TY - JOUR
T1 - Giant Circulating Cancer-Associated Macrophage-Like Cells Are Associated With Disease Recurrence and Survival in Non–Small-Cell Lung Cancer Treated With Chemoradiation and Atezolizumab
AU - Augustyn, Alexander
AU - Adams, Daniel L.
AU - He, Jianzhong
AU - Qiao, Yawei
AU - Verma, Vivek
AU - Liao, Zhongxing
AU - Tang, Cha Mei
AU - Heymach, John V.
AU - Tsao, Anne S.
AU - Lin, Steven H.
N1 - Funding Information:
S.H.L. has received research funding from Hitachi Chemical , Roche / Genentech , New River Labs , and Beyond Spring Pharmaceuticals ; has served on the advisory boards for AstraZeneca and Beyond Spring Pharmaceuticals; and has received honoraria from Varian Medical Systems. D.L.A. and C.M.T. are employees of Creatv MicroTech Inc. The other authors have stated that they have no conflict of interest.
Funding Information:
Funded in part by Cancer Center Support (Core) grant CA016672 from the National Cancer Institute, National Institutes of Health , to The University of Texas MD Anderson Cancer Center; and Small Business Innovation Research grant R43CA206840 with Creatv MicroTech Inc from the National Institutes of Health (S.H.L.)
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/5
Y1 - 2021/5
N2 - Background: Cancer-associated macrophage-like cells (CAMLs) are a potential peripheral blood biomarker for disease progression. This study used data from a phase 2 clinical trial to evaluate prognostic utility of CAMLs for locally advanced non–small-cell lung cancer treated with definitive chemoradiotherapy (CRT) and atezolizumab (DETERRED; ClinicalTrials.gov NCT02525757). Patients and Methods: Sample collection occurred at baseline (T0), during CRT (T1), at end of CRT (T2), and at first follow-up (T3). CAMLs were captured and quantified by the CellSieve system using multiplex immunostaining. Giant CAMLs were defined as characteristic CAMLs ≥ 50 μm. Kaplan-Meier methodology estimated progression-free survival, distant failure-free survival, relapse-free survival, and overall survival at 30 months. Results: Thirty-nine patients were evaluated between December 2015 and March 2018. Median follow-up was 27 months. Most disease was stage III (85%) and comprised squamous-cell carcinoma (38%) or adenocarcinoma (59%). In total, 267 blood samples were analyzed. Giant CAMLs were identified in 57%, 60%, 64%, and 63% of patients at T0, T1, T2, and T3, respectively. Patients with giant CAMLs at T3, occurring at a median of 30 days after completion of CRT, had significantly worse distant failure-free survival (hazard ratio [HR] 4.9, P = .015), progression-free survival (HR 2.5, P = .025), recurrence-free survival (HR 2.4, P = .036), and overall survival (HR 3.5, P = .034) compared to patients with small or no CAMLs. Conclusions: Presence of giant CAMLs after CRT completion was associated with development of metastatic disease and poorer survival despite the use of maintenance immunotherapy. Monitoring CAMLs may help risk-stratify patients for adaptive treatment strategies.
AB - Background: Cancer-associated macrophage-like cells (CAMLs) are a potential peripheral blood biomarker for disease progression. This study used data from a phase 2 clinical trial to evaluate prognostic utility of CAMLs for locally advanced non–small-cell lung cancer treated with definitive chemoradiotherapy (CRT) and atezolizumab (DETERRED; ClinicalTrials.gov NCT02525757). Patients and Methods: Sample collection occurred at baseline (T0), during CRT (T1), at end of CRT (T2), and at first follow-up (T3). CAMLs were captured and quantified by the CellSieve system using multiplex immunostaining. Giant CAMLs were defined as characteristic CAMLs ≥ 50 μm. Kaplan-Meier methodology estimated progression-free survival, distant failure-free survival, relapse-free survival, and overall survival at 30 months. Results: Thirty-nine patients were evaluated between December 2015 and March 2018. Median follow-up was 27 months. Most disease was stage III (85%) and comprised squamous-cell carcinoma (38%) or adenocarcinoma (59%). In total, 267 blood samples were analyzed. Giant CAMLs were identified in 57%, 60%, 64%, and 63% of patients at T0, T1, T2, and T3, respectively. Patients with giant CAMLs at T3, occurring at a median of 30 days after completion of CRT, had significantly worse distant failure-free survival (hazard ratio [HR] 4.9, P = .015), progression-free survival (HR 2.5, P = .025), recurrence-free survival (HR 2.4, P = .036), and overall survival (HR 3.5, P = .034) compared to patients with small or no CAMLs. Conclusions: Presence of giant CAMLs after CRT completion was associated with development of metastatic disease and poorer survival despite the use of maintenance immunotherapy. Monitoring CAMLs may help risk-stratify patients for adaptive treatment strategies.
KW - Biomarker
KW - CAML
KW - Chemoradiation
KW - Immunotherapy
KW - NSCLC
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U2 - 10.1016/j.cllc.2020.06.016
DO - 10.1016/j.cllc.2020.06.016
M3 - Article
C2 - 32798130
AN - SCOPUS:85089288302
SN - 1525-7304
VL - 22
SP - e451-e465
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 3
ER -