Dose escalation in stereotactic body radiation therapy for pancreatic cancer

Objective: To determine whether increasing biologically effective dose (BED) with stereotactic body radiation therapy (SBRT) is associated with improved local control (LC) or toxicities in patients with locally advanced pancreatic cancer. Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify 15 studies across 12 institutions in 5 countries where patients received definitive SBRT for nonmetastatic disease. Biologically equivalent doses were calculated with an α/β of 10 (ie, BED 10) for LC and acute toxicity and 3 (ie, BED 3) for late toxicity. Fixed and random effects models were used to characterize LC and grade 3/4 toxicities by BED. Results: There were 508 patients included with a median follow-up time of 9.1 months. The median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. There was no significant difference in LC rates at 1 year between the BED 10 <70 Gy versus ≥70 Gy groups, with an estimate of 0.60 (95% confidence interval [CI], 0.36-0.81) versus 0.83 (95% CI, 0.63-0.97), respectively. There was no significant difference in acute toxicity rates between the BED 10 <70 Gy versus ≥70 Gy groups, with an estimate of 0.02 (95% CI, 0.00-0.08) versus 0.05 (95% CI, 0.00-0.22), respectively. Given the dose distribution across studies, 3 intervals were used to characterize BED 3. There were no significant differences in late toxicity among those receiving BED 3 <100, 100 to 200, or >200 Gy. Conclusions: SBRT for pancreatic cancer results in LC rates of 60% to 83% and clinically significant toxicity of <7%. Increasing BED 10 beyond 70 Gy was not associated with increased rates of 1-year LC or acute toxicity. Increasing BED 3 beyond 100 Gy was not associated with increased rates of late toxicity.