Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma
Authors: Panwar Aru , Shah Swapnil , Reid Abigail E. , Lydiatt William , Holcomb Andrew J. , Osmolak Angela , Coughlin Andrew , Militsakh Oleg , Su Yungpo B. , Mirmiran Alireza , Huang Tien-Shew , Nolan Nicole , Duckert Randall , Barney Christian , Chiu Max , Nguyen Cam , Sayles Harlan , Ganti Apar Kishor , Lindau Robert 
Published: April 2024

ImportanceDespite interest in therapy de-escalation for survivors of human papillomavirus–mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear.ObjectiveTo identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial.Design, Setting, and ParticipantsIn this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice.Main Outcomes and MeasuresThe main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy–Head &amp;amp; Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs.ResultsA total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, −0.66 [95% CI, −1.09 to −0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and −2.17 [−3.49 to −0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and −2.80 [−4.55 to −1.04]).Conclusions and RelevanceIn this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose.Trial RegistrationClinicalTrials.gov Identifier: NCT04638465