Since their introduction to the International Neuroblastoma Risk Group (INRG) staging system in 2009, the role of Image-Defined Risk Factors (IDRFs) in predicting outcomes has been studied in heterogeneous populations with varying results. We conducted a systematic review and meta-analysis in order to determine quantitative measures of precisely how well pre-treatment IDRFs predict surgical outcomes and survival.
A systematic review was performed for studies between January 1990 and July 2019 that compared surgical outcomes and/or survival in pediatric neuroblastoma patients with one or more IDRFs to patients without IDRFs. Summary risk ratios (RR) and hazard ratios (HR) were calculated using a random-effects model.
19 retrospective cohort studies were included, representing data from 1132 patients. The risk ratio (RR) of incomplete surgical resection in IDRF-positive patients compared to IDRF-negative patients was 2.45 (95% CI 1.51–3.97). The RR of surgical complications was 2.30 (95% CI 1.46–3.61). The hazard ratio (HR) for 5-year EFS was 2.08 (95% CI 2.93–4.13) while the 5-year HR for OS was 2.44 (95% CI 1.46–4.08).
IDRF-positive neuroblastoma patients have a higher risk of incomplete surgical resection, surgical complications, and 5-year mortality and/or relapse. Our results affirm that IDRFs remain a useful prognostic tool for neuroblastoma patients both for short and long-term outcomes.
Level of evidence
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Image-defined risk factor
International neuroblastoma risk group
International neuroblastoma risk group staging system
Matthay KK (1995) Neuroblastoma: a clinical challenge and biologic puzzle. CA Cancer J Clin 45:179–192
Gajjar A, Packer RJ, Foreman NK et al (2013) Children’s oncology group’s 2013 blueprint for research: central nervous system tumors. Pediatr Blood Cancer 60:1022–1026
Cohn SL, Pearson AD, London WB et al (2009) The International neuroblastoma risk group (INRG) classification system: an INRG task force report. J Clin Oncol 27:289–297
Heck JE, Ritz B, Hung RJ et al (2009) The epidemiology of neuroblastoma: a review. Paediatr Perinat Epidemiol 23:125–143
Castleberry RP, Pritchard J, Ambros P et al (1997) The international neuroblastoma risk groups (INRG): a preliminary report. Eur J Cancer 33:2113–2116
Monclair T, Brodeur GM, Ambros PF et al (2009) The International neuroblastoma risk group (INRG) staging system: an INRG task force report. J Clin Oncol 27:298–303
Fumino S, Kimura K, Iehara T et al (2015) Validity of image-defined risk factors in localized neuroblastoma: a report from two centers in Western Japan. J Pediatr Surg 50:2102–2106
Simon T, Hero B, Benz-Bohm G et al (2008) Review of image defined risk factors in localized neuroblastoma patients: results of the GPOH NB97 trial. Pediatr Blood Cancer 50:965–969
Gunther P, Holland-Cunz S, Schupp CJ et al (2011) Significance of image-defined risk factors for surgical complications in patients with abdominal neuroblastoma. Eur J Pediatr Surg 21:314–317
Yoneda A, Nishikawa M, Uehara S et al (2016) Can Image-defined risk factors predict surgical complications in localized neuroblastoma? Eur J Pediatr Surg 26:117–122
Pohl A, Erichsen M, Stehr M et al (2016) Image-defined risk factors correlate with surgical radicality and local recurrence in patients with neuroblastoma. Klin Padiatr 228:118–123
Brisse HJ, Blanc T, Schleiermacher G et al (2017) Radiogenomics of neuroblastomas: Relationships between imaging phenotypestumor, genomic profile and survival. PLoS One 12(9):e0185190. https://doi.org/10.1371/journal.pone.0185190
Zhang A-A, Pan C, Xu M et al (2019) Association of image-defined risk factors, tumor resectability, and prognosis in children with localized neuroblastoma. World J Pediatrics 15:572–579
Monclair T, Mosseri V, Cecchetto G et al (2015) Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European international society of paediatric oncology neuroblastoma group. Pediatr Blood Cancer 62:1536–1542
Rossa A, Cacciavillano W, Rose A et al (2016) Neuroblastoma in patients under 18 months, single institution experience in Argentina. Pediatr Blood Cancer 63(Supplement 3):S202
Penazzi ACS, Tostes VS, Duarte AAB et al (2017) Do the radiological criteria with the use of risk factors impact the forecasting of abdominal neuroblastic tumor resection in children? Arq Bras Cir Dig 30:88–92
Moher D, Liberati A, Tetzlaff J et al (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8:336–341
Wells G, Shea B, O’Connell D, et al. Ottawa Hospital Research Institute. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses, https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 3 Aug 2019.
