Reduced Aspiration Rates for 50 Gy Postoperative Radiation in HPV-Associated Oropharynx Cancer in E3311: A Trial of the ECOG-ACRIN Cancer Research Group

Abstract

<h3>Purpose/Objective(s)</h3> E3311 was a Phase II randomized trial that demonstrated excellent disease control (95% PFS) after primary transoral surgery (TOS) with de-escalated postoperative radiotherapy (RT) for intermediate risk HPV associated oropharyngeal cancer (OPC). De-escalation of postoperative RT to 50 Gy was largely motivated by the need to improve functional outcomes. Our objective was to explore over time and across arms: 1) aspiration rates per modified barium swallow (MBS) studies as reported by site clinicians, and 2) accuracy of site reporting against central review of MBS images. <h3>Materials/Methods</h3> 495 patients underwent TOS. MBS was included as an optional procedure in 316 patients from 50 of 59 sites at baseline, post-TOS, 6- and 24-months. Aspiration by site clinicians' MBS reading was logged in the trial database. MBS images were also centrally reviewed at MD Anderson Cancer Center using Penetration-Aspiration Scale criteria. Exploratory post hoc analyses compared aspiration rates baseline to post-TOS in all patients using McNemar's test, and between all arms at the post-TOS time point and between the two randomized arms at 6 and 24 months using Fisher's exact test. Kappa assessed agreement of site clinicians and central review. <h3>Results</h3> Pooling all arms, aspiration was reported at baseline in 2.4% of MBS studies increasing to 13.3% after TOS (p < 0.01), then decreasing to 10.8% and 9.0% at 6-months and 24-months, respectively. Post-TOS aspiration rates did not significantly differ between all arms (p = 0.97). After RT, aspiration rates were significantly different at 6 months (p=0.04) but not at 24 months between randomized arms. In a subset of 62 MBS, site clinicians demonstrated substantial reliability grading aspiration on MBS in comparison to central review (92% exact agreement; <i>k</i> = 0.62, 95% CI: 0.32-0.92). <h3>Conclusion</h3> Using a standardized MBS protocol, site clinicians reported aspiration with high accuracy relative to central image review. Aspiration rates were low overall, increasing significantly after TOS. De-escalated radiotherapy was associated with significantly lower aspiration rates at 6 months, not maintained at 24 months.