Central nervous system (CNS) tumors account for a quater of all childhood cancers, and has been the most common solid tumors, of which brain tumors takes up the majority[4-6]. In the United States, brain tumors make up more than 1% of newly diagnosed cancer cases. Despite of improved treatment for the past years, brain tumors are still the leading cause of cancer-related death among children. Brain tumors are heterogeneous, which varies from race, gender, age and so on[9-11]. The epidemic studies in China are scare and are based on dated CNS WHO classification. Hence it is meaningful to summary and validate the epidemic information again. Besides, this study collected and described other important information, such as medical expenditure, manifestation, prognosis and so on.
The most frequent initial symptoms were nausea and vomiting (23.95%), and headache (23.43%). Motor impairment only accounted for 12.59% of all brain tumor children. The results are consistent with a previous meta study. Manifestations are associated with brain tumors’ location. Visual impairment is frequently seen in sellar tumor, while nausea and vomiting, and headache are more common in cerebellum and forth ventricle tumors. Due to these common symptoms are not specific to CNS tumors, it might lead to misdiagnosis and delay of diagnosis. Our data showed the rate of misdiagnosis reached to 32.5%. We found that superior tentorial tumors are more insidious than inferior tentorial tumors. The general median duration of symptoms across all brain tumors is 4 weeks, while tumors of temporal lobe experience the longest duration for median of 18 weeks. General median symptom duration of posterior fossa tumors is 4 weeks. This result implies that the diagnostic capability in China has reached to the international level. However, the longest symptom duration of posterior fossa tumors was more than 10 years. Increasing awareness of the varied and complex symptomatology that often occurs with CNS tumors in China is necessary and could help reduce misdiagnosis and achieve early diagnosis.
The number of brain tumors cases decrease with advancing age, which is consistent with the CBTRUS 2015 report (apart from tumors of pituitary). The median age of the group was 4.62 [2.19, 8.17] years old years old, with median age of malignant tumor 5.36 [2.78, 8.84] years old, a bit of older than the benign group of 4.07 [1.64, 7.13] years old. This trend is consistent of a previous report. However the recent CBTRUS indicates that malignant tumors tend to affect younger children compared with non-malignant tumors. This might be due to the sampling bias on tumor histology. Benign tumors of pituitary tend to affect adolescents (15-19 years old), which will cause an increase in median age of benign tumors group, which were not sufficiently enrolled in our data. Our data shows that craniopharyngioma, ependymal tumors, embryonal tumors, metastatic tumors, germ cell tumors, meningiomas and tumors of Cranial and paraspinal nerves tend to affect older children, while choroid plexus tumors, melanocytic tumors, tumors of pineal region, neuronal and mixed neuronal-glial tumor, and astrocytomas prefer to affect infants and toddlers. This is in according with previous CBTRUS reports.
Across all brain tumors, sex distribution is almost balanced, with a male to female ratio of 1.33:1. However, In the subgroup analysis, males took up a greater proportion in malignant tumors than benign tumors (62.9% vs 52.1%). This is in accordance with the previous report that malignant tumors occurring much more frequently in males. We found that sex difference varies by histology. Germ cell tumors, embryonal tumors, ependymal tumors, and choroid plexus tumors see more males than females, while little gender bias is noted in gliomas (including diffuse astrocytic and oligodendroglial tumors, other astrocytic tumors, and neuronal and mixed neuronal-glial tumors) and craniopharyngioma. These results is similar with the data of CBTRUS report.
Same as the previous studies, supratentorial tumors are preponderant (57.38%) compared with infratentorial tumors (42.62%). To be specific, the most three common sites are the cerebellum or fourth ventricle, sellar region and ventricles. This is a little different from the CBTRUS report, which showed that the three most common sites are sellar region, the cerebellum and other brain. Furthermore, proportion of tumors in cerebellum in our center is about two times of that in the US. This might be due to that we put tumors in cerebellar and forth ventricle into one group, but CBTRUS did not classify tumor in this way. Given the difficulty to differentiate tumors of cerebellum or the fourth ventricle in magnetic resonance image (MRI), we believe it is more applicable to categorize these two sites into one group site. Besides, our data is lack of population aged between 15-19 years old who are fragile to sellar region tumors. When looking the benign and malignant groups respectively, the sites distribution pattern is different. The most common site in malignant tumors is the cerebellum or fourth ventricles, while sellar region is the most common site in benign tumors. In the cerebellum or forth ventricle, embryonal tumors (account for almost 50% of tumors in this area), other astrocytic tumors and ependymal tumors are the top three types. And in sellar region, the most three common types are craniopharyngioma, astrocytoma and germ cell tumors. In the ventricles, choroid plexus tumors, germ cell tumors, and other astrocytic tumors are the three most common types. This is in accordance with previous studies. With these figures, our data might help Chinese clinicians have better understanding of differential diagnosis of pediatric brain tumors.
