Paediatric brain tumours treated at a single, tertiary paediatric neurosurgical referral centre from 1999 to 2010 in Australia

Paediatric brain tumours treated at a single, tertiary paediatric neurosurgical referral centre from 1999 to 2010 in Australia

Journal of Clinical Neuroscience 19 (2012) 1387–1391 Contents lists available at SciVerse ScienceDirect Journal of Clinical Neuroscience journal hom...

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Journal of Clinical Neuroscience 19 (2012) 1387–1391

Contents lists available at SciVerse ScienceDirect

Journal of Clinical Neuroscience journal homepage:

Clinical Study

Paediatric brain tumours treated at a single, tertiary paediatric neurosurgical referral centre from 1999 to 2010 in Australia Mahesh Ramanan ⇑, Raymond Chaseling TY Nelson Department of Neurology and Neurosurgery, Childrens Hospital Westmead, Hawkesbury Road, Westmead, New South Wales 2145, Australia

a r t i c l e

i n f o

Article history: Received 16 September 2011 Accepted 10 January 2012

Keywords: Central nervous system Childhood Epidemiology Paediatric brain tumours WHO classification of tumours

a b s t r a c t Paediatric brain tumours are the most common solid tumour of childhood and the most common cancer cause of death among children. A retrospective review of 313 histopathologically proven brain tumours over an 11-year period has been performed at the Children’s Hospital Westmead, New South Wales, Australia, to determine proportions and locations of different tumours, age distribution, survival rates and usage of various treatment modalities. Pilocytic astrocytoma was the most common paediatric brain tumour (29%) followed by medulloblastoma (12%) and ependymoma (6%). Most tumours were histologically benign (59%), and 42% of tumours were located in the posterior fossa. The average age at diagnosis was 7.9 years. About 50% of children were treated with surgery alone, whereas the other 50% had surgery or biopsy plus adjuvant treatment. The overall one-year survival rate was 89% and the five-year survival rate was 80%. The five-year survival rates for pilocytic astrocytoma was 91%; medulloblastoma, 75%; ependymoma, 82%; and high grade glioma, 15%. Thus, a large proportion of paediatric brain tumours were histologically benign and were treated with surgery alone, but a subset of benign tumours required adjuvant treatment and were associated with mortality (25%). The overall survival rates were high and are improving, although for some tumours, such as high grade glioma, the outlook remains poor. Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.

1. Introduction Brain tumours are the most common solid tumours, and the leading cause of cancer deaths, in childhood. They are the second most common neoplasm after haematopoietic cancers. The incidence of paediatric brain tumours in the USA is 4.71 per 100,000 person-years.1 Various institutions have reported their experience with paediatric brain tumours,2–11 with wide variations in proportions of certain tumours. There have been no reports, however, on the epidemiology of paediatric brain tumours in Australia. We undertook this review to determine the number, histopathological and age distribution, survival rates and modalities of treatment for paediatric patients with brain tumours treated at the Children’s Hospital Westmead, a large tertiary paediatric neurosurgical referral centre in Sydney, Australia. We also compared our results with those reported in various locations globally. 2. Methods We conducted a retrospective review of all patients with brain tumours who underwent surgery at our institution from July 1999 ⇑ Corresponding author. Tel.: +61 2 98452646; fax: +61 2 98453905. E-mail address: [email protected] (M. Ramanan).

to December 2010. All patients were younger than 18 years of age. Patients were identified using a database of all operations conducted by the Department of Neurosurgery. Data (including radiology, histopathology and treatment details) were extracted from medical records, stored in an electronic format on Cerner Powerchart (Version 2009.06.1.6). Microsoft Excel was used for data analysis. Statistical Analysis Software 9.2 (SAS, Cary, NC, USA) was used to perform Kaplan–Meier survival analysis. The log-rank test statistic was calculated to compare survival between groups with p = 0.05 as the threshold of significance. Ethics approval was obtained from the relevant authority prior to commencement. 3. Results A total of 313 paediatric brain tumours in 313 patients were identified over the study period. There were a total of 393 operations; the re-operation rate was 22.5%. This included patients who underwent ‘‘second-look’’ surgery soon after the initial surgery for excision of residual disease detected on routine postoperative imaging, as well as those who developed a later recurrence. The mean age at diagnosis was 7.86 years. Most patients (166, 53%) were male, consistent with the slight male preponderance observed in most childhood brain tumour cohorts. There were 60 deaths in our cohort of 313 patients, which represents a fiveyear survival rate (5YSR) of 80% and a one-year survival rate

