Background
Phase II multi-institutional trial. 49 patients with locally advanced, unresectable pancreatic cancer. Treated with gemcitabine 1,000 mg/m² × 1 cycle followed by stereotactic body radiotherapy (SBRT) 33 Gy in 5 fractions. Designed to evaluate SBRT as definitive local therapy after induction chemotherapy.
Interventions and follow up
Arm A: Gemcitabine 1,000 mg/m² (1 cycle: 3 weeks) → SBRT 33 Gy in 5 fractions → gemcitabine continuatio
Primary endpoint: Freedom from local progression at 1 year
mFollow up: NR
Primary endpoint: Freedom from local progression at 1 year
mFollow up: NR
Results
Local progression-free survival at 1 year: 78%
mOS: 13.9 months
1-yr OS: 59%
Grade ≥2 late GI toxicity: 10.7%
Grade ≥3 late toxicity: 11%
mOS: 13.9 months
1-yr OS: 59%
Grade ≥2 late GI toxicity: 10.7%
Grade ≥3 late toxicity: 11%
Adverse events
Main adverse events: Grade ≥2 late GI toxicity 10.7%, grade ≥3 late GI toxicity 11%. Acute toxicity was modest. One patient with duodenal ulceration requiring intervention. No treatment-related deaths.
Conclusions
SBRT (33 Gy in 5 fractions) after one cycle of gemcitabine achieves 78% freedom from local progression at 1 year with 13.9-month mOS and acceptable late GI toxicity rates. SBRT represents a promising short-course alternative to conventional fractionated CRT for local consolidation in LAPC.
Key Limitations
Key Limitations: Single-arm phase 2 study — no comparator. Small sample size (n=49). Only 1 cycle of induction gemcitabine prior to SBRT; modern practice uses multiple cycles of induction FOLFIRINOX or nab-P + gem before SBRT. No comparison to conventional CRT or continued chemotherapy alone. Late GI toxicity (11% grade ≥3) is non-trivial given proximity of duodenum. Not all SBRT plans met strict dose constraints in this early experience.
Clinical Context
Herman's trial was foundational in establishing SBRT as a viable local therapy for LAPC. Subsequent institutional series and Alliance A021501 have further refined SBRT technique and dose. SBRT after FOLFIRINOX induction (or nab-P + gem) is increasingly used as local consolidation. The ongoing ABLATE study and NRG GI-002 are evaluating ablative RT strategies in LAPC with modern chemotherapy backbones.
References