January 6, 2021
Journal Article

Platelet Cloaking of Circulating Tumour Cells in Patients with Metastatic Prostate Cancer: Results from the ExPeCT, a Randomised Controlled Trial

Juliette Hussey
Lauren Brady
Brian Hayes
Grainne Sheill
Anne-Marie Baird
Emer Guinan
Bryan Stanfill
Tatjana Vlajnic
Orla Casey
Verena Murphy
John Greene
Emma Allot
Fidelma Cahill
Mieke Van Hemelrijck
Nicola Peat
Lorelei Mucci
Moya Cunningham
Liam Grogan
Thomas Lynch
Rustom Manecksha
John McCaffrey
Dearbhaile O'Donnell
Orla Sheils
John O'Leary
Sarah Rudman
Ray McDermott
Stephen Finn

Abstract

The ExPeCT trial sought to examine the effectiveness of a structured exercise programme in modulating levels of circulating tumour cells (CTCs) and platelet cloaking in patients with metastatic prostate cancer. Five hospital sites in Dublin, Ireland and 1 hospital site in London, England, United Kingdom (UK). Participants Sixty-one men (>18 years) with metastatic prostate cancer capable of participating safely in the proposed exercise intervention as assessed and signed off by a treating physician; with no history of a radical prostatectomy or no previous diagnosis of any other malignant tumour (patients with non-melanoma skin cancer or carcinoma in situ of any type were not excluded provided they had undergone complete resection). Participants were randomised into control or exercise arms and assessed across three time points, baseline (T0), three months (T3) and six months (T6). Participants in the exercise arm completed six months of prescribed aerobic exercise, which was monitored using percentage heart-rate reserve. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking using the ScreenCell® CTC isolation platform, in conjunction with an MGG stain. CTC data was correlated with clinico-pathological information. Measure The primary endpoint was to examine the effect of a structured exercise intervention on CTC number and the presence of platelet cloaking between the exercise and control groups. Results Sixty-one participants were included in this study, with no significant differences in baseline characteristics observed between the exercise and control arms. Significant changes in CTC number were observed within group over time (Irish cohort T0 vs. T3 p=0.0001, T3 vs. T6 p=0.0011, London cohort T0 vs. T3 p=0.0026, T3 vs. T6 p=0.0011, T0 vs. T6 p=0.0003), however no significant difference in CTC number was observed between the exercise and control groups over time (p=0.2360). Platelet cloaking was identified in 29.5% of ExPeCT participants, with greater platelet cloaking observed in the control group (p=0.1005). Clinical variables were correlated with CTC number, platelet cloaking and CTC clusters. A significant positive correlation between CTC number and white cell count was observed (p=0.0001), in addition to a significant positive relationship between CTC clusters and PSA levels (p=0.0393). The ExPeCT trial demonstrated the feasibility for participants with metastatic prostate cancer to participate safely and effectively in a structured exercise intervention programme. In this study, the presence of platelet cloaking has been observed in this patient population for the first time. A novel correlation was identified between CTC number and white cell count. Thus, this possible synergistic relationship warrants further investigation in the metastatic cascade in prostate cancer.

Revised: January 6, 2021 | Published: December 18, 2020

Citation

Brady L., B. Hayes, G. Sheill, A. Baird, E. Guinan, B.A. Stanfill, and T. Vlajnic, et al. 2020. "Platelet Cloaking of Circulating Tumour Cells in Patients with Metastatic Prostate Cancer: Results from the ExPeCT, a Randomised Controlled Trial." PLOS ONE 15, no. 12:Article No. e0243928. PNNL-ACT-SA-10402. doi:10.1371/journal.pone.0243928