Abstract

Circulating tumor cells (CTCs) and immune status are strongly related to cancer prognosis, although few studies have examined both factors. This prospective observational study (ClinicalTrials.gov: NCT02420600) evaluated whether CTCs, circulating cancer stem-like cells (cCSCs), and peripheral lymphocytes with/without Programmed cell death protein 1 (PD-1) expression were associated with prognosis among patients receiving palliative chemotherapy for initially unresectable, recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). Thirty-four patients were enrolled between January 2015 and June 2016. Overall survival (OS) was associated with a higher CTC number (hazard ratio [HR]: 1.01, p = 0.0004) and cCSC ratio (HR: 29.903, p < 0.0001). Progression-free survival (PFS) was also associated with CTC number (HR: 1.013, p = 0.002) and cCSC ratio (HR: 10.92, p = 0.003). A CD8+ proportion of ≥ 17% was associated with improved OS (HR: 0.242, p = 0.004). A CD4: CD8 ratio of >1.2 was associated with poorer trend of PFS (HR: 2.12, p = 0.064). PD-1 expression was not associated with survival outcomes. Baseline CTCs, cCSC ratio, and CD8+ ratio may predict prognosis in rmHNSCC.

Highlights

  • There are >500,000 new cases of head and neck squamous cell carcinoma (HNSCC) annually, with approximately 400,000 deaths worldwide [1,2]

  • HNSCC to examine whether chemotherapy response could be predicted using circulating tumor cells (CTC), circulating cancer stem-like cells (cCSC), and peripheral lymphocyte expression of PD-1

  • The results indicate that CTCs and cCSCs were independent predictors of cancer progression and overall survival (OS) and that patients with a high baseline CD8+ proportion had longer OS, while patients with a lower CD4: CD8 ratio had longer progression-free survival (PFS)

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Summary

Introduction

There are >500,000 new cases of head and neck squamous cell carcinoma (HNSCC) annually, with approximately 400,000 deaths worldwide [1,2]. One promising biomarker is circulating tumor cells (CTCs), which can predict prognosis before starting therapy for various types of cancer [7,8,9]. These CTCs are shed from the primary tumor and can be detected in the patient’s bloodstream, where they often express epithelial markers, such as epithelial cell adhesion molecule (EpCAM) [10] or cytokeratins [11], but typically do not express white and red blood cell markers, such as CD45 [12] and CD235a [13].

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