Metastatic Neuroblastoma Confined to Distant Lymph Nodes Associated With Better Survival Compared With Other Stage IV Disease


Key Points

  • Patients with IV-N disease were more likely to be younger and to have tumors with favorable characteristics, including absence of MYCN amplification.
  • Patients with IV-N disease had significantly longer event-free and overall survival compared with non–IV-N patients.

The pattern of metastatic spread is not incorporated into current risk-stratification systems for neuroblastoma. In a retrospective study reported in the Journal of Clinical Oncology, Morgenstern et al found that patients with neuroblastoma with metastatic disease limited to distant lymph nodes (stage IV-N disease) have better outcomes than other stage IV patients.

Study Details

In the study, review of data from the International Neuroblastoma Risk Group database for patients diagnosed from 1990 to 2002 identified 2,250 patients with International Neuroblastoma Staging System (INSS) stage IV disease with complete data, of whom 146 (6.5%) had stage IV-N disease.

Patients with IV-N disease were significantly more likely to be younger (median, 423 vs 929 days, P < .001; 58% vs 30% < 18 months, P < .001) and to have earlier year of diagnosis, lower mean ferritin level, favorable histology (63% vs 26%, P < .001), differentiated histology (21% vs 8%, P = .0058), low mitosis karyorrhexis index (MKI; 76% vs 45%, P = .0011 for trend), nonamplified MYCN status (89% vs 69%, P < .001), and no initial treatment/surgery/conventional treatment (77% vs 30%, P < .001). They were also less likely to have adrenals (40% vs 60%, P < .001) and more likely to have thorax (26% vs 10%, P < .001) as the site of primary tumor.

Event-Free and Overall Survival

Five-year event-free survival (77% vs 35%, P < .001) and overall survival (85% vs 42%, P < .001) were significantly better in IV-N patients vs non–IV-N patients on unadjusted analysis. In multivariate analysis adjusting for INSS stage, age, MYCN status, year of diagnosis, serum ferritin level, and lactate dehydrogenase level, stage IV-N disease was an independent predictor of event-free survival (hazard ratio [HR] for non–IV-N vs IV-N = 3.40, P < .001) and overall survival (HR = 3.69, P < .001). Similar results were obtained when histology, ploidy, grade, MKI status, and 11q, 1p, and 17q status were incorporated into the model. Patients with IV-N disease also had significantly better outcomes in subgroups defined by age at diagnosis and MYCN status.

The investigators concluded: “[IV-N] represents a subgroup with better outcome than that of other patients with metastatic disease. These findings suggest that the biology and treatment response of [IV-N] tumors differ from other [stage IV] tumors, and less intensive therapy should be considered for this cohort. Future exploration of biologic factors determining the pattern of metastatic spread is warranted.”

Meredith Irwin, MD, of The Hospital for Sick Children, Toronto, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by the Hospital for Sick Children Research Training Competition, Sears Fellowship, Hospital Corporation of America International Foundation, Canada Research Chair and James Birrell Fund for Neuroblastoma Research, Cancer Research United Kingdom Life Chair and Programme, and National Institute for Health Research Royal Marsden/Institute of Cancer Research Biomedical Research Centre. The study authors reported no potential conflicts of interest.

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