Highlights from

ASCO 2021

American Society of Clinical Oncology annual meeting

Virtual 4-8 June 2021

Circulating tumour DNA to evaluate response in children with neuroblastoma

Summary: In the phase II NANT2011-01 trial, levels of circulating tumour DNA (ctDNA) were evaluated during treatment. In patients with a clinical response, ctDNA becomes undetectable over time.

Neuroblastoma is the most common extracranial solid tumour in paediatrics. High-risk disease comprises about half of all diagnoses and long-term survival is poor. Plasma ctDNA has been demonstrated to be present at high levels in neuroblastoma and provides an important tool and surrogate for tumour molecular analyses.1 Metaiodobenzylguanidine (MIBG) is used as both a diagnostic and therapeutic agent for neuroblastoma. Plasma samples from the NANT2011-01 trial (NCT02035137), a multicentre, open-label, randomised, phase II clinical trial evaluating MIBG with or without radiation sensitisers for patients with relapsed or refractory neuroblastoma, were used to evaluate the potential use of ctDNA as a biomarker to evaluate response to MIGB. Plasma was collected at baseline prior to MIBG and at 4, 5, 15, and 50 days after MIBG. Samples were analysed for percentage ctDNA levels using ultra-low passage whole-genome sequencing.

Dr Kevin Campbell (Dana-Farber Cancer Institute, MA, US) presented the results of this preplanned exploratory analysis of NANT2011-01 [2]. A total of 84 patients, median age 6.25 years, were included in this analysis. Of the 37 patients (44%) with detectable ctDNA at baseline, the median ctDNA level was 32%. Baseline ctDNA levels showed a significant positive correlation with percentage involvement in bone marrow and Curie score, but not RECIST sum of diameters for soft tissue sites. Following therapy, the proportions of patients with detectable ctDNA were 47% at day 4, 62% at day 5, 33% at day 15, and 14% at day 50. Rate of ctDNA detection was similar between responders and non-responders at baseline, and at days 4 and 5, but undetectable in responders at day 15 and day 50 versus 37% and 20% in non-responders. Based on these results, Dr Campbell concluded that “ctDNA is detectable in a substantial proportion of patients with relapsed or refractory neuroblastoma, with levels correlated with conventional measures of disease burden. Following MIBG therapy, early timepoints are less informative, whereas ctDNA becomes undetectable at day 15 and day 50 more commonly in patients with clinical response. This warrants further use of ctDNA to evaluate the response on treatment in children with relapsed or refractory neuroblastoma. For example, to study how copy number alterations or segmental chromosomal aberrations detectable in ctDNA might be associated with differential response to MIBG therapy.”

  1. Klega K, Imamovic-Tuco A et al. Detection of somatic structural variants enables quantification and characterization of circulating tumor DNA in children with solid tumors. JCO Presic Oncol 2018;2:PO.17.00285 [full text]
  2. Campbell K M et al. Changes in ctDNA levels after MIBG therapy in patients with relapsed or refractory neuroblastoma. Abstract 10012, ASCO 2021, 4-8 June 2021

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