This study is based on WHO 2016 classification, which is different form the existing studies. Tumors accounting for less than 5% were assigned into “others group”. Above all, the most common pathology type was embryonal tumors accounting for 22.45% of all brain tumors, followed by other astrocytic tumors and diffuse astrocytic and oligodendroglial tumors. This is consistent with a previous study about Chinese population. However, CBTRUS reported that pilocytic astrocytoma is the most common pathology type[1, 2, 9, 14]. This is due to different approaches of classification. We put all the embryonal tumors into one group, leading to the increase in the proportion of embryonal tumors. Distinguished with a previous study in China, we showed that medulloblastoma was more frequent than craniopharyngioma, and ependymal tumors was more common than GCTs, which is consistent with the previous reports[14, 16, 17]. We speculate, there might exist the sample bias in the previous chinses report. Because, it is not a children hospital, and the younger patient might prefer to refer to a children hospital, rather than a general hospital. GCTs only takes up 6.65% of the whole brain tumors, which is similar with the investigation in China, but distinguished from other reported in Japan, Taiwan (China) and far eastern countries with an incidence of 10–14% of the brain tumors. This difference might be explained that patients with germinomas often undergo nonsurgical treatments, the actual number of GCTs might be significantly underestimated in this study.
It is known that survival of patients with brain tumors varies by histology, age at diagnosis, tumor location and so on. And Our data showed that the 5-year overall survival (OS) of benign tumors was 90.0%, consistent with previous studies. In the United States, 96% of children 0–19 years old with nonmalignant tumors survived 10 years after diagnosis. Tore Stokland reported that the 5-years overall survival (OS) of low grade glioma (LGG) up to 96.4%. However, the outcome of LGG could be variable with extent of resection. If complete surgical resection is possible, 10-year progression-free survival (PFS) exceeds 85%, but drops below 50% if there is radiologically visible residual tumor. Sahaja Acharya reported the 10-years OS of LGG reached to 76.4% (high risk) ~ 95.6% (low risk). Alvaro Lassaletta reported the 10-year progression-free survival are 27% and 60.2% respectively in BRAF VE600 mutation and wild type cohort. Overall survival of craniopharyngioma (CP)ranges from 83% to 96% at 5 years, from 65% to 100% at 10 years[24-26] and is, on average, 62% at 20 years. At present whether age at diagnosis of CP, sex, and pathologic subtype are prognostic factors for survival remain controversial.
The 5-year OS of malignant tumors was 65.3%, similar with previous reports(75.4%). The 10-year survival for children ages 0–19 diagnosed with malignant brain and other CNS tumors was estimated at 72% with lowest (17%) being attributable to glioblastoma. Other studies reported that less than 5.5% Glioblastoma survived more than 5 years[28, 29]. Another malignant tumor, diffuse intrinsic pontine glioma (DIPG) had an overall survival of less than 1 year generally. Atypical teratoid/rhabdoid tumor (AT/RT) was reported to had a four years OS of 43%, and another study reported a 6-year OS of 35%. High dose chemotherapy and radiation therapy were associated with better survival, while tumour metastasis, intrathecal chemotherapy and extent of resection do not significantly affect survival. All in all, the prospect of malignant tumors remains unsatisfied and more resource need to be introduced in this fields. Due to the limitation of sample size, we did not calculate the survial rate of the specific tumor type. We hope to add this analysis in the future study.
So far, little information of epidemiology about Chinese is known. As national center for children’s health, we summarized out data and hope that our experience could provide more information about pediatric brain tumors in China. At the same time, we acknowledge that due to lack of national wide registration system of brain tumors, there might exist some inevitable bias. Apart from that, children aged from 15-18 in China prefer to general hospitals, rather than children’s hospital. Hence, the number patients of adolescence are relatively small in this study.
Al in all, epidemiology of brain tumors in our center presented similar pattern with previous reports. Ratio of benign and malignant tumors approach to 1:1.03. And males are more vulnerable to malignant tumors. The site distribution patterns of benign and malignant brain tumors are significantly different. These demographic characteristics provide us further understanding of pediatric brain tumors, like sex predisposition, predilection age of onset. And our data might be able to reflect the real situation of pediatric brain tumors in Chinese.