The Role of Circulating Tumour DNA as a Marker of Adequate Resection in Oral Cancer and its Correlation with Clinico-pathologic Parameters: A Prospective Study

Abstract

Introduction: Oral Cavity Squamous Cell Carcinoma (OSCC) is prevalent worldwide. The genetic heterogeneity of this disease and the limitation of biopsy in selective mapping, made use of conventional biopsy sub-optimal for advanced molecular profiling. There is a lacuna for non-invasive tests which are easy to perform, helpful in diagnosis, follow-up and in analysing the completeness of treatment. Sensitive and specific detection of circulating tumour DNA (ctDNA) has potential to direct early treatment and permits monitoring of systemic dissemination. Aim: To evaluate ctDNA as response assessment tool and as a clinico-pathological parameter. Materials and Methods: This prospective study of 25 patients, carried out at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh India, from May 2017 to November 2018. The study evaluated ctDNA as a marker of completeness of resection after upfront surgery for OSCC. ctDNA levels were assessed in peripheral blood, before and after surgery to determine whether its quantification can be useful in evaluation of response to surgery and if circulating DNA levels correlate with clinic-pathological prognostic variables. Data analysis was done using Cox proportional model with univariate and multivariate analysis. Results: The ctDNA levels were higher among the patient with age ≤40, females, short duration of disease (≤3 months), infiltrative variety of tumours and lower tumour volume. The levels increase with increase in mitotic index, lymphocytic infiltrate, tumour budding and decrease with the amount of necrosis, and dysplasia but none reached statistical significance. The level of pre-operative ctDNA does not vary widely with margin status, with treatment and do not correlate with the percentage of positive nodes among the total number of nodes dissected. The cases with local recurrence or death had higher pre-operative ctDNA values (Mean pre-operative ctDNA were 294.725 and 185.6, respectively, with a p-value 0.3673). Conclusion: The ctDNA levels are persistently elevated in OSCC and may be a measure of aggressiveness. The surgical treatment of resectable oral cavity cancers may lead to the decrease of ctDNA levels. ctDNA maybe used as a complementary method along with biopsy/histopathological findings.

Keywords

• prognosis
• resectable
• response