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Circulating Tumour Cells (CTC), Head and Neck Cancer and Radiotherapy; Future Perspectives.

ABSTRACT: Head and neck cancer is the seventh most common cancer in Australia and globally. Despite the current improved treatment modalities, there is still up to 50?60% local regional recurrence and or distant metastasis. High-resolution medical imaging technologies such as PET/CT and MRI do not currently detect the early spread of tumour cells, thus limiting the potential for effective minimal residual detection and early diagnosis. Circulating tumour cells (CTCs) are a rare subset of cells that escape from the primary tumour and enter into the bloodstream to form metastatic deposits or even re-establish themselves in the primary site of the cancer. These cells are more aggressive and accumulate gene alterations by somatic mutations that are the same or even greater than the primary tumour because of additional features acquired in the circulation. The potential application of CTC in clinical use is to acquire a liquid biopsy, by taking a reliable minimally invasive venous blood sample, for cell genotyping during radiotherapy treatment to monitor the decline in CTC detectability, and mutational changes in response to radiation resistance and radiation sensitivity. Currently, very little has been published on radiation therapy, CTC, and circulating cancer stem cells (CCSCs). The prognostic value of CTC in cancer management and personalised medicine for head and neck cancer radiotherapy patients requires a deeper understanding at the cellular level, along with other advanced technologies. With this goal, this review summarises the current research of head and neck cancer CTC, CCSC and the molecular targets for personalised radiotherapy response.

SUBMITTER: Perumal V

PROVIDER: S-EPMC6468366 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Circulating Tumour Cells (CTC), Head and Neck Cancer and Radiotherapy; Future Perspectives.

Perumal Vanathi V Corica Tammy T Dharmarajan Arun M AM Sun Zhonghua Z Dhaliwal Satvinder S SS Dass Crispin R CR Dass Joshua J

Cancers 20190315 3

Head and neck cancer is the seventh most common cancer in Australia and globally. Despite the current improved treatment modalities, there is still up to 50⁻60% local regional recurrence and or distant metastasis. High-resolution medical imaging technologies such as PET/CT and MRI do not currently detect the early spread of tumour cells, thus limiting the potential for effective minimal residual detection and early diagnosis. Circulating tumour cells (CTCs) are a rare subset of cells that escape ...[more]

PMID: 30875950

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Project description:Research demonstrates strong evidence that circulating tumour cells (CTCs) can provide diagnostic and/or prognostic biomarkers in head and neck squamous cell carcinoma (HNSCC) and a potential tool for therapeutic stratification. However, the question still remains as to the optimum method of CTC enrichment and how this can be translated into clinical practice. We aimed to evaluate the Parsortix microfluidic device for CTC enrichment and characterisation in HNSCC, seeking to optimise a sample collection and processing protocol that preserves CTC integrity and phenotype. Spiking experiments of the FaDu and SCC040 HNSCC cell lines were used to determine the Parsortix capture rate of rare "CTC-like" cells. Capture rates of cancer cells spiked into EDTA blood collections tubes (BCTs) were compared to the Transfix fixative BCT and Cytodelics whole blood freezing protocol. The Lexogen Quantseq library preparation was used to profile gene expression of unfixed cells before and after microfluidic enrichment and enriched cell line spiked Transfix blood samples. An antibody panel was optimised to enable immunofluorescence microscopy CTC detection in HNSCC patient Transfix blood samples, using epithelial (EpCAM) and mesenchymal (N-cadherin) CTC markers. Across a spiked cell concentration range of 9-129 cells/mL, Parsortix demonstrated a mean cell capture rate of 53.5% for unfixed cells, with no significant relationship between spiked cell concentration and capture rate. Samples preserved in Transfix BCTs demonstrated significantly increased capture rates at 0 h (time to processing) compared to EDTA BCTs (65.3% vs. 51.0%). Capture rates in Transfix BCTs were maintained at 24 h and 72 h timepoints, but dropped significantly in EDTA BCTs. Gene expression profiling revealed that microfluidic enrichment of unfixed cell lines caused downregulation of RNA processing/binding gene pathways and upregulation of genes involved in cell injury, apoptosis and oxidative stress. RNA was successfully extracted and sequenced from Transfix preserved cells enriched using Parsortix, demonstrating epithelial specific transcripts from spiked cells. In a proof-of-concept cohort of four patients with advanced HNSCC, CTCs were successfully identified and visualised with epithelial and epithelial-mesenchymal phenotypes. We have optimised a protocol for detection of CTCs in HNSCC with the Parsortix microfluidic device, using Transfix BCTs. We report a significant benefit, both in terms of cell capture rates and preserving cell phenotype, for using a fixative BCT- particularly if samples are stored before processing. In the design of large cohort multi-site clinical trials, such data are of paramount importance.

Project description:Treatment of locoregionally advanced head and neck squamous cell carcinoma involves a multidisciplinary approach that combines surgery, radiotherapy, and systemic therapy. These curative strategies are associated with significant acute and long-term toxicities. With the emergence of human papillomavirus (HPV) as an etiologic factor associated primarily with oropharyngeal squamous cell carcinoma, higher cure rates juxtaposed with substantial treatment-related morbidity and mortality has led to interest in de-escalated therapeutic strategies, with the goal of optimizing oncologic outcomes while reducing treatment-related toxicity. Currently explored strategies include replacing, reducing, or omitting cytotoxic chemotherapy; reducing dose or volume of radiotherapy; and incorporation of less-invasive surgical approaches. Potential biomarkers to select patients for treatment de-escalation include clinical risk stratification, adjuvant de-escalation based on pathologic features, response to induction therapy, and molecular markers. The optimal patient selection and de-escalation strategy is critically important in the evolving treatment of locoregional head and neck cancer. Recently, two large phase III trials, RTOG 1016 and De-ESCALaTE, failed to de-escalate treatment in HPV-associated head and neck cancer by demonstrating inferior outcomes by replacing cisplatin with cetuximab in combination with radiation. This serves as a cautionary tale in the future design of de-escalation trials in this patient population, which will need to leverage toxicity and efficacy endpoints. Our review summarizes completed and ongoing de-escalation trials in head and neck cancer, with particular emphasis on biomarkers for patient selection and clinical trial design. IMPLICATIONS FOR PRACTICE: The toxicity associated with standard multimodality treatment for head and neck cancer underscores the need to seek less-intensive therapies with a reduced long-term symptom burden through de-escalated treatment paradigms that minimize toxicity while maintaining oncologic control in appropriately selected patients. Controversy regarding the optimal de-escalation strategy and criteria for patient selection for de-escalated therapy has led to multiple parallel strategies undergoing clinical investigation. Well-designed trials that optimize multimodal strategies are needed. Given the absence of positive randomized trials testing de-escalated therapy to date, practicing oncologists should exercise caution and administer established standard-of-care therapy outside the context of a clinical trial.

Dataset Information

Circulating Tumour Cells (CTC), Head and Neck Cancer and Radiotherapy; Future Perspectives.

Publications

Circulating Tumour Cells (CTC), Head and Neck Cancer and Radiotherapy; Future Perspectives.

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