Department of Otolaryngology-Head and Neck Surgery and Communicative Disorders, University of Louisville School of Medicine, Louisville, Kentucky.
University of Louisville Healthcare-Brown Cancer Center, Louisville, Kentucky.
JAMA Otolaryngol Head Neck Surg. 2024 May 1;150(5):405-413. doi: 10.1001/jamaoto.2024.0231.
Patients with head and neck cancer experience high rates of depression. Depression and systemic inflammation have been found to be associated in numerous cancer types, often independently from disease status. Depression-related inflammation may elevate the risks for poor tumor response to treatment and early mortality, and comprises a mechanism by which depression is associated with survival in head and neck cancer.
To assess mediation pathways incorporating pretreatment depressive symptoms, pretreatment inflammation, and tumor response posttreatment on overall survival among patients with head and neck cancer.
DESIGN, SETTING, AND PARTICIPANTS: This was a prospective observational cohort study of patients with head and neck cancer treated in a single multidisciplinary head and neck cancer clinic from May 10, 2013, to December 30, 2019, and followed up for 2 years. Data analysis was performed from June 29, 2022, to June 23, 2023.
Patient-reported depressive symptoms using the Patient Health Questionnaire-9 item (PHQ-9) at treatment planning; pretreatment hematology workup for systemic inflammation index (SII) score; and clinical data review for tumor response (complete vs incomplete) and overall survival.
Two-year overall survival.
The total study cohort included 394 patients (mean [SD] age, 62.5 [11.5] years; 277 [70.3%] males) with head and neck cancer. Among 285 patients (72.3%) who scored below the clinical cutoff for depression on the PHQ-9, depressive symptoms were significantly associated with inflammation (partial r, 0.168; 95% CI, 0.007-0.038). In addition, both depression and inflammation were associated with early mortality (PHQ-9: hazard ratio [HR], 1.04; 95% CI, 1.02-1.07; SII: HR, 1.36; 95% CI, 1.08-1.71). The depression-survival association was fully mediated by inflammation (HR, 1.28; 95% CI, 1.00-1.64). Depressive symptoms were also associated with poorer tumor response (odds ratio, 1.05; 95% CI, 1.01-1.08), and the depression-survival association was partially mediated by tumor response (HR, 9.44; 95% CI, 6.23-14.32). Systemic inflammation was not associated with tumor response.
In this cohort study, systemic inflammation emerged as a novel candidate mechanism of the association of depression with mortality. Tumor response partially mediated effects of depression on mortality, replicating prior work. Thus, depression stands out as a highly feasible target for renewed clinical attention. Even mild symptoms of depression during the treatment-planning phase may be associated with higher systemic inflammation in addition to poorer tumor response to treatment and survival outcomes; therefore, depression should be clinically addressed.
头颈部癌症患者的抑郁发生率很高。在许多癌症类型中，已经发现抑郁和系统性炎症有关，且通常与疾病状况无关。与抑郁相关的炎症可能会增加肿瘤对治疗反应不良和早期死亡的风险，并构成抑郁与头颈部癌症患者生存相关的一种机制。
评估纳入头颈部癌症患者治疗前抑郁症状、治疗前炎症和治疗后肿瘤反应的中介途径，以评估其对总体生存的影响。
设计、设置和参与者：这是一项单中心多学科头颈部癌症诊所对 2013 年 5 月 10 日至 2019 年 12 月 30 日期间接受治疗的头颈部癌症患者进行的前瞻性观察队列研究，并随访 2 年。数据分析于 2022 年 6 月 29 日至 2023 年 6 月 23 日进行。
患者在治疗计划时使用患者健康问卷-9 项（PHQ-9）报告抑郁症状；治疗前血液学检查评估系统性炎症指数（SII）评分；以及临床数据回顾肿瘤反应（完全缓解与不完全缓解）和总体生存情况。
2 年总体生存率。
总研究队列包括 394 名（平均[标准差]年龄 62.5[11.5]岁；277[70.3%]名男性）头颈部癌症患者。在 285 名（72.3%）PHQ-9 评分低于临床抑郁临界值的患者中，抑郁症状与炎症显著相关（部分 r，0.168；95%CI，0.007-0.038）。此外，抑郁和炎症均与早期死亡率相关（PHQ-9：风险比[HR]，1.04；95%CI，1.02-1.07；SII：HR，1.36；95%CI，1.08-1.71）。抑郁与生存的关联完全通过炎症来介导（HR，1.28；95%CI，1.00-1.64）。抑郁症状也与肿瘤反应较差相关（比值比，1.05；95%CI，1.01-1.08），抑郁与生存的关联部分通过肿瘤反应来介导（HR，9.44；95%CI，6.23-14.32）。系统性炎症与肿瘤反应无关。
在本队列研究中，系统性炎症成为抑郁与死亡率相关的一个新的候选机制。肿瘤反应部分介导了抑郁对死亡率的影响，复制了先前的研究。因此，抑郁作为一个高度可行的治疗靶点，值得重新引起临床关注。即使在治疗计划阶段出现轻度抑郁症状，除了治疗反应不良和生存结局较差外，还可能与更高的全身炎症相关；因此，应进行临床处理。
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