The LUSTRE trial, a phase 3 randomized clinical trial conducted across 16 Canadian centers, compared stereotactic body radiotherapy (SBRT) with hypofractionated conventional radiotherapy (CRT) in patients with medically inoperable stage I non-small cell lung cancer (NSCLC). The study aimed to determine if SBRT improves local control (LC) compared to CRT, while also assessing toxic effects.
Trial Design and Patient Population
From May 2014 to January 2020, 233 patients with stage I NSCLC (≤5 cm) were randomized in a 2:1 ratio to receive either SBRT or CRT. Patients receiving SBRT were administered 48 Gy in 4 fractions for peripheral tumors or 60 Gy in 8 fractions for central tumors, while the CRT group received 60 Gy in 15 fractions. The primary endpoint was local control at 3 years, with secondary outcomes including event-free survival, overall survival, and toxic effects. All radiation plans underwent rigorous review.
Key Findings
The trial results, analyzed from July 2022 to July 2023, indicated a non-significant improvement in local control with SBRT compared to CRT. At 3 years, LC was 87.6% (95% CI, 81.9%-93.4%) for SBRT and 81.2% (95% CI, 71.9%-90.5%) for CRT (HR, 0.61; 95% CI, 0.31-1.20; P = .15). Event-free survival and overall survival were also similar between the two groups. The hazard ratio was 1.02 (95% CI, 0.72-1.45; P = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; P = .40) for overall survival.
Toxicity Profile
Minimal acute toxic effects were observed in both groups. Late grade 3 or 4 toxic effects occurred in 5 of 45 patients (11%) with central NSCLC in the SBRT group and 1 of 19 patients (5%) in the CRT group. Among patients with peripheral NSCLC, late grade 3 or 4 toxic effects occurred in 2 of 109 (1.8%) in the SBRT group and 1 of 60 (2%) in the CRT group. One patient receiving SBRT for an ultracentral lesion experienced a possible treatment-related grade 5 event (hemoptysis).
Implications and Context
These findings suggest that hypofractionated CRT may offer comparable tumor control to SBRT with limited toxic effects, even in patients with central tumors. According to the study, modest hypofractionation could be used as a low-risk SBRT alternative, especially in resource-limited jurisdictions, and in scenarios where SBRT may be technically challenging.
The LUSTRE trial is the largest reported NSCLC SBRT RCT to date. While SBRT was associated with a nonsignificant improvement in LC compared with hypofractionated CRT, the CRT hypofractionation performed better than expected, which may have contributed to the nonsignificant difference observed between groups, according to the researchers.
Study Limitations
Limitations of the study include low accrual/statistical power and the inclusion of non-biopsy-proven NSCLC in more than half of patients (118 of 233 [51%]).
