What is the Impact of Treatment De-Escalation on Patient Reported Outcomes in Patients with T1-T2 Oropharyngeal Cancers? A Secondary Analysis of the ORATOR Studies.

Abstract

This study evaluates the impact of treatment de-escalation from 70 Gy to 60 Gy on patient-reported outcomes (PROs) and toxicity for patients with T1-2 p16-positive oropharyngeal squamous cell carcinoma (OPSCC) treated with primary radiotherapy as part of the BLINDED-FOR-REVIEW trials. Patients with p16-positive OPSCC treated with primary radiotherapy in the BLINDED-FOR-REVIEW randomized trials were included in this post-hoc analysis. Patient demographics, tumor and treatment characteristics were compared between patients who received radiation with 70 Gy (BLINDED-FOR-REVIEW, usually with cisplatin every 3 weeks) vs. 60 Gy (BLINDED-FOR-REVIEW, usually with weekly cisplatin). Outcomes examined included PROs and quality of life (QOL) metrics, including the MD Anderson Dysphagia Inventory (MDADI), European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 (C30) and Head-and-Neck 35 (H&N35) scales, toxicity, overall survival (OS) and progression-free survival (PFS). The cohort included 59 patients, 29 patients treated with 60 Gy and 30 patients with 70 Gy. Comparing QOL changes at 1-year in the 60 Gy vs. 70 Gy cohort respectively, the 60 Gy cohort demonstrated improved MDADI total (mean ± SD change: +1.9 ± 12.2 vs. -5.8 ± 11.3, p=0.035), and functional (+5.5 ± 12.7 vs. -3.3 ± 12.2, p=0.023) scores. The 60 Gy cohort demonstrated significantly better outcomes at 1-year in several EORTC QOL domains: global health status, fatigue, nausea/vomiting, appetite, constipation, pain, xerostomia, sticky saliva, and coughing (all p < 0.05). Patients treated with 60 Gy had significantly lower rates of grade 2-3 dysphagia and grade 2-3 mucositis (all p < 0.05). This comparison of arms from the separate ORATOR trials suggests that de-escalation from 70 Gy to 60 Gy for p16-positive patients with early-stage OPSCC may lead to better PROs across numerous domains, and reduced toxicity. Results from direct comparisons of these two doses are awaited.