006 by the Society for Neuro-Oncology
The purpose of this study was to assess the impact of
early radiation therapy and extent of surgical resection
on progression-free survival (PFS) and overall survival
(OS) in children with WHO grade II low-grade gliomas
(LGGs). We conducted a historical cohort study of 90
patients, ages 21 or younger, diagnosed with WHO grade
II LGGs between 1970 and 1995. Median follow-up for
surviving patients was 9.4 years (range, 0.5–22.6 years).
Tests for variables correlating with OS and PFS were
conducted by using log-rank tests and Cox proportional
Brain Tumor Research Center and Departments of Radiation Oncology (K.K.M., B.T.M., W.M.W., D.A.H.-K.)
and Neurosurgery (K.R.L., M.D.P., M.S.B., A.B., N.G.), University of California, San Francisco, San Francisco,
CA 94143; and Memorial Sloan-Kettering Cancer Center, New York, NY 10022 (D.R.P.); USA
hazards models. Eleven patients underwent gross total
resections (GTRs), 43 had subtotal resections, and 34
underwent biopsy only at diagnosis. Two patients under-
went biopsy at time of recurrence. Of the 90 patients,
52 received radiation as part of their initial therapy fol-
lowing diagnosis (early-RT group). The overall five-year
PFS and OS rates 6 SE were 56% 6 5% and 90% 6
3%, respectively. Ten-year PFS and OS rates were 42%
6 6% and 81% 6 5%, respectively. For patients older
than three years and without GTRs, administration of
early radiation did not appear to influence PFS or OS
(P 5 0.98 and P 5 0.40, respectively; log-rank test). This
was confirmed by multivariate analyses (P 5 0.95 and
P 5 0.33 for PFS and OS, respectively). Of the 11 patients
with GTRs, disease progressed in only two, and all
were alive with no evidence of disease at last follow-up.
Patients who underwent GTRs had significantly longer
PFS (P 5 0.02), but did not have significantly improved
OS. Excellent long-term survival rates were achieved for
children with WHO grade II LGGs. We were unable to
demonstrate a benefit for administering radiation as part
of initial treatment. An outcome benefit was seen with
greater extent of resection. Neuro-Oncology 8, 166–174,
2006 (Posted to Neuro-Oncology [serial online], Doc.
05-112, February 22, 2006. URL www.dukeupress.edu/
neuro-oncology; DOI: 10.1215/15228517-2005-011)
Keywords: low-grade glioma, pediatric, radiation,
Neuro-Oncology? ■? APrIL?2006?
(Halperin et al., 2005). However, many aspects of treat-
ment remain poorly defined, particularly with respect
to nonpilocytic, WHO grade II lesions (Halperin et al.,
2005; Rilliet and Vernet, 2000; Schmandt and Packer,
2000; Stother et al., 2002). One such controversy is
whether to administer postoperative radiation to chil-
dren with WHO grade II tumors, balancing the poten-
tial effectiveness of radiation with long-term toxicities.
Historically, treatment of incompletely resected tumors
frequently involved postoperative radiation and/or che-
motherapy. However, the morbidity of radiation therapy
(RT) in children has prompted many physicians to replace
early radiation with chemotherapy or observation (Avi-
zonis et al., 1992; Chadderton et al., 1995; Cohen and
Duffner, 1991; Duffner and Cohen, 1991; Ellenberg et
al., 1987; Reddy and Packer, 1998; Schmandt and Packer,
2000; Watson et al., 2001).
