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Indian Journal of Medical and Paediatric Oncology
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Year : 2019  |  Volume : 40  |  Issue : 5  |  Page : 13-15  

Treatment refusal and abandonment remain major concerns despite good outcomes with multi-modality management in pediatric medulloblastoma: Experience from a cancer center in Eastern India

1 Department of Paediatric Haematology-Oncology, Tata Medical Centre, Kolkata, West Bengal, India
2 Department of Radiation Oncology, Tata Medical Centre, Kolkata, West Bengal, India
3 Department of Histopathology, Tata Medical Centre, Kolkata, West Bengal, India
4 Department of Radiology, Tata Medical Centre, Kolkata, West Bengal, India

Date of Web Publication25-Jul-2019

Correspondence Address:
Anirban Das
Department of Paediatric Haematology-Oncology, Tata Medical Centre, 14 Major Arterial Road (EW), Rajarhat, Kolkata - 700 160, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmpo.ijmpo_213_17

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Context: Survival in medulloblastoma, the most common pediatric brain tumor, has lagged behind in developing countries in comparison to the West. Aim: The aim of this study was to analyze the clinical profile and outcome in a cancer center in Eastern India. Methods: Twenty-nine children were retrospectively analyzed over 6 years. Results: Vomiting (79%), headache (69%), and unsteadiness (55%) were the presenting complaints. The majority (67%) had classical histology. High-risk (HR) disease (61.6%) exceeded average-risk (AR) (38.4%) disease in numbers. Treatment-refusal (27.6%) and abandonment (6.9%) were major concerns. Four-year EFS was 81% and 52%, excluding and including refusal/abandonment, respectively. There was no relapse/progression among AR patients. Four-year EFS in HR was 63%. Posterior fossa syndrome (37.5%), febrile neutropenia (29%), and ototoxicity (16.7%) were the main treatment-related morbidities. Implications: Following this audit, patient tracking to reduce abandonment, coordination to limit delay in postsurgical referral, developing strategies for molecular subgrouping, and reducing cumulative cisplatin exposure were measures adopted to improve outcome in the unit.

Keywords: Brain tumor, defaulter, ototoxicity, posterior fossa

How to cite this article:
Das A, Achari RB, Zameer L, Sen S, Krishnan S, Bhattacharyya A. Treatment refusal and abandonment remain major concerns despite good outcomes with multi-modality management in pediatric medulloblastoma: Experience from a cancer center in Eastern India. Indian J Med Paediatr Oncol 2019;40, Suppl S1:13-5

How to cite this URL:
Das A, Achari RB, Zameer L, Sen S, Krishnan S, Bhattacharyya A. Treatment refusal and abandonment remain major concerns despite good outcomes with multi-modality management in pediatric medulloblastoma: Experience from a cancer center in Eastern India. Indian J Med Paediatr Oncol [serial online] 2019 [cited 2020 Jun 5];40, Suppl S1:13-5. Available from: http://www.ijmpo.org/text.asp?2019/40/5/13/263310

  Introduction Top

Central nervous system tumors are second only to hematological malignancies among childhood cancers. Medulloblastoma is the most frequent brain tumor in children.[1] Cure rates with multimodality treatment approaches 85% for average-risk (AR) and 75% for high-risk (HR) patients.[2] Data from India are limited.[3],[4],[5],[6],[7] The aim of the study was to analyze the clinical profile and outcome in a referral oncology center in Eastern India over the last 6 years.

  Materials and Methods Top

All children, <18-years at diagnosis, were retrospectively included between May 2011 and April 2017. Patients were referred, after surgery from different neurosurgical centers in the region, for adjuvant radiation and chemotherapy. Diagnosis was confirmed on histopathology after procuring blocks and slides, if available. Staging investigations included magnetic resonance imaging (MRI) of the spine, postoperative MRI of the brain (for assessing residual disease), and analysis of the cerebrospinal fluid (CSF). Children >3-years at diagnosis, with postoperative residual <1.5-cm 2, normal CSF, and a nonlarge cell/anaplastic (non-LCA) histopathology were classified as AR. They received craniospinal irradiation with 23.4 Gy in 13-fractions, while children >3-years with HR disease received 36 Gy in 20-fractions. All children >3-years received boost to the posterior fossa/tumor bed with a dose of 55.8 Gy in 31-fractions. None received concurrent chemotherapy with radiation. Children <3-years were candidates for radiation-sparing or delaying strategies using chemotherapy. Adjuvant chemotherapy for AR included cisplatin, vincristine and lomustine, and for HR included cisplatin, vincristine and cyclophosphamide, both for eight cycles, lasting 6 weeks each, with each cycle starting following recovery of blood counts. Survival analysis was performed using the Kaplan–Meier method.