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M. Ramanan, R. Chaseling / Journal of Clinical Neuroscience 19 (2012) 1387–1391

(1YSR) of 89%. The mean length of survival for those who died was 1.6 years. The average age at diagnosis for the patients who died was 7.6 years, similar to the 7.9 years observed in those who survived. The tumours were located in the posterior fossa (134; 42.8%), in the lobes of the cerebral hemispheres (70, 22.4%), in the hypothalamus or optic pathways (33, 11.5%), in the sellar or suprasellar region (21, 6.7%), in the pineal region (17, 5%), in the lateral ventricles (15, 4.8%) and in various other locations (20, (6.4%) (Fig. 1). There were 136 (43.5%) astrocytic tumours, 50 (16%) embryonal tumours, 30 (9.6%) glioneuronal tumours, 22 (7%) germ cell tumours (GCT) and 20 (6.4%) ependymal tumours. Pilocytic astrocytoma (PA, 29.7%) was the most common histopathological diagnosis (Table 1). Medulloblastoma (11.8%) and ependymoma (6.4%) were the next most common. There were 4.8% Grade 2, 2.9% Grade 3 and and 4.5% Grade 4 World Health Organization (WHO) astrocytomas. Germinoma (4.8%) and craniopharyngioma (4.8%) were the equal fourth most common tumours along with WHO Grade 2 astrocytoma. The average age at diagnosis for the various tumours, as well as location and mortality data, are listed in Table 2. The age distribution for the eight most common tumours is shown in Fig. 2. The lowest survival rates were observed in WHO Grade 3 astrocytoma (anaplastic astrocytoma) and Grade 4 astrocytoma (glioblastoma multiforme), with 5YSR rates of 16.7% and 14.3% (Fig. 3). Medulloblastoma had a 5YSR of 74.8%, and ependymoma 82.3%. Medulloblastoma was categorised into average risk and high risk groups for the purposes of the survival analysis. There was a statistically significant difference in survival rates between average risk and high risk medulloblastoma (log-rank chi-squared = 8.02, degrees of freedom (d.f.) = 1, p = 0.005). The 1YSR for average and high risk medulloblastoma were 95% and 67% and the corresponding 5YSR were 90% and 50%. There were no deaths among patients with craniopharyngioma, germinoma or WHO Grade 2 astrocytoma. Patients with optic pathway PA had a 5YSR of 81.5%, while PA at other locations had a 5YSR of 93.4%. Overall, there were 190 benign and 123 malignant tumours with respective 5YSR of 94.5% and 57.3%. Of the 272 tumours that were gradable accordable to the WHO classification of brain tumours, 139 (51.1%) were classed as Grade 1, and 14.3%, 11.0% and 23.5% were Grades 2, 3 and 4 respectively. Just over half (50.2%) of childhood brain tumours were treated with surgery alone (Fig. 4); 25.6% of patients underwent chemotherapy and radiotherapy following surgery, whereas 15.7% were treated with surgery and chemotherapy, and 4.2% had surgery and radiotherapy. Only 4.5% of patients had surgical biopsy only, with or without adjuvant treatment.

Fig. 1. Graph showing the distribution of brain tumour locations.

Table 1 Distribution of paediatric brain tumours according to tumour histology treated from July 1999 to December 2010 at the Children’s Hospital, Westmead, New South Wales, Australia Tumour



Pilocytic astrocytoma Medulloblastoma Ependymoma WHO Grade 2 astrocytoma Germinoma Craniopharyngioma WHO Grade 4 astrocytoma Dysembryoplastic neuroepithelial tumour Ganglioglioma WHO Grade 3 astrocytoma Choroid plexus carcinoma Atypical rhabdoid teratoid tumour Supratentorial PNET WHO Grade 1 Meningioma Metastatic WHO Grade 1 astrocytoma (other) DNET Mature teratoma Acute lymphoblastic leukaemia Hypothalamic hamartoma Oligodendroglioma WHO Grade 2 Choroid plexus papilloma Cerebral neuroblastoma Yolk sac tumour WHO Grade 2 meningioma Pineoblastoma Schwannoma Oligodendroglioma WHO Grade 3 Non-germinomatous germ cell tumour Immature teratoma Papillary glioneuronal tumour Malignant glioneuronal tumour Neurocytoma Erythroid leukaemia Large B cell lymphoma Pineocytoma Pituitary adenoma Dermoid cyst Granular cell tumour of peripheral nerve Haemangioblastoma Total

93 37 20 15 15 15 14 13 11 9 6 6 5 5 5 4 4 3 3 3 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 313

29.7 11.8 6.4 4.8 4.8 4.8 4.5 4.2 3.5 2.9 1.9 1.9 1.6 1.6 1.6 1.3 1.3 1 1 1 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 100

DNET = dysembryoplastic neuroepithelial tumour, PNET = primitive neuroectodermal tumour, WHO = World Health Organization.

