Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients

Izhar S. Batth, Long Dao, Arun Satelli, Abhisek Mitra, Sofia Yi, Hyangsoon Noh, Heming Li, Zachary Brownlee, Shouhao Zhou, Jeffrey Bond, Jing Wang, Jonathan Gill, Giselle S. Sholler, Shulin Li

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Neuroblastoma (NB) is a deadly childhood disease that carries a 50% chance of relapse for anyone in remission and similar level of 5-year survival. We investigated the value of our proprietary approach—cell surface vimentin (CSV) positive circulating tumor cells (CTC) to monitor treatment response and predict relapse in NB patients under remission in a Phase II long-term preventative clinical trial. We longitudinally analyzed peripheral blood samples from 93 patients for 27 cycles (~25 months) and discovered that the presence of CSV+ CTCs in the first two sequential samples (baseline, cycle 4 [month 3-4]) was a significant indicator of earlier relapse. We observed strong correlation between relapse-free survival (RFS) and lack of CSV+ CTCs in first 4 cycles of therapy (95%). There was sensitivity reaching 100% in predicting RFS in patients who had neither CSV+ CTCs nor MycN amplification. Of note, the low number of CSV+ CTCs seems equivalent to low tumor load because the prevention therapy difluoromethylornithine yields faster reduction of relapse risk when none or only 1-2 CSV+ CTCs (every 6 mL) are present in the blood samples compared to >3 CSV+ CTCs. To the best of our knowledge, this is the first study that directly observes CTCs in under remission NB patients for relapse prediction and the first to gather sequential CSV+ CTC data in any study in a long-term longitudinal manner.

Original languageEnglish (US)
Pages (from-to)3550-3559
Number of pages10
JournalInternational Journal of Cancer
Volume147
Issue number12
DOIs
StatePublished - Dec 15 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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