Lack of consensus regarding the optimal treatment of
pediatric grade II gliomas is in part due to the absence of
randomized prospective trials. Although pediatric con-
sortia and cooperative groups had designed a prospec-
tive, randomized, phase 3 trial (POG 9130/CCG 9891/
INT 0128 trial) to evaluate neurosurgical and radiother-
apeutic treatments of children with LGGs (Wisoff et al.,
1996), practitioner bias forced early closure of this trial
(Dhodapkar et al., 1999; Watson et al., 2001). Further-
more, most previous retrospective studies of LGGs have
included limited numbers of children and grade II lesions
(Bernstein et al., 1984; Bloom et al., 1990; Bowers et al.,
2002; Butler et al., 1994; Desai et al., 2001; Deutsch,
1982; Dewit et al., 1984; Dohrmann et al., 1985; Erkal et
al., 1997; Gajjar et al., 1997; Garcia et al., 1985; Hirsch
et al., 1989; Hoffman et al., 1993; Kandil et al., 1999;
Karim et al., 1998; Laws et al., 1984; Leibel et al., 1975;
Lote et al., 1997; Marsa et al., 1973; Medbery et al.,
1988; Mercuri et al., 1981; Pencalet et al., 1999; Pollack
et al., 1995; Scanlon and Taylor, 1979; Sgouros et al.,
1995; Shaw et al., 1989; Shibamoto et al., 1993; Wara,
1985; Weir and Grace, 1976; Yeh et al., 2002).
Given the relative paucity of data relating to the role of
radiation therapy in pediatric grade II gliomas, we hoped
to shed additional light on this and other key treatment
issues by evaluating the experience of the University of
California, San Francisco (UCSF). The primary focus
of this study was the role of radiation therapy in the up-
front treatment of pediatric grade II gliomas. In address-
ing this issue, we concentrated on a specific subgroup
of patients for whom the use of radiation at the time of
initial diagnosis is controversial, namely, children who
are older than three years of age and patients who have
undergone incomplete surgical resections. We reviewed
our cohort of pediatric patients treated for WHO grade
II LGGs and estimated differences in survival outcomes
based on prognostic and therapeutic factors. In particu-
lar, we sought to assess, first, the impact of radiation
therapy at initial presentation and, second, the effect of
extent of resection on progression-free survival (PFS)
and overall survival (OS).
ow-grade gliomas (LGGs)4 are the most common
pediatric brain tumors, comprising 35% of child-
hood primary central nervous system malignancies
We conducted a historical cohort study of 90 patients,
ages 21 years and younger, with WHO grade II gliomas,
diagnosed at UCSF between 1970 and 1995. All patient
characteristics, treatment parameters, and survival data
were extracted from clinical records, radiographic infor-
mation, and active follow-up obtained from the Depart-
ments of Radiation Oncology, Neuro-oncology, and/or
Neurosurgery at UCSF. Table 1 summarizes the clinical
characteristics for the entire cohort. Patients with grade
II brainstem and spinal cord lesions were excluded, as
were those with prior radiation or chemotherapy, previ-
ous cancers, second concurrent malignancies, or extra-
cranial metastases at diagnosis.
All patients in the study population had pathologically
confirmed WHO grade II gliomas. Subjects’ original
pathological diagnoses from UCSF neuropathology were
used for classification. Histology was defined by WHO
criteria as grade II astrocytoma, oligodendroglioma, or
mixed oligoastrocytoma. Extent of resection was based
on preoperative and postoperative radiographic imaging
studies as well as operative reports. Extent of resection
was defined as gross total resection (GTR: all visible tu-
mor removed and postoperative film negative for residual
tumor), subtotal resection (STR: bulk tumor resection
50%–95% and residual tumor on film), and biopsy (less
than 50% of the tumor volume removed). Chemotherapy
details, including agents, dates, and protocols, were col-
lected. The most common chemotherapy regimens were
nitrosourea-based multiagent chemotherapy and single-
agent carboplatin, as previously published (Levin et al.,
2000; Prados et al., 1997). All 90 patients underwent
postoperative imaging. Sixty-eight cases were followed
by MRI alone, 14 by CT initially and then MRI until last
follow-up, and eight by CT alone.
Patients were analyzed according to whether they re-
ceived radiation at diagnosis (early RT) or did not re-
ceive radiation at diagnosis (no early RT). The decision
of whether to administer early radiation was made at the
discretion of the treating physician. Some patients who
did not receive radiation at diagnosis subsequently were
treated with radiation at the time of progression. Radia-
tion was directed to the primary tumor volume plus mar-
gin, with a median dose of 54 Gy (range, 45–60 Gy).
