Look AT, Hayes FA, Shuster JJ, et al. Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. 1991 Apr. 9(4):581-91. [QxMD MEDLINE Link].
Challagundla KB, Wise PM, Neviani P, Chava H, Murtadha M, Xu T, et al. Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy. J Natl Cancer Inst. 2015 Jul. 107 (7):[QxMD MEDLINE Link].
[Guideline] Shimada H, Chatten J, Newton WA Jr, et al. Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst. 1984 Aug. 73(2):405-16. [QxMD MEDLINE Link].
[Guideline] Cohn SL, Pearson AD, London WB, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2009 Jan 10. 27(2):289-97. [QxMD MEDLINE Link]. [Full Text].
Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008 Oct 16. 455(7215):930-5. [QxMD MEDLINE Link]. [Full Text].
Schleiermacher G, Javanmardi N, Bernard V, et al. Emergence of New ALK Mutations at Relapse of Neuroblastoma. J Clin Oncol. 2014 Sep 1. 32(25):2727-34. [QxMD MEDLINE Link].
De Brouwer S, De Preter K, Kumps C, Zabrocki P, Porcu M, Westerhout EM. Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. Clin Cancer Res. 2010 Sep 1. 16(17):4353-62. [QxMD MEDLINE Link].
Capasso M, Devoto M, Hou C, et al. Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nat Genet. 2009 Jun. 41(6):718-23. [QxMD MEDLINE Link]. [Full Text].
Diskin SJ, Hou C, Glessner JT, Attiyeh EF, Laudenslager M, Bosse K. Copy number variation at 1q21.1 associated with neuroblastoma. Nature. 2009 Jun 18. 459(7249):987-91. [QxMD MEDLINE Link].
Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C. Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature. 2011 Jan 13. 469(7329):216-20. [QxMD MEDLINE Link].
Nguyen le B, Diskin SJ, Capasso M, Wang K, Diamond MA, Glessner J. Phenotype restricted genome-wide association study using a gene-centric approach identifies three low-risk neuroblastoma susceptibility Loci. PLoS Genet. 2011 Mar. 7(3):e1002026. [QxMD MEDLINE Link].
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan. 71 (1):7-33. [QxMD MEDLINE Link]. [Full Text].
National Cancer Institute. SEER Pediatric Monograph. National Cancer Institute. Available at http://www-seer.ims.nci.nih.gov/Publications/PedMono/sympathetic.pdf. Accessed: February 25, 2002.
Stiller CA, Parkin DM. International Variations in the incidence of neuroblastoma. International Journal of Cancer. 1992. 52:538-543.
Haupt R, Garaventa A, Gambini C, et al. Improved Survival of Children with Neuroblastoma Between 1979 and 2005: A Report of the Italian Neuroblastoma Registry. J Clin Oncol. 2010 Mar 29. [QxMD MEDLINE Link].
George RE, Li S, Medeiros-Nancarrow C, et al. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol. 2006 Jun 20. 24(18):2891-6. [QxMD MEDLINE Link].
[Guideline] 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 Jan 10. 27(2):298-303. [QxMD MEDLINE Link]. [Full Text].
London WB, Castleberry RP, Matthay KK, et al. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. J Clin Oncol. 2005 Sep 20. 23(27):6459-65. [QxMD MEDLINE Link].
London WB, Castleberry RP, Matthay KK, Look AT, Seeger RC, Shimada H. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. J Clin Oncol. 2005 Sep 20. 23(27):6459-65. [QxMD MEDLINE Link].
Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma. Lancet. 2007 Jun 23. 369(9579):2106-20. [QxMD MEDLINE Link].
Strother DR, London WB, Schmidt ML, et al. Outcome After Surgery Alone or With Restricted Use of Chemotherapy for Patients With Low-Risk Neuroblastoma: Results of Children's Oncology Group Study P9641. J Clin Oncol. 2012 May 20. 30(15):1842-8. [QxMD MEDLINE Link].
Baker DL, Schmidt ML, Cohn SL, et al. Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med. 2010 Sep 30. 363(14):1313-23. [QxMD MEDLINE Link].
FDA grants accelerated approval to naxitamab for high-risk neuroblastoma in bone or bone marrow. Food and Drug Administration. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-naxitamab-high-risk-neuroblastoma-bone-or-bone-marrow. November 25, 2020; Accessed: April 10, 2021.
Naranjo A, Parisi MT, Shulkin BL, et al. Comparison of ¹²³I-metaiodobenzylguanidine (MIBG) and ¹³¹I-MIBG semi-quantitative scores in predicting survival in patients with stage 4 neuroblastoma: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Jul 1. 56(7):1041-5. [QxMD MEDLINE Link].
Mueller S, Yang X, Sottero TL, Gragg A, Prasad G, Polley MY. Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: efficacy and underlying mechanisms. Cancer Lett. 2011 Jul 28. 306(2):223-9. [QxMD MEDLINE Link].
Federico SM, McCarville MB, Shulkin BL, Sondel PM, Hank JA, Hutson P, et al. A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma. Clin Cancer Res. 2017 Sep 22. [QxMD MEDLINE Link].
Ladenstein R, Valteau-Couanet D, Brock P, et al. Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study. J Clin Oncol. 2010 Jul 20. 28(21):3516-24. [QxMD MEDLINE Link].
Agarwal S, Lakoma A, Chen Z, Hicks J, Metelitsa LS, Kim ES, et al. G-CSF Promotes Neuroblastoma Tumorigenicity and Metastasis via STAT3-Dependent Cancer Stem Cell Activation. Cancer Res. 2015 Jun 15. 75 (12):2566-79. [QxMD MEDLINE Link].
Lowry F. Is it Safe to Use G-CSF in Neuroblastoma Patients?. Medscape Medical News. Available at http://www.medscape.com/viewarticle/845310. May 26, 2015; Accessed: March 18, 2016.

