The QUARTZ Trial
The QUARTZ (Quality of Life after Treatment for Brain Metastases) trial was a phase 3, non-inferiority randomized controlled trial that demonstrated whole brain radiotherapy (WBRT) provides minimal clinically significant benefit over optimal supportive care alone for patients with non-small cell lung cancer (NSCLC) and inoperable brain metastases. 1
Trial Design and Population
The QUARTZ study enrolled 538 patients between March 2007 and August 2014 across 69 UK and 3 Australian centers 1. The trial specifically targeted:
- Patients with NSCLC and brain metastases unsuitable for surgical resection or stereotactic radiotherapy 1
- Median age of 66 years (range 38-85 years) 1
- 50% had Karnofsky Performance Status <70, indicating poor functional status 2
Patients were randomized 1:1 to receive either optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in 5 daily fractions) versus OSC alone with dexamethasone 1. The dexamethasone dose was titrated based on symptom control 1.
Primary Outcome and Key Findings
The primary outcome was quality-adjusted life-years (QALYs), with OSC alone considered non-inferior if it was no more than 7 QALY days worse than WBRT plus OSC 1. The trial results showed:
- No difference in overall survival: hazard ratio 1.06 (95% CI 0.90-1.26) 1
- Mean QALY difference of only 4.7 days (46.4 days for WBRT group vs 41.7 days for OSC alone) 1
- Median survival was 49 days for OSC + WBRT versus 51 days for OSC alone 2
- No evidence of difference in overall quality of life or dexamethasone use between groups 1
Safety and Tolerability
WBRT was associated with significantly more treatment-related toxicities without improving outcomes 1:
- More episodes of drowsiness, hair loss, nausea, and dry or itchy scalp during WBRT 1
- No difference in serious adverse event rates between groups 1
- 85% of patients allocated to WBRT actually received the treatment 2
Clinical Implications
The combination of minimal QALY difference and absence of survival or quality of life benefit suggests WBRT provides little additional clinically significant benefit for this patient population 1. This challenges the widespread practice of routinely offering WBRT to all patients with inoperable brain metastases from NSCLC.
Important Caveats
One retrospective analysis suggested potential survival benefit in patients with favorable prognostic features (age <60 years or graded prognostic assessment score 2.5-3 points) 3. This subgroup analysis found:
- Median survival of 3.2 months after WBRT (5 fractions of 4 Gy) versus 1.2 months with best supportive care alone 3
- Survival remained significantly better after WBRT in multivariate analyses 3
However, this contradicts the primary QUARTZ trial findings and represents lower-quality retrospective evidence 3. The prospective randomized QUARTZ trial data should take precedence in clinical decision-making 1.
Trial Methodology Context
The QUARTZ trial employed a non-inferiority design, which is appropriate when evaluating whether a less intensive treatment (OSC alone) is not meaningfully worse than standard treatment (WBRT plus OSC) 4. The prespecified non-inferiority margin of 7 QALY days was clinically reasonable 1.