We calculated PFS and OS rates from date of diagno-
sis. All of the patients had been diagnosed prior to 1995.
Life-table methods were used to estimate PFS and OS
(Kaplan and Meier, 1958). Five-year and ten-year PFS
and OS estimates were calculated by the Kaplan-Meier
method, with standard errors calculated by Greenwood’s
formula. Elapsed time from diagnosis to an event or last
follow-up was used to compute PFS and OS probabili-
ties. In analyses of PFS, last follow-up dates for patients
not experiencing an event were based on imaging studies
that delineated disease status. For OS, deaths, regard-
less of cause, were coded as events. For PFS, an event
was defined as relapse, progression, or death during the
period of active follow-up. Kaplan-Meier curves for PFS
and OS were calculated for the subgroups that did and
did not have radiation administered at diagnosis. Addi-
Ninety patients with WHO grade II gliomas were in-
cluded in the study. Table 1 delineates patient character-
istics and treatment factors. The median age for all pa-
tients was 9.0 years (range, 0.5–20.7 years). Thirty-nine
(43%) patients were female and 51 (57%) were male.
Thirty-nine tumors (43%) were located primarily in the
cerebrum, 42 (47%) in midline structures (20, thalamus;
5, hypothalamus; 2, optic pathway; 7, optic-hypotha-
lamic; 6, pineal; 1, third ventricle; and 1, tectal plate)
and nine (10%) in the cerebellum.
Histologic confirmation was obtained in all cases.
Sixty-eight patients (76%) had astrocytomas, seven (8%)
had oligodendrogliomas, and 15 (17%) had mixed oligo-
astrocytomas. Two of the 90 patients did not have biopsy
confirmation at initial diagnosis, but biopsies at the time
of recurrence confirmed grade II lesions. For analyses
involving extent of resection, these two patients were
included in the biopsy group.
Median follow-up for surviving patients was 9.4
years (range, 0.5–22.6 years). Among the 90 patients, 19
deaths were documented during the follow-up period.
Of the remaining 71 surviving children, 61 had more
tional sets of Kaplan-Meier curves were derived to deter-
mine the PFS and OS of patients by extent of resection
at original diagnosis.
To assess variables influencing PFS and OS, uni-
variate analyses using log-rank tests and proportional
hazards models were performed to evaluate treatment
with early radiation and extent of original tumor re-
section. To further verify results of univariate analyses,
Cox proportional hazards multivariate analyses were
conducted, including treatment with early radiation and
extent of resection as well as additional variables con-
sidered possibly prognostic. The additional variables
were age at diagnosis, tumor location, and tumor histol-
ogy. Age was analyzed as a continuous variable. Tumor
location was defined as midline versus nonmidline on
the basis of radiographic and surgical findings. Histol-
ogy was defined as a categorical variable, including as-
trocytoma, oligodendroglioma, and mixed pathology.
For evaluation of extent of resection as a predictor of
outcome, extent of resection was considered as a cat-
egorical variable, and for multivariate analyses, two
variables were included indicating whether a patient
had an STR and whether the patient had a GTR. This
study was performed after approval by local human in-
Variable? No?Yes? Total
Neuro-Oncology? ■? APrIL?2006?
than five years of follow-up from time of diagnosis, and
32 had more than 10 years of follow-up.
Progression-Free Survival and Overall Survival
For the entire cohort of 90 patients, the five-year PFS
rate was 56% 6 5%, and the ten-year PFS rate was 42%
6 6%. Five-year and ten-year OS rates were 90% 6 3%
and 81% 6 5%, respectively. The median PFS for all
patients was 80.4 months (95% confidence interval [CI],
Of the cohort of 90 patients, 49 experienced disease
progression. The median time to progression for these
49 patients was 25.0 months (range, 2.4–259.2 months).
Twelve (24.5%) of these patients progressed at five or
more years after diagnosis. Of the 49 patients who pro-
gressed, at last follow-up 19 had died, five remained alive
with disease, and 25 had no evidence of disease (NED).
