The Prognostic Significance of Circulating Tumour Cells in Head and Neck and Non-Small Cell Lung Cancer

Abstract

Tumour biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumours change dynamically in response to therapy and there remains a need for a more representative biomarker that can be assayed over the course of treatment. Circulating tumour cells (CTCs), may provide clinically important and comprehensive tumoural information, predictive of therapy outcome. Blood samples were processed for CTCs from 56 patients using the ClearCell FX system. Captured cells were phenotyped for CTC clusters and markers for immunotherapy (PD-L1), CTC chromosomal architecture (ALK, EGFR). CTCs were isolated in 11/23(47.8%) of Head and neck cancer (HNC) patients and 17/33(51/5%) of non-small cell lung cancer (NSCLC) patients. CTCs were determined to be PD-L1-positive in 6/11 (54.4%) HNC and 11/17(64.7%) NSCLC cases respectively. 3D chromosomal DNA FISH for ALK and EGFR molecular targets showed better resolution than in 2D when imaging CTCs. HNC CTC-positive patients had shorter progression free survival (PFS) (Hazard ratio[HR]: 4.946; 95% confidence internal[CI]:1.571-15.57;P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159;95% [CI]:1.011-26.33; P=0.0485). In the advanced stage NSCLC patient cohort, PFS was not found to be associated with CTCs prior to therapy ([HR]:2.246;95% [CI]:0.9565-5.273; P=0.0632), nor the presence of PD-L1 expression ([HR]:1.646;95% [CI]:0.5128-5.283; P=0.4023). This study demonstrated that CTCs are predictive of poorer outcomes in HNC and provides distinct and separate utility for CTCs in HNC and NSCLC, which may be more representative of the disease burden and overall survival than the parameters used to measure them. Funding: The Translational Research Institute (TRI) receives funding from the Australian government. This study was supported by a SPORE grant from TRI. Declaration of Interest: No conflict of interest exist. Ethical Approval: Ethics approval was obtained from the Metro South Health District Human Research Ethics Committee in accordance with the National Health and Medical Research Council’s guidelines (HREC/11/QPAH/331 and HREC/12/QPAH/381) to collect blood samples from the Princess Alexandra Hospital (PAH) and Royal Brisbane and Women’s Hospital (RBWH).