Advertisement

Blood Test Could Improve Treatment for Children With Late-Stage Neuroblastoma

Advertisement

Key Points

  • High levels of TH, PHOX2B, or DCX mRNA in peripheral blood or bone marrow at diagnosis strongly predicted worse event-free survival and overall survival in children with stage IV neuroblastoma.
  • Detection of neuroblastoma mRNAs in peripheral blood and bone marrow aspirates of children with stage IV neuroblastoma could help identify those with ultra high–risk disease who may benefit from novel treatment approaches.

Research by Viprey et al has found that the detection of neuroblastoma mRNAs in peripheral blood and bone marrow aspirates from children diagnosed with stage IV neuroblastoma are independent predictors of event-free survival and overall survival. Their findings could help identify children with ultra high–risk disease who may benefit from novel treatment approaches. The study is published in the Journal of Clinical Oncology.

The researchers investigated the clinical significance of detecting a selected panel of three neuroblastoma mRNAs (paired-like homeobox 2b [PHOX2B], tyrosine hydroxylase [TH], and doublecortin [DCX]) by reverse transcriptase quantitative polymerase chain reaction in bone marrow and peripheral blood from children enrolled in the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group. The biospecimen samples were collected at the time of diagnosis and after dose-intensive induction chemotherapy (rapid cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide).

Study Results

The scientists found that high levels of TH, PHOX2B, or DCX mRNA in the peripheral blood or bone marrow at diagnosis strongly predicted worse event-free survival and overall survival in a cohort of 290 children. The median age of patients was 35 months. After induction therapy, high levels of these mRNAs predicted worse event-free survival and overall survival in bone marrow but not in peripheral blood.

Combinations of mRNAs in bone marrow did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) peripheral blood cohorts, high TH (log10TH > 0.8) or high PHOX2B (log10PHOX2B > 0.28) identified 19% of children as ultra high risk, with 5-year event-free and overall survival rates of 0%. In the remaining children, the overall survival rate was 25% (95% confidence interval [CI] = 16%–36%), and the event-free survival rate was 38% (95% CI = 28%–49%).

According to the study, the magnitude of reduction in mRNA level between diagnosis and postinduction therapy in bone marrow and peripheral blood was not of additional predictive value.

“The results from this [reverse transcriptase quantitative polymerase chain reaction] study warrant a biomarker qualification study, stratifying children with high-risk neuroblastoma for therapy based on the level of TH and PHOX2B mRNAs in peripheral blood at diagnosis. The dynamic range and prognostic value of these neuroblastoma mRNAs may contribute to the development of a prognostic score for integration into clinical practice, informing treatment choice for children with high-risk neuroblastoma,” concluded the researchers.

According to St. Jude Children’s Research Hospital, neuroblastoma accounts for 7% to 10% of childhood cancers and for 50% of all cancers in infants, making it the most common tumor in infants younger than 1 year. This year, 800 new cases of neuroblastoma will be diagnosed in the United States.

Susan A. Burchill, PhD, BSc, of the Leeds Institute for Cancer and Pathology, St. James University Hospital, Leeds, UK, is the corresponding author for the Journal of Clinical Oncology article.

Funding for this study was provided by Cancer Research UK, the Neuroblastoma Society, the Italian Neuroblastom Foundation, the French National Hospital, University Hospital Motol, and the University of Leeds. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement



Advertisement