Clinical and Biologic Features Predictive of Survival After Relapse of Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project
Open accessAbstract
Purpose: Survival after neuroblastoma relapse is poor. Understanding the relationship between clinical and biologic features and outcome after relapse may help in selection of optimal therapy. Our aim was to determine which factors were significantly predictive of postrelapse overall survival (OS) in patients with recurrent neuroblastoma—particularly whether time from diagnosis to first relapse (TTFR) was a significant predictor of OS. Patients and Methods: Patients with first relapse/progression were identified in the International Neuroblastoma Risk Group (INRG) database. Time from study enrollment until first event and OS time starting from first event were calculated. Cox regression models were used to calculate the hazard ratio of increased death risk and perform survival tree regression. TTFR was tested in a multivariable Cox model with other factors. Results: In the INRG database (N = 8,800), 2,266 patients experienced first progression/relapse. Median time to relapse was 13.2 months (range, 1 day to 11.4 years). Five-year OS from time of first event was 20% (SE, ± 1%). TTFR was statistically significantly associated with OS time in a nonlinear relationship; patients with TTFR of 36 months or longer had the lowest risk of death, followed by patients who relapsed in the period of 0 to less than 6 months or 18 to 36 months. Patients who relapsed between 6 and 18 months after diagnosis had the highest risk of death. TTFR, age, International Neuroblastoma Staging System stage, and MYCN copy number status were independently predictive of postrelapse OS in multivariable analysis. Conclusion: Age, stage, MYCN status, and TTFR are significant prognostic factors for postrelapse survival and may help in the design of clinical trials evaluating novel agents.
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Cites
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1992) · Springer series in statistics · doi:10.1007/978-1-4612-4380-9_25 · Cited by 45,232 · see citing works
Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793 · see citing works
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1958) · Journal of the American Statistical Association · doi:10.1080/01621459.1958.10501452 · Cited by 39,158 · see citing works
Regression Models and Life-Tables
Cox, D. R. (1992) · Springer Series in Statistics · doi:10.1007/978-1-4612-4380-9_37 · Cited by 26,297 · see citing works
Counting Processes and Survival Analysis.
Dabrowska, D. M., Fleming, T. R., & Harrington, D. P. (1992) · Journal of the American Statistical Association · doi:10.2307/2290673 · Cited by 2,300 · see citing works
Peto, R., Pike, M. C., Armitage, P., Breslow, N. E., Cox, D. R., Howard, S. V., Mantel, N., McPherson, K., Peto, J., & Smith, P. G. (1976) · British Journal of Cancer · doi:10.1038/bjc.1976.220 · Cited by 2,294 · see citing works
The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report
Cohn, S. L., Pearson, A. D. J., London, W. B., Monclair, T. F., Ambros, P. F., Brodeur, G. M., Faldum, A., Hero, B., Iehara, T., Machin, D., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.6785 · Cited by 1,915 · see citing works
Self-citationNguyen, K., Devidas, M., Sc, C., La, M., Raetz, E. A., Carroll, W. L., Winick, N. J., Hunger, S. P., Gaynon, P. S., Loh, M. L., et al. (2008) · Leukemia · doi:10.1038/leu.2008.251 · Cited by 584 · see citing works
Regression Trees for Censored Data
Segal, M. R. (1988) · Biometrics · doi:10.2307/2531894 · Cited by 497 · see citing works
Ambros, P. F., Ambros, I. M., Brodeur, G. M., Haber, M., Khan, J. I., Nakagawara, A., Schleiermacher, G., Speleman, F., Spitz, R. E., London, W. B., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605014 · Cited by 403 · see citing works
Self-citationSurvival Trees by Goodness of Split
LeBlanc, M. L., & Crowley, J. J. (1993) · Journal of the American Statistical Association · doi:10.1080/01621459.1993.10476296 · Cited by 374 · see citing works
Survival After Recurrence of Ewing’s Sarcoma Family of Tumors
Barker, L., Pendergrass, T. W., Sanders, J. E., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.105 · Cited by 222 · see citing works
Leavey, P. J., Mascarenhas, L., Marina, N. M., et al. (2008) · Pediatric Blood & Cancer · doi:10.1002/pbc.21618 · Cited by 207 · see citing works