4. Discussion We have presented a single institution experience of all paediatric brain tumours with histopathological confirmation over an 11-year period in Australia. We have reported survival rates and modalities of treatment used, which have been infrequently reported in similar studies. The distribution of tumour location has also been provided. The proportions of the various tumour types, the average ages of presentation and gender distribution is similar to other reports globally, with some important variations. Overall, our results were similar to a comparable study from New Zealand.11 Due to the changes in the conventions of histopathological classification of central nervous system tumours,12 the reported relative proportions of various paediatric brain tumours have changed. This phenomenon is seen with the reported percentages of PA (29.4% of tumours in our study), the highest among contemporary reports. The reported proportion of PA ranges from 1.1%8 to 24.1%.11 Kaderali et al.2 have noted that over three decades (from 1980 to 2008), the proportion of PA had gradually increased, but not the overall proportion of astrocytoma, or the relative proportion of low grade and high grade astrocytoma. Some variation can be attributed to genetic differences in the popula-


M. Ramanan, R. Chaseling / Journal of Clinical Neuroscience 19 (2012) 1387–1391 Table 2 Characteristics of ten most common, paediatric brain tumours at the Children’s Hospital, Westmead, New South Wales, Australia, from July 1999 to December 2010 Tumour

Total No. operations Chemotherapy (%) XRT (%) Chemo + XRT (%) Mean age (years) % Males %Infratentorial % Supratentorial 1YSR 5YSR

Pilocytic astrocytoma Medulloblastoma Ependymoma WHO Grade 2 astrocytoma Germinoma Craniopharyngioma Glioblastoma multiforme DNET Ganglioglioma Anaplastic astrocytoma

93 37 20 15 15 15 14 13 11 9

120 47 24 20 15 23 20 14 11 20

14(15) 9(24) 2(10) 2(13) 2(13) 0(0) 3(21) 0(0) 3(27) 2(22)

5(5) 0(0) 6(30) 0(0) 1(7) 0(0) 0(0) 0(0) 0(0) 1(11)

8(9) 26(70) 9(45) 4(27) 12(80) 0(0) 8(57) 0(0) 0(0) 6(67)

7.44 6.5 4.6 8.3 13.2 9.8 10.2 8.7 9.1 7.8

49.5 75.7 50 46.7 66.7 53.3 64.3 38.5 54.4 22.2

62.4 100 80 46.7 6.7 0 7.1 0 9.1 22.2

37.6 0 20 53.3 93.3 100 92.9 100 90.9 77.8

98.9 83.8 95 100 100 100 57.1 100 100 55.6

91.2 74.8 82.3 100 100 100 14.3 100 100 16.7

Chemo = chemotherapy, DNET = dysembryoplastic neuroepithelial tumour, XRT = radiotherapy, WHO = World Health Organization.

Fig. 2. Histogram of age distribution of patients with types of common brain tumours.

tions studied, and temporal differences associated with exposure to unidentified environmental risk factors. The introduction of atypical teratoid/rhabdoid tumour (ATRT) into the WHO classification has affected the histopathological diagnosis of medulloblastoma.2 Medulloblastoma comprised 11.8% of brain tumours in our study, which is lower than in most other studies. Kadri et al.7 and Karkouri et al.6 found, however, that 27.5% and 28.9% of their tumours were medulloblastoma, approximately twice the proportion found in most other studies. Given the rarity of ATRT, this alone in unlikely to be a sufficient explanation for this observation. There are perhaps unidentified genetic susceptibilities to medulloblastoma in North African and Middle Eastern populations. Monteith et al.11 reported a high incidence of medulloblastoma among the Maori population in their cohort and concluded that the reasons for this should be investigated further. We found a similar rate of ependymoma (6.4%) to other studies, though the highest rates were observed, similar to medulloblastoma, in Syria7 and Morocco.6