Media Gallery

Histologic subtypes of neuroblastoma. Top right panel, neuroblastoma: A monotonous population of hyperchromatic cells with scant cytoplasm. Bottom left panel, ganglioneuroblastoma: Increased schwannian stroma. Bottom right panel, ganglioneuroma: Mature ganglion cell with schwannian stroma.
CT scan of abdomen in a patient with a retroperitoneal mass arising from the upper pole of the left kidney and elevated urine catecholamines.
MRI of a left adrenal mass. The mass was revealed by fetal ultrasonography at 30 weeks' gestation. During infancy, the mass was found on the inferior pole of the left adrenal and was completely resected. Before surgery, the metastatic workup was negative. Surgical pathology service confirmed a diagnosis of neuroblastoma. After 3 years of follow-up care, no recurrence was observed.
A one-week-old neonate had abdominal ultrasonography for evaluation of projectile vomiting. A right adrenal mass (100% cystic) was an incidental finding. Evaluation of the mass by CT was consistent with an adrenal bleed (3.6 x 3.1 x 2.4 cc). The infant was followed at 2 weeks (2-dimensional size diminished to 1.5 x. 2.4 cm2 on ultrasonography) and then at 6 weeks to document that the adrenal bleed continued to involute. Urine catecholamines were normal.
Table. A Consensus Pretreatment Classification schema by the International Neuroblastoma Risk Group (INRG). This schema is based in the INRG stage, age, histologic category, tumor grade of differentiation, MYCN sastus, 11q-aberrations and DNA ploidy. A combination of these characteristics results in four risk groups noted in the last column: very low, low, intermediate and high risk, with the following 5 year EFS: >85%, >75%-85%, >50%-75%, and < 50%. These risk groups are distributed among the different stages and labeled alphabetically from A to R (without letters L and M to avoid confusion with the INRG stage notation). Notations in the table are as follow: L1, localized tumor confined to one body compartment; L2, locoregional tumor with presence of one or more risk factors defined radiologically; M, distant metastatic disease (except stage MS); MS, metastatic disease confined to skin, liver and/or bone marrow in children < 18 months of age. GN, ganglioneuroma; GNB, ganglioneuroblastoma; Amp, amplified; n/amp, not amplified. (Adapted from The International Neuroblastoma Risk Group (INRG) Classifications System: An INRG Task Force Report by Cohn, et al. Journal of Clinical Oncology 27(2):289-297, 2009).

of 5

Table 1. Current COG Neuroblastoma Risk Stratification

Table 1. Current COG Neuroblastoma Risk Stratification

Risk Group	Stage	Age	MYCN Amplification Status	Ploidy	Shimada
Low	1	Any	Any	Any	Any
Low	2a/2b	Any	Non-amp	Any	Any
High	2a/2b	Any	Amp	Any	Any
Intermediate	3	< 547d	Non-amp	Any	Any
Intermediate	3	≥547d	Non-amp	Any	Favorable
High	3	Any	Amp	Any	Any
High	3	≥547d	Non-amp	Any	Unfavorable
High	4	< 365d	Amp	Any	Any
Intermediate	4	< 365d	Non-amp	Any	Any
High	4	365-547d	Amp	Any	Any
High	4	365-547d	Any	Diploid	Any
High	4	365-547	Any	Any	Unfavorable
Intermediate	4	365-547d	Non-amp	Hyper	Favorable
High	4	≥547d	Any	Any	Any
Low	4s	< 365d	Non-amp	Hyper	Favorable
Intermediate	4s	< 365d	Non-amp	Diploid	Any
Intermediate	4s	< 365d	Non-amp	Any	Unfavorable
High	4s	< 365d	Amp	Any	Any

Back to List

Pediatric Neuroblastoma Questions & Answers

References

Tables

Contributor Information and Disclosures

What would you like to print?