Vocalization is a complex process that involves multiple anatomical structures which act in coordination. Due to this complexity, the definition of the most important anatomic sites whose dose-volume parameters would have a major effect on vocal function has been studied only in recent years and it is still controversial.

Dornfeld et al. (2007) considered various structures in the head and neck to be related to vocal injury: the superior and inferior base of tongue, the epiglottis, the lateral pharyngeal walls at the level of the inferior base of tongue, the pre-epiglottic space, the aryepiglottic folds, the false vocal cords, the lateral pharyngeal walls at the level of the false vocal cords, and the upper esophageal sphincter.

Sanguineti et al. (2007) evaluated the correlation between dose-volume parameters and edema, and contoured the larynx from the tip of the epiglottis superiorly to the bottom of the cricoid inferiorly; the external cartilage framework was excluded from the laryngeal volume.

Radiation-induced late toxicities, including swallowing disorders, are unevenly distributed, with some patients exhibiting more cellular radiosensitivity. Conflicting data have emerged related to target-tissue sensitivity (fibroblast vs. DNA repair capacity vs. lymphocytic chromosomal damage) and late radiation damage (Rudat et al. 1999; Borgmann et al. 2002; Geara et al. 1992). Denham et al. (2001) have categorized radiation-induced normal tissue injury as direct, indirect, and functional, in addition to resulting from genetic susceptibility. A number of tumor and radiation variables (Mittal et al. 2001; Eisbruch et al. 2002; Ang et al. 1997; Maciejewski et al. 1983; Fu et al. 1995; Taylor et al. 1992) also influence the incidence of late damage. Several investigators have documented cervical and pharyngeal fibrosis and laryngeal dysfunction resulting in swallowing disorders following standard or accelerated radiation schemes (Delaney et al. 1995; Horiot et al. 1992; Nguyen et al. 1988; Olmi et al. 1990; Marks et al. 1982; Cooper et al. 1995). Therefore, it is essential to understand the biomechanics of swallowing disorders and to know the anatomical organs that are critical for swallowing and the radiation dose-volume relationship of these organs, in order to prevent and reduce the incidence of swallowing disorders and devise effective rehabilitation techniques (Mittal et al. 2003) (Table 1).

Acute dysphasia during, and soon after, RT may result from alterations in saliva, and/or short-term laryngopharyngeal edema, resulting in acute dysphagia. This is usually limited as the salivary function and edema usually resolve within a few weeks post-RT. If these issues persist, they can lead to persistent dysphagia: e.g. long-term xerostomia can hinder swallowing function.

Radiation-induced swallowing disorders can manifest months to years later as a result of extensive fibrosis and vascular and neural damage of the pharyngeal region (Dejaeger and Goethals 1995). The biomechanics of these disorders have been studied by Lazarus (1993) using VFG in a group of patients with dysphagia 10 years following radiation. These patients demonstrated a number of oropharyngeal motility disorders, including reduced tongue-base contact with the posterior pharyngeal wall, reduced laryngeal elevation, and compromised vestibule and true vocal cord closure. These disorders resulted in pharyngeal residue, which was aspirated after swallow. Despite different tumor sites, all patients exhibited similar altered biomechanics, which most likely resulted from the large radiation doses and volumes that encompassed the orolaryngopharyngeal area during treatment. In 1995, a similar observation was made by Dejaeger and Goethals (1995) who used manofluorography in a patient 5 years following radiotherapy for a pharyngeal carcinoma. Kendall et al. (1998, 2000) used VFG to evaluate 20 patients with head and neck cancer previously treated with radiation. These patients were able to maintain nutrition and none complained of dysphagia. When compared with 60 normal subjects, all 20 patients demonstrated abnormal swallow mechanics and prolonged oropharyngeal time for all bolus sizes. The onset of aryepiglottic fold closure relative to the onset of swallow was delayed and there was a trend toward delayed hyoid elevation. In this study, there was a trend toward earlier opening of the upper esophageal sphincter relative to the arrival of the bolus, most likely as a compensatory mechanism. Patients with base of tongue cancer had worse swallow mechanics compared to patients with pharyngolaryngeal cancers.

To assess pharyngeal dysfunctions following radiation, Wu et al. (2000) used fiberoptic endoscopic examination in 31 patients with dysphagic nasopharyngeal cancer, with a mean follow-up of 8.5 years following radiation. They observed pharyngeal retention (93.5 %), post-swallow aspiration (77.4 %), atrophic changes in the tongue with or without fasciculation (54.8 %), vocal cord paralysis (29 %), velopharyngeal incompetence (58 %), delay or absence of swallow reflex (87.1 %), and poor pharyngeal constriction (80.6 %).

