Contralateral Constrictor Dose Predicts Swallowing Function After Radiation for Head and Neck Cancer
Background: Radiation therapy can cause long-term dysphagia that seriously affects quality of life for survivors of head and neck cancer. This study evaluates a novel organ at risk, the contralateral pharyngeal constrictor muscles, to find out whether radiation dose to this structure predicts late swallowing function in patients with head and neck cancer.
Methods: The study included patients with head and neck cancer treated with radiation and concurrent systemic therapy at a single institution over 3 years. One-year dysphagia was defined as either the presence of a gastrostomy tube or an abnormal modified barium swallow ≥ 1 year after completion of radiation.
Results: Fifty-five patients met inclusion criteria, of which 46 were alive at 1 year. One-year dysphagia was present in 37% (n = 17) of this population. Contralateral constrictor V60 < 40% was associated with a 1-year dysphagia rate of 6%, compared with 57% in patients with V60 ≥ 40% (P < .001). An uninvolved pharynx mean dose < 45 Gy was associated with a 1-year dysphagia rate of 22%, compared with 52% in patients with an uninvolved pharynx mean dose ≥ 45 Gy (P = .03). Editing the clinical target volume off air cavities was associated with a decrease in 1-year dysphagia from 67% to 12% (P < .001), and with a reduction of contralateral constrictor V60 from 62% to 33% (P < .001). Air cavity editing was not associated with a change in locoregional recurrence or 1-year survival.
Conclusions: This is the first study to report a connection between contralateral constrictor dose and late swallowing function. The correlation between air cavity editing and contralateral constrictor V60 suggests that contralateral constrictor dose may depend partly on technique. Further studies are needed to explore whether these findings can be replicated prospectively and in other practice settings.
One-year dysphagia was defined as having a gastronomy tube (G-tube) in place or an abnormal modified barium swallow (MBS) ≥ 12 months after the completion of radiation. At the study institution, MBS is not routinely done after therapy but is ordered if a patient or clinician has concerns about swallowing function. MBS was considered abnormal if there was laryngeal penetration that reached the level of the glottis or was not ejected from the larynx.
Results
The VA Cancer Registry identified 113 patients treated for H&N cancer during the study period. Of these, 55 patients met the inclusion criteria. No patients were lost to follow-up. The median follow-up was 29 months. The median age was 67 years (range, 41-83) (Table 1). 
All patients were treated with intensity-modulated radiotherapy (IMRT). Patients treated with a sequential boost had an initial dose of 54 Gy and/or 50 Gy, followed by a boost to a total of 70 Gy at 2 Gy per fraction. Patients treated with a simultaneous integrated boost (SIB) technique received 69.96 Gy in 33 fractions, with elective volumes treated to 54.45 Gy in 33 fractions. Both patients with nasopharyngeal cancer were treated with SIB plans and had an intermediate dose volume of 59.4 Gy.
Systemic therapy was weekly cisplatin in 41 patients (75%) and cetuximab in 14 (25%). Twenty percent of patients receiving cisplatin switched to an alternative agent during treatment, most commonly carboplatin.
Forty-nine patients (89%) had a G-tube placed before starting radiation. G-tubes were in place for an interval of 0 to 47 months (mean, 8.6); 12 (22%) had a G-tube > 12 months. After completion of radiation, 18 patients (33%) had an abnormal MBS. These were done 1 to 50 months (mean, 14.8) after completion of radiation. Abnormal MBS occurred ≥ 12 months after radiation in 9 patients, 5 of whom had their G-tube in place for less than a year.
Forty-six patients (84%) survived more than 1 year and could be evaluated for late swallowing function. One-year dysphagia was seen in 17 (37%) of these patients. Recurrence was seen in 20 patients (36%), with locoregional recurrence in 12 (60%) of these cases. Recurrence occurred at a range of 0 to 15 months (mean, 5.6). Neither recurrence (P = .69) nor locoregional recurrence (P = .11) was associated with increased 1-year dysphagia.
In patients who could be evaluated for long-term swallowing function, contralateral constrictor V60 ranged from 0% to 100% (median, 51%). V60 was < 40% in 18 patients (39%). With V60 < 40%, there was a 6% rate of 1-year dysphagia compared with 57% for V60 ≥ 40% (P < .001).
Patients with contralateral constrictor V60 < 40 and V60 ≥ 40 both had a mean age of 65 years. χ2 analysis did not show a difference in T stage or systemic treatment but did show that patients with V60 < 40% were more likely to have N1 disease (P = .01), and less likely to have N2 disease (P = .01) compared with patients with V60 ≥ 40%. The difference in 1-year dysphagia between N0 to N1 patients (27%) and N2 to N3 patients (46%) was not statistically significant (P = .19).
In patients who could be evaluated for long-term swallowing function, the uninvolved pharynx volume median of the total constrictor volume was 32% (range, < 1%-62%). The uninvolved pharynx mean dose ranged from 28 to 68 Gy (median, 45). When the uninvolved pharynx mean dose was < 45 Gy, 1-year dysphagia was 22% compared with 52% with a dose ≥ 45 Gy (P = .03).
Air cavity editing was performed in 27 patients (49%). One-year survival was 93% with air cavity editing, and 75% without, which was not statistically significant. Locoregional recurrence occurred in 3 patients (11%) with air cavity editing, and 9 (32%) without, which was not statistically significant. In patients surviving at least 1 year, contralateral constrictor V60 averaged 33% with editing and 62% without editing (P < .001). One-year dysphagia was 12% with air cavity editing and 67% without editing (P < .001).
An SIB technique was done in 26 patients (47%). One-year survival was 85% (n = 22) with SIB and 83% (n = 24) with sequential boost, which was not statistically significant. Locoregional recurrence occurred in 19% with SIB, and 32% with sequential boost, which was not statistically significant. For SIB patients alive at 1 year, the median contralateral V60 was 28%, compared with 66% for patients treated with sequential technique. Seventeen patients (77%) with SIB had V60 < 40%. Nineteen (86%) of SIB plans also had air cavity editing. One patient (5%) with SIB had dysphagia at 1 year, compared with 16 (67%) sequential patients (P < .001).
