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.

Abstract

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.

• Authors: Alexander Augustyn, Daniel L Adams, Jianzhong He, Yawei Qiao, Vivek Verma, Zhongxing Liao, Cha-Mei Tang, John V Heymach, Anne S Tsao, Steven H Lin
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 22 Issue 3 Pg. e451-e465 (05 2021) ISSN: 1938-0690 [Electronic] United States
• PMID: 32798130 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• atezolizumab

Topics

• Adenocarcinoma of Lung (pathology, therapy)
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (pathology, therapy)
• Carcinoma, Squamous Cell (pathology, therapy)
• Chemoradiotherapy (methods)
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (pathology, therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Neoplastic Cells, Circulating (metabolism)
• Prognosis
• Progression-Free Survival
• Prospective Studies
• Survival Rate