Clinical Factors Associated With Post-Treatment Aspiration in Patients Receiving Radiotherapy for Squamous Cell Carcinomas of the Head and Neck.

PURPOSE/OBJECTIVE(S) Radiotherapy (RT) is an integral component of curative treatment of head and neck squamous cell carcinomas (HNSCC). Compromise of dysphagia/aspiration-related structures remains a clinically significant, and potentially life threatening, treatment complication. We hypothesized that treatment intensification might increase the long term risk of aspiration events, and investigated clinical factors contributing to this risk. MATERIALS/METHODS A single institution database of patients who received curative-intent RT for HNSCC from 1996 to 2018 was queried. Included patients had laryngeal/hypopharyngeal, oral cavity, or oropharyngeal cancers and did not experience locoregional failure. An aspiration event was defined as aspiration on modified barium swallow, or aspiration pneumonia, > 3 months after RT. 324 patients were eligible, with a median follow up of 42 months (range 4-195). Independent variables investigated included age, primary site, sex, T stage, N stage, overall stage, IMRT vs 3D RT, standard vs altered fractionation, prior vs never smoker, definitive vs post-operative RT, and the use of chemotherapy with RT. Univariate logistic regression was used to identify statistically significant risk factors and multivariate regression was then used to derive the final model. Kaplan Meier analysis was used to assess time to last aspiration event; significance was assessed via the log-rank test. RESULTS On univariate analysis patients who received chemotherapy (P = 0.007), were treated using 3D RT (P = 0.0009), or were prior smokers (P = 0.02) had a significantly increased risk of an aspiration event. No differences were seen with respect to age, sex, site, overall stage, T stage, N stage, postoperative vs definitive therapy, or fractionation. On multivariate analysis the use of chemotherapy [P = 0.004, OR 3.5 (95% CI 1.5 - 8.2)] and prior smoking [P = 0.03, OR 2.7 (95% CI 1.1 - 6.7)] remained significantly associated with increased risk, while use of IMRT significantly diminished risk [P = 0.001, OR 0.35 (0.19 - 0.35)]. In patients who received chemotherapy, the actuarial risk of aspiration via Kaplan Meier was 24% at five years, as opposed to 8% for RT alone (P = 0.007). Of the six patients who died secondary to aspiration pneumonia, five received chemotherapy with RT. CONCLUSION In this analysis the use of chemotherapy, prior smoking, and the use of 3D RT increased the odds of aspiration in patients receiving RT for HNSCC. Of note, use of chemotherapy increased this risk almost three-fold; this risk persisted long term, supporting the hypothesis that treatment intensification has a significant, persistent clinical impact on dysphagia-related structures. These data highlight the need to refine criteria for the use of chemotherapy with RT in the adjuvant setting, and support diminished dysphagia risk seen in de-intensification trials in HPV-associated oropharyngeal cancers.