Micrometastatic Tumor Detection in Patients With Head and Neck Cancer

Wirtschafter, Ari; Benninger, Michael S.; Moss, Thomas J.; Umiel, Tehila; Blazoff, Kathleen; Worsham, Maria J.

doi:10.1001/archotol.128.1.40

Cited by 34 publications

(24 citation statements)

References 6 publications

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“…A variety of techniques have been employed to identify these tumour cells including immunocytochemistry, typically using antibodies to detect cytokeratins, and RT-PCR analysis using total RNA extracted from the nucleated cell fraction in whole blood and lineage specific markers [8,29-32]. More recently, methods for the positive or negative enrichment of tumour cells, prior to detection using PCR and RT-PCR assays, have reduced the rate of false positivity from illegitimate expression of some more commonly used markers in normal blood cells [33-35]. …”

Section: Discussionmentioning

confidence: 99%

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

et al. 2009

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BackgroundTechniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment.MethodsReconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas.ResultsSeven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival.ConclusionFor the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further.

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Section: Discussionmentioning

confidence: 99%

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

et al. 2009

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“…Although computed tomography, MRI, tissue/sentinel lymph node biopsy, and serum cancer marker analysis can all detect some level of residual disease, the presence of circulating tumor cells (CTCs) is reported to correlate most sensitively with cancer progression and metastasis (1,2). Measurement of CTCs, however, remains difficult, with most methods relying on quantitation of cells expressing epithelial markers after their isolation from peripheral blood samples (1)(2)(3)(4)(5)(6). Noninvasive imaging of these CTCs in real time as they flow through the peripheral vasculature could improve detection sensitivity by enabling analysis of significantly larger blood volumes (potentially the entire blood volume of the patient), but to date such analyses have proven successful only when cancer cells are labeled ex vivo before their i.v.…”

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confidence: 99%

In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

He¹,

Wang

Hartmann

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

270

276

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Quantitation of circulating tumor cells (CTCs) constitutes an emerging tool for the diagnosis and staging of cancer, assessment of response to therapy, and evaluation of residual disease after surgery. Unfortunately, no existing technology has the sensitivity to measure the low numbers of tumor cells (<1 CTC per ml of whole blood) that characterize minimal levels of disease. We present a method, intravital flow cytometry, that noninvasively counts rare CTCs in vivo as they flow through the peripheral vasculature. The method involves i.v. injection of a tumor-specific fluorescent ligand followed by multiphoton fluorescence imaging of superficial blood vessels to quantitate the flowing CTCs. Studies in mice with metastatic tumors demonstrate that CTCs can be quantitated weeks before metastatic disease is detected by other means. Analysis of whole blood samples from cancer patients further establishes that human CTCs can be selectively labeled and quantitated when present at Ϸ2 CTCs per ml, opening opportunities for earlier assessment of metastatic disease.folate conjugates ͉ in vivo imaging ͉ multiphoton microscopy ͉ metastasis ͉ cancer diagnosis

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“…A simple blood test would, in contrast to bone marrow aspiration, allow for the analysis to be frequently repeated and thus used for staging at diagnosis as well as for therapy monitoring and long-term patient management. Using sensitive molecular and cell-based methods, OTCs have been successfully detected and isolated from blood in various solid malignancies, such as breast, prostate, colorectal, pancreatic, ovarian, and head and neck cancers, as well as malignant melanoma (12)(13)(14)(15)(16)(17)(18). However, the frequency of positive samples in studies of different cancers varies considerably, ranging between 95% in untreated breast cancer (12) and 12% in ovarian cancer (13).…”

Section: Introductionmentioning

confidence: 99%

“…The frequency of OTCs in peripheral blood specimens of solid malignancies has yet to be determined. Reported numbers of cell-based assays range from as low as 0.2 of 10 7 in head and neck cancer (17) to as high as 150 of 10 6 in ovarian cancer (13). Identifying and enumerating very rare tumor cells by microscopy is highly laborious, and the accuracy and sensitivity of the analysis is potentially impacted by the fatigue of the reviewer.…”

Section: Introductionmentioning

confidence: 99%

Reliable and Sensitive Identification of Occult Tumor Cells Using the Improved Rare Event Imaging System

Kraeft

Ladányi²,

Galiger

et al. 2004

Clinical Cancer Research

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Purpose: The purpose of this study was to assess the feasibility of using rare event imaging system (REIS)-assisted analysis to detect occult tumor cells (OTCs) in peripheral blood (PB). The study also sought to determine whether REIS-assisted OTC detection presents a clinically viable alternative to manual microscopic detection to establish the true significance of OTC from solid epithelial tumors.Experimental Design: We recently demonstrated proof of concept using a fluorescence-based automated microscope system, REIS, for OTC detection from the PB. For this study, the prototype of the system was adopted for highthroughput and high-content cellular analysis.Results: The performance of the improved REIS was examined using normal blood (n ‫؍‬ 10), normal blood added to cancer cells (n ‫؍‬ 20), and blood samples obtained from cancer patients (n ‫؍‬ 80). Data from the screening of 80 clinical slides from breast and lung cancer patients, by manual microscopy and by the REIS, revealed that as many as 14 of 35 positive slides (40%) were missed by manual screening but positively identified by REIS. In addition, REIS-assisted scanning reliably and reproducibly quantified the total number of cells analyzed in the assay and categorized positive cells based on their marker expression profile.Conclusions: REIS-assisted analysis provides excellent sensitivity and reproducibility for OTC detection. This approach may enable an improved method for screening of PB samples and for obtaining novel information about disease staging and about risk evaluation in cancer patients.

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Micrometastatic Tumor Detection in Patients With Head and Neck Cancer

Cited by 34 publications

References 6 publications

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

Reliable and Sensitive Identification of Occult Tumor Cells Using the Improved Rare Event Imaging System

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