# Mechanisms Underlying Tongue Muscle Dysfunction and Dysphagia Following Concurrent Chemoradiation Therapy

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $254,250

## Abstract

Project Summary/Abstract
 Concurrent chemoradiation therapy (CCRT) is a common treatment modality for head and neck
cancers. Chemotherapy acts as a radiation therapy sensitizer, enhancing the effects of radiation on the target
head and neck tissues and increasing oncologic efficacy. Due to its comparable cure rates to surgical
management and benefit of organ preservation, CCRT has been increasingly utilized for various head and
neck cancers with excellent curative results. However, this treatment modality is associated with significant
side effects within the head and neck such as xerostomia, trismus, osteoradionecrosis, mucositis, dysgeusia,
dysphonia, and dysphagia, primarily due to the radiation effects on normal tissue surrounding the tumor.
Dysphagia can be particularly devastating, as it significantly alters quality of life and is associated with
increased risk of aspiration pneumonia.
 Although muscle weakness and fibrosis are putative causes for swallow dysfunction following CCRT,
very little research has been performed to study the underlying mechanisms of this dysfunction. Radiation
therapy resulting in fibrosis and, therefore, decreased function has been documented in human tissue within
the heart, lungs, and breast. However, within the tongue, and, specifically skeletal muscle, the effects of
radiation remain controversial. Multiple translational studies have demonstrated that decreased tongue
strength occurs after radiation, but the cause of this weakness is unknown. Four predominant hypotheses have
been proposed to explain the skeletal muscle changes following radiation exposure: 1) alteration in cellular
metabolism and protein degradation, 2) altered satellite cell concentration and function, 3) fibrosis and muscle
atrophy and 4) failure of tissue regeneration. To date, few of these hypotheses have been systematically
pursued to the degree required to determine etiology. Most of the literature has focused on fibrosis, but studies
have yet to definitively demonstrate consistent fibrosis in muscle as a result of CCRT. In fact, the only human
study to specifically examine tissue from the head and neck following CCRT failed to demonstrate significant
fibrosis.
 Most studies have focused solely on animal models of radiation therapy and deliver very high doses of
non-targeted radiation, limiting the translational value of the data. In order to better understand the etiology of
muscle injury following CCRT, proper dosing must be applied and the tissues fully analyzed to test various
hypotheses for muscle dysfunction. The current proposal seeks to elucidate the pathophysiology of muscle
dysfunction following delivery of concurrent chemoradiation to the head and neck for definitive treatment of
malignancy. The study is translational in that it tests the various hypotheses in both animal and human models.

## Key facts

- **NIH application ID:** 9979402
- **Project number:** 1R21DC018081-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Milan R. Amin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979402

## Citation

> US National Institutes of Health, RePORTER application 9979402, Mechanisms Underlying Tongue Muscle Dysfunction and Dysphagia Following Concurrent Chemoradiation Therapy (1R21DC018081-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979402. Licensed CC0.

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