Potentially curative radiation treatment of children with brain
tumors resulted from the introduction of megavoltage irradiation
nearly 50 years ago, and initially carried out principally with
cobalt gamma rays. Common childhood brain tumors are infrequently
cured with radiation doses below 5,000 cGy in 180 cGy fractions.
The practical level of radiation tolerance of the brain is 5,500
cGy. Megavoltage irradiation allowed such doses to be delivered
without major short-term toxicity. Thus, adults may now be seen
who were cured of a childhood brain tumor many years ago.
In practice, curative radiation treatment was introduced slowly,
principally during the 1950s and '60s, so that it is still uncommon
to see a survivor treated more than 30 years ago. However, enough
years have passed that it is now possible to evaluate factors
that are predictive of long-term survival in children with brain
tumors and to estimate some of the risks associated with having
a brain tumor eradicated by surgical and radiation treatment.
This analysis updates and expands on a previous publication focusing
on these issues .
A University of Toronto database exists for children who underwent
irradiation for brain tumors diagnosed from 1958 to 1995. A total
of 1,034 children up to and including the age of 16 years received
radiation treatment for a brain tumor during that 38-year period.
With only rare exceptions, initial investigation and surgical
management took place at the Hospital for Sick Children and subsequent
radiation treatment was carried out at either the Princess Margaret
Hospital (1958 to 1986) or Toronto-Sunnybrook Regional Cancer
Centre (1986 to 1995). Long-term follow-up was provided at the
Hospital for Sick Children until the children were 18 years of
age and thereafter at either the Princess Margaret Hospital or
Toronto-Sunnybrook Regional Cancer Centre. Radiation treatment
was commonly administered postoperatively as a component of primary
treatment (87%), rather than at the time of progression or relapse.
This patient series is essentially population-based for the greater
metropolitan Toronto region and northern Ontario.
The 5-, 10-, 20-, and 30-year survival rates for all 1,034 patients
were 52%, 44%, 38%, and 30%, respectively (Figure 1). One in three
of the patients who were alive at 10 years was dead at 30 years.
Relapse- or progression-free survival rates at 5, 10, 20, and
30 years were 47%, 45%, 44%, and 44%, respectively.
Age and Gender
Age at diagnosis was not a prognostic factor. The 20-year survival
rate was 36% for children less than 4 years old at diagnosis (N
= 225), 39% for those 4 to 8 years old (N = 384), and 38% for
those 8 to 16 years old (N = 419).
Also, there was no overall difference in survival by gender. As
shown in Figure 2, the 20-year survival rate was 37% for boys
(N = 582) and 40% for girls (N = 449). However, after 20 years,
a greater number of deaths occurred in girls.
For the 607 patients for whom adequate surgical data were available,
total resection (N = 143) resulted in a 20-year survival rate
of 64% and less than total resection (N = 464), a rate of 36%
(P < .0001; Figure 3).
The median radiation dose was 5,086 cGy, but the range was narrow.
The 10th percentile was 4,000 cGy and the 90th percentile, 5,400
cGy. No significant survival difference was noted when patients
who received a radiation dose above the median (5,086 cGy) were
compared with those who received a lower dose (4,000 to 5,086
cGy). Respective 20-year survival rates for the two groups were
38% and 43%.
Year of Diagnosis
Overall, no significant improvement in survival occurred for patients
treated in 1975 or afterward (N = 562), compared to those treated
before 1975 (N = 464). The respective 20-year survival rates for
the two groups were 42% and 36% (P = .11; Figure 4).
Table 1 summarizes 10- and 20-year survival rates by tumor histology.
(Patients with brainstem tumors, optic nerve gliomas, and basal
ganglia tumors include those with and without a tissue diagnosis.)
The survival curves for patients with low- and high-grade astrocytomas
are shown in Figure 5.
Second Malignant Tumors
The cumulative incidence of second malignant tumors was 13% at
20 years and 19% at 30 years (Figure 6). To date, 31 patients
have developed a second malignant tumor and 2 patients, a third
malignancy. The most common second malignant tumors were gliomas
(9 patients), meningiomas (7), acute leukemia (5), sarcoma (3),
and other tumors (7).
Survival from the date of diagnosis of a second malignant tumor
was 58% at 5 years. None of the five patients who developed acute
leukemia and only one of four patients who developed a high-grade
astrocytoma survived. In contrast, all seven patients with a meningioma
are currently alive. All meningiomas were included in this analysis,
regardless of the degree of malignancy.
Cause of Death
Among the 546 patients who died, the cause of death was "disease"
in 514 patients (94%), toxicity in 6 (1%), second malignant tumor
in 12 (2%), and miscellaneous in 14 (3%). The classification "disease"
was used when death was due to uncontrolled tumor, whether progressive
or recurrent disease, and also for a very small number of patients
who underwent prolonged hospitalization for irreversible neurologic
damage and in whom no other cause of death was established.
The distribution of the cause of death varied with time (Table
2). In the first 5 years after diagnosis, disease was the cause
of death in 97% of patients. After 20 years, disease was responsible
for death in 30% of patients. A second malignant tumor became
an increasingly important cause of death beyond 5 years after
At 10 years after diagnosis, 269 patients were alive, 69 of whom
had previously suffered a relapse and 209 of whom were relapse
free. Survival rates at 25 years (from diagnosis) in the relapsed
and relapse-free patients were 49% and 94%, respectively (P
Survival After Relapse
Survival, measured from the date of first relapse (or progression)
for 533 relapsed patients was 22% at 5 years and 12% at 20 years.
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survival and mortality for children younger than age 15 years.
Cancer 58:598-602, 1986.
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4. Hawkins MM: Long-term survival and cure after childhood cancer.
Arch Dis Child 64:798-807, 1989.
5. Hawkins MM, Kingston JE, Kinnier-Wilson L.M: Late deaths after
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