Long-Term Risk of Subsequent Neoplasms in 5-Year Survivors of Childhood Neuroblastoma: A Dutch Childhood Cancer Survivor Study-LATER 3 Study
Abstract
PURPOSE Neuroblastoma survivors have an increased risk of developing subsequent malignant neoplasms (SMNs), but the risk of subsequent nonmalignant neoplasms (SNMNs) and risk factors are largely unknown. We analyzed the long-term risks and associated risk factors for developing SMNs and SNMNs in a well-characterized cohort of 5-year neuroblastoma survivors. METHODS We included 563 5-year neuroblastoma survivors from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort, diagnosed during 1963-2014. Subsequent neoplasms were ascertained by linkages with the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank (Palga) and medical chart review. We calculated standardized incidence ratios (SIRs), absolute excess risk (AER), and cumulative incidences. Multivariable competing risk regression analysis was used to evaluate risk factors. RESULTS In total, 23 survivors developed an SMN and 60 an SNMN. After a median follow-up of 23.7 (range, 5.0-56.3) years, the risk of SMN was elevated compared with the general population (SIR, 4.0; 95% CI, 2.5 to 5.9; AER per 10,000 person-years, 15.1). The 30-year cumulative incidence was 3.4% (95% CI, 1.9 to 6.0) for SMNs and 10.4% (95% CI, 7.3 to 14.8) for SNMNs. Six survivors developed an SMN after iodine-metaiodobenzylguanidine ( 131I MIBG) treatment. Survivors treated with 131I MIBG had a higher risk of developing SMNs (subdistribution hazard ratio [SHR], 5.7; 95% CI, 1.8 to 17.8) and SNMNs (SHR, 2.6; 95% CI, 1.2 to 5.6) compared with survivors treated without 131I MIBG; results for SMNs were attenuated in high-risk patients only (SMNs SHR, 3.6; 95% CI, 0.9 to 15.3; SNMNs SHR, 1.5; 95% CI, 0.7 to 3.6). CONCLUSION Our results demonstrate that neuroblastoma survivors have an elevated risk of developing SMNs and a high risk of SNMNs. 131I MIBG may be a treatment-related risk factor for the development of SMN and SNMN, which needs further validation. Our results emphasize the need for awareness of subsequent neoplasms and the importance of follow-up care.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (15)
Aimée S.R. Westerveld
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Godelieve A.M. Tytgat
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Hanneke M. van Santen
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Max M. van Noesel
Jacqueline Loonen
Department of Hematology, Radboudumc Center of Expertise for Cancer Survivorship, Radboud University Medical Center, Nijmegen, the Netherlands
Andrica C.H. de Vries
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Marloes Louwerens
Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands
Maria M.W. Koopman
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Margriet van der Heiden-van der Loo
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Geert O. Janssens
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Ronald R. de Krijger
Princess Máxima Center for Pediatric Oncology
Cecile M. Ronckers
Constance A. Owens, PhD, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; Ethan B. Ludmir, MD, Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX; Qi Liu, PhD, and Weiyu Qiu, PhD, Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada; Aashish C. Gupta, MS, Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; Susan A. Smith, MPH, and Bastien Rigaud, PhD, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; Kristy K. Brock, PhD, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; James E. Bates, MD, Department of Radiation Oncology, Winship Cancer Institute, ...
Helena J.H. van der Pal
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Leontien C.M. Kremer
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Jop C. Teepen
Constance A. Owens, PhD, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; Ethan B. Ludmir, MD, Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX; Qi Liu, PhD, and Weiyu Qiu, PhD, Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada; Aashish C. Gupta, MS, Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; Susan A. Smith, MPH, and Bastien Rigaud, PhD, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; Kristy K. Brock, PhD, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX; James E. Bates, MD, Department of Radiation Oncology, Winship Cancer Institute, ...