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Cell surface vimentin‐positive circulating tumor cell‐based relapse prediction in a long‐term longitudinal study of postremission neuroblastoma patients
Author(s) -
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
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33140
Subject(s) - circulating tumor cell , medicine , neuroblastoma , oncology , vimentin , peripheral blood , primary tumor , predictive value , cancer , immunohistochemistry , metastasis , biology , cell culture , genetics
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.