TY - JOUR
T1 - Can Whole Brain Radiotherapy be omitted from the treatment of Non-Small Cell Lung Cancer patients with brain metastases not amenable to stereotactic radiotherapy or surgery?
T2 - Results from the UK Medical Research Council QUARTZ randomised clinical trial
AU - Mulvenna, Paula
AU - Nankivell, Matthew
AU - Barton, Rachael
AU - Faivre-Finn, Corinne
AU - Wilson, Paula
AU - McColl, Elaine
AU - Moore, Barbara
AU - Brisbane, Iona
AU - Ardron, David
AU - Holt, Tanya
AU - Morgan, Sally
AU - Lee, Caroline
AU - Waite, Kathryn
AU - Bayman, Neil
AU - Pugh, Cheryl
AU - Sydes, Benjamin
AU - Stephens, Richard
AU - Paramar, Mahesh
AU - Langley, Ruth
PY - 2016/9/4
Y1 - 2016/9/4
N2 - 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 (RCTs) demonstrating that WBRT improves either quality of life (QoL) or overall survival (OS).
Methods
QUARTZ (Quality of Life after Radiotherapy and Steroids) was a non-inferiority, phase III randomised clinical trial (ISRCTN: 3826061) with a primary outcome measure of quality adjusted life years (QALYs). NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly allocated (1:1) to optimal supportive care including dexamethasone plus WBRT (20 Gy/5 daily fractions) (OSC+WBRT) or OSC alone (including dexamethasone.) QALYs were generated from OS and patients’ weekly completion of the EQ-5D questionnaire. OSC alone was considered non-inferior if no more than 7 QALY days worse, which required 534 patients (80% power, 5% (one-sided) significance level).
Findings
Between 2007 and 2014, 538 patients were recruited from 69 UK and 3 Australian centres. Baseline characteristics were balanced between arms: male 58%; median age 66 years (range 38 – 85); Karnofsky performance status > 70 62%. There was no evidence of a difference in the rate of adverse events between the two groups. By October 2015, 536 patients had died. There was no evidence of a difference in OS (hazard ratio 1•06 (95% CI 0•90 – 1•26)), overall QoL, or steroid use between the 2 groups. The difference between the mean QALYs was 4•7 days (OSC+WBRT 46•4 QALY days vs OSC 41•7 QALY days), two-sided 90% CI of the difference -12•7 to +3•3 QALY days. Pre-specified subgroup analyses suggested a trend to benefit from WBRT in younger, better performance status patients.
Interpretation
Although the primary outcome measure result includes the pre-specified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and QoL between the 2 arms suggests that WBRT provides little additional clinically significant benefit for this patient group.
AB - 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 (RCTs) demonstrating that WBRT improves either quality of life (QoL) or overall survival (OS).
Methods
QUARTZ (Quality of Life after Radiotherapy and Steroids) was a non-inferiority, phase III randomised clinical trial (ISRCTN: 3826061) with a primary outcome measure of quality adjusted life years (QALYs). NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly allocated (1:1) to optimal supportive care including dexamethasone plus WBRT (20 Gy/5 daily fractions) (OSC+WBRT) or OSC alone (including dexamethasone.) QALYs were generated from OS and patients’ weekly completion of the EQ-5D questionnaire. OSC alone was considered non-inferior if no more than 7 QALY days worse, which required 534 patients (80% power, 5% (one-sided) significance level).
Findings
Between 2007 and 2014, 538 patients were recruited from 69 UK and 3 Australian centres. Baseline characteristics were balanced between arms: male 58%; median age 66 years (range 38 – 85); Karnofsky performance status > 70 62%. There was no evidence of a difference in the rate of adverse events between the two groups. By October 2015, 536 patients had died. There was no evidence of a difference in OS (hazard ratio 1•06 (95% CI 0•90 – 1•26)), overall QoL, or steroid use between the 2 groups. The difference between the mean QALYs was 4•7 days (OSC+WBRT 46•4 QALY days vs OSC 41•7 QALY days), two-sided 90% CI of the difference -12•7 to +3•3 QALY days. Pre-specified subgroup analyses suggested a trend to benefit from WBRT in younger, better performance status patients.
Interpretation
Although the primary outcome measure result includes the pre-specified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and QoL between the 2 arms suggests that WBRT provides little additional clinically significant benefit for this patient group.
M3 - Article
SN - 0140-6736
JO - The Lancet
JF - The Lancet
ER -
