Late effects after high-risk neuroblastoma (LEAHRN): a multicentre, cross-sectional cohort study from the Children's...

New treatment regimens have resulted in increasing numbers of children who survive high-risk neuroblastoma, but late effects of cancer therapy are not well studied. We aimed to explore treatment-related risk factors associated with late effects of modern therapies for high-risk neuroblastoma.

This multicentre, cross-sectional cohort study of survivors of high-risk neuroblastoma was done at 88 hospitals participating in the Children's Oncology Group (COG) in North America, Australia, and New Zealand. Eligible participants were aged 5-50 years at enrolment, were enrolled on ANBL00B1, were diagnosed with high-risk neuroblastoma on or after Jan 1, 2000, were alive at least 5 years after diagnosis, and had language skills in English, French, or Spanish. Individuals with active neuroblastoma relapse (cytotoxic chemotherapy in the previous 2 years) were ineligible. Participant evaluations included an audiogram, pulmonary function test, echocardiogram, and laboratory studies. Exposures were abstracted via chart review. Prevalence of a specific late effect was calculated as the number of participants with the late effect divided by the sample size with known data for that late effect. Multivariable logistic regression models examined associations between treatment-related risk factors versus hearing loss, growth failure, underweight, and restrictive lung disease.

Between June 5, 2017 and Sept 17, 2021, 375 eligible participants were enrolled from 890 potentially eligible individuals. Median age at high-risk neuroblastoma diagnosis was 2·5 years (range 0·2-15·8), median age at enrolment was 12·0 years (5·0-24·0), and median time from diagnosis to enrolment was 9·0 years (5·1-18·2). All participants received chemotherapy, 363 (97%) of 375 received at least one stem cell transplant and 231 (64%) of 363 patients with known data received anti-GD2 therapy. Moderate-to-severe hearing loss was identified in 236 (72%) of 327 participants. Growth failure was identified in 87 (24%) of 360 and underweight in 190 (51%) of 373. Pulmonary function tests revealed moderate-to-severe restrictive lung disease in 17 (8%) of 207 participants. Longer follow-up was associated with a higher prevalence of late effects. Compared with single stem-cell transplant, exposure to tandem stem-cell transplant was associated with increased risk of growth failure (odds ratio [OR] 3·4 [95% CI 1·6-7·2], p=0·0016] and moderate-to-severe restrictive lung disease (OR 4·5 [1·1-18·3]; p=0·033). Neither conditioning regimen exposure (carboplatin-etoposide-melphalan vs busulfan-melphalan) nor anti-GD2 therapy was associated with increased risk of hearing loss, underweight, growth failure, or restrictive lung disease.

Survivors of high-risk neuroblastoma treated with modern therapies demonstrated a substantial burden of late effects, providing crucial information for future care and clinical trial design.

The Children's Oncology Group National Clinical Trials Network (NCTN) Statistics and Data Center, NCTN Operations Center, St Baldrick's Foundation Consortium, National Cancer Institute Community Oncology Research Programme, and Dana-Farber Cancer Institute Neuroblastoma Research Fund.