|Year : 2015 | Volume
| Issue : 4 | Page : 575-578
An analysis of medulloblastoma: 10 year experience of a referral institution in South India
S Gaur, SS Kumar, P Balasubramaniam
Department of Radiation Oncology, Barnard Institute of Radiation Oncology, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai, Tamil Nadu, India
|Date of Web Publication||10-Mar-2016|
Department of Radiation Oncology, Barnard Institute of Radiation Oncology, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
BACKGROUND: Medulloblastoma is an embryonal tumor with aggressive behavior and is more commonly seen in children than adults. The aim of this study was to determine the epidemiological patterns of medulloblastoma in a tertiary care center in Southern India. MATERIALS AND METHODS: It is a retrospective study, in which the records of all the clinically diagnosed medulloblastoma cases in the last 10 years (2002-2012) were analyzed. RESULTS: A total of 58 cases were found, with the mean age at diagnosis being 10 years. There was a slight predilection for the male sex (58.62%). The first presenting symptom was mostly related to raise intracranial pressure and the mean duration of symptoms was 200 days. Nearly, 89.6% of patients were in Stage 0 and had a central tumor location. Multimodality treatment included surgery followed by craniospinal irradiation up to 36 gray followed by posterior fossa boost up to 54 gray. Median radiation therapy duration was 6.5 weeks and concurrent single agent vincristine was the most common chemotherapy used. Most of the patients showed only a partial response to treatment, mainly because of large tumors at presentation, which could be attributed to the lack of awareness, delayed medical attention and poor follow-up. CONCLUSION: Early diagnosis and treatment is the key to management of medulloblastoma, which still needs to be achieved. Bulky tumors have a poor outcome, efforts should be aimed at complete surgery and giving risk stratification based treatment. Resources need to be allocated to make more conformal methods of radiotherapy available, which will decrease the growth abnormalities and cognitive impairments.
Keywords: Epidemiology, medulloblastoma, prognosis, radiotherapy, surgery
|How to cite this article:|
Gaur S, Kumar S S, Balasubramaniam P. An analysis of medulloblastoma: 10 year experience of a referral institution in South India. Indian J Cancer 2015;52:575-8
| » Introduction|| |
Medulloblastoma is one of the most common brain tumors in the pediatric age group. The incidence in children varies between 12% and 25% and less than 1% in adults.,,, According to a recent pediatric multi-institutional study in India, its incidence was 22.4% of all the central nervous system tumors. This tumor is known to respond very well to radiation and chemotherapy following surgery. Being of common occurrence, the epidemiology should be well understood to help in the management of this potentially curable disease.
Though there is data about various management profiles, molecular biology and risk stratification, there are few articles in the literature discussing the epidemiological pattern, prognosis, treatment and outcome of this particular tumor, from developing countries. Medulloblastoma has been found to be second only after glioma in incidence in the pediatric age group. There is no study from India discussing medulloblastoma from a socio-demographic aspect in the literature. The main objective of this study was to analyze the socio-demographic data with emphasis on the pattern of the disease, prognostic factors, and outcome.
| » Materials and Methods|| |
The records of patients diagnosed with medulloblastoma at our institute in the last 10 years (2002-2012) were retrieved and thoroughly studied. Various aspects were explored such as epidemiology, disease pattern, presentation, treatment and its outcome, survival and disease status at follow-up visits. Emphasis was given on prognostic factors and their effect on treatment outcome. Chi-square test was used to determine the significance of the relation. Any obvious differences noticed when compared with other institutional studies published in the literature Have been discussed.
| » Results|| |
A total of 58 cases of medulloblastoma were diagnosed and treated in the 10 years period from 2002 to 2012. Out of this 58.62% were males and the rest were females.
Maximum number of cases belonged to the age group of 3-20 years (76%) [Figure 1]. The mean age at diagnosis was 10 years. Almost 90% showed a classical type of histopathology, and 5% each of desmoplastic and large cell anaplastic variants. Homer wright rosettes were observed in 82% cases. Medulloblastoma is known to be associated with syndromes such as Gorlin's or Turcot, but no association with any syndrome was found in any patient in our study.
Diagnosis was mainly established by symptomatology at presentation, imaging and histopathological examination. Due to paucity of resources and financial constraints, immunohistochemistry was available only for two patients.
