The 6212 cases of pediatric glioma in the SEER 17 database (70% of all pediatric CNS tumors diagnosed during the years 1973 through 2005) allowed us to perform a population-based analysis of clinical features and outcome in the arbitrarily defined age groups (<1 year, 1–3 years, 3–5 years, and 5–20 years). We observed significant differences across these groups in tumor histology, grade, and primary site, although the distribution of tumor grade and the predominance of cerebral tumors were similar in patients < 1 year old and those 5 to 20 years old ().
Among patients with low-grade gliomas (n=3419, 55.5%), grade I predicted better survival than grade II () except among infants (). Reports of the prognostic value of grade I vs. grade II LGG are inconsistent. Some studies have found no difference in outcome between grades I and II,6–8
possibly because of the small number of subjects. A larger study (n= 278) showed that tumor grade (after pathology review) significantly influenced survival estimates, which were 92% for pilocytic astrocytoma, 86% for glioma not otherwise specified, and 48% for diffuse astrocytoma (P< 0.0001).4
Interestingly, our study found that age less than one year at diagnosis of grade I and II glioma had a negative impact on survival (). Further, survival of patients with grade I gliomas was significantly better in the 1–3 and 3–5–-year age groups than in patients <1 year old (log-rank test for trend, P=0.0033; ). Few previous studies have addressed the negative impact of age less than 5 years on progression-free survival, but not on overall survival in pediatric LGG. 5,14
High-grade gliomas represented 17% of the studied tumors; however, their frequency differed according to primary site and age (). Most high-grade tumors occurred in the cerebrum and brainstem, and fewer occurred in children 1 to 5 years old than in other age groups. Younger patients with high-grade tumors, particularly grade III, had higher survival estimates than did older patients (log-rank test for trend, P=0.067; ). Only 3 studies of children younger than three years with HGG have been reported, and they included only 16 to 39 subjects.15, 18, 19
Ours reports on the largest group to date of patients less than 3 years old with HGG (99 patients) () to show improved survival in this age group.
Among patients with HGG, the extent of surgery was a major factor in survival. Patients with HGG who underwent GTR (23%) had the best survival in all age groups. Both GTR and grade were shown to influence the survival of patients with HGG in the largest studies reported to date, the Children’s Cancer Group (CCG)-943, and CCG-945 studies. 9,10
CCG-943 included 58 patients, 18 with AA and 40 with GBM; the latter group had significantly worse survival (p = 0.012). Patients who underwent only biopsy (n=11) had significantly worse survival than those who had partial resection (n=39) or GTR (n=8) (p < 0.001). In CCG-945 (172 children aged 18 months to 21 years), histologic subtype (AA vs. GBM) and percent resection (> 90% vs. <90%) were significantly associated with better prognosis (p < 0.02 and p < 0.04, respectively). Our larger, population-based analysis of 485 patients with grade III glioma and 552 with grade IV glioma confirmed these findings.
As expected, we found that brainstem gliomas carried the poorest prognosis (). Interestingly, however, survival was inversely associated with age. Patients less than one year old had the best outcome, followed by age 1–3 years (; log-rank test for trend, P
= 0.0036). There has been only one reported study to date of infantile brainstem glioma; this report describes 10 patients, only one of whom was less than one year old.12
In that study the 3-year survival was69% ± 19% which is higher than other groups. Another study on pontine gliomas by Wagner et al found that age younger than 4 years (n= 13) was also associated with better prognosis.22
The positive impact of age on brain stem gliomas has been an area of debate with cases of spontenous regression in the neonatal peroid.23
Our study reports on the largest group of infantile glioma so far; 136 less than 3-year old ( 26 less than one year old). We believe this provides a basis for further research on this unique group of patients.
This study, like other population-based studies, was limited by the lack of central pathology review, which is considered important in confirming both low-grade and high-grade pediatric gliomas.4, 20, 21
In the CCG-945 study, 70 (28%) of 250 tumors originally designated as high-grade gliomas were found to be low-grade gliomas on central pathology review, and these patients fared better than the rest of the HGG cohort.20
However, after these 70 tumors were excluded from analysis, the final conclusions remained the same.21
The much greater size of our study population suggests that the absence of central pathology review was unlikely to confound our analysis. In addition, the importance of pathology review of LGGs is controversial. Fisher et al. reported a 39% (97/246) rate of discordance in their study of LGGs, whereas Gajjar et al. had only 2% discordance in their cohort of 145 tumors.4, 5
Our study was also limited by the lack of complete data about radiotherapy and surgery. The use of radiotherapy increased gradually with age at diagnosis (from 12.4% in patients <1 year old to 42% in children > 5 years old, P<0.0001). The use of radiotherapy was independently associated with poorer survival, but this finding is likely to reflect other prognostic factors, including resectability, anatomic site, tumor grade, and relation to nearby critical structures, that influenced the decision to use radiotherapy. Further, the majority of tumors with available grade in our cohort were LGGs (77%), for which radiation therapy is usually deferred or used only for recurrent or high-risk tumors. Signs and symptoms at presentation and association with neurofibromatosis may also have been factors in considering radiotherapy but were not available for analysis.
Notwithstanding its limitations, the SEER database provides a useful tool for the study of rare pediatric CNS tumors. Inclusion of more data about treatment, associated conditions such as neurofibromatosis, tumor size, and extent of disease will allow a better understanding of these tumors as well as other rare childhood cancers.