Swallowing-related outcomes and organ-at-risk dosimetry after proton versus photon radiotherapy in nasopharyngeal carcinoma.

PURPOSE: To prospectively compare dose to swallowing-related organs-at-risk (OARs) and swallowing outcomes between proton (intensity-modulated proton therapy, IMPT) and photon (volumetric modulated arc therapy, VMAT) radiotherapy (RT), and to characterize dose-response relationships associated with dysphagia in nasopharyngeal carcinoma (NPC).

METHODS

In total, 104 patients with NPC received definitive chemoradiotherapy (IMPT, n = 58; VMAT, n = 46). Mean OAR doses were compared. Swallowing-related quality of life (QoL) was assessed using the MD Anderson Dysphagia Inventory (MDADI) at baseline (T1), end of RT (T2), and one-year post-RT (T3). Logistic regression evaluated predictors of ≥ 10-point MDADI decline or > 10% weight loss; linear mixed-effects and multivariable linear models assessed OAR dose-response relationships.

RESULTS

IMPT delivered lower mean doses to the oral cavity, middle pharyngeal constrictor muscle (M-PCM), and inferior pharyngeal constrictor muscle (all P < 0.01), with similar sparing of salivary glands and the superior pharyngeal constrictor muscle (S-PCM). IMPT resulted in less weight loss at T2 (3.4% vs 5.5%; P = 0.019) and lower odds of > 10% loss (OR 0.10; 95% CI, 0.01-0.80). MDADI Composite and domain scores did not differ by RT modality. Higher baseline MDADI predicted better T2 and T3 scores, and older age reduced the risk of ≥ 10-point decline at T2. Higher S-PCM dose was consistently associated with worse MDADI at T2 and T3, while M-PCM dose was associated with acute declines at T2.

CONCLUSIONS

IMPT improves sparing of several swallowing-related OARs and reduces early weight loss, but swallowing-related QoL is associated with dose at pharyngeal constrictor muscles, particularly the S-PCM.