The first symptom in the maximum number of cases was a raised intracranial pressure (93.10%) manifesting as headache, vomiting and hydrocephalus on the magnetic resonance imaging (MRI). Ataxia and progressive weakness were the other early manifesting signs [Figure 2]. Raised intracranial pressure developed in 98.2% cases eventually. Cranial nerve deficit developed in 15.5% patients, with the 6th nerve being the most affected. Ataxia was not seen in 46.5%, but those who developed ataxia, had truncal type (41.37%) more than the lateral ataxia. Long tract signs were observed in 17.2% patients.
MRI and cerebrospinal fluid (CSF) analysis, which is a standard investigation for medulloblastoma, was not available for many of patients, especially for cases in the earlier part of the decade under study. This highlights the limitations and lack of resources at the hospital level. However, CSF was found to be positive for atypical cells in approximately 4%, negative in around 14% of the total number. About 40% cases showed T1 hypo- to isointense mass lesion on MRI, typical of medulloblastoma. Most patients had a computed tomography brain, which is a cheaper investigation and it showed typical features in 71% cases. According to the modified Chang staging, 89.6% were Stage 0, 1.7% Stage 1, 3.4% Stage 2 and 4 each. 82.7% had a centrally located tumor, involving the 4th ventricle in 55.1%.
Upfront ventriculoperitoneal shunting was needed in 90% cases while 10% did not require it at any stage. Subtotal excision was performed for 43% tumors, almost an equal percentage could be biopsied only and around 7% were completely excised. Incomplete tumor resection resulted in a larger residual, more than 1.5 cm 2 in the majority (93%), consequently increasing the percentage of high risk cases to 94%.
Children under 3 years of age (10.3%) were treated only with chemotherapy, while all other cases received radiation. The dose to the craniospinal axis was 36 gray, followed by a posterior fossa boost up to 54 gray. Nearly, 29% patients failed to report for radiotherapy. The median gap between surgery and radiation was 5 weeks and the overall treatment time for radiation was 6.5 weeks for the majority. In 6% cases radiation therapy (RT) was suspended due to very poor performance status, causing major RT violations. Concurrent chemotherapy was given to around 9% cases, while 18% were followed by adjuvant chemotherapy no chemotherapy was administered to the rest. The most common regimen was (procarbzine, cisplatinum, vincristine), but single agent vincristine was preferred concurrently.
On response evaluation after RT, subjective improvement was seen in 31% and objective improvement in almost the same percentage. Post RT subsequent imaging showed a partial response in the maximum cases (43%), complete response in 7% and static disease in the rest. A similar trend was seen after completion of chemoradiation. However, 3% still had progressive disease. Majority of the cases were lost for follow-up, but from those on regular follow-up (7%), disease progression was seen in 8.6% cases, after a mean duration of 1.5 years. At the last follow-up, 91% cases were seen to be alive with disease, while 3.4% without disease and the rest succumbed to death.
Correlation between various prognostic factors such as age, histology, type of surgery and the outcome was not found to be statistically significant in our study for the simple reason of a small study population.
| » Discussion|| |
Medulloblastoma was first described by Bailey and Harvey Cushing in 1929. Back then, surgery was the main or only modality of management, but there has been continuous development in its management over the years. Multimodality approach (surgery, radiation, chemotherapy) is the cornerstone for the treatment of medulloblastoma.
This tumor accounts for about 20% of childhood brain tumors globally and almost the same incidence has been found in India. The incidence of medulloblastoma in various studies was initially found to increase with passing years, but after the segregation of medulloblastoma from primitive neuroectodermal tumor,,,, the recent studies have found that the incidence of medulloblastoma has not increased with time. At our center, 58 cases of medulloblastoma were diagnosed in the 10 years period studied. This is slightly higher than found in western literature from a single institution.,,, The reason for this might be the referral tertiary center status of the institution.
The mean age at diagnosis was 10 years, with most cases between the age of 3 and 20 years. There is a steep drop in the incidence after the age of 15 years, as also observed in the recent SEER database analysis.
None of the cases had any syndromal association. The mean duration of symptoms was 200 days, which was mainly because of the lack of awareness in the rural areas and added to the morbidity of the disease. A similar observation was made in a study conducted in Brazil, proving that lack of awareness and difficult access to medical help are few of the main reasons for increased morbidity of the disease and mortality in developing countries.