Nineteen patients experienced multiple recurrences (two
or more), with seven having disease progression that led
to death, three remaining alive with disease, and nine
having NED at last follow-up.
The median survival time for the 19 patients who
died was 69.6 months (range, 4.8–276 months). Nine
(47%) of these 19 children died within five years of diag-
nosis. Five of the 19 died more than 10 years after their
original diagnoses. Of the 49 patients whose disease
progressed, a limited number had repeat tissue diagno-
ses at the time of progression, revealing 11 grade II, 13
grade III, and three grade IV tumors.
Impact of Early Radiation
Thirty-eight patients received no radiation at diagnosis
(no-early-RT group), and 52 children did receive radia-
tion as part of their initial treatment regimen (early-RT
group). The median age of children receiving no early
RT was 3.9 years (range, 0.5–18.0 years), and median
age for those receiving early RT was 12.5 years (range,
1.2–20.7 years). Long-term follow-up was achieved for
most surviving patients. The median follow-up for sur-
viving patients in the no-early-RT and early-RT groups
was 8.9 years (range, 0.5–16.4 years) and 10.6 years
(range, 0.5–22.6 years), respectively. Follow-up of five
or more years was achieved for most surviving children,
83% and 89%, respectively, for the no-early-RT and
early-RT groups. Of the 20 patients whose disease pro-
gressed in the no-early-RT group, 13 received radiation
upon progression. Table 1 describes the patient charac-
teristics and treatment details of the no-early-RT and
Five-year and ten-year PFS rates were, respectively,
50% 6 8% and 43% 6 9% for those not receiving early
radiation, as compared with 61% 6 7% and 43 6 7%
for the early-RT group. Five-year and ten-year OS rates
were, respectively, 97% 6 3% and 92% 6 6% for those
receiving no radiation at diagnosis, as compared with
84% 6 5% and 74% 6 6% for those receiving RT at
A multivariate logistic regression was used to con-
firm predictors for early RT use, and as expected, lesser
extent of resection and older age increased the likelihood
of patients receiving RT as part of their initial treatment
(P , 0.01 for both variables). Indeed, none of the 11
patients who underwent GTRs and only three of 19 chil-
dren under three years of age received early RT, which
substantiates the rationale to exclude these patients in
order to limit bias in analyses of potential effects of early
RT and to focus on the group of patients for whom the
use of RT at time of diagnosis is most controversial. All
subsequent analyses comparing the cohorts that did and
did not receive early RT excluded patients who underwent
GTRs and those younger than three years of age at diag-
nosis. In using these exclusions, we sought to eliminate
subgroups for which a compelling bias existed against
early RT administration. After excluding all children with
GTRs and those younger than three years of age at diag-
nosis, 61 children remained in the cohort and were ana-
lyzed, 15 in the no-early-RT group and 46 in the early-RT
group. Among these 61 patients, the disease of 32 had
progressed and 15 had died at the time of this analysis.
For the subgroup of children who did not undergo
GTRs and who were older than three years of age, the
respective five-year and ten-year PFS rates were 59% 6
13% and 43% 6 14% for those receiving no radiation at
diagnosis, as compared with 60% 6 7% and 44 6 8%
for those receiving radiation at diagnosis. The respec-
tive five-year and ten-year OS rates were 93% 6 6% and
82% 6 12% for those receiving no radiation at diagno-
sis, as compared with 84% 6 5% and 77 6 7% for those
receiving RT at diagnosis.
A comparison of the two groups using the log-rank
test revealed no statistical difference in PFS or OS be-
tween those who did and did not receive radiation at
diagnosis (P 5 0.98 and P 5 0.40, respectively). We also
conducted a multivariate analysis to confirm that inclu-
sion of other factors would not change these conclu-
sions. A Cox proportional hazards model was derived
after adjusting for potentially confounding variables,
including histology, location of primary tumor, patient
age, and extent of surgical resection. The PFS and OS
hazard ratios (HRs) for the early-RT versus no-early-RT
groups were not statistically significant. For PFS, the HR
was 0.97 (P 5 0.95; 95% CI, 0.41–2.6), and for OS, the
hazard ratio was 2.5 (P 5 0.33; 95% CI, 0.40–16.4). A
hazard ratio of less than 1 would have implied a benefit
to early RT. Figure 1 shows the Kaplan-Meier curves for
radiation therapy administered or not administered at
the time of original diagnosis.
