Abstract 2915: A circulating stromal cell subpopulation that accurately predicts resistance and progression in treatment naïve lung cancer patients receiving definitive radiotherapy
Authors: Daniel L. Adams, Jianzhong He, Yawei Qiao, Hui Gao, James Reuben, Ignacio I. Wistuba, Cha-Mei Tang, Steven H. Lin
Journal: Cancer Research (2019)

Abstract Background: Cancer Associated Macrophage-Like cells (CAMLs) are recently described circulating stromal cells common in the peripheral blood of cancer patients hypothesized to be a mechanism in cancer pathogenesis. We previously described that treatment naive patients with circulating CAMLs ≥50µm is a significant independent prognostic indicator of shorter progression free survival (PFS) in a variety of cancers. However, the clinical value of CAMLs in specific diseased cohorts for predicting response to treatment has not been evaluated. We present the results of a prospective study on treatment naive lung cancer patients before induction and directly after completion of definitive radiotherapy to determine if CAMLs are predictive of treatment response and cancer progression. Methods: A 2 year single blind prospective study was undertaken, testing the relationship of enlarged CAMLs (≥50µm) to PFS of lung cancer patients before &amp; after induction of definitive radiation therapy. To achieve a 2-tailed 95% power (α=0.05) we recruited a training set of 55 patients, all with pathologically confirmed lung cancer: Stage I (n=13), Stage II (n=7), Stage IIIa (n=10), Stage IIIb (n=18) &amp; Stage IV (n=7). Baseline (BL) blood samples were taken prior to start of therapy. If possible, a second blood sample (T1) was taken after completion of radiotherapy (~60 days), n=46 patients. Blood was filtered by CellSieveTM filtration and CAMLs quantified. Analysis by CAML size of &amp;lt;50 µm or ≥50 µm was used to evaluate PFS hazard ratios (HRs) by censored univariate &amp; multivariate analyses. Results: CAMLs were found in 93% of BL samples averaging 3.2 CAMLs/7.5mL. Patients with at least one CAML ≥50 µm had reduced PFS (HR=2.9, 95%CI 1.4-6.0, p=0.010). 46 patients agreed to a follow up blood draw. 13 of the 46 patients had an increase of CAML size to ≥50 µm, but 3 patients had a decrease to &amp;lt;50 µm, resulting in an increase of PFS (HR=7.7, 95%CI 2.6-12.5, p&amp;lt;0.001). Combined, 90% of patients with a ≥50 µm CAML at BL progressed within 2 years vs 46% of patients with &amp;lt;50 µm CAMLs. Enlarged CAMLs at T1 was more predictive of progression, with 92% of patients with a ≥50 µm CAML progressing vs 21% of patients with &amp;lt;50 µm CAMLs. Notably, 100% of patients that had a ≥50 µm CAML at both BL and T1 progressed. By comparison, only 11% of patients with &amp;lt;50 µm CAMLs at both BL and T1 progressed. In a multivariate analysis, CAML size was the most significant indicator of PFS and OS, independent of all other clinical variables, including stage. Conclusions: Our data suggests that for lung cancer patients undergoing definitive radiation therapy, the presence of enlarged CAMLs appears to predict patients that are resistant to treatment. Furthermore, these circulating stromal cells appear useful for sequential monitoring of patients that may prognosticate who are likely to progress after treatment. Citation Format: Daniel L. Adams, Jianzhong He, Yawei Qiao, Hui Gao, James Reuben, Ignacio I. Wistuba, Cha-Mei Tang, Steven H. Lin. A circulating stromal cell subpopulation that accurately predicts resistance and progression in treatment naïve lung cancer patients receiving definitive radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2915.