Adams, Diane K.

11503 Background: Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell subtype commonly found in the peripheral blood of patients in all stages of solid malignancies and in a variety of cancer subtypes. However, while their biological association to cancer is being studied, their clinical utilization as it relates to cancer prognosis has not been evaluated. Methods: A two year prospective study was undertaken to evaluate the relationship of CAMLs and overall survival (OS) in 6 solid tumor types. The single blind multi-institutional study consisted of 269 stage I-IV patients; breast (n = 57), esophageal (n = 21), prostate (n = 43), pancreatic (n = 59), lung (n = 54), and renal cell (n = 35), in treatment (n = 134) and untreated baseline (n = 135). 7.5mL of whole blood was filtered by CellSieve microfiltration assay and CAMLs enumerated, as previously described. Patients were grouped by CAML number ( < 6 or ≥6) and by size ( < 49 or ≥50 µm) to evaluate hazard ratios (HR) by censored univariate & multivariate analysis. Results: CAMLs were identified in 93% of samples, averaging 8.2 CAMLs/7.5mL blood sample, and found in all 6 cancers at baseline and during treatment. Average CAML number was associated with disease stage and CAML positivity was 4.4 & 80% (Stage I), 4.7 & 93% (Stage II), 9.3 & 98% (Stage 3), 12.1 & 97% (Stage IV). Univariate analysis of patients (n = 269) stratified by ≥6 CAMLs had reduced OS (HR = 1.8, 95%CI 1.1-2.9, p = 0.03). Further, CAML size also had reduced OS in patients with ≥50 µm CAMLs (HR = 2.7, 95%CI 1.8-4.0, p < 0.0001). Conclusions: Our data suggests that in solid malignancies, CAML number and size appear to clinically correlate with OS in early and late stage disease. Given these results relating CAMLs with OS, further analysis is warranted to determine if CAMLs can serve as a clinically-relevant blood-based marker.

Abstract Background: Blood-based testing can be used as a noninvasive method to recover and analyze circulating tumor-derived cells for clinical use. Circulating cancer-associated macrophage-like cells (CAML) are specialized myeloid cells found in peripheral blood and associated with the presence of solid malignancies. We measured CAMLs prospectively in peripheral blood to ascertain their prevalence, specificity, and sensitivity in relation to breast disease status at clinical presentation. Methods: We report on two related but separate studies: 1) CellSieve microfilters were used to isolate CAMLs from blood samples of patients with known malignant disease (n = 41). Prevalence and specificity was compared against healthy volunteers (n = 16). 2) A follow-up double-blind pilot study was conducted on women (n = 41) undergoing core-needle biopsy to diagnose suspicious breast masses. Results: CAMLs were found in 93% of known malignant patients (n = 38/41), averaging 19.4 cells per sample, but none in the healthy controls. In subjects undergoing core biopsy for initial diagnosis, CAMLs were found in 88% of subjects with invasive carcinoma (n = 15/17) and 26% with benign breast conditions (n = 5/19). Conclusion: These preliminary pilot studies suggest that the presence of CAMLs may differentiate patients with malignant disease, benign breast conditions, and healthy individuals. Impact: We supply evidence that this previously unidentified circulating stromal cell may have utility as a screening tool to detect breast cancer in various malignancies, irrespective of disease stage. Cancer Epidemiol Biomarkers Prev; 25(7); 1037–42. ©2016 AACR.

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