Abstract
Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age ≥ 18 months, LDH ≥ 1400 U/L, and BP ≥ 7 correlated with lower overall and event-free survival rates (p < 0.05). The genome subgroup GG-P2s (partial chromosome gain/loss type with 1p/11q losses and 17q gain, n = 30) was strongly associated with a lower overall survival rate (5-year survival rate: 34%, p < 0.05). Therefore, the combination of the tumor genomic pattern (GG-P2s and BP ≥ 7) with age at diagnosis and LDH will be a promising predictor for MYCN-non-amplified high-risk NBs in patient subsets, in accordance with previous findings from the INRG project.
Highlights
Neuroblastomas (NBs), the most common extracranial solid cancer occurring in childhood, are characterized by broad and divergent clinical behaviors [1,2,3,4]
As a cooperative effort by the Japan Neuroblastoma Study Group (JNBSG) in 2014 (JNB-FU-2014), follow-up data of 1985 NB patients were collected from 112 hospitals in Japan
30 items were surveyed according to common INRG queries, including age at diagnosis, year of diagnosis, initial treatment, tumor stage, MYCN status, DNA ploidy, chromosomal aberrations in 1p, 11q, and 17q, serum ferritin and LDH levels, primary tumor sites, metastatic tumor sites, pathological information, race, sex, site of relapse, secondary malignancy, and Overall survival (OS) and event-free survival (EFS)
Summary
Neuroblastomas (NBs), the most common extracranial solid cancer occurring in childhood, are characterized by broad and divergent clinical behaviors [1,2,3,4]. Tumors in infants are mostly favorable and often show spontaneous maturation or regression, whereas those in patients older than 18 months are more likely to grow aggressively and are often associated with a fatal outcome even with multimodality therapy. Risk stratification based on patient and tumor characteristics at diagnosis is vital for selecting the most appropriate treatment. Multiple genome analyses have been conducted to characterize and classify tumor subsets with a heterogeneous clinical phenotype.
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