The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing

Pei-Hung Chang; Min-Hsien Wu; Sen-Yu Liu; Hung-Ming Wang; Wen-Kuan Huang; Chun-Ta Liao; Tzu-Chen Yen; Shu-Hang Ng; Jen-Shi Chen; Yung-Chang Lin; Hung-Chih Lin; Jason Chia-Hsun Hsieh

doi:10.3390/cancers11040540

The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing

Cancers (Basel). 2019 Apr 15;11(4):540. doi: 10.3390/cancers11040540.

Authors

Pei-Hung Chang^{1

2

3

4}, Min-Hsien Wu^{5

6

7}, Sen-Yu Liu^{8

9}, Hung-Ming Wang^{10

11}, Wen-Kuan Huang^{12

13}, Chun-Ta Liao^{14

15

16}, Tzu-Chen Yen^{17

18

19}, Shu-Hang Ng^{20

21

22}, Jen-Shi Chen^{23

24}, Yung-Chang Lin^{25

26}, Hung-Chih Lin^{27

28}, Jason Chia-Hsun Hsieh^{29

30}

Affiliations

¹ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
² Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung 20401, Taiwan. [email protected].
³ Cancer Center, Chang Gung Memorial Hospital, Keelung 20401, Taiwan. [email protected].
⁴ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
⁵ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
⁶ Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan. [email protected].
⁷ Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan. [email protected].
⁸ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
⁹ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
¹⁰ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
¹¹ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
¹² Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
¹³ Department of Oncology⁻Pathology, Karolinska Institutet, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, SE-17176 Stockholm, Sweden. [email protected].
¹⁴ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
¹⁵ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
¹⁶ Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan 333, Taiwan. [email protected].
¹⁷ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
¹⁸ Molecular Imaging Center, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan 333, Taiwan. [email protected].
¹⁹ Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan 333, Taiwan. [email protected].
²⁰ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
²¹ Department of Diagnostic Radiology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan 333, Taiwan. [email protected].
²² Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan. [email protected].
²³ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
²⁴ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
²⁵ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
²⁶ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
²⁷ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
²⁸ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].
²⁹ Chang Gung University, College of Medicine, Taoyuan 333, Taiwan. [email protected].
³⁰ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo 333, Taiwan. [email protected].

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.

Keywords: PD-1; cancer stem-like cells; circulating tumor cells; head and neck cancer; peripheral lymphocytes.

Associated data

ClinicalTrials.gov/NCT02420600

Abstract

Associated data

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