The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

Abstract

Tumor biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumors 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 tumor cells (CTCs) may provide clinically important and comprehensive tumoral information that is predictive of treatment response and 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.

Detection of circulating tumor cells in patients with laryngeal cancer using ScreenCell: Comparative pre- and post-operative analysis and association with prognosis

“…The results of the present study are in accordance with other studies investigating CTCs in solid cancers, including the head and neck, which revealed that the presence of CTCs may influence prognosis (11)(12)(13)(14)(15)(16)(17)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57) similar to what was observed in the patients in the present study (6/8 were positive to CTC preoperatively). A recent meta-analysis comprised of 17 studies confirmed the significant prognostic value of CTCs in patients with head and neck cancer, wherein positive CTCs were significantly associated with poor overall, disease-free and progression-free survival (61).…”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…It is generally accepted that CTCs may play an important role in cancer metastasis . Data suggest that an elevated baseline CTC count is associated with advanced stage of HNSCC, risk of relpase, and a poor prognosis, while a declining CCRT could indicate an improved prognosis and treatment response . In some patients, an increased CTC count has been observed after HNSCC treatment by surgery and radiotherapy, which is thought to possibly reflect stimulation of tumor cell dissemination and a poorer prognosis; although, the exact reasons for this observation remain unclear.…”

Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer

“…Previous research has shown that CTCs can also cause tumor recurrence and are related to patient prognosis . The ability to obtain more information from CTCs may therefore offer an avenue toward the early detection of cancer, allowing researchers to gain insight into its the aggressive nature of the tumor and offering a means of monitoring therapeutic responses and disease progression in patients …”

“…Therefore, developing an assay not reliant upon EpCAM for effective capture and identification of additional subtypes of CTCs is imperative. Because chromosomal instability can cause aneuploidy in human solid tumor cells, an assay integrating EpCAM‐independent subtraction and immunostaining‐fluorescence in situ hybridization (FISH) has been reported in previous studies …”