Do bone marrow isolated tumor cells influence long-term survival of NSCLC?

Objective: To evaluate the survival for NSCLC in a group of patients in which the presence of bone marrow isolated tumor cells (ITC) and their DNA ploidy, was assessed. Methods: Before 2002 seventy patients (58 male [83%] median age 70 years r. 49–89) with clinical T1-4 N0 M0 status underwent surgery. None received neoadjuvant therapy. Bone marrow was extracted from a rib. ITC were identified using pan-cytokeratin antibody MNF116. DNAploidy was assessed by propridiumiodide staining. Bone marrow flow cytometry was diagnostic for ITC when >10% of cells reacted to MNF116. Immunohistochemistry and H and E staining assessed the biopsies. Follow-up was ruled on by chest X-ray and abdominal US at 6 month, CT/PET scan at 12 months for at least five years after surgery. Causes of death were assessed. Results: Flow cytometry was negative in 52 patients (74%), (P-stage: I 32; II 8; III 10; IV 2); positive for ITC in 18 patients (26%): 6 with DNA euploidy (P-stage: I 4; III 2); and 12 with DNA aneuploidy (P-stage: I 5; II 4; III 3). Intraoperative mortality was 0, median follow-up was 61 months, 21 patients died for causes unrelated to NSCLC. Significant survival differences were calculated according to stage, presence/absence of ITC and DNA aneuploidy. In P-stage Ia-b the disease free survival of patients with aneuploid ITC was significantly worse than the survival of patients without ITC or with euploid ITC (Mantel-Cox P=0.0001) (Fig. 1). Conclusions: Aneuploid ITC influences negatively NSCLC survival particularly in stage I NSCLC.