Predictors of mortality in children with neuroblastoma

  • Rusida Harjayanti Sanindya Arum FKKMK UGM
  • Kristia Hermawan Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Central Java
  • Pudjo Hagung Widjajanto Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Central Java
  • Sutaryo Sutaryo Department of Child Health, Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Central Java
Keywords: child; neuroblastoma; cancer; solid tumor; predictor; survival rate

Abstract

Background Neuroblastoma is an extracranial solid tumor originating from neural crest cells which failed to properly migrate. Neuroblastoma is commonly found in children under 12 months of age. The survival rate of these patients is still relatively low, both in developed countries and Indonesia.

Objective To determine whether age, sex, primary tumor location, degree of cell differentiation, and patient compliance are associated with the survival of children with neuroblastoma at Dr.Sardjito Hospital.

Methods This retrospective cohort study included pediatric neuroblastoma patients at Dr. Sardjito Hospital, Yogyakarta, Central Java, between January 2012 to September 2020, however there has been no evaluation about survival of neuroblastoma. We collected secondary data from medical records and registration data of pediatric cancer patients in the Pediatric Hematology Oncology Department of Dr. Sardjito Hospital, we matched te data based on medicals records and manual data in the ward and olyclinic, which included age at diagnosis, sex, primary tumor location, degree of cell differentiation, and patient adherence to therapy. To confirm weather the information about survived or death, apart from medical record we do tracking by telephone to the parent.

Results we do the observation and calculating based on our retrospective data , Of 54 pediatric neuroblastoma patients, 54% were female. The median length of observation was 13.25 months, with an incidence rate of 62/100 person-years and a median survival of 13 months from the time of diagnosis. The 5-year survival rate in our study was 21.3%. Multivariate analysis revealed that stage IV patients had higher risk of death (HR 10.9; 95%CI 1.47 to 81.01; P=0.02) compared to other stages. Sub-group follow-up analysis revealed no significant difference in stage IV male patients compared to female patients (HR 1.62; 95%CI 0.81 to 3.22; P=0.172). The survivial in group with primary tumor location outside the adrenal medulla and stage IV was not significantly different from patients whose tumor location was unknown (HR 2.45; 95%CI 0.71 to 8.43; P=0.155). The group whose primary tumor location was in the adrenal medulla did not have a significant difference in survival compared to patients whose primary tumor location was unknown (HR 2.09; 95%CI 0.84 to 5.22; P=0.114).

Conclusion The predictor factors studied are not significantly associated with mortality in children with neuroblastoma.

