Radiation and Cancer Biology
SS 40 - Biology 8 - Biomarkers of Response
236 - Presence of Giant Circulating Cancer-Associated Macrophage-like Cells after Definitive Chemoradiation Predicts for Progression in Locally Advanced Non-Small Cell Lung Cancer Patients
Wednesday, September 18
3:35 PM - 3:45 PM
Location: Room W179
Presence of Giant Circulating Cancer-Associated Macrophage-like Cells after Definitive Chemoradiation Predicts for Progression in Locally Advanced Non-Small Cell Lung Cancer Patients
A. Augustyn1, D. L. Adams2, J. He1, Y. Qiao1, T. Xu1, A. Raghavakaimal3, Z. Liao1, P. Amstutz4, C. M. Tang4, and S. H. Lin1; 1MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX, 2CreatvMicroTech, Inc., Monmouth Junction, NJ, 3Rutgers University, New Brunswick, NJ, 4CreatvMicroTech, Inc., Potomac, MD
Purpose/Objective(s): Circulating cancer-associated macrophage-like cells (CAMLs) are a recently described stromal cell found in the peripheral blood of cancer patients that have been shown to be associated with disease progression. Giant CAMLS (≥50 µm) observed at baseline, before initiation of treatment, were previously reported to be predictive of disease progression in non-small cell lung cancer (NSCLC). In this prospective analysis of patients with unresectable locally advanced NSCLC, we explored the utility of CAMLs in predicting progression based on blood samples collected before, during, and at the completion of definitive chemoradiation therapy (CRT).
Materials/Methods: This 3 year prospective single blinded study assessed the role of CAMLs in determining clinical outcomes in patients undergoing definitive CRT for unresectable, locally advanced NSCLC (stage IIB n=7, stage IIIA n=22, stage IIIB n=11, and stage IIIC n=3). Patients were enrolled between December 2015 and January 2018. Median follow up after the completion of CRT was 14.9 months. CAMLs were collected by obtaining peripheral blood from patients at baseline before treatment (T0), during treatment (T1), and at the completion of treatment (T2). Blood was filtered using filtration and CAMLs quantified. CAML size ≤49 µm or ≥50 µm was quantified with the observer blinded to clinical information. Relapse free survival (RFS), progression free survival (PFS), and overall survival (OS) were analyzed at each time point.
Results: We evaluated 43 patients with unresectable locally advanced NSCLC and obtained a total of 172 samples. CAMLs were identified in 78% of samples (81% at T0, 86% at T1, and 74% at T2), averaging 2.28 CAMLs per 7.5 mL sample. Patients with giant CAMLs (≥50 µm) compared to those with smaller CAMLs (≤49 µm) at T0 or T1 exhibited no difference in RFS, PFS, or OS. Patients with detectable giant CAMLS at the completion of treatment (T2) demonstrated significantly worse RFS (HR=7.66, 95% CI 1.87-31.4, p=0.0047), PFS (HR=4.51, 95% CI 1.36-14.96, p=0.0139) and OS (HR=3.86 95% CI 1.02-14.59, p=0.0465). Median RFS, PFS, and OS for patients without giant CAMLs was not reached, while median RFS, PFS, and OS for patients with giant CAMLs was 7, 13, and 13 months, respectively.
Conclusion: Our data suggest that the presence of giant CAMLs at the completion of definitive chemoradiation for locally advanced NSCLC is predictive of disease progression and death. Continued prospective validation of CAMLs as a peripheral blood-based biomarker is needed to validate these findings. Accurate stratification of individual patients based on the presence of giant CAMLs may aid in more personalized therapeutic regimes, particularly in the era of adjuvant immunotherapy, while determining the role of CAMLs in the disease process may uncover new therapeutic modalities.
Author Disclosure: A. Augustyn: None. D.L. Adams: Stock; CreatvMicrotech, Inc. J. He: None. Y. Qiao: None. A. Raghavakaimal: None. Z. Liao: Past Chair; ASTRO IES. C. Tang: Stock; CreatvMicrotech, Inc. S.H. Lin: Research Grant; Hitachi Chemical, Inc, New River Labs, Beyond Spring Pharmaceuticals, Inc. Advisory Board; AstraZeneca Inc.