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Abstract

BACKGROUND:

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.

METHODS:

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.

FINDINGS:

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.

INTERPRETATION:

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.​ 

Author information​

Mulvenna P1, Nankivell M2, Barton R3, Faivre-Finn C4, Wilson P5, McColl E6, Moore B7, Brisbane I8, Ardron D9, Holt T10, Morgan S11, Lee C12, Waite K13, Bayman N4, Pugh C2, Sydes B2, Stephens R2, Parmar MK2, Langley RE14.

1Northern Centre for Cancer Care, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

2Medical Research Council Clinical Trials Unit at University College London, London, UK.

3Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Hull, UK.

4Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK.

5Bristol Haematology and Oncology Centre, Bristol, UK.

6Newcastle Clinical Trials Unit and Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.

7Wales Cancer Research Network, Cardiff UK.

8The Beatson West of Scotland Cancer Centre, Greater Glasgow Health Board and Clyde, Glasgow, UK.

9Patient representative, Manchester, UK.

10Trans Tasman Radiation Oncology Group, Waratah, NSW, Australia; University of Queensland, QLD, Australia.

11Nottingham University Hospital, Nottingham, UK.

12Weston Park Hospital, Sheffield, UK.

13Queen Elizabeth Hospital, Kings Lynn, UK.

14Medical Research Council Clinical Trials Unit at University College London, London, UK. Electronic address: ruth.langley@ucl.ac.uk.