References

1. Ahmed AA, Zhang L, Reddivalla N, Hetherington M. Neuroblastoma in children: Update on clinicopathologic and genetic prognostic factors. Pediatr Hematol Oncol. 2017;34:165–85. DOI: https://doi.org/10.1080/08880018.2017.1330375.
2. Louis CU, Shohet JM. Neuroblastoma: molecular pathogenesis and therapy. Annu Rev Med. 2015;66:49–63. DOI: https://doi.org/ 10.1146/annurev-med-011514-023121.
3. Gatta G, Ferrari A, Stiller CA, Pastore G, Bisogno G, Trama A, et al. Embryonal cancers in Europe. Eur J Cancer. 2012;48:1425–33. DOI: https://doi.org/10.1016/j.ejca.2011.12.027.
4. Cohn SL, Pearson ADJ, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG task force report. J Clin Oncol. 2009;27:289–97. DOI: https://doi.org/ 10.1200/JCO.2008.16.6785.
5. Sutaryo, Kristian, S. D. (2019) ‘A five-year review of children with neuroblastoma at Dr. Sardjiro General Hospital,Yogyakarta, Indonesia’ Paediatr Indones. 2019;51:207–12. DOI: https://doi.org/10.14238/pi59.3.2019.157-63
6. Garniasih RD, Windiastuti E, Gatot D. Karakteristik dan kesintasan neuroblastoma pada anak di Departemen Ilmu Kesehatan Anak Fakultas Kedokteran Universitas Indonesia Rumah Sakit Cipto Mangunkusumo. Sari Pediatr. 2009;11:39-46. DOI: https:// doi.org/10.14238/sp11.1.2009.39-46.
7. Hallett A, Traunecker H. A review and update on neuroblastoma. Paediatr Child Health (Oxford). 2012;22:103–7. DOI: https://doi.org/10.1016/j.paed.2011.08.005.
8. Sandoval JA, Malkas LH, Hickey RJ. Clinical significance of serum biomarkers in pediatric solid mediastinal and abdominal tumors. Int J Mol Sci 2012;13:1126–53. DOI: https://doi.org/1 0.3390/ijms13011126.
9. El-Sayed MI, Ali AM, Sayed HA, Zaky EM. Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study. Int Arch Med 2010;3:37. DOI: https://doi.org/ 10.1186/1755-7682-3-37.
10. Hale G, Cula MJ, Blatt J. Impact of gender on the natural history of neuroblastoma. Pediatr Hematol Oncol. 1994;11:91–7. DOI: https://doi.org/ 10.3109/08880019409141905.
11. Bown N, Cotterill S, Lastowska M, O'Neill S, Pearson AD, Plantaz D, et al. Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. N Engl J Med. 1999;340:1954-61. DOI: https://doi.org/10.1056/NEJM199906243402504.
12. Komotar RJ, Otten ML, Starke RM, Anderson RCE. Chromosome 1p and 11q deletions and outcome in neuroblastoma—a critical review. Clin Med Oncol. 2008;2:419–20. DOI: https://doi.org/ 10.4137/cmo.s391.
13. Chistison-Lagay ER, La Quaglia MP. Neuroblastoma and other adrenal tumors. In: Carachi R, Grosfedd JL, eds. The surgery of childhood tumors. 2nd edn. Heidelberg: Springer Berlin; 2016. p. 231-56. DOI: https://doi.org/10.1007/978-3-662-48590-3. ISBN: 978-3-662-48590-3.
15. Goldsby RE, Matthay KK. Neuroblastoma: evolving therapies for a disease with many faces. Paediatr Drugs. 2004;6:107–22. [cited YEAR MONTH DATE]. Available from: https://link.gale.com/apps/doc/A199991057/AONE?u=anon~e84d0ab3&sid=googleScholar&xid=89182a78.
16. Taggart DR, London WB, Schmidt M Lou, DuBois SG, Monclair TF, Nakagawara A, et al. Prognostic value of the stage 4S metastatic pattern and tumor biology in patients with metastatic neuroblastoma diagnosed between birth and 18 months of age. J Clin Oncol. 2011;29:4358–64. DOI: https://doi.org/ 10.1200/JCO.2011.35.9570.
17. Permono B, Ugrasena I. Neuroblastoma. Jakarta: Ikatan Dokter Anak Indonesia; 2018. p. 315–23.
18. Shay JW, Wright WE. Role of telomeres and telomerase in cancer. Semin Cancer Biol. 2011;21:349–53. DOI: https://doi.org/ 10.1016/j.semcancer.2011.10.001.
19. Sung KW, Yoo KH, Koo HH, Kim JY, Cho EJ, Seo YL, et al. Neuroblastoma originating from extra-abdominal sites: association with favorable clinical and biological features. J Korean Med Sci. 2009;24:461–7. DOI: https://doi.org/ 10.3346/jkms.2009.24.3.461.
20. Sun J, Wang D, Guo L, Fang S, Wang Y, Xing R. Androgen receptor regulates the growth of neuroblastoma cells in vitro and in vivo. Front Neurosci. 2017;11:116. DOI: https://doi.org/ 10.3389/fnins.2017.00116.
21. Roche J. The epithelial-to-mesenchymal transition in cancer. Cancers (Basel). 2018;10:9–12. DOI: https://doi.org/ 10.3390/cancers10020052.
22. Koen EJ, Coolier AB, Maharaj SK. Particle-in-cell simulations of a beam driven plasm. Physics of Plasmas. 2012;19:1420–28. DOI: https://doi.org/10.1063/1.3695402.
23. Sastry KSR, Karpova Y, Prokopovich S, Smith AJ, Essau B, Gersappe A, et al. Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation. J Biol Chem. 2007;282:14094–100. DOI: https://doi.org/10.1074/jbc.M611370200.
24. Ayurini RI. Kepatuhan pengobatan pada pasien kanker. Psikodimensia. 2015;14:83–95. DOI: https://doi.org/10.24167/psiko.v14i2.973.
25. Budiman A, Khambri D, Bachtiar H. Faktor yang mempengaruhi kepatuhan berobat pasien yang diterapi dengan tamoxifen setelah operasi kanker payudara. J Kesehat Andalas. 2013;2:20. DOI: https://doi.org/10.25077/jka.v2i1.60.
26. Ricafort R. Tumor markers in infancy and children. Pediatr Rev. 2011;32:306–8. DOI: https://doi.org/ 10.1542/pir.32-7-306.
Published
2023-04-11
How to Cite
1.
Sanindya Arum R, Hermawan K, Widjajanto P, Sutaryo S. Predictors of mortality in children with neuroblastoma. PI [Internet]. 11Apr.2023 [cited 5Oct.2024];63(2):73-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2922
Section
Pediatric Hemato-Oncology
Received 2022-01-02
Accepted 2023-04-11
Published 2023-04-11