Parmar MKB, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834
Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8. DOI: 10.1186/1745-6215-8-16. (Epub ahead of print December 2007).
Higgins J, Thomas J, Chandler J et al (2019) Cochrane handbook for systematic reviews of interventions, 2nd edn. Wiley, Chichester
Duval S, Tweedie R (2000) Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56:455–463
Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Sterne JAC, Sutton AJ, Ioannidis JPA et al (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002–d4002
Simon T, Haberle B, Hero B et al (2013) Role of surgery in the treatment of patients with stage 4 neuroblastoma age 18 months or older at diagnosis. J Clin Oncol 31:752–758
Koivusalo AI, Pakarinen MP, Rintala RJ et al (2014) Surgical treatment of neuroblastoma: twenty-three years of experience at a single institution. Surg Today 44:517–525
Irtan S, Brisse HJ, Minard-Colin V et al (2015) Image-defined risk factor assessment of neurogenic tumors after neoadjuvant chemotherapy is useful for predicting intra-operative risk factors and the completeness of resection. Pediatr Blood Cancer 62:1543–1549
Yeung F, Chung PH, Tam PK et al (2015) Is complete resection of high-risk stage IV neuroblastoma associated with better survival? J Pediatr Surg 50:2107–2111
Yoneda A, Nishikawa M, Uehara S et al (2016) Can neoadjuvant chemotherapy reduce the surgical risks for localized neuroblastoma patients with image-defined risk factors at the time of diagnosis? Pediatr Surg Int 32:209–214
Avanzini S, Pio L, Erminio G, et al. Image-defined risk factors in unresectable neuroblastoma: SIOPEN study on incidence, chemotherapy-induced variation, and impact on surgical outcomes. Pediatr Blood Cancer 64. DOI: 10.1002/pbc.26605 (Epub ahead of print 2017).
Shirota C, Tainaka T, Uchida H et al (2017) Laparoscopic resection of neuroblastomas in low- to high-risk patients without image-defined risk factors is safe and feasible. BMC Pediatr 17:71
Tanaka Y, Kawashima H, Mori M et al (2016) Contraindications and image-defined risk factors in laparoscopic resection of abdominal neuroblastoma. Pediatr Surg Int 32:845–850
We would like to thank Michael Stoto, Ph.D. for his assistance in developing and reviewing our search strategy.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
Research involving human and/or animal participants
This article does not contain any studies with human participants or animals performed by any of the authors
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Appendix A: search strategy
Appendix A: search strategy
(“Neuroblastoma” [mesh] OR “Neuroblastoma/diagnosis” [mesh] OR “Neuroblastoma/complications” [mesh] OR “Neuroblastoma/pathology” [mesh] OR “Neuroblastoma/surgery” [mesh]).
(“Risk factors” [mesh] OR “image-defined risk factors” [tiab] OR “image defined risk factors” [tiab] OR IDRF [tiab] OR “Neoplasm staging” [mesh] OR staging [tiab] OR stage [tiab]).
(“esthesioneuroblastoma, olfactory” [mesh] OR “case reports” [pt]).
About this article
Cite this article
Parhar, D., Joharifard, S., Lo, A.C. et al. How well do image-defined risk factors (IDRFs) predict surgical outcomes and survival in patients with neuroblastoma? A systematic review and meta-analysis. Pediatr Surg Int 36, 897–907 (2020). https://doi.org/10.1007/s00383-020-04696-y
- Risk factor