Influence of Extent of Surgical Resection
A secondary analysis to evaluate the impact of extent
of surgical resection was performed including all 90
patients. It was recognized that extent of resection may
be a surrogate for other factors such as tumor location,
tumor size, or performance status. Included in this anal-
ysis were 11 patients with GTRs, 43 with STRs, and
36 with biopsies. As noted earlier, the two patients who
underwent biopsies at time of recurrence were included
in the biopsy group for analyses involving extent of
Five-year PFS rates were 79% 6 13% for patients
treated with GTRs, 60% 6 8% for those with STRs,
and 46% 6 8% for those with biopsies alone. Five-year
OS rates were 100% for those treated with GTRs, 88%
6 5% for those with STRs, and 89% 6 5% for those
with biopsies alone. Ten-year PFS rates were 45% 6 8%
for patients with STRs and 30% 6 8% for those with
biopsies alone. Ten-year OS rates were 82% 6 6% for
patients with STRs and 76% 6 8% for those with biop-
Eleven patients in the no-early-RT and no patients
in the early-RT group underwent GTRs at initial pre-
sentation. Eight of the 11 patients had more than five
years of follow-up, and of these, three had more than
10 years of follow-up. All 11 patients were alive without
evidence of disease at last follow-up. Of the 11 patients,
two experienced recurrences: one at 28 months and one
at 36 months. These patients were salvaged at recurrence
by repeat GTR and chemotherapy, respectively, and had
NED at last follow-up, 48 and 88 months from their
In analyzing the entire cohort of 90 patients and
adjusting for location, histology, age, and early radia-
tion, an improved PFS was evident for patients with
GTRs as compared to those with biopsy only (P 5 0.02;
HR 5 0.14; 95% CI, 0.02–0.76). Comparison of STRs
and biopsy revealed an HR of 0.63, which did not reach
statistical significance (P 5 0.31; 95% CI, 0.26–1.54).
Although none of the patients with a GTR had died,
there was no statistically significant difference in overall
survival depending on extent of resection (P 5 0.2, log-
rank test). Figure 2 shows Kaplan-Meier curves accord-
ing to extent of surgical resection at the time of original
The issue of optimal treatment for these WHO grade II
LGGs remains unsettled, largely because of the paucity
of prospective randomized trials, coupled with small
pediatric populations and limited follow-up in most ret-
rospective studies to date. Although children with LGGs
have favorable overall survival rates, controversy persists
regarding when to incorporate radiation therapy into the
treatment of incompletely resected tumors. Our data, in
conjunction with the current literature, do not support a
survival benefit for early initiation of postoperative radia-
tion, even in the setting of subtotal resections. Our data
do, however, support aggressive, maximal surgical resec-
tion as a factor associated with superior PFS, an advan-
tage driven by gross total resections.
This study provides very long follow-up for a large
cohort of children with pathological documentation of
WHO grade II LGGs. The data reinforce the approach of
maximal surgical resection, reserving postoperative ra-
diation for patients with progressive tumors and/or neu-
rological deficits (Campbell and Pollack, 1996; Fisher et
al., 1998, 2001; Watson et al., 2001). According to ob-
jective radiologic confirmation, 11 patients in our cohort
underwent GTRs. Only two of these patients required
additional salvage therapy upon disease recurrence, and
all 11 had NED at last follow-up. Many studies to date
have recognized similarly that extent of resection is a
A. Progression-free survival
B. Overall survival
Neuro-Oncology? ■? APrIL?2006?
key covariate in survival modeling (Berger, 1996; Bloom
et al., 1990; Campbell and Pollack, 1996; Desai et al.,
2001; Dhodapkar et al., 1999; Lo et al., 2001; Pencalet
et al., 1999; Pollack, 1999; Pollack et al., 1995). How-
ever, surgical resectability may be considered a proxy
for other prognostic variables, including tumor location.
