Moffitt Cancer Center, Tampa, Florida.
University of South Florida, Tampa, Florida.
Cancer. 2021 May 1;127(9):1476-1482. doi: 10.1002/cncr.33397. Epub 2020 Dec 30.
Increases in fatigue, depressive symptomatology, and cognitive impairment are common after the initiation of androgen deprivation therapy (ADT) for prostate cancer. To date, no studies have examined the potential role of inflammation in the development of these symptoms in ADT recipients. The goal of the current study was to examine circulating markers of inflammation as potential mediators of change in fatigue, depressive symptomatology, and cognitive impairment related to the receipt of ADT.
Patients treated with ADT for prostate cancer (ADT+; n = 47) were assessed around the time of the initiation of ADT and 6 and 12 months later. An age- and education-matched group of men without a history of cancer (CA-; n = 82) was assessed at comparable time points. Fatigue, depressive symptomatology, and cognitive impairment were assessed with the Fatigue Symptom Inventory, the Center for Epidemiological Studies Depression Scale, and a battery of neuropsychological tests, respectively. Circulating markers of inflammation included interleukin 1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), soluble tumor necrosis factor receptor II (sTNF-RII), and C-reactive protein (CRP).
Fatigue, depressive symptomatology, and serum IL-6 increased significantly over time in the ADT+ group versus the CA- group; rates of cognitive impairment also changed significantly between the groups. No significant changes in IL-1RA, sTNF-RII, or CRP over time were detected. Treatment-related increases in IL-6 were associated with worsening fatigue but not depressive symptomatology or cognitive impairment.
Results of this preliminary study suggest that increases in circulating IL-6, perhaps due to testosterone inhibition, may play a role in fatigue secondary to receipt of ADT. Additional research is needed to determine whether interventions to reduce circulating inflammation improve fatigue in this population.
在开始接受前列腺癌去势治疗(ADT)后,疲劳、抑郁症状和认知障碍的发生率会增加。迄今为止,尚无研究探讨炎症在 ADT 接受者这些症状发展中的潜在作用。本研究的目的是研究循环炎症标志物是否可能成为 ADT 相关疲劳、抑郁症状和认知障碍变化的中介。
接受 ADT 治疗的前列腺癌患者(ADT+;n=47)在 ADT 开始时、6 个月和 12 个月后接受评估。一组年龄和教育程度匹配、无癌症病史的男性(CA-;n=82)在相应时间点接受评估。疲劳、抑郁症状和认知障碍分别用疲劳症状量表、流行病学研究中心抑郁量表和一系列神经心理测试进行评估。循环炎症标志物包括白细胞介素 1 受体拮抗剂(IL-1RA)、白细胞介素 6(IL-6)、可溶性肿瘤坏死因子受体 II(sTNF-RII)和 C 反应蛋白(CRP)。
与 CA-组相比,ADT+组的疲劳、抑郁症状和血清 IL-6 在随访期间显著增加;两组的认知障碍发生率也发生了显著变化。未发现 IL-1RA、sTNF-RII 或 CRP 随时间的变化。与治疗相关的 IL-6 增加与疲劳恶化相关,但与抑郁症状或认知障碍无关。
这项初步研究的结果表明,循环 IL-6 的增加,可能是由于睾酮抑制,可能在 ADT 后出现的疲劳中起作用。需要进一步研究以确定减少循环炎症的干预措施是否能改善该人群的疲劳。