Abstract
Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and γ-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the γ-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients.
Highlights
Head and Neck Squamous Cell Carcinoma (HNSCC), including oral squamous cell carcinoma and oropharynx tumour, is the most common type of head and neck cancer [1].Different therapeutic strategies are used for the non-operable stages (III–IV) of HNSCC, including induction chemotherapy (cisplatin, 5-fluorouracil (5-FU) and docetaxel) followed by radiotherapy, radiotherapy alone, or more recently the use of immune checkpoint inhibitors such as pembrolizumab alone or in combination with platinum and 5-FU [2,3].tumours display heterogeneity in terms of clinical outcome and response to treatment, even among patients who are assigned with the same level of risk.biomarkers are needed to help clinicians choose the best treatment for personalized therapy
All 28 patients were diagnosed histologically with HNSCC localized in the oropharynx, the oral cavity or both (Table 1)
No correlation was found between these markers and the response to treatment
Summary
Tumours display heterogeneity in terms of clinical outcome and response to treatment, even among patients who are assigned with the same level of risk. Biomarkers are needed to help clinicians choose the best treatment for personalized therapy. Numerous alterations at the genomic [4], proteomic [5,6], and radiomic levels [7] have been proposed as predictive biomarkers of a treatment response, very few have been validated up to now [8]. Human papillomavirus (HPV) expression is broadly recognized by clinicians as a predictive biomarker in HNSCC. HPV-positive tumours respond better to radio- or chemotherapy prompting a de-escalation of treatment, whereas HPV-negative tumours show a worse response [9]
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