Davis, R. B., & Anderson, J. R. (1989) · Statistics in Medicine · doi:10.1002/sim.4780080806 · Cited by 189 · see citing works
Garaventa, A., Parodi, S., Bernardi, B. D., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2009.06.010 · Cited by 131 · see citing works
Dantonello, T. M., Int‐Veen, C., Winkler, P., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.2382 · Cited by 115 · see citing works
Malempati, S., Gaynon, P. S., Sather, H. N., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.10.7508 · Cited by 108 · see citing works
Conte, M., Parodi, S., Bernardi, B. D., et al. (2006) · Cancer · doi:10.1002/cncr.21751 · Cited by 81 · see citing works
Factors Influencing Survival in Children With Recurrent Neuroblastoma
Lau, L. M. S., Tai, D., Weitzman, S. S., Grant, R. M., Baruchel, S., & Malkin, D. M. (2004) · Journal of Pediatric Hematology/Oncology · doi:10.1097/00043426-200404000-00003 · Cited by 56 · see citing works
Neuroblastoma in Adults and Adolescents. An Indolent Course With Poor Survival
Franks, L. M., Bollen, A. W., Seeger, R. C., et al. (1998) · The Journal of Urology · doi:10.1016/s0022-5347(01)63326-3 · Cited by 50 · see citing works
Ceschel, S., Casotto, V., Valsecchi, M. G., Tamaro, P., Jankovic, M., Hanau, G., Fossati, F., Pillon, M., Rondelli, R., Sandri, A., et al. (2006) · Pediatric Blood & Cancer · doi:10.1002/pbc.20726 · Cited by 44 · see citing works
The age peak in childhood acute lymphoblastic leukemia
Swensen, A. R., Ross, J. A., Severson, R. K., Pollock, B. H., & Robison, L. L. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970515)79:10 · Cited by 44 · see citing works
Disease control intervals in high‐risk neuroblastoma
Santana, V. M., Furman, W. L., McGregor, L. M., et al. (2008) · Cancer · doi:10.1002/cncr.23507 · Cited by 37 · see citing works
Kushner, B. H., Kramer, K., & Cheung, N. V. (2002) · Cancer · doi:10.1002/cncr.10800 · Cited by 28 · see citing works
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Research works printed but not linked: 2
- [21]George RE, Variend S, Cullinane C, et al. Relationship between histopathological features, MYCN amplification, and prognosis: A UKCCSG study United Kingdom Children Cancer Study Group. Med Pediatr Oncol. 2001;36:169–176. doi: 10.1002/1096-911X(20010101)36:1<169::AID-MPO1041>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar] · DOI
- [24]Simon T, Berthold F, Klingenbiel T, et al. Do relapsed high risk neuroblastoma patients have a second chance. Pediatr Blood Cancer. 2009;53(5):736. [Google Scholar]
Cited by
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Arnhold, V., Schmelz, K., Proba, J., Winkler, A., Wünschel, J., Toedling, J., Deubzer, H. E., Künkele, A., Eggert, A., Schulte, J. H., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.23409 · Cited by 85 · see citing works
Roberts, H. J., Comeau, H., Klega, K., DuBois, S. G., Lazo de la Vega, L., Ceca, E., Mullen, E. A., Smith, G. A., Tukachinsky, H., Huang, R. S. P., et al. (2026) · JCO Precision Oncology · doi:10.1200/po-25-01125
- Authors
- London, W. B., Castel, V., Monclair, T., Ambros, P. F., Pearson, A. D. J., Cohn, S. L., Berthold, F., Nakagawara, A., Ladenstein, R. L., Iehara, T., & Matthay, K. K.
- Affiliations
- Oslo University Hospital (NO)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2011-08-20
- Volume
- 29
- Issue
- 24
- Pages
- 3286-3292
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC3158599
- OpenAlex
- W2110788947
- Cited by
- 318
- References
- 25
- Citations by year
- 2026: 19 · 2025: 20 · 2024: 31 · 2023: 19 · 2022: 38 · 2021: 35 · 2020: 30 · 2019: 16 · 2018: 18 · 2017: 14 · 2016: 18 · 2015: 19 · 2014: 14 · 2013: 16 · 2012: 11
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dougherty Foundation
- William Guy Forbeck Research Foundation
- Generalitat Valenciana
- U.S. Public Health Service (P01 81403)
- Japan Society for the Promotion of Science (21390317)
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- neuroblastoma, relapse, prognostic factors, time to relapse, INSS, patient age
- MeSH terms
- N-Myc Proto-Oncogene Protein, Age Factors, Humans, Infant, Neoplasm Staging, Neuroblastoma, Nuclear Proteins, Prognosis, Recurrence, Oncogene Proteins, Thymopentin, DNA Copy Number Variations
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