A Dosimetric Model of Duodenal Toxicity After Stereotactic Body Radiotherapy for Pancreatic Cancer

Introduction: Dose escalation for pancreas cancer is limited by the tolerance of adjacent normal tissues, especially with stereotactic body radiotherapy (SBRT). The duodenum is generally considered to be the organ at greatest risk. This study reports on the dosimetric determinants of duodenal toxicity with single-fraction SBRT. Methods and Materials: Seventy-three patients with locally advanced unresectable pancreatic adenocarcinoma received 25Gy in a single fraction. Dose–volume histogram (DVH) endpoints evaluated include V5 (volume of duodenum that received 5Gy), V10, V15, V20, V25, and Dmax (maximum dose to 1cm3). Normal tissue complication probability (NTCP) was evaluated with a Lyman model. Univariate and multivariate analyses were conducted with Kaplan-Meier and Cox regression models. Results: The median time to Grade 2–4 duodenal toxicity was 6.3 months (range, 1.6–11.8 months). The 6- and 12-month actuarial rates of toxicity were 11% and 29%, respectively. V10–V25 and Dmax all correlated significantly with duodenal toxicity (p <0.05). In particular, V15 ≥9.1cm3 and V15 <9.1cm3 yielded duodenal toxicity rates of 52% and 11%, respectively (p =0.002); V20 ≥3.3cm3 and V20 <3.3cm3 gave toxicity rates of 52% and 11%, respectively (p =0.002); and Dmax ≥23Gy and Dmax <23Gy gave toxicity rates of 49% and 12%, respectively (p =0.004). Lyman NTCP model optimization generated the coefficients m =0.23, n =0.12, and TD50 =24.6Gy. Only the Lyman NTCP model remained significant in multivariate analysis (p =0.001). Conclusions: Multiple DVH endpoints and a Lyman NTCP model are strongly predictive of duodenal toxicity after SBRT for pancreatic cancer. These dose constraints will be valuable in future abdominal SBRT studies. [Copyright &y& Elsevier]