Lack-LUSTRE.

Headline: We now have phase 3 data comparing stereotactic body radiation (SBRT) to hypofractionated radiation (HFRT) for stage I non-small cell lung cancer (NSCLC).

The Study: In the phase 3 LUSTRE trial, patients were randomized to receive SBRT (48Gy/4 for peripheral tumors and 60Gy/8 for central tumors) or hypofractionated RT (60Gy/15). Just over a quarter of patients (27%) had central tumors. The study was designed to detect an improvement in local control at 3 years of 75 → 87.5% with SBRT. Fewer than planned patients were enrolled (233 of a planned 324) as the trial was closed early due to slow accrual. In addition, HFRT performed better than anticipated. At 3 years, local control was numerically higher with SBRT compared to HFRT (87.6% v 81.2%), but the difference wasn’t statistically significant (HR 0.61, p=0.15). There was also no difference in disease-free or overall survival There was no acute grade 4 or 5 toxicity, and only 1 grade 3 toxicity event in each arm. Late toxicity was similar between arms and predominantly seen among those with central tumors. While the results of LUSTRE don’t really question the role of SBRT in treating stage I NSCLC, it does show the spectrum of local control outcomes with different fractionation regimens. The CHISEL trial showed that local control is better with SBRT than conventional fractionation (89% v 65%). As one might expect with a higher BED, local control with 60 Gy/15 performed better than would be expected with conventional fractionation alone. In addition, 5-fraction SBRT was very safe with toxicity that was comparable to the more fractionated regimen.

TBL: In the underpowered LUSTRE trial, local control was numerically better with SBRT with no difference in toxicity compared to HFRT. | Swaminath, ASTRO 2022