Lessons Learned About Acute and Late Toxicity After Two Decades of Experience With Pancreatic SBRT

Stereotactic body radiotherapy (SBRT) is increasingly used to treat pancreatic cancer. However, data on acute morbidity, mortality, and late gastrointestinal toxicity risk following SBRT have not been reported. This study analyzed acute (≤90 days) morbidity and mortality rates and the incidence of grade ≥3 gastrointestinal toxicity at any point following SBRT for pancreatic cancer.

We analyzed 507 patients from a single-institution registry, abstracting outcomes from electronic medical records. Toxicity risk was quantified using descriptive statistics and Cox regression.

The median patient age was 70 years (range, 32-91), with 49.7% of patients being women. SBRT was administered perioperatively in 190 (37.5%) patients (75 preoperatively, 115 postoperatively). Other indications included unresectable disease (n=198; 39.1%), medically inoperable disease (n=53; 10.5%), and locally recurrent disease (n=38; 7.5%). Most patients received 9 to 12 Gy in 3 fractions (n=278; 54.8%); 78 (15.4%) received single-fraction SBRT (18-25 Gy), and 147 (29.0%) received 5 to 8 Gy in 5 fractions. Within 90 days of SBRT, 38 (7.5%) patients died, most commonly due to disease progression. Hospitalization occurred in 123 (24.3%) patients, most often for infection. Severe gastrointestinal toxicity was predominantly a late occurrence (median onset, 10.9 months post-SBRT), with a crude rate of 13.3% (59/445). Higher-dose regimens and lack of surgical resection were associated with an increased risk of late grade ≥3 toxicity. The 2-year actuarial risk of high-grade gastrointestinal toxicity was 25.0%, 19.4%, and 16% for very-high, high, and moderate biologically effective dose regimens, respectively, with corresponding crude rates of 12.8%, 13.3%, and 8.2%, respectively.

Acute mortality rates following SBRT for pancreatic cancer are relatively low. However, infections and early disease progression contribute significantly to hospitalization and death in this medically fragile population. Severe gastrointestinal toxicity occurs primarily as a late effect, with risk potentially modified by radiation dosing and the use of more protracted fractionation schedules.