Swallowing Kinematics in Rats Treated with Low Dose Chemotherapy Concurrently with Fractionated Radiation

Abstract

Dysphagia is a common consequence of chemotherapy and radiation treatment for oropharyngeal cancer. Injury is thought to occur due to damage to the muscle and/or nerves. This can severely impair swallowing function, leading to serious negative outcomes such as aspiration related pneumonia or tube feeding placement to maintain nutrition. Currently, there are only strategies to prevent swallowing dysfunction; however, the development of chronic radiation associated dysphagia persists effecting ~25% of head and neck cancer survivors. Therefore, there is a need to study the mechanisms associated with radiation associated dysphagia to help guide new treatments to improve swallowing outcomes. The present study investigated the effects of concurrent chemoradiation on swallowing function. We tested the hypothesis that fractionated radiation with low doses of chemotherapy alters swallowing kinematics and bolus transit compared to radiation alone or normal controls. We monitored the functional extent of chemoradiation or radiation treatment using videofluoroscopy swallow study in self feeding rats (n=16) at four weeks post treatment. Twelve rats underwent 48Gy of fractionated radiation to the submental muscles using a clinical linear accelerator given in 12 fractions of 4Gy. Irradiated rats received either cisplatin 1mg/kg or saline IP once per week for four weeks during radiation treatment. Four rats received no treatment. During videofluoroscopy, thin liquids and puree consistencies mixed with 40% w/v barium sulfate were given ad libitum. The movement trajectories of the tongue, mandible, and hyoid bone were quantitatively tracked from video data. Changes in the speed of the jaw and hyoid during swallowing were observed between treated and control rats. No differences were observed in bolus flow parameters i.e. pharyngeal transit speed, inter‐swallow interval, and swallow frequency between treatment groups. The average size of the bolus in vallecula decreased by ~4% prior to initiating pharyngeal swallow with chemoradiated rats (p < 0.05). Results suggest that low doses of chemotherapy in conjunction with radiation appear to have minimal differences in swallowing kinematics compared to radiation alone. Higher doses of chemotherapy may be needed to induce similar abnormalities in swallowing as seen clinically.