Can baseline or Ra-223-induced changes in the plasma predict progressive disease mCRPC patients?
Lunj, S. Song, Yee Pei Hudson, Andrew M Patel, Kamlesh Nightingale, Hannah Smith, Tim A D Hoskin, Peter J Bristow, Robert G West, Catharine M L
Lunj, S.
Song, Yee Pei
Hudson, Andrew M
Patel, Kamlesh
Nightingale, Hannah
Smith, Tim A D
Hoskin, Peter J
Bristow, Robert G
West, Catharine M L
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Abstract
Purpose or Objective
Bone targeting agents such as Radium-223 (Ra-223) have changed the landscape for managing metastatic castration-resistant prostate cancer (mCRPC). Ra-223 is approved for men with symptomatic bone metastases but no known visceral
metastases. Not all patients respond to Ra-223, thus early stratification of patients can aid personalisation of treatment
plans. Our study aimed to explore the feasibility of measuring baseline and early Ra-223 induced changes in circulating
cytokines, chemokines and growth factors involved in the immune response.
Materials and Methods
Fifty patients with mCRPC with bone disease were recruited into the CAPRA study and received up to six four weekly
injections of Ra-223 (Figure 1). Patients were labelled responders (R) or non-responders (NR) depending on whether they
had improvement or progression of symptoms. Plasma was isolated from whole blood immediately after collection, then
frozen and stored at -80oC. Using a 30-plex Luminex assay, a technology that detects fluorescence (MFI) to estimate the
concentration of protein, we identified plasma-based cytokines, chemokines and growth factors and compared the levels
between Ra-223 responders and non-responders. Results
Analysis of the first seven patients in our pilot cohort at baseline (T1) and after the first three injections of Ra-223 (T4)
suggests that there are differences between baseline levels of some cytokines, with higher expression of the immune
stimulating cytokine; IL-12 observed in the responders (n = 4) versus non-responders (n = 3) (MFI:189.8±33 vs. 79.5±13
respectively) (Figure 2). In addition, the pilot data suggests that there is an increase in the immunosuppressive cytokine,
IL-6 in the non-responders (n = 2) after treatment with
Ra-223 (T1 vs. T4: 34.8±3 vs. 43.9±8) and a decrease in IL-6 in the responders (n = 4) (T1 vs. T4: 47.9±8 vs. 42.5±8) after
treatment with Ra-223 Our pilot data demonstrates the feasibility of using a multiplexed assay to measure differences in baseline and Ra-223-
induced changes in circulating markers in non-responders and responders. Further study is worthwhile to explore whether
these circulating markers can predict response to Ra-223.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Lunj S, Song YP, Hudson A, Patel K, Nightingale H, Smith T, et al. Can baseline or Ra-223-induced changes in the plasma predict progressive disease mCRPC patients? Radiotherapy and Oncology. 2021;161:S1646-S8.