Impact of radiotherapy on laryngeal intrinsic muscles

Abstract

Ionizing radiation as a cancer therapy is associated with a variety of undesirable side effects. Consequently, radiotherapy can negatively affect neuromuscular function. Clinical observations have identified problems with swallowing and voice function. Our study aims to evaluate the impact of radiotherapy on laryngeal soft tissues using image analysis to quantify its effect on the structure of the vocalis and thyroarytenoid muscles. Case control study, retrospective analysis. We collected total laryngectomy specimens from six patients with persistent or recurrent cancer who had received preoperative radiotherapy (60-66 Gy). The control group consisted of total laryngectomy specimens from six patients who underwent surgery as primary treatment. Sampling of the specimens only included non-cancerous laryngeal tissue. Laryngeal histological slices were evaluated using digital morphometric analysis system. Percentage of fibrosis and density of muscle fibers within the thyroarytenoid muscle were evaluated in both groups. We found no significant quantitative differences in muscle fibrosis (7.92% vs. 7.52%, P > 0.1). Changes were rather qualitative and included changes in the organization of the muscular fibers. A significant reduction in muscle fibers, however, was observed in the samples from irradiated larynges (66.45% vs. 42.03%, P < 0.01). Our analysis suggests that radiotherapy is responsible for a significant reduction in muscle fibers in the thyroarytenoid muscle and that these changes occur during treatment or relatively early after its completion. Loss of muscle mass after irradiation correlates with clinical observations of muscle weakness and decreased function in patients who undergo radiotherapy.

Therapeutic Potential of Adipose Stem Cells in Tissue Repair of Irradiated Skeletal Muscle in a Rabbit Model

“…Due to a better radiotolerance, the exposure dose of skeletal muscle was usually ignored compared with that of the organs at risk, such as spinal cord, lung, and small intestine, in the radiotherapy planning. Skeletal muscle injury induced by high-dose irradiation has been commonly reported, resulting in myasthenia, abnormality of the muscular tension, fatigue, pain, convulsion, and dysfunction (Bey et al, 2007;Gillette et al, 1995;Krasin et al, 2012;Tedla et al, 2012). For instance, difficulty in opening the mouth and trismus were evoked by radiation-induced injury to masticatory muscles in the patients with nasopharyngeal neoplasms and oropharyngeal neoplasms (Krasin et al, 2012;Marcus and Tishler, 2010).…”

“…The exposure of the pharyngeal constrictor muscle to high-dose irradiation resulted in dysphagia and even longterm use of tube feeding in patients with head and neck cancer (Caudell et al, 2010;Gokhale et al, 2010). Phonatory and swallowing dysfunction was evoked by radiation-induced thyroarytenoid injury (Tedla et al, 2012). Pectoralis muscle injury and necrosis, together with skin damage, were reported in the patients with breast cancer after high-dose irradiation, resulting in intractable chronic ulcer (Rigotti et al, 2007).…”

Impact of Irradiation on laryngeal hydration and lubrication in rat larynx

“…Several studies have characterized pathological changes in laryngeal structural levels in human specimens . It is believed that radiation‐induced fibrosis is critical to late effects of radiation damage to the larynx.…”

“…Mechanisms by which radiation leads to fibrosis in the larynx have been investigated in human and rodent larynges in vivo, as well as a fibroblast culture model in vitro . Histologic changes in laryngeal muscle after irradiation have also been investigated, and reduction of muscle fibers in irradiated VFs has been shown to be involved in decreased vocal functions after radiotherapy …”

Swallow and breathing coordination following suprahyoid muscle injury.

“…Further studies have shown significant decreases in the frequency of functional swallows (i.e., no aspiration and minimal residue) and in the portion of patients tolerating normal diets, at 3-and 12-months post-radiotherapy (Logemann et al, 2008). Histological studies of intrinsic laryngeal muscles have shown significant changes in fibril organization and reductions in the average area occupied by muscle fibers 7 to 15 months postradiotherapy (Tedla et al, 2012). These late effects appear to coincide with the disruptions in swallow and breathing described previously (Brodsky et al, 2010).…”