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Published in: Indian Journal of Pediatrics 5/2019

01-05-2019 | Neuroblastoma | Original Article

Real World Experience of Treating Neuroblastoma: Experience from a Tertiary Cancer Centre in India

Authors: Venkatraman Radhakrishnan, Anand Raja, Manikandan Dhanushkodi, T. S. Ganesan, G. Selvaluxmy, T. G. Sagar

Published in: Indian Journal of Pediatrics | Issue 5/2019

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Abstract

Objectives

Management of neuroblastoma, especially high-risk (HR) disease is difficult in a resource-limited setting. There is a paucity of literature on outcomes of patients treated in India. The present study was conducted to analyse the clinical profile, treatment, and outcomes of patients with neuroblastoma treated at authors’ centre.

Methods

The study was a retrospective analysis of newly diagnosed patients with neuroblastoma treated at authors’ centre between 2000 to 2017. The International Neuroblastoma Staging System and risk grouping were used to classify patients as low-risk (LR), intermediate-risk (IR) and high-risk (HR). Treatment was individualised and risk-adapted. Kaplan-Meier method was used to calculate the event-free survival (EFS) and overall survival (OS).

Results

The study included 85 patients with a median age of 4 y and 67% were males. Malnutrition was observed in 55% of patients. Adrenal gland was the most common site in 75% patients followed by mediastinum in 12%. LR was observed in 7/85 (8%) patients, IR 20/85 (24%) and HR in 58/85 (68%) patients. The CCG-3891 protocol was used to treat 80% of the patients. Autologous stem cell transplantation (ASCT) was performed in 32% of HR patients. The median follow-up was 16.6 mo. The median EFS and OS for all patients were 19.2 mo and 26.9 mo respectively and the 3 y EFS and OS was 36% and 47% respectively. The 3y EFS for LR, IR and HR patients was 100%, 54%, and 18.9% respectively (P < 0.001) and for OS was 100%, 77%, and 34% respectively (P = 0.002). On multivariate analysis, a hemoglobin less than 10 g% predicted inferior EFS (P = 0.002) and OS (p = 0.005) for all patients. For patients with high-risk disease, on multivariate analysis, hemoglobin (P = 0.002) and 13-Cis Retinoic acid maintenance (P = 0.002) predicted EFS and only radiotherapy to the primary (P = 0.01) predicted OS. Only 4/19 (21%) are alive and in remission post ASCT.