For example, in our database, the vast majority of biop-
sies (32 of 36) were performed for midline tumors that,
relative to nonmidline lesions, have been found in some
series to result in worse outcomes.
Despite the successful long-term results of children
undergoing GTRs alone, there remains uncertainty re-
garding the use of adjunctive RT for pediatric patients
with incomplete resections. The value of RT in these
cases is unclear, given potential adverse effects balanced
against a divergence of opinions regarding survival ben-
efit. Previous reports have documented possible short-
term and long-term consequences on cognitive develop-
ment, vascular integrity, endocrine function, and general
quality of life (Avizonis et al., 1992; Chadderton et al.,
1995; Cohen and Duffner, 1991; Duffner and Cohen,
1991; Ellenberg et al., 1987; Reddy and Packer, 1998).
These radiation-induced sequelae, though not particu-
larly studied in our data set, clearly help inform deci-
sions about the appropriate use of RT in the pediatric
Compounding the aforementioned potential adverse
effects, few available studies have suggested an overall
survival advantage for children undergoing postopera-
tive radiation in the setting of incomplete surgical resec-
tions (Shaw et al., 1989; Shibamoto et al., 1993; Watson
et al., 2001). Serious obstacles are posed by the miscel-
lany of grade I and II lesions analyzed together, small
numbers of children, and short follow-up periods that
characterize many published studies (Fisher et al., 1998,
2001; Kandil et al., 1999; Karim et al., 1998; Lote et al.,
1997; Medbery et al., 1988; Pencalet et al., 1999; Pollack
et al., 1995; Sgouros et al., 1995). Numerous contempo-
rary series indicate no significant benefit in OS with early
postoperative radiation in pediatric LGGs. Fouladi et al.
(2003) analyzed children with LGGs who were enrolled
in Children’s Cancer Group high-grade glioma study
CCG-945. In accordance with our findings, the authors
found no benefit to frontline combined chemoradiation.
In a handful of retrospective reviews, benefits of early
postoperative radiation for PFS do not translate into OS
benefits, likely because salvage therapy is successful in
a significant number of progressive cases (Karim et al.,
1998; Pollack et al., 1995).
To describe survival effects of early RT in our patient
population, we attempted to analyze a more homoge-
neous group of patients. We included only WHO grade
II lesions that generally have a distinct biological course
and prognosis as compared with grade I lesions (Fuller
and Perry, 2001; Gjerris and Klinken, 1978; Hayostek
et al., 1993; Herfarth et al., 2001). Brainstem and spinal
cord lesions were also excluded from the current study,
given different natural histories and therapeutic options
relative to other tumor locations (Desai et al., 2001;
Farwell et al., 1977; Merchant et al., 2000; Pencalet
et al., 1999; Sgouros et al., 1995). Finally, in the com-
parison of early radiation versus no early radiation, we
excluded patients who had undergone GTRs and those
younger than three years of age, because these patients
rarely receive radiation at the time of diagnosis unless
extremely poor prognostic features exist (Berger, 1996;
Jenkin et al., 1998; Sala et al., 1999).
The data from our cases followed for a median of
9.4 years (for surviving patients) corroborate much of
the available historical data that describe no benefit in
A. Progression-free survival
B. Overall survival
survival with early RT. Controlling for potential con-
founding sources, early radiation compared with no
early radiation does not confer PFS or OS benefit in our
cohort. Our study is, however, limited by its retrospec-
tive nature. One must consider unidentified sources of
selection bias that a retrospective review cannot well
control. Those patients referred for radiation likely car-
ried poorer initial prognoses. Hence, the fact that there
is no survival difference may indicate that these children
benefited from RT, perhaps because RT conferred com-
parable survival rates despite worse prognostic features.
