Background
Phase 2 single-arm trial. 55 patients with biopsy-proven medically inoperable stage I (T1–T2N0) NSCLC; peripheral tumors ≤5 cm. Patients inoperable due to cardiopulmonary comorbidities. No prior thoracic RT. Enrolled at 28 institutions.
Interventions and follow up
Arm A: SBRT 54 Gy in 3 fractions (18 Gy/fraction) delivered over 1.5–2 week
Primary endpoint: Primary tumor local control rate at 3 year
mFollow up: Median 34.4 month
Primary endpoint: Primary tumor local control rate at 3 year
mFollow up: Median 34.4 month
Results
3-yr primary tumor control: 97.6%
3-yr OS: 55.8%
3-yr DFS: 48.3%
Median OS: 48.1 months
Grade ≥3 toxicity: 12.7% protocol-specified toxicities
3-yr OS: 55.8%
3-yr DFS: 48.3%
Median OS: 48.1 months
Grade ≥3 toxicity: 12.7% protocol-specified toxicities
Adverse events
Main adverse events: Grade ≥3 protocol-specified events 12.7%. Grade 5 events: 4 total (3 possibly/probably treatment-related). No treatment-related deaths in first 30 patients enrolled on lower-dose protocol. Pulmonary toxicity and chest wall pain were most common grade ≥3 events. Esophagitis was rare given peripheral tumor exclusivity.
Conclusions
SBRT 18 Gy × 3 fractions achieved 97.6% local tumor control at 3 years for medically inoperable peripheral stage I NSCLC — vastly superior to historical conventional RT (~50%). This phase 2 trial established SBRT as the standard of care for inoperable peripheral early-stage NSCLC.
Key Limitations
Key Limitations: Single-arm phase 2 with no comparator; historical comparisons are confounded by patient selection differences. Peripheral tumors only — central tumors were excluded due to toxicity concerns. N=55 provides limited precision for OS and toxicity estimates. Three grade 5 events (possibly treatment-related) raise concern though rate is low. Long-term (5-year) data not mature at time of publication.
Clinical Context
Practice-defining trial establishing SBRT as standard for medically inoperable peripheral stage I NSCLC. Biologically effective dose (BED) 180 Gy₃ substantially exceeds conventional RT (~100 Gy₃). Central tumors require alternative regimens (RTOG 0813: 60 Gy/5 fx). STARS-ROSEL pooled data later suggested SBRT may match lobectomy in operable patients. CHISEL (Ball, Lancet Oncol 2019) confirmed SBRT superiority over conventional RT in a phase 3 RCT.
References
References: Timmerman R et al, JAMA 2010 (RTOG 0236)