AIM: To determine swallowing outcomes and hyolaryngeal mechanics associated with post radiation therapy head and neck cancer (rtHNC) patients using videofluoroscopic swallow studies.

METHODS: In this retrospective cohort study, videofluoroscopic images of rtHNC patients (n = 21) were compared with age and gender matched controls (n = 21). Penetration-aspiration of the bolus and bolus residue were measured as swallowing outcome variables. Timing and displacement measurements of the anterior and posterior muscular slings elevating the hyolaryngeal complex were acquired. Coordinate data of anatomical landmarks mapping the action of the anterior muscles (suprahyoid muscles) and posterior muscles (long pharyngeal muscles) were used to calculate the distance measurements, and slice numbers were used to calculate time intervals. Canonical variate analysis with post-hoc discriminant function analysis was performed on coordinate data to determine multivariate mechanics of swallowing associated with treatment. Pharyngeal constriction ratio (PCR) was also measured to determine if weak pharyngeal constriction is associated with post radiation therapy.

RESULTS: The rtHNC group was characterized by poor swallowing outcomes compared to the control group in regards to: Penetration-aspiration scale (P < 0.0001), normalized residue ratio scale (NRRS) for the valleculae (P = 0.002) and NRRS for the piriform sinuses (P = 0.003). Timing and distance measurements of the anterior muscular sling were not significantly different in the two groups, whereas for the PMS time of displacement was abbreviated (P = 0.002) and distance of excursion was reduced (P = 0.02) in the rtHNC group. A canonical variate analysis shows a significant reduction in pharyngeal mechanics in the rtHNC group (P < 0.0001). The PCR was significantly higher in the test group than the control group (P = 0.0001) indicating reduced efficiency in pharyngeal clearance.

CONCLUSION: Using videofluoroscopy, this study shows rtHNC patients have worse swallowing outcomes associated with reduced hyolaryngeal mechanics and pharyngeal constriction compared with controls.

The oropharyngeal phase of swallowing is a complex physiological process involving the conversion of a respiratory conduit into an alimentary canal in less than one second. Videofluoroscopic swallowing studies, also known as modified barium swallows (MBS), are the standard instrumental tool for assessing oropharyngeal swallowing safety and efficiency. Swallowing safety is threatened when a bolus penetrates or is aspirated into the airway. The retention of a bolus in the valleculae or piriform sinuses is an indication of swallowing inefficiency. Reduced hyolaryngeal elevation is thought to underlie incomplete clearance of the bolus from the pharynx[1]. Residual bolus retained in pharyngeal spaces such as the piriform sinuses (residue) is predictive of aspiration[2]. Both outcomes are observed among post radiation therapy head and neck cancer (rtHNC) patients[3]. However, the underlying mechanics associated with these outcomes is poorly understood.

Recent anatomical and magnetic resonance imaging (MRI) studies have shown that two muscular slings elevate the hyolaryngeal complex to stretch open the upper esophageal sphincter in young healthy adults[4-6]. It is not known if altered function of one or both of these slings is associated with poor swallowing outcomes (penetration, aspiration, or residue). To determine if poor swallowing outcomes are associated with altered function of the two-sling mechanism, we compared kinematic and morphological data collected from MBS imaging of rtHNC patients with age and gender matched controls.

The hyolaryngeal complex is comprised of the hyoid bone, laryngeal cartilages, and associated structures including the cricopharyngeus muscle, which forms the upper esophageal sphincter. Two muscular slings elevate the hyolaryngeal complex in swallowing[5] (Figure 1). The suprahyoid muscles (mylohyoid, geniohyoid, stylohyoid, and digastric) form an anterior sling with proximal attachments to the mandible and cranial base and distal attachments to the body of the hyoid, which translates force to the larynx via the thyrohyoid membrane and likely assisted by the thyrohyoid muscle[4]. A posterior sling comprised of the long pharyngeal muscles (stylopharyngeus, palatopharyngeus and salpingopharyngeus) has superior attachments to the styloid process, auditory tube, and structures associated with the palate, and inferior attachments inserting primarily on the lateral pharyngeal wall and thyroid cartilage[7,8]. These muscular slings function to elevate the hyolaryngeal complex and stretch open the upper esophageal sphincter, but it is unknown whether pathology changes the function of the two-sling mechanism.