Conclusions

Majority of patients with neuroblastoma presented to authors’ centre with advanced disease. Survival outcomes of patients with LR disease are excellent. However, patients with HR disease have poor outcomes despite multimodality management. Non-availability of N-MYC testing in few patients could have falsely down-staged them to IR from HR. A low hemoglobin at diagnosis is a poor predictor of outcome.
Literature
1.
go back to reference Parikh NS, Howard SC, Chantada G, et al. International Society of Pediatric Oncology. SIOP-PODC adapted risk stratification and treatment guidelines: recommendations for neuroblastoma in low- and middle-income settings. Pediatr Blood Cancer. 2015;62:1305–16.CrossRefPubMedPubMedCentral Parikh NS, Howard SC, Chantada G, et al. International Society of Pediatric Oncology. SIOP-PODC adapted risk stratification and treatment guidelines: recommendations for neuroblastoma in low- and middle-income settings. Pediatr Blood Cancer. 2015;62:1305–16.CrossRefPubMedPubMedCentral
2.
go back to reference Monclair T, Brodeur GM, Ambros PF, et al. The international neuroblastoma risk group (INRG) staging system: an INRG task force report. J Clin Oncol. 2009;27:298–303.CrossRefPubMedPubMedCentral Monclair T, Brodeur GM, Ambros PF, et al. The international neuroblastoma risk group (INRG) staging system: an INRG task force report. J Clin Oncol. 2009;27:298–303.CrossRefPubMedPubMedCentral
3.
go back to reference Oberthuer A, Juraeva D, Hero B, et al. Revised risk estimation and treatment stratification of low- and intermediate- risk neuroblastoma patients by integrating clinical and molecular prognostic markers. Clin Cancer Res. 2015;21:1904–15.CrossRefPubMed Oberthuer A, Juraeva D, Hero B, et al. Revised risk estimation and treatment stratification of low- and intermediate- risk neuroblastoma patients by integrating clinical and molecular prognostic markers. Clin Cancer Res. 2015;21:1904–15.CrossRefPubMed
4.
go back to reference Baker DL, Schmidt ML, Cohn SL, et al. Children’s Oncology Group Outcome after reduced chemotherapy for intermediate-risk neuroblastoma N Engl J Med. 2010;363:1313–23.PubMed Baker DL, Schmidt ML, Cohn SL, et al. Children’s Oncology Group Outcome after reduced chemotherapy for intermediate-risk neuroblastoma N Engl J Med. 2010;363:1313–23.PubMed
5.
go back to reference Matthay KK, Perez C, Seeger RC, et al. Successful treatment of stage III neuroblastoma based on prospective biologic staging: a children’s cancer group study. J Clin Oncol. 1998;16:1256–64.CrossRefPubMed Matthay KK, Perez C, Seeger RC, et al. Successful treatment of stage III neuroblastoma based on prospective biologic staging: a children’s cancer group study. J Clin Oncol. 1998;16:1256–64.CrossRefPubMed
6.
go back to reference Yu AL, Gilman AL, Ozkaynak MF, et al. Children's oncology group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363:1324–34.CrossRefPubMedPubMedCentral Yu AL, Gilman AL, Ozkaynak MF, et al. Children's oncology group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363:1324–34.CrossRefPubMedPubMedCentral
7.
go back to reference Matthay KK, Reynolds CP, Seeger RC, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. J Clin Oncol. 2009;27:1007–13.CrossRefPubMedPubMedCentral Matthay KK, Reynolds CP, Seeger RC, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. J Clin Oncol. 2009;27:1007–13.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;11:1466–77.CrossRefPubMed Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;11:1466–77.CrossRefPubMed
10.
go back to reference Shimada H, Ambros IM, Dehner LP, et al. The international neuroblastoma pathology classification (the Shimada system). Cancer. 1999;86:364–72.CrossRefPubMed Shimada H, Ambros IM, Dehner LP, et al. The international neuroblastoma pathology classification (the Shimada system). Cancer. 1999;86:364–72.CrossRefPubMed
11.
go back to reference Pritchard J, Cotterill SJ, Germond SM, Imeson J, de Kraker J, Jones DR. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European neuroblastoma study group. Pediatr Blood Cancer. 2005;44:348–57.CrossRefPubMed Pritchard J, Cotterill SJ, Germond SM, Imeson J, de Kraker J, Jones DR. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European neuroblastoma study group. Pediatr Blood Cancer. 2005;44:348–57.CrossRefPubMed
12.
