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Circulating tumour DNA to evaluate response in children with neuroblastoma

Presented by
Dr Kevin Campbell, Dana-Farber Cancer Institute, MA, USA
ASCO 2021
Phase 2, NANT2011-01
In the phase 2 NANT2011-01 trial, levels of circulating tumour DNA (ctDNA) were evaluated during treatment. In patients with a clinical response, ctDNA became 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].

The multicentre, open-label, randomised, phase 2 NANT2011-01 trial (NCT02035137) evaluated the diagnostic and therapeutic agent metaiodobenzylguanidine (MIBG) with or without radiation sensitisers for patients with relapsed or refractory neuroblastoma. In a pre-planned exploratory analysis, presented by Dr Kevin Campbell (Dana-Farber Cancer Institute, MA, USA), plasma samples from the NANT2011-01 trial, were used to evaluate the potential use of ctDNA as a biomarker to evaluate response to MIBG [2]. 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.

This analysis included 84 patients with a median age of 6.25 years. 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. The rate of ctDNA detection was similar between responders and non-responders at baseline, day 4, and day 5, but undetectable in responders at day 15 and day 50 versus 37% and 20% in non-responders (see Table).

Table: Proportion of patients with detectable ctDNA according to response to first course [2]

Dr Campbell concluded that these results warrant further use of ctDNA to evaluate the response to treatment in children with relapsed or refractory neuroblastoma. For example, it should be investigated how copy number alterations or segmental chromosomal aberrations detectable in ctDNA might be associated with differential response to MIBG therapy.

  1. Klega K, et al. JCO Presic Oncol. 2018;2:PO.17.00285.

  2. Campbell KM, et al. Changes in ctDNA levels after MIBG therapy in patients with relapsed or refractory neuroblastoma. Abstract 10012, ASCO 2021 Virtual Meeting, 4–8 June.

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