Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska.
Methodist Estabrook Cancer Center, Nebraska Methodist Hospital, Omaha.
JAMA Otolaryngol Head Neck Surg. 2024 May 1;150(5):429-435. doi: 10.1001/jamaoto.2024.0262.
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.
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.
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.
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]).
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.
ClinicalTrials.gov Identifier: NCT04638465.
尽管人们对 HPV 介导的口咽鳞状细胞癌（HPV 阳性 OPSCC）幸存者的治疗降级治疗感兴趣，但降级治疗与患者报告的生活质量（QoL）结局和抑郁症状负担之间的关联仍不清楚。
确定 HPV 阳性 OPSCC 患者的临床病理和治疗变量与患者报告的 QoL 结局和抑郁症状负担之间的关联，这些患者参加了一项治疗降级试验。
设计、地点和参与者：在这项针对 HPV 阳性 OPSCC Ⅰ、Ⅱ和Ⅲ期成人的非随机对照、开放标签、治愈性意向治疗降级临床试验中，患者是从一个大容量的头颈部肿瘤学实践中招募的。
本研究的主要结局包括基于经过充分验证的清单的定量、患者报告的 QoL 和抑郁症状。患者报告的 QoL 基于功能评估癌症治疗-头颈部（FACT-HN）评分（范围为 0-148；较低的分数表示 QoL 较差）。患者报告的与抑郁相关的症状负担基于快速抑郁症状清单自我报告（QIDS-SR）评分（范围为 0-27；较高的分数表示抑郁症状负担较高）。在基线、3、6、12、24 和 36 个月时，将基线临床病理和治疗变量与 FACT-HN 和 QIDS-SR 评分配对。对于每个参与者，使用带有随机截距的线性混合效应模型，并对其他测量值使用固定效应。报告回归系数及其 95%置信区间。
共 95 名患者随访了中位数（IQR）为 2.2（1.6-3.2）年。其中，93 名患者（98%）为男性，平均年龄（SD）为 60.5（8.2）岁。总体而言，54 名参与者（57%）有当前或既往吸烟史，47 名（50%）接受了根治性手术（伴或不伴辅助治疗），48 名（50%）接受了原发性放疗（伴或不伴化疗）。中位（IQR）放疗剂量为 60（60-70）Gy。观察到 5 例死亡和 2 例复发事件（平均[SD]复发间隔为 1.4[1.5]年）。只有可改变的放疗剂量与较差的患者报告的 QoL（较低的 FACT-HN）（系数，-0.66 [95%CI，-1.09 至-0.23]）和更大的与抑郁相关的症状负担（较高的 QIDS-SR）（系数，0.11 [95%CI，0.04-0.19]）相关。以 70-Gy 剂量为参考，当患者接受 51 至 60 Gy（系数，12.75 [95%CI，4.58-20.92]和-2.17 [-3.49 至-0.85]）和 50 Gy 或更低剂量时，FACT-HN 和 QIDS-SR 评分有所改善。（系数，15.03 [4.36-25.69]和-2.80 [-4.55 至-1.04]）。
在这项非随机对照、开放标签、治愈性意向治疗降级试验中，较高的放疗剂量与患者报告的 QoL 较差和与抑郁相关的症状负担增加相关。这表明通过降低放疗剂量，可以改善 QoL 结局并减轻抑郁症状负担。
ClinicalTrials.gov 标识符：NCT04638465。
