Cell surface vimentin‐positive circulating tumor cell‐based relapse prediction in a long‐term longitudinal study of postremission neuroblastoma patients. Issue 12 (23rd June 2020)

• Record Type: Journal Article
• Authors: Batth, Izhar S.; Dao, Long; Satelli, Arun; Mitra, Abhisek; Yi, Sofia; Noh, Hyangsoon; Li, Heming; Brownlee, Zachary; Zhou, Shouhao; Bond, Jeffrey; Wang, Jing; Gill, Jonathan; Sholler, Giselle S.; Li, Shulin
• Is Part Of: International journal of cancer. Volume 147:Issue 12(2020)
• Page Start: 3550
• Page End: 3559
• Publication Date: 2020-06-23
• Subjects: circulating tumor cell -- difluoromethylornithine -- liquid biopsies -- neuroblastoma -- relapse; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33140
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Neuroblastoma is an aggressive childhood cancer with a 50% chance of relapse for patients in remission and a similar level of 5‐year survival. While circulating tumor cells (CTCs) are instrumental in the early prediction of relapse in various cancers, their potential in neuroblastoma remains understudied. This Phase II long‐term preventative clinical trial of patients under remission showed that cell surface vimentin (CSV) could be used as a marker for CTCs in neuroblastoma. Moreover, CSV+ CTCs could be used alongside analysis of MycN amplification to predict relapse. These two factors, when combined, showed 100% sensitivity in predicting relapse‐free survival in patients.