Jensen et al. (2007) made a similar observation using functional endoscopic evaluation of swallowing (FEES) and EORTC-QOL questionnaires in 25 patients with pharyngeal cancer treated with radiation alone and followed up for a minimum of 2.5 years (mean 5 years). Of these patients, 83 % had subjective swallowing complaints. The most frequent objective finding was reduced sensitivity in the oropharynx (94 %) and reduced range of motion at the tongue base (79 %). Pharyngeal residue appeared in 88 % of these patients, 59 % experienced laryngeal penetration, and 18 % aspirated. Penetration and aspiration were observed primarily with thin liquids. All of the six patients with aspiration were smokers. Thus, based on these studies, it is generally considered that the structures are critical for the maintenance of swallowing.

Several tools are available to assess short- and long-term cancer treatment-induced swallowing dysfunctions. Common Terminology Criteria for Adverse Events (CTCAE) are frequently used to assess acute toxicity. Late toxicities can be assessed using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) criteria and the Subjective Objective Management Analytic (SOMA) scale (Cox et al. 1995; Pavi et al. 1995; Denis et al. 2003).

Some of the instruments used to assess quality of life (QOL) in patients with head and neck cancer, including swallowing dysfunctions, include: the University of Washington Quality of Life tool (UWQOL) (Hassan and Weymuller 1993); the M.D. Anderson Dysphagia Symptom Inventory (MADSI-HN) (Rosenthal et al. 2007); the EORTC-QLQ H&N (Bjordal et al. 1995); the Performance Status Scale for Head and Neck Cancer patients (PSS-H&N) (List et al. 1996); the Radiation Therapy Instrument Head and Neck (QOL-RTI/H&N) (Trotti et al. 1998); the Functional Assessment of Cancer Therapy-H&N (FACT-H&N) (Long et al. 1996); and the Head and Neck Radiotherapy Questionnaire (HNRQ) (Browman et al. 1993). While these instruments all measure some aspects of head and neck cancer-related QOL, it is not clear which one best applies to the assessment of swallowing dysfunctions in patients with head and neck cancer and to various treatment modalities.

Subjective: if laryngeal cancer is present prior to treatment, it is difficult to distinguish changes due to treatment. Perhaps hoarseness and pain, which is occasional becomes intermittent and persists. Likewise, difficulty in breathing can be assessed as minimal to labored strider. Various endpoints have been suggested to assess and grade radiation effects on the larynx (Table 1a, b).

Rubin et al. (1991) suggested a 5 and 50 % risk of pharynx and larynx edema at 5 years with doses of 45 and 80 Gy, respectively. Moreover, it was felt that irradiation of less than 50 % of the larynx would not have changed these estimates (Figs. 6, 7, and 8).

Laryngopharyngeal disorders resulting in late dysphagia and aspiration are not regimen-specific and are the result of edema and fibrosis (Pauloski et al. 1994). To correlate the relationship of radiation dose-volume-effect, it is critical to know the relative importance of the organs involved in swallowing physiology. Pauloski et al. (2006) used VFG to evaluate the “organ at risk” in 170 patients. Laryngeal elevation, tongue-base retraction, and the cricopharyngeal opening consistently predicted patients’ ability to swallow different food consistencies. Eisbruch et al. (2004) reviewed the literature and identified the structures that, if damaged, could potentially cause abnormal swallowing physiology. From their study of 26 patients assessed with VFG, direct endoscopy, and CT scan, they identified pharyngeal constrictors (PC) and glottic and supraglottic larynx (GSL) as dysphagia- and/or aspiration-related structures (DARS). In a prospective study, Feng et al. (2007) established the dose-volume-effect relationship for DARS and the esophagus in 36 patients with stage 3/4 head and neck cancers treated with chemoradiation. For intensity modulated radiation therapy (IMRT) dose optimization, planning treatment volume (PTV) was excluded from the target organ (swallowing structures, major salivary glands, and oral cavity). However, the entire organ was used to establish the dose-volume-effect relationship. A strong correlation was observed between the mean dose to DARS and dysphagia endpoints Aspiration was observed when the PC mean dose exceeded 60 Gy and the dose-volume threshold was V40 = 90 %, V50 = 80 %, V60 = 70 %, and V65 > 50 %. For aspiration to occur, the GSL dose–volume threshold was V50 > 50 % (>50 % of volume receiving 50 Gy). For stricture, a mean dose of ≥66 Gy and a dose-volume threshold of V50 = 85 %, V60 = 70 %, and V65 = 60 % for PC was observed. For stricture formation to occur, no relationship between mean dose to the GSL and esophagus was observed. The mean dose to the PC and esophagus was correlated with liquid swallowing, while only the mean dose to PC was correlated with solid swallowing on patient-reported and observer-rated swallowing scores (Table 2; Figs. 6, 7, and 8).