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Figure 1 Two-sling mechanism for hyolaryngeal elevation in swallowing.

High quality MBS imaging that is well collimated provides data useful for analyzing outcomes as well as the underlying mechanisms of swallowing[9]. In this study, outcome variables measuring penetration-aspiration and residue were used to verify differences between test and control groups[10], whereas kinematic measurements[11,12] and multivariate morphometric analysis[6] were used to determine which of the two slings described above is impaired. Additionally, the pharyngeal constriction ratio (PCR), a reliable surrogate for strength of pharyngeal constriction, was measured for each group to document the effect of treatment on the pharyngeal constrictor muscles and the long pharyngeal muscles[13]. We hypothesized that swallowing outcome variables, kinematic measurements, multivariate morphometric analysis, and PCR of the rtHNC group will indicate impairment when compared to the control group.

Under a research protocol approved by the Boston University Medical Campus Institutional Review Board, a review of patient records was used to establish a test and control group. MBS imaging studies were recorded under routine radiographic protocols. An attempt was made to attach a radiopaque marker to each subject as an external scalar. Images were produced by a GE Precision Fluoroscopic unit and recorded digitally by a computer workstation at 30 frames/s. QuickTime™ software was used to trim each imaging study to include one episode of cued lateral view 5 mL swallows of thin liquid barium solution [Varibar Thin Liquid (40% wt/vol)].

Ninety-three patients with MBS studies were identified. Dysphagic patients related to rtHNC were placed in the test group (n = 28), while patients complaining of swallowing difficulty who showed no instrumental evidence of dysphagia were placed in the control group (n = 45). Of the 28 subjects in the rtHNC group, two lacked scalars and five could not be age or gender matched with the “normal” group. This left a final cohort of 21 subjects in each group composed of 14 males and 7 females with a mean age of 64 ± 13 years (test group) and 63 ± 11 years (control group).

Swallowing outcomes were collected along with spatial and temporal data from video files using ImageJ image analysis software equipped with QuickTime™ plug-ins (http://rsbweb.nih.gov/ij). Raters blinded to group assignment analyzed video files. Reliability was tested for all measurements by using a second judge to re-measure variables in 50% of MBS studies. Inter-rater reliability is reported in Table 1. In swallowing episodes requiring more than one swallow to clear the bolus, measurements were taken from the first swallow.

To measure penetration and aspiration we used a 1-8 ordinal scale called the penetration-aspiration scale (PAS)[14]. In the PAS scoring system 1-2 is considered functionally normal, 3-5 indicates bolus penetration into the laryngeal vestibule, and 6-8 indicates aspiration of the bolus into the airway. To quantify residue we used the normalized residue ratio scale (NRRS) for the valleculae and piriform sinuses[15]. The NRRS is a continuous measurement that incorporates the ratio of residue relative to pharyngeal space (valleculae and piriform sinuses) and the amount of residue scaled by an internal anatomical scalar (C2-C4 measurement described above). Differences in PAS in the two groups were evaluated using Mann-Whitney U tests, and differences in NRRS for the valleculae and piriform sinuses were compared using two-tailed t-tests with Bonferroni correction (α = 0.05, P < 0.025).

Kinematic data collected from video files included duration and displacement measurements representing the anterior and posterior slings. The movement of the hyoid towards the mandible represented the action of the anterior muscular sling (AMS). The movement of the larynx towards the cranial base represented the action of the posterior muscular sling (PMS). Each AMS and PMS time and distance measurement was measured at minimum and maximum elevation. For the AMS, the minimum position was defined as one frame prior to the first rostral movement of the hyoid related to pharyngeal swallowing and maximum position was defined as the most rostral movement of the hyoid during swallowing. For the PMS, the minimum position was defined as one frame prior to the first rostral movement of the larynx during pharyngeal swallowing and maximum position was defined as the frame where the larynx reaches its superior position during swallowing.

Duration of AMS and PMS movement was determined by dividing the difference in minimum and maximum frame numbers by 30 (fps). Displacement of the hyoid (representing the action of the AMS) and elevation of the posteroinferior edge of the cricoid toward the cranial base (representing the action of the PMS) were calculated using a coordinate mapping technique designed to track the components of the two-sling mechanism of hyolaryngeal elevation[16] (Figure 2). Displacement measurements of the hyoid and larynx were mathematically calculated from coordinate data. Timing and spatial measurements were compared using two-tailed t-tests with Bonferroni correction (α = 0.05, P < 0.025).

