Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.
Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.
复制标题
DOI：
10.1016/s0140-6736(16)30825-x
复制
发表时间：
2016-10-22
期刊：
影响因子：
168.9
通讯作者：
Langley, Ruth E.
中科院分区：
文献类型：
--
作者：
Mulvenna, Paula;Nankivell, Matthew;Barton, Rachael;Faivre-Finn, Corinne;Wilson, Paula;McColl, Elaine;Moore, Barbara;Brisbane, Iona;Ardron, David;Holt, Tanya;Morgan, Sally;Lee, Caroline;Waite, Kathryn;Bayman, Neil;Pugh, Cheryl;Sydes, Benjamin;Stephens, Richard;Parmar, Mahesh K.;Langley, Ruth E.
全脑放疗（WBRT）和地塞米松被广泛用于治疗非小细胞肺癌（NSCLC）的脑转移，尽管没有随机临床试验表明WBRT可以改善生活质量或总生存期。即使在WBRT治疗后，该患者组的预后也很差。我们的目的是确定是否可以省略WBRT，而不会对生存率或生活质量产生显著影响。脑转移瘤治疗后的生活质量（QUARTZ）研究是一项非劣效性、3期随机试验，在69个英国和3个澳大利亚中心进行。不适合手术切除或立体定向放射治疗的脑转移瘤非小细胞肺癌患者被随机分配（1：1）接受最佳支持治疗（OSC），包括地塞米松加WBRT（20戈伊，每日5次）或单独使用OSC（包括地塞米松）。地塞米松的剂量由患者的症状决定，如果症状改善，则向下滴定。通过从医院致电伦敦大学学院医学研究理事会临床试验部门，使用随机元素的最小化方案并按中心、Karnofsky体能状态（KPS）、性别、脑转移状态和原发性肺癌状态分层，完成治疗组分配。主要结果测量是质量调整生命年（Qs）。根据总生存期和患者每周完成的EQ-5D问卷生成QFD。如果OSC单药治疗比WBRT + OSC治疗（需要534例患者）差不超过7个QALY天，则认为其非劣效性（80%把握度，5% [单侧]显著性水平）。对所有随机分配的患者进行意向治疗分析。该试验在ISRCTN注册，编号ISRCTN 3826061。在2007年3月2日至2014年8月29日期间，从69个英国和3个澳大利亚中心招募了538名患者，并随机分配接受OSC + WBRT（269）或单独使用OSC（269）。基线特征在组间平衡，参与者的中位年龄为66岁（范围38-85）。当患者接受WBRT治疗时，嗜睡、脱发、恶心和头皮干燥或瘙痒的事件明显更多，尽管没有证据表明两组之间严重不良事件的发生率存在差异。没有证据表明两组之间的总生存率（风险比1.06，95%CI 0.90 - 1.26）、总体生活质量或地塞米松使用存在差异。平均QALY之间的差异为4.7天（OSC + WBRT组为46.4 QALY天，OSC组为41.7 QALY天），双侧90% CI为− 12.7至3.3。尽管主要结局指标结果包括预先规定的非劣效性界值，但两组之间QOL的微小差异以及生存期和生活质量无差异表明WBRT对该患者组几乎没有额外的临床显著获益。英国癌症研究所、伦敦大学学院医学研究理事会临床试验单位和澳大利亚国家健康和医学研究理事会。
Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061. Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to receive either OSC plus WBRT (269) or OSC alone (269). Baseline characteristics were balanced between groups, and the median age of participants was 66 years (range 38–85). Significantly more episodes of drowsiness, hair loss, nausea, and dry or itchy scalp were reported while patients were receiving WBRT, although there was no evidence of a difference in the rate of serious adverse events between the two groups. There was no evidence of a difference in overall survival (hazard ratio 1·06, 95% CI 0·90–1·26), overall quality of life, or dexamethasone use between the two groups. The difference between the mean QALYs was 4·7 days (46·4 QALY days for the OSC plus WBRT group vs 41·7 QALY days for the OSC group), with two-sided 90% CI of −12·7 to 3·3. Although the primary outcome measure result includes the prespecified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and quality of life between the two groups suggests that WBRT provides little additional clinically significant benefit for this patient group. Cancer Research UK, Medical Research Council Clinical Trials Unit at University College London, and the National Health and Medical Research Council in Australia.