Background
Phase 3 open-label RCT. 101 patients with inoperable clinical stage I NSCLC (T1N0M0 ≤3 cm or T2aN0M0 ≤5 cm), unsuitable for surgery due to comorbidities or refusal. Enrolled at 7 Australian sites (2012–2018). Randomized 3:1 (SABR:conventional RT) to enable SABR site experience while maintaining a control arm.
Interventions and follow up
Arm A: SABR: 54 Gy/3 fractions (peripheral) or 48 Gy/4 fractions (ultracentral); N=66
Arm B: Conventional fractionated RT: 50–66 Gy in 20–33 fractions; N=35
Primary endpoint: Freedom from local failure at 2 year
mFollow up: Median 31.4 month
Arm B: Conventional fractionated RT: 50–66 Gy in 20–33 fractions; N=35
Primary endpoint: Freedom from local failure at 2 year
mFollow up: Median 31.4 month
Results
2-yr freedom from local failure: 89% (SABR) vs 65% (conventional RT), HR 0.25 (95% CI 0.10–0.62), P=.003
2-yr OS: 77% (SABR) vs 59% (conventional RT)
Grade ≥3 toxicity: 11% SABR vs 14% conventional RT (not significantly different)
2-yr OS: 77% (SABR) vs 59% (conventional RT)
Grade ≥3 toxicity: 11% SABR vs 14% conventional RT (not significantly different)
Adverse events
Main adverse events: Grade ≥3 toxicity 11% (SABR) vs 14% (conventional RT) — comparable. No grade 5 toxicity in SABR arm. Radiation pneumonitis grade ≥3: ~5% SABR. Fatigue and dyspnea most common. Esophagitis low in both arms given T1-2 primary disease.
Conclusions
SABR significantly reduced local failure risk by approximately 75% (HR 0.25) compared to conventional fractionated RT in inoperable stage I NSCLC, with comparable toxicity. This phase 3 RCT definitively establishes SABR as the preferred radiation approach for inoperable early-stage NSCLC when surgery is not feasible.
Key Limitations
Key Limitations: Open-label design with potential for response assessment bias. Unequal 3:1 randomization provides fewer control arm patients, limiting precision of comparative estimates. Conventional RT regimen was heterogeneous (50–66 Gy across varying schedules) — optimal comparator fractionation is unclear. OS was not the primary endpoint and the trial was not powered for OS. Predominantly Australian population; generalizability across health systems with different RT practices requires consideration.
Clinical Context
CHISEL provides the first phase 3 RCT confirmation that SABR is superior to conventional fractionated RT for inoperable stage I NSCLC, validating the phase 2 RTOG 0236 findings in a randomized setting. Conventional palliative-style RT (e.g., 50 Gy/20 fx or 30 Gy/10 fx) should no longer be used when SABR is available and technically feasible. Together with RTOG 0236 and STARS-ROSEL, CHISEL establishes SABR as the definitive local treatment for early-stage inoperable NSCLC.
References
References: Ball D et al, Lancet Oncol 2019 (CHISEL)