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Disseminated Tumor Cells in Bone Marrow and the Natural Course of Resected Esophageal Cancer

Vashist, Yogesh K. MD*; Effenberger, Katharina E. PhD*,†; Vettorazzi, Eik; Riethdorf, Sabine PhD; Yekebas, Emre F. MD*; Izbicki, Jakob R. FACS*; Pantel, Klaus PhD

doi: 10.1097/SLA.0b013e3182565b0b
Original Articles

Objective: To assess the impact of disseminated tumor cells (DTC) in bone marrow on recurrence and survival in complete resected esophageal cancer (EC).

Background: Current modalities to predict tumor recurrence and survival in EC are insufficient. Here, we evaluated in a prospective study the prognostic relevance of DTC in bone marrow for the natural postoperative course of EC.

Methods: We enrolled 370 consecutive EC patients (1995–2009). All tumors, 189 squamous cell carcinomas and 181 adenocarcinomas, were completely surgically resected (R0), and patients received neither neoadjuvant nor adjuvant therapy. Disseminated tumor cells were detected by an immunocytochemical cytokeratin assay in preoperatively taken bone marrow aspirates. The results were correlated with clinic-pathological parameters and clinical outcome.

Results: Overall 120 (32.4%) patients harbored DTC in their bone marrow. Presence of DTC significantly correlated with aggressive tumor biology as indicated by increased tumor size (P = 0.026), regional (P = 0.002) and distant (P = 0.012) lymph node metastases, and higher relapse rate (P < 0.001, χ2 test). A gradual decrease in disease-free (P < 0.001) and overall (P < 0.001, log-rank test) survival was observed between DTC-negative and DTC-positive patients and was evident in subgroup analysis stratified for nodal status, lymph node yield, lymph node ratio, and tumor subtypes. Disseminated tumor cells were identified as a strong independent prognosticator of tumor recurrence (hazard ratio [HR] 4.0, 95% confidence interval [CI]: 2.96–5.45, P < 0.001) and overall survival (HR 3.1, 95% CI: 2.37–4.09, P < 0.001, Cox regression analysis).

Conclusions: The presence of DTC in bone marrow is a strong and independent prognostic factor in patients with resectable EC.

Supplemental Digital Content is available in the text.Recurrence even in node-negative patients is common in esophageal cancer. Utilization of available multimodal therapy concepts requires stratification into different risk profiles for recurrence and poor survival. Detection of disseminated tumor cells in bone marrow may serve as a stage-independent prognostic marker in complete resected esophageal cancer.

*Department of General, Visceral and Thoracic Surgery

Department of Tumor Biology

Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistrasse, Hamburg, Germany.

Reprints: Klaus Pantel, MD, PhD, Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. E-mail:

Y.K.V. and K.E.E. contributed equally.

Disclosure: The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

© 2012 Lippincott Williams & Wilkins, Inc.