Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer

Abstract

Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival. Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation. Statistical models were used to test associations between clinical characteristics and outcomes, including upper GI bleeding, radiation treatment breaks, and weight loss during therapy. Between 1999 and 2012, 211 patients were treated with radiation for pancreatic cancer. All patients received concurrent chemotherapy with either gemcitabine (174) or 5-fluorouracil (27), and 67 received intensity modulated radiation therapy (IMRT). Overall, 18 patients experienced an upper GI bleed related to treatment, with 70% of bleeds occurring in the stomach or duodenum, and among those patients, 11 (61%) patients had a pancreatic head tumor and 17 (94%) patients had a metallic biliary stent. IMRT was associated with decreased risk of postradiation nausea (odds ratio, 0.27 [0.11, 0.67], P=.006) compared with 3-dimensional conformal radiation. Regarding long-term toxicities, patients with a metallic biliary stent at the time of radiation therapy were at a significantly higher risk of developing upper GI bleeding (unadjusted hazard ratio [HR], 15.41 [2.02, 117.42], P=.008), even after controlling for radiation treatment modality and prescribed radiation dose (adjusted HR, 17.38 [2.26, 133.58], P=.006). Furthermore, biliary stent placement was associated with a higher risk of death (HR, 1.99 [1.41, 2.83], P < .001) after adjusting for demographic, treatment-related, and patient-related variables. Metallic biliary stents may be associated with an increased risk of upper GI bleeding and mortality. Furthermore, IMRT was associated with less nausea and short-term toxicity compared with 3-dimensional conformal therapy.