Abstract
Simple SummaryThe conventional methods that seek to predict clinical treatment response are based on the number of circulating tumor cells (CTCs) present in liquid biopsies or genetic profiling of extracted CTCs. This paper presents a novel process by which CTCs can be extracted from blood samples taken from head and neck cancer patients and then expanded ex vivo to form organoids that can be tested with a panel of anti-cancer treatments. The resulting drug sensitivity profiles derived from cisplatin treatment of organoids were subsequently found to correlate with clinical treatment response to cisplatin in patients. CTCs extracted from liquid biopsies for ex vivo expansion negates the need for complicated and potentially risky biopsies of tumor material, thereby supporting the application of this procedure for checkups and treatment monitoring.The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.
Highlights
Head and neck cancer (HNC) is the seventh most common cancer globally, constituting approximately 5.5% of newly diagnosed cancer cases [1]
This study presents an innovative process by which circulating tumor cells (CTCs) can be extracted from peripheral blood liquid biopsies of patients with locally advanced head and neck cancer (HNC) and expanded ex vivo over four weeks to form CTC-derived organoids in a biomimetic cell culture system known as eSelect
The results showed that the relative cell viability derived from cisplatin sensitivity assays significantly correlated with clinical response to cisplatin treatment in patients with HNC, suggesting that this process can potentially be used in a clinical setting to monitor and guide treatments of patients with HNC
Summary
Head and neck cancer (HNC) is the seventh most common cancer globally, constituting approximately 5.5% of newly diagnosed cancer cases [1]. Over 60% of patients with HNC present with locally-advanced (stage III or IV) disease at diagnosis, with a high risk of local recurrence and distant metastasis [5]. In those advanced HNC patients, cisplatin plays a crucial role in treatment. TPF (docetaxel, cisplatin, and 5-fluorouracil (5-FU)) induction therapy before concomitant chemoradiotherapy is a key treatment option [2,5] Despite these available treatments, the prognosis for locoregionally-advanced HNC patients remains poor, with 5-year survival rates of less than 50% [5]. Studies have sought to identify genetic signatures [8,10] and other predictive factors [11] of cisplatin response, none are clinically applicable as yet
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