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Figure 2 Pictured here are the nine coordinates mapping three skeletal levers (in red) and muscular slings displacing the hyolaryngeal complex with coordinates 1, 3, 8, 9 mapping the anterior muscular sling (in blue) and coordinates 2, 3, 6, 7 mapping the posterior muscular sling (in green).

The nine coordinates mapping the elements of the anterior and PMSs in order to calculate kinematic variables were also used in a computational analysis of swallowing mechanics. The coordinate data set included nine coordinates for each subject at minimum and maximum excursion for the test group and control group. MorphoJ, software for geometric morphometric analysis, was used to perform a procrustes fit of all coordinates[17] (Figure 3). The procrustes fit resolved differences in scale and rotation between all subjects at both excursion points. Following the procrustes superimposition of coordinates, a canonical variate analysis was executed with classification variables assigned to each set of coordinates named by condition (test and control group) and excursion (minimum and maximum position of the hyolaryngeal complex).

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Figure 3 Procrustes fit of coordinates adjusts for differences in rotation and scale.

To evaluate differences in pharyngeal constriction between test and control groups, the PCR was measured using the lateral view MBS studies[13]. PCR is a ratio of the area of the hypopharynx at maximum constriction to the area of the hypopharynx at rest. Significance of differences in PCR was determined using a two-tailed t-test.

All swallowing outcome variables indicated significantly worse swallowing in the rtHNC group than in the control group. PAS scores were highly significantly (P < 0.0001) greater in rtHNC (4.43 ± 2.42) than in the control (1.29 ± 0.56), NRRS scores for the valleculae were significantly (P = 0.002) greater in rtHNC (0.22 ± 0.20) than in the control (0.05 ± 0.11), and NRRS scores for the piriform sinuses were significantly (P = 0.003) greater in HNC (0.31 ± 0.36) than in the control (0.05 ± 0.14).

The duration of PMS elevating the larynx was significantly (P = 0.002) briefer in rtHNC (0.29 ± 0.11 s) than in the control (0.48 ± 0.23 s), and the displacement of the larynx by the posterior sling muscles is significantly (P = 0.02) reduced in rtHNC (0.89 ± 0.63 cm) than in the control (1.41 ± 0.73 cm). While these PMS measurements showed significant differences, the AMS measurements did not (Figure 4).

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Figure 4 Significant differences between control and test groups. HNC: Head and neck cancer.

PCR was highly significantly (P = 0.0001) worse in rtHNC (0.16 ± 0.11) than in the control (0.05 ± 0.04).

The scatter plot of canonical variate scores with classification variable highlighted indicated that CV1 is associated with the excursion of the hyolaryngeal complex and CV2 is associated the test and control groups (Figure 5). Swallowing mechanics indicated by differences in shape change was highly significantly (P < 0.0001) reduced in the rtHNC (D = 2.98) than in the control (D = 4.54). Eigenvectors for each coordinate demonstrate the direction and degree of covariant shape change of the control (Figure 6) and test (Figure 7) groups for visual comparison.

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Figure 5 Canonical variate analysis showing differences in coordinate configuration plotted by canonical variate scores with classification variables highlighted. rtHNC: Radiation therapy head and neck cancer.

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Figure 6 Eigenvectors indicating mechanics of hyolaryngeal elevation of the control group from minimum (dotted lines) to maximum (solid lines) excursion.

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Figure 7 Eigenvectors indicating mechanics of hyolaryngeal elevation of the radiation therapy head and neck cancer group from minimum (dotted lines) to maximum (solid lines) excursion.

This study shows significant differences in swallowing safety and efficiency as measured by PAS and NRRS, respectively. Kinematic measurements showed that reduced function of the PMS which elevates the hyolaryngeal complex is associated with rtHNC. In contrast, the anterior sling was not significantly reduced in the test group. Finally, a computational analysis of swallowing mechanics confirms that the long pharyngeal muscles are implicated in this cohort of dysphagic patients, and that extending the head and neck while swallowing is presumably attempted to compensate for loss of pharyngeal function.