Dosimetric Predictors of Long-term Dysphagia Following Oropharyngeal IMRT

Abstract

Recent studies have focused on identification of vulnerable bystander anatomy associated with acute dysphagia following head and neck intensity modulated radiotherapy (IMRT). No data are currently available for chronic swallowing outcomes (≥6 months post-treatment). We investigated the impact of specific regional doses delivered by IMRT on long-term swallowing function in oropharyngeal cancer patients prospectively evaluated with serial modified barium swallow (MBS) studies and the M.D. Anderson Dysphagia Inventory (MDADI) up to two years. Forty-eight patients with stage IV head and neck squamous cell carcinoma were enrolled on an institutional trial examining induction chemotherapy followed by IMRT +/− chemotherapy. We studied a subgroup of 31 oropharyngeal cancer patients who were evaluated with MBS and MDADI at baseline, 6, 12, and 24 months after radiation. Oropharyngeal swallow efficiency (OPSE) was defined as the ratio of the percent swallowed into the esophagus divided by oropharyngeal transit time. Potential dysphagia-associated structures, including oral cavity, pharyngeal constrictors, larynx, tongue base, and salivary glands were retrospectively contoured. These structures were not assigned specific cost functions for IMRT planning. Twenty-one (68%) patients had disease of the base of tongue, and 10 (32%) had tonsillar disease. T stage distribution was T1 (12), T2 (10), T3 (4), T4 (2), and TX (3); N stage distribution was N2 (24), N3 (5), and NX (2). Median age was 52.8 years (range: 42-78). Thirteen patients (42%) received concurrent chemotherapy during radiation. Long-term OPSE was most closely associated with oral cavity dose (V30Gy, V50Gy) and baseline OPSE scores (p < 0.001) using a random-effects linear regression model to evaluate changes in OPSE at 6-, 12-, and 24-months from scores obtained at baseline. Mean doses to pharyngeal constrictors, tongue base, and larynx were also associated with worse long-term OSPE (p < 0.04). Patients with base of tongue cancer had better OPSE than patients with tonsillar cancer (p = 0.01). Mean MDADI scores were lower than baseline at 6 months post-IMRT, but improved by 12 months (p = 0.04). Only mean doses to the ipsilateral parotid were significantly associated with MDADI scores (p = 0.04). No patient demonstrated aspiration per MBS study at 24 months. This is the first investigation to associate long-term swallowing outcomes with detailed doses to normal anatomy in patients with oropharyngeal cancer treated with IMRT. Although pharyngeal and laryngeal doses were important, oral cavity doses were most closely associated with long-term dysphagia in this cohort. The relationship between perceptual and instrumental measures of dysphagia in patients treated with different cancer regimens needs to be clarified.