Even though, tumors were bulky in size, majority were Stage 0 lesions with only around 3.4% presenting with metastasis. The most common site of metastasis was bone, more often vertebrae.
Due to the relatively bigger sized lesions and high vascularity, a gross total resection was possible in very few. Subtotal or partial excision was commonly carried out and sometimes biopsy only was feasible due to very poor performance status of the children. This is in contrast to other studies, which have quoted up to 90% total excision of the tumor. Partial excision was resulted in larger residual tumors, which made most cases being categorized as high risk and hence relatively carrying a worse prognosis.
All patients were treated with post-operative radiotherapy. The standard protocol of 1.8 gray per fraction, 5 fractions per week to a total dose of 36 gray to the craniospinal axis was followed, with an additional boost to the posterior fossa up to 54 gray. In about 6% cases major treatment violations were observed, which were – dose to craniospinal axis, less than 28 gray and posterior fossa dose less than 43 gray. This resulted due to poor performance status and inability to continue further treatment.
Cases of age less than 3 years (10.3%) were treated only with chemotherapy, mostly with vincristine based regimen.
Subjective and objective improvement was seen in 31% each after completion of radiotherapy. Post radiation imaging showed a partial response in maximum cases (43%), complete response in 7% and static disease in the rest. A similar trend was seen after completion of chemoradiation. However, 3% still had progressive disease, compared with the post-surgery status. Complete response was seen in those who had a total resection of the tumor. Had there been more total resections possible, the outcome would have been much better.
The prognosis depended on age, histology, tumor stage, type of surgery, performance status and part of the decade in which patient was treated, as the treatment policies varied over the 10 years period. Later half of the time period saw more aggressive surgery and chemotherapy, with better radiation techniques. However, no statistically significant relation was found in our study.
The poor follow-up and late reporting to the hospital can be attributed to the fact that most population had a rural background with lack of awareness, financial constraints and lack of easy hospital access.
As noticed toward the later part of the decade, with subsidizing the treatment and more easy accessibility, an improvement in patient reporting and further management was seen. However, there is still a long way to go and active measures are in line for the same.
For those patients who were on regular follow-up, disease progression was seen in 8.6% cases, after a mean duration of 1.5 years. The maximum duration of follow-up was 3 years and the mean duration was 1.5 years. At the last follow-up, 91% cases were seen to be alive with disease while 3.4% without disease and the rest succumbed to death. The figures here are saddening as the rate of complete response CR is much lower than expected.,,, Consequently, the death rates have also been higher.
As the treatment of medulloblastoma has evolved, we have seen the change from surgery only to more complete surgery plus high dose radiation. This was followed by low dose of radiation with concurrent chemotherapy in standard risk patients. Now with more and more advances in both treatment modality and technique, trials are showing more promising results. On the basis of molecular stratification of the disease, individualized targeted treatment  is the center point of ongoing studies now. A recent study presented in the American Society of Clinical Oncology meet advocated the reconsideration of histology as a significant contributor to treatment tailoring. Use of conformal techniques of radiation delivery and proton therapy has gone a long way in decreasing toxicity and improving results.
Our study has shown the general presentation and management of the disease and pointed out the areas of improvement. A study conducted in India and published by the Indian Academy of Pediatrics has highlighted the recommendations on diagnosis and management of brain tumors. Data from such indigenous studies should be utilized to help in improving the treatment outcome. All institutes should have a protocol based approach so that the loopholes in management are not missed. The treating physicians should work as part of a multidisciplinary team to improve the survival, quality-of-life, neurocognitive outcomes and standards of care for children with medulloblastoma.
| » Acknowledgment|| |
We wish to acknowledge the Departments of Neurosurgery, Neuro-pathology and Radiology in Madras Medical College for their contribution. No financial grants or funding were used for this study.
| » References|| |
Arseni C, Ciurea AV. Statistical survey of 276 cases of medulloblastoma (1935–1978). Acta Neurochir (Wien) 1981;57:159-62.
Farwell JR, Dohrmann GJ, Flannery JT. Medulloblastoma in childhood: An epidemiological study. J Neurosurg 1984;61:657-64.
Giangaspero F, Bigner SH, Kleihues P, Pietch T, Trojanowski JOl
. Medulloblastoma. In: Kleihues P, Cavenee WK, editors. World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of the Nervous System. Lyon, France: IARC Press; 2000. p. 129-37.