go back to reference Berthold F, Boos J, Burdach S, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005;6:649–58.CrossRefPubMed Berthold F, Boos J, Burdach S, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005;6:649–58.CrossRefPubMed
13.
go back to reference Park JR, Kreissman SG, London WB, et al. A phase III randomized clinical trial (RCT) of tandem myeloablative autologous stem cell transplant (ASCT) using peripheral blood stem cell (PBSC) as consolidation therapy for high-risk neuroblastoma (HR-NB): A Children’s Oncology Group (COG) study. 2016 ASCO Annual Meeting. J Clin Oncol. 2016;34:15_suppl, LBA3-LBA3. Park JR, Kreissman SG, London WB, et al. A phase III randomized clinical trial (RCT) of tandem myeloablative autologous stem cell transplant (ASCT) using peripheral blood stem cell (PBSC) as consolidation therapy for high-risk neuroblastoma (HR-NB): A Children’s Oncology Group (COG) study. 2016 ASCO Annual Meeting. J Clin Oncol. 2016;34:15_suppl, LBA3-LBA3.
14.
go back to reference Peinemann F, van Dalen EC, Berthold F. Rapid COJEC induction therapy for high-risk neuroblastoma patients - cochrane review. Klin Padiatr. 2016;228:130–4.CrossRefPubMed Peinemann F, van Dalen EC, Berthold F. Rapid COJEC induction therapy for high-risk neuroblastoma patients - cochrane review. Klin Padiatr. 2016;228:130–4.CrossRefPubMed
15.
go back to reference Agarwala S, Mandelia A, Bakhshi S, et al. Neuroblastoma: outcome over a 14 year period from a tertiary care referral Centre in India. J Pediatr Surg. 2014;49:1280–5.CrossRefPubMed Agarwala S, Mandelia A, Bakhshi S, et al. Neuroblastoma: outcome over a 14 year period from a tertiary care referral Centre in India. J Pediatr Surg. 2014;49:1280–5.CrossRefPubMed
16.
go back to reference Bansal D, Marwaha RK, Trehan A, Rao KL, Gupta V. Profile and outcome of neuroblastoma with conventional chemotherapy in children older than one year: a 15-years’ experience. Indian Pediatr. 2008;45:135–9.PubMed Bansal D, Marwaha RK, Trehan A, Rao KL, Gupta V. Profile and outcome of neuroblastoma with conventional chemotherapy in children older than one year: a 15-years’ experience. Indian Pediatr. 2008;45:135–9.PubMed
17.
go back to reference Kusumakumari P, Ajithkumar TV, Hariharan S, et al. Intensive chemotherapy in children with stage IV neuroblastoma. Indian J Pediatr. 1999;66:867–72.CrossRefPubMed Kusumakumari P, Ajithkumar TV, Hariharan S, et al. Intensive chemotherapy in children with stage IV neuroblastoma. Indian J Pediatr. 1999;66:867–72.CrossRefPubMed
18.
go back to reference DuBois SG, Mody R, Naranjo A, et al. MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2017;64:e26545. https://doi.org/10.1002/pbc.26545. DuBois SG, Mody R, Naranjo A, et al. MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2017;64:e26545. https://​doi.​org/​10.​1002/​pbc.​26545.
19.
go back to reference Sharp SE, Trout AT, Weiss BD, Gelfand MJ. MIBG in neuroblastoma diagnostic imaging and therapy. Radiographics. 2016;36:258–78.CrossRefPubMed Sharp SE, Trout AT, Weiss BD, Gelfand MJ. MIBG in neuroblastoma diagnostic imaging and therapy. Radiographics. 2016;36:258–78.CrossRefPubMed
20.
go back to reference Sharp SE, Shulkin BL, Gelfand MJ, Salisbury S, Furman WL. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med. 2009;50:1237–43.CrossRefPubMed Sharp SE, Shulkin BL, Gelfand MJ, Salisbury S, Furman WL. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med. 2009;50:1237–43.CrossRefPubMed
21.
go back to reference Cangemi G, Barco S, Reggiardo G, et al. Interchangeability between 24-hour collection and single spot urines for vanillylmandelic and homovanillic acid levels in the diagnosis of neuroblastoma. Pediatr Blood Cancer. 2013;60:E170–2.CrossRefPubMed Cangemi G, Barco S, Reggiardo G, et al. Interchangeability between 24-hour collection and single spot urines for vanillylmandelic and homovanillic acid levels in the diagnosis of neuroblastoma. Pediatr Blood Cancer. 2013;60:E170–2.CrossRefPubMed
Metadata
Title
Real World Experience of Treating Neuroblastoma: Experience from a Tertiary Cancer Centre in India
Authors
Venkatraman Radhakrishnan
Anand Raja
Manikandan Dhanushkodi
T. S. Ganesan
G. Selvaluxmy
T. G. Sagar
Publication date
01-05-2019
Publisher
Springer India
Published in
Indian Journal of Pediatrics / Issue 5/2019
Print ISSN: 0019-5456
Electronic ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-018-2834-6

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