Chemo-IMRT of oropharyngeal cancer aiming to reduce dysphagia: swallowing organs late complication probabilities and dosimetric correlates

Abstract

Purpose: Assess dosimetric correlates of long-term dysphagia after chemo-intensity-modulated radiotherapy (IMRT) of oropharyngeal cancer (OPC) sparing parts of the swallowing organs.

Patients and methods: Prospective longitudinal study: weekly chemotherapy concurrent with IMRT for Stages III/IV OPC, aiming to reduce dysphagia by sparing noninvolved parts of swallowing-related organs: pharyngeal constrictors (PC), glottic and supraglottic larynx (GSL), and esophagus, as well as oral cavity and major salivary glands. Dysphagia outcomes included patient-reported Swallowing and Eating Domain scores, Observer-based (CTCAEv.2) dysphagia, and videofluoroscopy (VF), before and periodically after therapy through 2 years. Relationships between dosimetric factors and worsening (from baseline) of dysphagia through 2 years were assessed by linear mixed-effects model.

Results: Seventy-three patients participated. Observer-based dysphagia was not modeled because at >6 months there were only four Grade ≥2 cases (one of whom was feeding-tube dependent). PC, GSL, and esophagus mean doses, as well as their partial volume doses (V(D)s), were each significantly correlated with all dysphagia outcomes. However, the V(D)s for each organ intercorrelated and also highly correlated with the mean doses, leaving only mean doses significant. Mean doses to each of the parts of the PCs (superior, middle, and inferior) were also significantly correlated with all dysphagia measures, with superior PCs demonstrating highest correlations. For VF-based strictures, most significant predictor was esophageal mean doses (48±17 Gy in patients with, vs 27±12 in patients without strictures, p = 0.004). Normal tissue complication probabilities (NTCPs) increased moderately with mean doses without any threshold. For increased VF-based aspirations or worsened VF summary scores, toxic doses (TDs)(50) and TD(25) were 63 Gy and 56 Gy for PC, and 56 Gy and 39 Gy for GSL, respectively. For both PC and GSL, patient-reported swallowing TDs were substantially higher than VF-based TDs.

Conclusions: Swallowing organs mean doses correlated significantly with long-term worsening of swallowing. Different methods assessing dysphagia resulted in different NTCPs, and none demonstrated a threshold.