Roberts RO, Lynch CF, Jones MP, Hart MN. Medulloblastoma: A population-based study of 532 cases. J Neuropathol Exp Neurol 1991;50:134-44.
Jain A, Sharma MC, Suri V, Kale SS, Mahapatra AK, Tatke M, et al
. Spectrum of pediatric brain tumors in India: A multi-institutional study. Neurol India 2011;59:208-11.
Muzumdar D, Deshpande A, Kumar R, Sharma A, Goel N, Dange N, et al
. Medulloblastoma in childhood-King Edward memorial hospital surgical experience and review: Comparative analysis of the case series of 365 patients. J Pediatr Neurosci 2011;6:S78-85.
Sarkar C, Deb P, Sharma MC. Medulloblastomas: New directions in risk stratification. Neurol India 2006;54:16-23.
Cushing H. Experiences with the cerebellar medulloblastomas: A critical review. Acta Pathol Microbiol Scand 1930;7:1-86.
McNeil DE, Coté TR, Clegg L, Rorke LB. Incidence and trends in pediatric malignancies medulloblastoma/primitive neuroectodermal tumor: A SEER update. Surveillance epidemiology and end results. Med Pediatr Oncol 2002;39:190-4.
Allen J, Donahue B, Mehta M, Miller DC, Rorke LB, Jakacki R, et al
. A phase II study of preradiotherapy chemotherapy followed by hyperfractionated radiotherapy for newly diagnosed high-risk medulloblastoma/primitive neuroectodermal tumor: A report from the Children's Oncology Group (CCG 9931). Int J Radiat Oncol Biol Phys 2009;74:1006-11.
Bunin GR, Gallagher PR, Rorke-Adams LB, Robison LL, Cnaan A. Maternal supplement, micronutrient, and cured meat intake during pregnancy and risk of medulloblastoma during childhood: A children's oncology group study. Cancer Epidemiol Biomarkers Prev 2006;15:1660-7.
Bunin GR, Kushi LH, Gallagher PR, Rorke-Adams LB, McBride ML, Cnaan A. Maternal diet during pregnancy and its association with medulloblastoma in children: A children's oncology group study (United States). Cancer Causes Control 2005;16:877-91.
Smoll NR, Drummond KJ. The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children. J Clin Neurosci 2012;19:1541-4.
Akyüz C, Varan A, Küpeli S, Akalan N, Söylemezoglu F, Zorlu F, et al
. Medulloblastoma in children: A 32-year experience from a single institution. J Neurooncol 2008;90:99-103.
Partap S, Curran EK, Propp JM, Le GM, Sainani KL, Fisher PG. Medulloblastoma incidence has not changed over time: A CBTRUS study. J Pediatr Hematol Oncol 2009;31:970-1.
Kombogiorgas D, Sgouros S, Walsh AR, Hockley AD, Stevens M, Grundy R, et al
. Outcome of children with posterior fossa medulloblastoma: A single institution experience over the decade 1994-2003. Childs Nerv Syst 2007;23:399-405.
Wolff JE, Huettermann U, Ritter J, Straeter R, Palm D, Ruebe C, et al
. Medulloblastoma: Experience of a single institution. Klin Padiatr 1998;210:234-8.
Pinho RS, Andreoni S, Silva NS, Cappellano AM, Masruha MR, Cavalheiro S, et al
. Pediatric central nervous system tumors: A single-center experience from 1989 to 2009. J Pediatr Hematol Oncol 2011;33:605-9.
Wolff JE, Brown RE, Buryanek J, Pfister S, Vats TS, Rytting ME. Preliminary experience with personalized and targeted therapy for pediatric brain tumors. Pediatr Blood Cancer 2012;59:27-33.
Massimino M, Gandola L, Biassoni V, Collini P, Pollo B, Giangaspero F. Medulloblastoma histological variants as the most powerful prognostic indicator: A 10-year mono-institutional experience. J Clin Oncol 2010;28:15.
Bhat S, Yadav SP, Suri V, Patir R, Kurkure P, Kellie S, et al
. Management of childhood brain tumors: Consensus report by the pediatric hematology oncology (PHO) chapter of Indian academy of pediatrics (IAP). Indian J Pediatr 2011;78:1510-9.
[Figure 1], [Figure 2]
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