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. 2022 Aug;45(4):543-555.
doi: 10.1007/s13402-022-00681-w. Epub 2022 Jun 23.

Application of circulating tumour cells to predict response to treatment in head and neck cancer

Xi Zhang  1   2 , Chameera Ekanayake Weeramange  1   2 , Brett G M Hughes  3   4 , Sarju Vasani  4   5 , Zhen Yu Liu  4   5   2 , Majid Ebrahimi Warkiani  6 , Gunter Hartel  7 , Rahul Ladwa  4   8 , Jean Paul Thiery  9 , Liz Kenny  3   4 , Chamindie Punyadeera  10   11   12
Affiliations

Application of circulating tumour cells to predict response to treatment in head and neck cancer

Xi Zhang et al. Cell Oncol (Dordr). 2022 Aug.

Abstract

Background: Local recurrence and metastasis remain the major causes of death in head and neck cancer (HNC) patients. Circulating tumour cells (CTCs) are shed from primary and metastatic sites into the circulation system and have been reported to play critical roles in the metastasis and recurrence of HNC. Here, we explored the use of CTCs to predict the response to treatment and disease progression in HNC patients.

Methods: Blood samples were collected at diagnosis from HNC patients (n = 119). CTCs were isolated using a spiral microfluidic device and were identified using immunofluorescence staining. Correlation of baseline CTC numbers to 13-week PET-CT data and multidisciplinary team consensus data were conducted.

Results: CTCs were detected in 60/119 (50.4%) of treatment naïve HNC patients at diagnosis. Baseline CTC numbers were higher in stage III vs. stage I-II p16-positive oropharyngeal cancers (OPCs) and other HNCs (p = 0.0143 and 0.032, respectively). In addition, we found that baseline CTC numbers may serve as independent predictors of treatment response, even after adjusting for other conventional prognostic factors. CTCs were detected in 10 out of 11 patients exhibiting incomplete treatment responses.

Conclusions: We found that baseline CTC numbers are correlated with treatment response in patients with HNC. The expression level of cell-surface vimentin (CSV) on CTCs was significantly higher in patients with persistent or progressive disease, thus providing additional prognostic information for stratifying the risk at diagnosis in HNC patients. The ability to detect CTCs at diagnosis allows more accurate risk stratification, which in the future may be translated into better patient selection for treatment intensification and/or de-intensification strategies.

Keywords: Biomarker, treatment response; Circulating tumour cells; Epithelial-mesenchymal transition; Head and neck cancer; Liquid biopsy; Prognosis.

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Conflict of interest statement

All authors have read the journal’s policy on disclosure of potential conflicts of interest. The authors declare that no competing interest exists.

Figures

Fig. 1
Fig. 1
Study flow chart
Fig. 2
Fig. 2
Enumeration of circulating tumour cells (CTCs) in p16 positive oropharyngeal cancer patients and other head and neck cancer patients
Fig. 3
Fig. 3
(A) Circulating tumour cell (CTC) numbers in all HNC patients (n = 119) with a complete response and an incomplete response. (B) Contingency analysis of baseline CTC circulating tumour cells by 13 weeks related to treatment response status
Fig. 4
Fig. 4
Enumeration of circulating tumour cells (CTCs) in p16-positive oropharyngeal cancer (OPC) patients categorised by (A) N stage, (B) tumour stage and (C) treatment response. (D) Contingency analysis of baseline CTCs by treatment response status in p16-positive OPC patients
Fig. 5
Fig. 5
Enumeration of circulating tumour cell (CTC) counts in other head and neck cancer patients by (A) N stage, (B) tumour stage and (C) treatment response. (D) Contingency analysis of baseline CTC by treatment response status
Fig. 6
Fig. 6
Cell surface vimentin expression on circulating tumour cells (CTC) isolated from locoregionally advanced head and neck cancer patients who had a complete treatment response versus those who had an incomplete response
Fig. 7
Fig. 7
Receiver Operative Characteristic (ROC) curve evaluation of the differentiating power of CTC numbers comparing head and neck cancer patients with a complete response with those with an incomplete response
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