Circulating tumor cells in patients with recurrent or metastatic head and neck carcinoma: prognostic and predictive significance

Salvatore Grisanti; Camillo Almici; Francesca Consoli; Michela Buglione; Rosanna Verardi; Andrea Bolzoni-Villaret; Andrea Bianchetti; Chiara Ciccarese; Monica Mangoni; Laura Ferrari; Gianpaolo Biti; Mirella Marini; Vittorio D Ferrari; Piero Nicolai; Stefano M Magrini; Alfredo Berruti

doi:10.1371/journal.pone.0103918

Circulating tumor cells in patients with recurrent or metastatic head and neck carcinoma: prognostic and predictive significance

PLoS One. 2014 Aug 8;9(8):e103918. doi: 10.1371/journal.pone.0103918. eCollection 2014.

Authors

Salvatore Grisanti¹, Camillo Almici², Francesca Consoli¹, Michela Buglione³, Rosanna Verardi², Andrea Bolzoni-Villaret⁴, Andrea Bianchetti², Chiara Ciccarese¹, Monica Mangoni⁵, Laura Ferrari¹, Gianpaolo Biti⁵, Mirella Marini², Vittorio D Ferrari¹, Piero Nicolai⁴, Stefano M Magrini³, Alfredo Berruti¹

Affiliations

¹ Medical Oncology Unit, University of Brescia and Spedali Civili Hospital, Brescia, Italy.
² Department of Transfusion Medicine, Laboratory for Stem Cell Manipulation and Cryopreservation, Spedali Civili Hospital, Brescia, Italy.
³ Radiation Oncology Unit, University of Brescia and Spedali Civili Hospital, Brescia, Italy.
⁴ Otorhinolaryngology, Head and Neck Surgery Unit, University of Brescia and Spedali Civili Hospital, Brescia, Italy.
⁵ Department of Radiation Oncology, University of Florence, Florence, Italy.

Abstract

Introduction: We investigated the frequency of detection and the prognostic and predictive significance of circulating tumor cells (CTCs) in patients with recurrent/metastatic (R/M) head and neck carcinoma (HNC) before starting systemic therapy.

Patients and methods: Using the CellSearch technology, CTCs were assessed prospectively in peripheral blood of 53 R/M-HNC patients. We performed spiking experiments to test the diagnostic performance of the CellSearch platform in identifying squamous carcinoma cells.

Results: CTCs were identified in 14 (26%) and 22 (41%) patients at baseline and at any time point, respectively. In univariate analysis ≥2 CTCs had a poorer prognostic role than 0-1 CTC. In multivariate analysis, the presence of one CTC or more was associated with a poor prognosis both in terms of progression-free survival (PFS) [Hazard Ratio (HR): 3.068, 95% confidence interval (CI): 1.53-6.13, p 0.002] and overall survival (OS) [HR: 3.0, 95% CI: 1.48-6.0, p 0.002]. A disease control after systemic therapy was obtained in 8% of CTC-positive patients as opposed to 45% in CTC-negative ones (p 0.03). The epidermal growth factor receptor (EGFR) expression was identified in 45% of CTC-positive patients.

Discussion: In conclusion, CTCs are detected in one out of three patients with RM-HNC. CTC detection is a strong prognostic parameter and may be predictive of treatment efficacy. The frequency of EGFR expression in CTCs seems to be lower than that expected in the primary tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor*
Disease-Free Survival
ErbB Receptors / metabolism
Head and Neck Neoplasms / diagnosis*
Head and Neck Neoplasms / pathology*
Humans
Multivariate Analysis
Neoplasm Metastasis / pathology*
Neoplastic Cells, Circulating / pathology*
Odds Ratio
Prognosis

Substances

Biomarkers, Tumor
EGFR protein, human
ErbB Receptors

Grants and funding

This work was supported in part by a grant from the Regione Lombardia Piano Sangue 2008–2010 and Piano Sangue 2010–2012, in part by a grant from the Ministero dell'Istruzione dell'Università e della Ricerca (MIUR) 2009, and in part by a donation of Mrs Marilena Bortolotti in memory of Carlo Ridon. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.