Radiotherapy and chemoradiation for head and neck cancer treatment exposes normal tissues to radiation, which has many devastating effects and often results in difficulty with communication and swallowing. While muscle weakness and fibrosis are possible etiologies for disruptions in critical communicative and deglutition functions following radiation, very little research has been performed on underlying biological changes within muscles of the head and neck following radiation, or possible treatments for these lasting negative effects. Skeletal muscles can adapt at multiple levels of structure and function to changing demands. Exercise training of the tongue, or enhanced muscle contraction via neuromuscular electrical stimulation (NMES) may be beneficial for preventing or reversing muscle tissue damage. However, controlled research examining these putative benefits has not been performed and optimal treatment modalities have not been established. Our hypothesis is that radiotherapy and chemoradiation-induced decline in speech and swallowing function is largely due to alterations in tongue muscle structure and function. Further, we hypothesize that tongue exercise or NMES will result in phenotypic changes in extrinsic tongue muscles that will improve tongue muscle function. To examine these clinically-relevant issues, we will use a rat model to test two different tongue treatment paradigms (tongue exercise; NMES) for remediation of radiotherapy and chemoradiation- induced muscle damage. The proposed research has two specific aims: 1) To determine how treatment modality affects morphological, biochemical, and physiological changes in radiotherapy and chemoradiation- induced muscle damage of the tongue, 2) To discover how tongue exercise and/or NMES treatment affects functional measures of deglutition following radiotherapy/chemoradiation. This work is innovative and significant because the mechanisms by which tongue exercise or NMES can prevent or treat the effects of radiation- or chemoradiation-induced communication and swallowing dysfunction is largely unexplored. Our animal model and treatments are analogs to treatments used in human patients and follow the Institute of Medicine guidelines for increasing probability of translation. Further, this work is highly significant in providing a basis for understanding the mechanisms underlying the potential of therapeutic interventions for radiation- and chemoradiation-induced cranial impairments. Translation of findings will assist with increasing the effectiveness of treatments for radiation- and chemoradiation-induced tongue muscle impairments that are so prevalent in patients with head and neck cancer.

Public Health Relevance

The proposed research examines how muscles involved in communication and swallowing are affected by radiotherapy and chemoradiation. Experiments will examine how increased muscle activity in the form of tongue exercise or neuromuscular electrical stimulation may mitigate radiotherapy and chemoradiation-induced deficits in the muscular microenvironment. Further, this work will determine how different treatment modalities induce biological changes and improved function in radiated and chemoradiated tongue muscles

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA225608-01
Application #
9424248
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
O'Mara, Ann M
Project Start
2018-01-01
Project End
2022-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715