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Cell-Free DNA Kinetics in a Pre-Clinical Model of Head and Neck Cancer.

ABSTRACT: In cancer patients, circulating tumour-derived DNA (ctDNA) levels imperfectly reflect disease burden apparent on medical imaging. Further evaluation of ctDNA levels over time is needed to better understand the correlation with tumour growth and therapeutic response. We describe ctDNA kinetics within an orthotopic, immunocompetent preclinical rabbit model of local-regionally advanced head and neck squamous cell carcinoma (HNSCC). Monitoring primary tumour and metastatic lymph node volume by computed tomography (CT), we observed a correlation between ctDNA levels and tumour burden. We found that ctDNA detection could precede evidence of tumour on CT. Sensitivity and specificity of ctDNA detection in this model was 90.2% (95% C.I.: 76.9-97.3%) and 85.7% (95% C.I.: 67.3-96.0%), respectively. Rapid tumour growth followed by auto-necrosis and tumour volume contraction produced a spike in ctDNA levels, suggesting that viable tumour cells may be required for sustained ctDNA release. Following surgical resection, both ctDNA and total plasma DNA were correlated with recurrent tumour volume. Our results reveal the complex kinetic behaviour of ctDNA and total plasma DNA upon tumour growth or surgery. This pre-clinical model could be useful for future studies focused on elucidating mechanisms of ctDNA release into the circulation from primary and metastatic sites.

SUBMITTER: Muhanna N

PROVIDER: S-EPMC5711859 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Cell-Free DNA Kinetics in a Pre-Clinical Model of Head and Neck Cancer.

Muhanna Nidal N Di Grappa Marco A MA Chan Harley H L HHL Khan Tahsin T Jin Cheng S CS Zheng Yangqiao Y Irish Jonathan C JC Bratman Scott V SV

Scientific reports 20171201 1

In cancer patients, circulating tumour-derived DNA (ctDNA) levels imperfectly reflect disease burden apparent on medical imaging. Further evaluation of ctDNA levels over time is needed to better understand the correlation with tumour growth and therapeutic response. We describe ctDNA kinetics within an orthotopic, immunocompetent preclinical rabbit model of local-regionally advanced head and neck squamous cell carcinoma (HNSCC). Monitoring primary tumour and metastatic lymph node volume by compu ...[more]

PMID: 29196748

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Project description:Background:Poor nutritional status among patients with advanced stage head and neck squamous cell carcinoma (HNSCC) is common. Albumin is a common indicator of nutritional status and has been shown to be a predictor of oncological outcomes and perioperative morbidity. This study aims to determine the prognostic value of the serum albumin level among patients with advanced HNSCC undergoing surgery with simultaneous free flap reconstruction. Methods:A total of 233 patients with advanced head and neck cancer undergoing tumor resection and immediate microvascular free flap reconstruction in a tertiary referral center were enrolled retrospectively between January 2009 and December 2011. Statistical analyses including Pearson's chi-squared test were used to determine whether there was a significant difference between each selected clinical factors and postoperative major wound infection. Multiple regression analysis was performed to reveal the relationship between postoperative major wound infection and clinical factors. Kaplan-Meier curves and multivariate Cox regression were applied to analyse survival outcome for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Results:Postoperative serum albumin level (p < 0.001) and tumor location were both significantly associated with postoperative major wound infection (p = 0.018) in univariate analysis. Multiple regression analysis showed a higher risk of postoperative major wound infection among patients with postoperative hypoalbuminemia than in their counterparts (odds ratio [OR] 9.811, 95% CI [2.288-42.065], p = 0.002). Patients with a tumor located over the hypopharynx experienced increased risk of postoperative major wound infection (OR 2.591, 95% CI [1.095-6.129], p = 0.030). With respect to oncological outcomes, preoperative serum albumin level is a significant independent prognostic factor for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Conclusions:Postoperative hypoalbuminemia is a useful indicator for the development of postoperative complications. In addition, preoperative hypoalbuminemia is a negative prognostic factor for patients who have undergone tumor excision and free flap reconstruction for the advanced stage of HNSCC.

Dataset Information

Cell-Free DNA Kinetics in a Pre-Clinical Model of Head and Neck Cancer.

Publications

Cell-Free DNA Kinetics in a Pre-Clinical Model of Head and Neck Cancer.

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