We found a high rate of GCT (7%) compared to other developed Western countries except New Zealand, particularly germinoma (4.8%). The rates of GCT in East Asian countries (Japan 14.3%,13 Korea 11.2%5 and China 7.9%8) were even higher. A possible contributor to the relatively high rate of GCT is the changing demographics of Sydney due to a large East Asian migrant population. During the study period, our institution has developed an active epilepsy service with a strong focus on neurosurgical treatment of epilepsy. This has led to the diagnosis of increasing numbers of low grade glioneuronal tumours, particularly dysembryoplastic neuroepithelial tumour (DNET, 3.8%) and ganglioglioma (3.5%). Glioneuronal tumours as a group formed 9.6% of all tumours, a larger percentage than reported elsewhere. A trend towards increasing diagnoses of glioneuronal tumours has also been observed in other studies.2,4 Kaderali et al.2 found that the rate of these tumours increased from 3.9% in the 1980s to 9.9% in the 2000s. We found an overall 1YSR of 89% and 5YSR of 80% for paediatric brain tumours. This compares favourably with reported survival


M. Ramanan, R. Chaseling / Journal of Clinical Neuroscience 19 (2012) 1387–1391

Fig. 3. One-year and five-year survival rates (1YSR and 5YSR) for common brain tumours. GCT = germ cell tumours, PA = pilocytic astrocytoma.

rates of 60% to 70%.9,14 Survival rates vary widely for different tumours.9 Histologically benign tumours had a 5YSR of 94.5%, while malignant tumours had a 1YSR of 74% and a 5YSR of 57.3%. Supplementary Table 1 shows reported survival rates for the three most common tumours. Our results (Table 2) demonstrate survival rates similar to, or better than, those reported elsewhere. We found high survival rates for patients with ependymoma in our study. This may be due to the aggressive nature of the surgery and radiotherapy offered for ependymoma (and other tumours) at our institution. All patients undergo early post-operative MRI to confirm

total macroscopic resection. Patients with residual tumour are routinely offered ‘‘second-look’’ surgery to resect the residual tumour. One weakness of our study is that quality of life measures are not reported. The diagnosis of a brain tumour in a child is generally associated with negative expectations for survival and quality of life. However, high survival rates are being achieved with aggressive surgery for brain tumours in children. Survival rates are high, with four out of five children being alive at five years after diagnosis. For high grade glioma, which is associated with very poor long-term survival in adults, we achieved a 1YSR greater than 50% and 5YSR of 15%. Medulloblastoma is a highly malignant tumour with low survival rates.18,19 However, a 5YSR greater than 70% has been reported in the 2000s.15–17 The 5YSR for germinoma is 100%, which essentially represents a cure. This is largely a consequence of the exquisite sensitivity of germinoma to radiotherapy and chemotherapy. Most tumours in our paediatric population were histologically benign, unlike in adult populations. About 50% of patients were treated with surgery alone, mostly resulting in cure or long-term disease control. In addition, of the 50% of patients who received some form of adjuvant therapy, a significant proportion also had histologically benign tumours. 5. Conclusion Paediatric brain tumours are associated with significant rates of morbidity and mortality. We have reported our single institution experience over an 11-year period with some similarities to reports from other countries. Important differences include a high

M. Ramanan, R. Chaseling / Journal of Clinical Neuroscience 19 (2012) 1387–1391

proportion of patients with PA, a higher proportion of GCT than in other Western countries but lower than East Asian countries and a relatively high proportion of glioneuronal tumours partly due to a busy surgical epilepsy program. The survival rates were comparable with results from other centres. Most childhood brain tumours were histopathologically benign. Further collaborative research is required within Australia and globally to obtain a better understanding of the epidemiology of paediatric brain tumours. Appendix A. Supplementary material Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2012.01.028. References 1. CBTRUS. Statistical report: Primary brain tumors in the United States, 2000–2004. Central Brain Tumor Registry of the United States: Hinsdale; 2008. 2. Kaderali Z, Lamberti-Pasculli M, Rutka JT. The changing epidemiology of pediatric brain tumours: a review from the Hospital for Sick Children. Childs Nerv Syst 2009;25:787–93. 3. Rickert CH, Paulus W. Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification. Childs Nerv Syst 2001;17:503–11. 4. Rosemberg S, Fujiwara D. Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1,195 cases from a single institution. Childs Nerv Syst 2005;21:940–4. 5. Cho KT, Wang KC, Kim SK, et al. Pediatric brain tumors: statistics of SNUH, Korea (1959–2000). Childs Nerv Syst 2002;18:30–7. 6. Karkouri M, Zafad S, Khattab M, et al. Epidemiologic profile of pediatric brain tumors in Morocco. Childs Nerv Syst 2010;26:1021–7.


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