  Results Top

Twenty-nine children were included in this study. Median age was 7 years (range: 0.9–14). Sixteen (55%) were male. Median symptom-interval was 3.7 months (range: 1–12). Clinical features at diagnosis included vomiting (23, 79%), headache (20; 69%), unsteadiness of gait (16; 55%), and cranial nerve palsy (3; 10%). On the preoperative MRI (n = 25), the location of the tumor was in the midline cerebellum (10; 40%), roof of the 4th ventricle (10; 40%), and lateral cerebellum (5; 20%). Surgical data were available in 19; 9 (47%) had gross tumor excision, 4 (21%) had near total removal, and 6 (31.5%) had subtotal resection. A ventriculoperitoneal shunt had been inserted in 14/23 (61%). Pathological subtype was documented in the reports of 12 patients: classical (8; 67%), desmoplastic/nodular (2; 16.5%), and LCA (2; 16.5%). Staging (n = 25) revealed 12 (48%) with localized disease, 3 (12%) with malignant cells in the CSF, 7 (28%) with disease in the spine, and 3 (12%) with distant metastasis in the liver and bones. Sixteen had HR (61.6%) and 10 (38.4%) had AR disease. Out of the 16 children with HR disease, 13, including two children <3-years, had metastatic disease; among the rest, two had residual disease >1.5 cm 2, and one was 1.7 years old. Data were incomplete in three children.

Among the 29 children, 8 (27.6%) refused treatment and 2 (6.9%) abandoned care. All had HR disease. One child (3.4%) opted for palliative care in view of metastatic disease. Three (10.3%) had recurrence/progressive disease on follow-up. The remaining 15 (51.7%) children are well on follow-up. Median follow-up duration for the entire cohort was 54 months. The median 4-year event-free survival (EFS) was 81.4% ± 0.1% and 51.2% ± 0.1%, excluding and including refusal/abandonment, respectively. There were no relapses/progressive disease, or refusal/abandonment among AR patients (EFS = 100%). Among HR patients, EFS, excluding refusal/abandonment was 63.4% ± 0.1% [Figure 1] and including refusal/abandonment was 31.1% ± 1.2%.
Figure 1: Event free survival in children with medulloblastoma: (a) excluding refusal and abandonment; (b) including refusal and abandonment as events; (c) event-free survival in children with average and high-risk disease at median follow-up of 54 months (cases with refusal/abandonment were censored)

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Data related to treatment-related toxicity was available in 24 children. About 9 (37.5%) had posterior fossa syndrome, 7 (29%) needed admissions for febrile neutropenia, 1 (4%) had a shunt block, and 4 (16.7%) had hearing loss. All needed nutritional support. There was no death related to treatment toxicity.

  Discussion Top

With the rapid introduction of molecular profiling in clinical classification, management of pediatric brain tumors, including medulloblastoma, is likely to undergo a paradigm change.[1] However, the developing countries are struggling with providing optimal care to children with potentially curable brain tumors. Access to care and treatment refusal/abandonment remain important concerns. This has been highlighted in previous studies from Asia, Africa, and Latin America.[8],[9],[10] The index series reports 35% refusing/abandoning care. The retrospective nature of the audit precluded detailed analysis of the possible reasons for default. However, patient tracking over telephone has been prospectively activated in our center to counter this menace, using workforce, and financial support from government and voluntary groups.

