Henderson TO, Bardwell JK, Kao PC, Nathan PC, Landier W, Mostoufi-Moab S, Brinkman TM, Schulte F, Park JR, Armenian SH, Naranjo A, Subramaniam M, Marachellian A, Diskin SJ, London WB, Diller LR. Late effects after high-risk neuroblastoma (LEAHRN): a multicentre, cross-sectional cohort study from the Children’s Oncology Group. Lancet Child Adolesc Health. 2025 Nov;9(11):776-786. doi: 10.1016/S2352-4642(25)00241-X. Epub 2025 Sep 25. PMID: 41016399; PMCID: PMC13251555.
Publication Citation
Abstract
New treatment regimens have resulted in increasing numbers of children who survive high-risk neuroblastoma (HRNBL), but late effects of cancer therapy are not well-studied. We aimed to explore treatment-related risk factors associated with late effects of modern HRNBL therapies. We conducted a multicenter, cooperative group cohort study of survivors; eligibility criteria included: aged 5-50 years at the time of enrollment, diagnosed after 2000, and at least five years from HRNBL diagnosis. Subject evaluations included an audiogram, pulmonary function test (PFT), echocardiogram, and laboratory studies. Exposures were abstracted via chart review. Multivariable logistic regression models examined associations between treatment-related risk factors versus hearing loss, growth failure, underweight, and restrictive lung disease (RLD). 375 eligible subjects enrolled between June 5, 2017 to September 17, 2021; Median age at HRNBL diagnosis was 2·5 years (range: 0·2-15·8), median age at enrollment was 12·0 years (range: 5·0-24·0), and median time from diagnosis to enrollment was 9·0 years (range: 5·1-18·2). All received chemotherapy, 97% (363/375) received at least one stem cell transplant (SCT) and 64% (231/363) received anti-GD2 therapy. Moderate to severe hearing loss was identified in 72% (236/327) of subjects. Growth failure or underweight were identified in 24% (87/360) and 51% (190/373), respectively. PFTs revealed moderate to severe RLD in 8% (17/207) of subjects. Longer follow-up was associated with a higher prevalence of late effects. Compared to single SCT, exposure to tandem SCT was associated with increased risk for growth failure [odds ratio (OR)=3·4, 95%CI: 1·6-7·2, p=0·0016] and moderate to severe RLD (OR=4·5, 95%CI: 1·1-18·3, p=0·033). Neither specific conditioning regimen exposure nor anti-GD2 therapy was associated with increased risk of hearing loss, underweight, growth failure, or RLD. Survivors of HRNBL treated with modern therapies demonstrated a substantial burden of late effects, providing critical information for future care and clinical trial design.