Pragmatic, Multicenter, Double-Blind Evaluation of Circulating Cancer-Associated Macrophage-Like Cells for Detection of Cancer in Indeterminate Pulmonary Nodules

PURPOSE: Cancer-associated macrophage-like cells (CAMLs) are specialized myeloid polyploid cells that emanate from primary tumor masses and transit circulation in a variety of malignancies, which have the potential to track cancer progression and therapy response. Previous studies have demonstrated that larger CAMLs (≥30 μM and ≥50 μM) are particularly associated with disease progression. We hypothesized that CAMLs could provide additional cancer risk information for patients with indeterminate lung nodules. MATERIALS AND METHODS: This was a double-blind, multicenter study to evaluate CAMLs in the blood as diagnostic biomarkers for malignancy. We enrolled 203 patients with indeterminate nodules (0.8-3 cm) and no diagnosis of cancer. Blood samples were obtained at the time of the initial evaluation and before diagnostic procedures; physicians were blinded to the CAML results. We determined the prevalence of CAMLs ≥30 μM (CAML+) at the initial screening and calculated screening statistics including positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of CAML+ for any malignancy detected during follow-up. RESULTS: Of the 203 enrolled patients, 200 had their samples sent for CAML analysis. For evaluable patients (n = 191), there were 41 with non-small cell lung cancer, four with small cell lung cancer, six with carcinoid, and five with other malignancies. For eight patients, a biopsy was either nondiagnostic or not feasible; they were treated for lung cancer with radiotherapy (and counted as cancer). CAMLs were detected in 45.0% of all patient samples (95% CI, 37.8% to 52.4%). For the detection of any malignancy, CAML PPV and NPV were 27.9% and 61.9%, respectively, and sensitivity and specificity were 37.5% and 51.2%, respectively. Defining CAML+ as larger CAML size (≥50 μM) did not significantly alter the results. CONCLUSION: CAMLs are neither sensitive nor specific to the presence of malignancy in indeterminate pulmonary nodules.