Despite limited numbers, the protocol-based standardized management for the AR patients produced satisfactory results. The higher proportion of HR patients was plausibly due to referral bias. The previous studies from India have reported the survival in the AR group varies between 73% and 83% and among HR, between 34% and 63%, similar to the index study [Table 1].[3],[4],[5],[6] Lack of molecular subgrouping is recognized as a lacuna in most of these studies. An additional limitation was that there were only three children below 3 years of age, one of whom had progressive disease, and the other two had defaulted. It is well established that this challenging subgroup of patients need a dedicated approach different from that for older children.
Table 1: Published reports on pediatric medulloblastoma from India

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Measures adopted in the unit following this audit included developing better coordination with referral centers to reduce delay, developing an electronic database, molecular studies for better subgrouping, and limiting the cumulative cisplatin exposure to reduce ototoxicity by adapting from results of international collaborative studies.[11] We hope that the recently published guidelines of the Indian Society of Neuro-Oncology and collaborative studies under the Indian Pediatric Oncology Group will help standardize management and improve outcomes in Indian children with medulloblastoma.[1]


The authors would like to thank Prof. Vaskar Saha, Professor of Pediatric Oncology, University of Manchester, and Director, Tata Translational Cancer Research Center, Dr. Revathi Rajagopal, Department of Pediatrics, University of Malaya, Malaysia, Dr. Gopal Achari, Department of Neurosurgery, Park Clinic, Kolkata, and the neurosurgical team at Institute of Neurosciences, Kolkata, for their contribution in the management of the patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Gupta T, Sarkar C, Rajshekhar V, Chatterjee S, Shirsat N, Muzumdar D, et al. Indian Society of Neuro-Oncology consensus guidelines for the contemporary management of medulloblastoma. Neurol India 2017;65:315-32.  Back to cited text no. 1
[PUBMED]  [Full text]  
Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St. Jude Medulloblastoma-96): Long-term results from a prospective, multicentre trial. Lancet Oncol 2006;7:813-20.  Back to cited text no. 2
Menon G, Nair S, Muthurethinam T, Krishnakumar K, Bhattacharya R N. Medulloblastoma in children: Prognostic factors and predictors of outcome. J Pediatr Neurosci 2006;1:16-20.  Back to cited text no. 3
  [Full text]  
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.  Back to cited text no. 4
Gupta T, Jalali R, Goswami S, Nair V, Moiyadi A, Epari S, et al. Early clinical outcomes demonstrate preserved cognitive function in children with average-risk medulloblastoma when treated with hyperfractionated radiation therapy. Int J Radiat Oncol Biol Phys 2012;83:1534-40.  Back to cited text no. 5
Kumar LP, Deepa SF, Moinca I, Suresh P, Naidu KV. Medulloblastoma: A common pediatric tumor: Prognostic factors and predictors of outcome. Asian J Neurosurg 2015;10:50.  Back to cited text no. 6
[PUBMED]  [Full text]  
Gaur S, Kumar SS, Balasubramaniam P. An analysis of medulloblastoma: 10 year experience of a referral institution in South India. Indian J Cancer 2015;52:575-8.  Back to cited text no. 7
[PUBMED]  [Full text]  
Rajagopal R, Abd-Ghafar S, Ganesan D, Bustam Mainudin AZ, Wong KT, Ramli N, et al. Challenges of treating childhood medulloblastoma in a country with limited resources: 20 years of experience at a single tertiary center in Malaysia. J Glob Oncol 2017;3:143-56.  Back to cited text no. 8
Wang C, Yuan XJ, Jiang MW, Wang LF. Clinical characteristics and abandonment and outcome of treatment in 67 Chinese children with medulloblastoma. J Neurosurg Pediatr 2016;17:49-56.  Back to cited text no. 9
Friedrich P, Lam CG, Kaur G, Itriago E, Ribeiro RC, Arora RS, et al. Determinants of treatment abandonment in childhood cancer: Results from a global survey. PLoS One 2016;11:e0163090.  Back to cited text no. 10
Nageswara Rao AA, Wallace DJ, Billups C, Boyett JM, Gajjar A, Packer RJ, et al. Cumulative cisplatin dose is not associated with event-free or overall survival in children with newly diagnosed average-risk medulloblastoma treated with cisplatin based adjuvant chemotherapy: Report from the Children's Oncology Group. Pediatr Blood Cancer 2014;61:102-6.  Back to cited text no. 11


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