Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study
Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study
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DOI：
10.1016/s1470-2045(15)00206-5
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发表时间：
2015-11-01
期刊：
影响因子：
51.1
通讯作者：
Mandelli, Franco
中科院分区：
文献类型：
--
作者：
Efficace, Fabio;Gaidano, Gianluca;Mandelli, Franco
骨髓增生异常综合征的临床表现是高度可变的，因此准确预测这些患者的预后是至关重要的。我们的目的是评估自我报告的疲劳严重程度是否能预测高风险骨髓增生异常综合征患者超过金标准预后指标的总生存率。方法：我们对来自欧洲、美国和东亚37个中心的患者进行了一项多中心、前瞻性、观察性、队列研究。根据国际预后评分系统（IPSS），骨髓增生异常综合征的成人（>= 18岁）在诊断后6个月内连续入组，评分为中-2风险或高风险。患者不论年龄、合并症、表现状态和低IPSS风险评分类别的进展情况而入组。所有患者必须在基线时完成生活质量评估。通过使用单变量和多变量Cox比例风险回归分析，我们构建了一个多变量模型，用于预测预后变量（包括来自欧洲癌症研究和治疗组织生活质量问卷-core 30的IPSS和疲劳评分）如何预测总体生存。主要终点是根据基线自我报告疲劳量表评分的总生存期。本研究已在ClinicalTrials.gov注册，注册号为NCT00809575。在2008年11月10日至2012年8月13日期间，我们纳入了280例患者，中位年龄为71岁（IQR 64-77）。中位随访15个月（IQR 8-27），最后一位患者于2015年2月16日接受评估。诊断后的中位总生存期为17个月（95% CI 15-19）。在单因素分析中，与总生存率降低显著相关的基线因素是年龄增加、输血依赖（定义为在4个月内每8周至少接受一次红细胞输血）、东部肿瘤合作组（ECOG）两次或两次以上的表现状态、白细胞计数增加、高风险IPSS评分和较高的自我报告疲劳严重程度。在多变量分析中，与总生存率降低独立相关的基线因素是高危IPSS评分（风险比[HR] 2.525, 95% CI 1.357-4.697; p=0.0035）和较高的疲劳评分（每10分疲劳恶化1.110,1.040-1.170;p=0.0007）。在进一步的多变量生存模型中，包括基于who的预后评分系统或修订版本的IPSS分类，疲劳仍然是具有统计学意义的独立预后因素，其HR分别为1.120 （1.050-1.180,p=0.0003）和1.130 （1.060-1.190,p=0.0002）。在新诊断的高风险骨髓增生异常综合征患者中，自我报告的疲劳严重程度提供了独立于金标准风险分类的生存预后信息。我们的研究结果表明，疲劳评估应纳入这些患者的常规诊断调查，并将其作为未来随机对照试验的标准基线分层因素。
Background The clinical presentation of myelodysplastic syndromes is highly variable and so accurate prediction of outcomes in these patients is crucial. We aimed to assess whether self-reported fatigue severity predicts overall survival beyond gold-standard prognostic indices in patients with higher-risk myelodysplastic syndromes.Methods We did a multicentre, prospective, observational, cohort study of patients from 37 centres in Europe, USA, and east Asia. Adults (>= 18 years) with myelodysplastic syndromes were consecutively enrolled within 6 months of diagnosis with an intermediate-2-risk or high-risk score according to the International Prognostic Scoring System (IPSS). Patients were enrolled irrespective of older age, comorbidities, performance status, and progression from a lower IPSS risk score category. All patients had to complete a quality of life assessment at baseline. With use of univariate and then multivariate Cox proportional hazards regression analysis, we constructed a multivariate model of how prognostic variables, including IPSS and fatigue score from the European Organisation for Research and Treatment of Cancer quality-oflife questionnaire-core 30, predicted overall survival. The primary endpoint was overall survival by baseline self-reported fatigue scale ratings. This study was registered with ClinicalTrials.gov, number NCT00809575.Findings Between Nov 10, 2008, and Aug 13, 2012, we enrolled 280 patients with a median age of 71 years (IQR 64-77). The median follow-up was 15 months (IQR 8-27), and the last patient was assessed Feb 16, 2015. The median overall survival from diagnosis was 17 months (95% CI 15-19). In univariate analysis, the baseline factors that were significantly associated with reduced overall survival were increasing age, transfusion dependency (defined as having received at least one red blood cell transfusion every 8 weeks over a period of 4 months), Eastern Cooperative Oncology Group (ECOG) performance status of two or more, increased white blood cell count, high-risk IPSS score, and higher self-reported fatigue severity. In multivariate analysis, baseline factors independently associated with reduced overall survival were high-risk IPSS score (hazard ratio [HR] 2.525, 95% CI 1.357-4.697; p=0.0035) and a higher score for fatigue (1.110, 1.040-1.170, for every ten points of fatigue deterioration; p=0.0007). In further multivariate models for survival, including either the WHO-based prognostic scoring system or the revised version of the IPSS classification, fatigue remained a statistically significant independent prognostic factor with a HR of 1.120 (1.050-1.180, p=0.0003) and a HR of 1.130 (1.060-1.190, p=0.0002), respectively.Interpretation In patients with newly diagnosed higher-risk myelodysplastic syndromes, self-reported fatigue severity provides prognostic information for survival independent from gold-standard risk classifications. Our findings suggest that fatigue assessment should be included in routine diagnostic investigation for these patients and considered as a standard baseline stratification factor in future randomised controlled trials.