Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Abstract

Importance:

Despite 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.

Objective:

To 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 Participants:

In 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 Measures:

The 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 & 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.

Results:

A 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 Relevance:

In 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 Registration:

ClinicalTrials.gov Identifier: NCT04638465.

• Authors: Aru Panwar, Swapnil Shah, Abigail E Reid, William Lydiatt, Andrew J Holcomb, Angela Osmolak, Andrew Coughlin, Oleg Militsakh, Yungpo B Su, Alireza Mirmiran, Tien-Shew Huang, Nicole Nolan, Randall Duckert, Christian Barney, Max Chiu, Cam Nguyen, Harlan Sayles, Apar Kishor Ganti, Robert Lindau
• Journal: JAMA otolaryngology-- head & neck surgery (JAMA Otolaryngol Head Neck Surg) Vol. 150 Issue 5 Pg. 429-435 (May 01 2024) ISSN: 2168-619X [Electronic] United States
• PMID: 38573597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Controlled Clinical Trial, Research Support, N.I.H., Extramural)

Topics

• Humans
• Quality of Life
• Male
• Oropharyngeal Neoplasms (therapy, virology, psychology, pathology)
• Female
• Middle Aged
• Depression (etiology)
• Papillomavirus Infections (complications, psychology)
• Aged
• Carcinoma, Squamous Cell (therapy, virology, psychology, pathology)
• Patient Reported Outcome Measures
• Neoplasm Staging