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头颈部癌患者神经认知缺陷与放射治疗或放化疗的关联

Association of Neurocognitive Deficits With Radiotherapy or Chemoradiotherapy for Patients With Head and Neck Cancer.

作者信息

Zer Alona, Pond Gregory R, Razak Albiruni R Abdul, Tirona Kattleya, Gan Hui K, Chen Eric X, O'Sullivan Brian, Waldron John, Goldstein David P, Weinreb Ilan, Hope Andrew J, Kim John J, Chan Kelvin K W, Chan Andrew K, Siu Lillian L, Bernstein Lori J

机构信息

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.

Department of Biostatistics, McMaster University, Hamilton, Canada.

出版信息

JAMA Otolaryngol Head Neck Surg. 2018 Jan 1;144(1):71-79. doi: 10.1001/jamaoto.2017.2235.

Abstract

IMPORTANCE

Neurocognitive deficits (NCD) have been observed in noncentral nervous system cancers, yet short- and long-term neurocognitive data on patients treated for head and neck cancer (HNC) are lacking.

OBJECTIVE

To assess objective neurocognitive function before and after definitive radiation therapy for HNC.

DESIGN, SETTING, AND PARTICIPANTS: In a prospective, longitudinal study, neurocognitive function and self-reported symptoms were assessed in 80 patients with histologically proven HNC requiring definitive chemoradiotherapy or radiotherapy and in 40 healthy controls 4 times (baseline, 6, 12, and 24 months after baseline) prior to commencing treatment at Princess Margaret Cancer Centre, Toronto, Canada.

MAIN OUTCOMES AND MEASURES

Neurocognitive test scores were converted to age-corrected z scores (mean, 0; standard deviation, 1) and reported as mean scores, standardized regression-based scores, and frequencies of impairments in intellectual capacity, concentration, memory, executive function, processing speed, and motor dexterity. Multivariable analysis was used to identify factors associated with NCD 2 years after treatment.

RESULTS

Eighty patients and 40 healthy controls enrolled. Analyses revealed significant differences between patient and control mean performance in some domains, with patient deficits increasing over time: intellectual capacity (Cohen d, effect sizes [95% CIs] of -0.46 [-0.64 to 0.30], -0.51 [-0.72 to -0.30], and -0.70 [-0.92 to -0.49] for time points 6, 12, and 24 months, respectively); concentration/short-term attention span (-0.19 [-0.37 to 0.00], -0.38 [-0.55 to -0.21], -0.54 [-0.71 to -0.37]); verbal memory (-0.16 [-0.33 to 0.02], -0.38 [-0.64 to -0.12], -0.53 [-0.74 to -0.32]); executive function (-0.14 [-0.27 to 0.00], -0.34 [-0.52 to -0.16], -0.43 [-0.64 to -0.22]), and global cognitive function composite (-0.38 [-0.55 to -0.22], -0.75 [-0.92 to -0.58], -1.06 [-1.26 to -0.86]). There was an increased rate of impaired global neurocognitive functioning among patients (38%) at 24 months compared with controls (0%). Neurocognitive deficits were not associated with baseline cytokines.

CONCLUSIONS AND RELEVANCE

Head and neck cancer survivors have neurocognitive sequelae up to 2 years after definitive chemoradiotherapy or radiation treatment. Patients and health care teams should know about such potential risks. Further research is warranted in search of strategies to avoid, reduce, and compensate for declines.

摘要

重要性

在非中枢神经系统癌症中已观察到神经认知缺陷(NCD),但缺乏针对头颈癌(HNC)患者的短期和长期神经认知数据。

目的

评估HNC患者根治性放射治疗前后的客观神经认知功能。

设计、背景和参与者:在一项前瞻性纵向研究中,对80例经组织学证实需要根治性放化疗或放疗的HNC患者以及40例健康对照者进行了神经认知功能和自我报告症状的评估,在加拿大安大略省多伦多市玛嘉烈公主癌症中心开始治疗前进行了4次评估(基线、基线后6、12和24个月)。

主要结局和测量指标

将神经认知测试分数转换为年龄校正的z分数(均值为0;标准差为1),并报告为平均分数、基于标准化回归的分数以及智力、注意力、记忆力、执行功能、处理速度和运动敏捷性受损的频率。采用多变量分析确定治疗后2年与NCD相关的因素。

结果

80例患者和40例健康对照者入组。分析显示,患者与对照在某些领域的平均表现存在显著差异,且患者的缺陷随时间增加:智力(时间点6、12和24个月时的Cohen d效应量[95%CI]分别为-0.46[-0.64至-0.30]、-0.51[-0.72至-0.30]和-0.70[-0.92至-0.49]);注意力/短期注意力广度(-0.19[-0.37至0.00]、-0.38[-0.55至-0.21]、-0.54[-0.71至-0.37]);言语记忆(-0.16[-0.33至0.02]、-0.38[-0.64至-0.12]、-0.53[-0.74至-0.32]);执行功能(-0.14[-0.27至0.00]、-0.34[-0.52至-0.16]、-0.43[-0.64至-0.22]),以及整体认知功能综合评分(-0.38[-0.55至-0.22]、-0.75[-0.92至-0.58]、-1.06[-1.26至-0.86])。与对照组(0%)相比,24个月时患者中整体神经认知功能受损的比例增加(38%)。神经认知缺陷与基线细胞因子无关。

结论和相关性

头颈癌幸存者在根治性放化疗或放疗后长达两年存在神经认知后遗症。患者和医疗团队应了解此类潜在风险。有必要进一步研究寻找避免、减少和补偿神经认知功能下降的策略。

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