Significance of Circulating Tumor Cells in Patients With Squamous Cell Carcinoma of the Head and Neck

Abstract

Objectives To present and discuss a high-performance negative depletion method for the isolation of circulating tumor cells (CTCs) in the blood of patients with head and neck cancer and to determine the correlation between the presence of CTCs and early clinical outcome in these patients. Design Prospective clinical follow-up study of patients with squamous cell carcinoma of the head and neck (SCCHN) undergoing surgical intervention, who had peripheral blood examined for the presence of CTCs. Patients The study population comprised 48 patients diagnosed as having SCCHN and undergoing surgical intervention. Intervention A negative depletion process to isolate and quantify CTCs from the blood of patients with SCCHN using immunomagnetic separation was developed and validated. Immunostaining for cytokeratin was performed on the enriched samples to determine the number of CTCs extracted from each patient’s blood sample. Correlation of the presence of CTCs, tumor stage, nodal status, clinical characteristics, and outcome was made. Main Outcome Measure Disease-free survival. Results Our initial data, that have a mean follow-up of 19.0 months, suggest that patients with no detectable CTCs per milliliter of blood had a significantly higher probability of disease-free survival (P=.01). There was no correlation between the presence of CTCs with regard to age, sex, tumor site, stage, or nodal involvement. Conclusions Our enrichment technology, based on the removal of normal cells, has been used on the peripheral blood of patients with head and neck cancer for which follow-up data were collected. If no CTCs were present, a statistically significant improved disease-free survival was observed in SCCHN. A blood test with such a prognostic capability could have important implications in the treatment of patients with head and neck cancer.

Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells

“…However, if such modifications were successful, the payoff for developmental therapeutics would be quite large, because the longitudinal assessment of drug action on molecular targets required to characterize the PD of a new drug and set its optimal scheduling cannot be achieved using tumor biopsies, but must rely on less invasive assessment strategies such as the CTC “liquid biopsy”. The main competition for cell surface biomarker-based capture of CTCs comes from EpCAM-independent platforms for isolating and evaluating CTCs, including filtration approaches, 29, 30 depletion of normal blood cells (negative selection), 31, 32 microchip technology, 33 and dielectrophoresis field-flow. 34, 35 …”

Squamous cell carcinoma of the oral cavity and circulating tumour cells

“…The spread of tumour cells during surgery remains unclear but has been proven for fine needle aspiration or incision biopsy in OSCC [85,108] . A total of 71% of 48 patients harboured CTCs detected by Jatana et al [30] in HN-SCC. Here, samples were taken at the time of surgery.…”

“…The clinical relevance of CTC/DTC detection in carcinoma patients has been part of extensive research, and encouraging results exist for an association between CTC detection and the prognosis in patients with other solid tumours, such as metastatic breast, prostate, and gastrointestinal cancers [20][21][22][23][24][25][26][27][28] . For HNSCC, a putative prognostic value was identified as well, revealing a positive correlation between CTCs/DTCs to relapse and metastasis [29][30][31][32] . In this context, it is important to note that the clinical behaviour and outcome of OSCC differ from those of the oropharynx and other HNSCC.…”

Circulating tumour cells in regionally metastatic cutaneous squamous cell carcinoma: A pilot study

“…Detectable CTCs have shown implications for disease-free survival, overall survival, risk of local reoccurrence and risk of metastases in subgroups of other solid tumour groups [15]. However no studies have as yet focused on CTCs as markers for primary or metastatic disease in patients with cSCC.…”