In our multivariate model, we have tried to control for
such confounding variables. However, because of sam-
ple size, potential missing covariates, and nonrandom-
ized administration of therapies, a benefit from early
RT may exist that was missed in this analysis. Although
our data show no clear benefit to early radiation, the
wide confidence intervals for the hazard ratios reflect
the possibility that early RT may be either beneficial or
Given the results of this and other recent publications,
no statistically significant benefit in overall survival has
been firmly established for immediate postoperative
radiation following incomplete resections. Following an
incomplete resection, the appropriate choice among sup-
portive care, radiation, and chemotherapy must be tai-
lored to a patient’s age, signs, symptoms, and personal
preference. Most practitioners would offer early radia-
tion to patients whose tumors or symptoms cannot be
controlled medically. Progressive neurological deteriora-
tion or radiographic evidence of tumor progression war-
rants consideration of radiation therapy. Importantly,
new developments in neurosurgery, chemotherapy, and
radiation treatment may advance survival and quality of
life significantly. Refinements potentially include lower
radiation doses, conformal treatment plans, and inten-
sity-modulated radiation therapy (Eder et al., 2001; Her-
farth et al., 2001; Hodgson et al., 2001; Saran, 2002;
Saran et al., 2002; Whittle, 2002).
Our cohort of children with pathologically confirmed
WHO grade II LGGs had excellent long-term survival
rates consistent with contemporary published literature.
We were unable to demonstrate a survival benefit for
administering radiation as part of initial management.
Lesser extent of surgical resection was associated with a
poorer outcome in this patient group. All patients with
GTR were alive with NED at last follow-up.
A?study?of?610?cases,?1950–1981?(erratum?in?Int. J. Radiat. Oncol. Biol.
Phys.??19,?829).?Int. J. Radiat. Oncol. Biol. Phys.?18,?723–745.
experience:?1978-1988.?Am. J. Clin. Oncol.?17,?475–479.
Nerv. Syst.??11,?715).?Childs Nerv. Syst.?11,?443–448.
surgery?and?radiation?therapy.?Acta Radiol. Oncol.?23,?1–8.
Med. Pediatr. Oncol.?33,?205?(abstract?P-35).
gamma?knife?radiosurgery?in?children.?Childs Nerv. Syst.?17,?341–346.
ment?of?pediatric?low?grade?gliomas.?Int. J. Radiat. Oncol. Biol. Phys.?
Neuro-Oncology? ■? APrIL?2006?
gliomas.?Semin. Radiat. Oncol.?11,?95–102.
research?Hospital.?J. Clin. Oncol.?15,?2792–2799.
ric Radiation Oncology,?4th?ed.?Philadelphia:?Lippincott?Williams?&?
apy?of?astrocytomas.?Semin. Surg. Oncol.?20,?13–23.
Radiat. Oncol. Biol. Phys.?50,?929–935.
plete?observations.?J. Am. Stat. Assoc.?53,?457–481.
supratentorial?low-grade?gliomas??Int. J. Cancer?96?(suppl.),?71–78.
study?in?379?patients.?J. Clin. Oncol.?15,?3129–3140.
prognostic?variables.?Int. J. Radiat. Oncol. Biol. Phys.?15,?837–841.
tumors.?Curr. Opin. Oncol.?10,?186–193.
Radiat. Oncol. Biol. Phys.?53,?43–51.
gliomas.?Curr. Opin. Oncol.?12,?194–198.
of?childhood:?Long-term?follow-up.?Childs Nerv. Syst.?11,?89–96.
Mishra?et?al.:?radiation?for?pediatric?low-grade?gliomas Download full-text
Pizzo,?P.A.,?and?Poplack,?D.G.?(eds.),?Principles and Practice of Pediat-
agement?of?pediatric?low-grade?gliomas.?Semin. Radiat. Oncol.?11,?
Whittle,?I.r.?(2002)?Surgery?for?gliomas.?Curr. Opin. Neurol.,?15,?663–
Radiat. Oncol. Biol. Phys.?54,?1405–1409.