Dosimetric and Clinical Predictors of Nausea and Vomiting: An Exploratory Analysis of a Prospective Phase I/II Trial With Neoadjuvant Accelerated Short Course Radiation Therapy With Capecitabine for Resectable Pancreatic Cancer

Abstract

Dosimetric predictors of nausea and vomiting in the setting of hypofractionated radiation therapy to the pancreas are not well elucidated. We performed an exploratory analysis to identify dose-volume parameters of normal organ structures and clinical factors that might predict for nausea, using percent weight loss during treatment as a surrogate marker. A retrospective analysis was performed of 50 patients with localized, resectable pancreatic adenocarcinoma of the head who were prospectively treated on a phase I/II protocol between 2007 and 2010. During the phase I portion of the study, proton beam radiation was delivered in a progressively accelerated course to the gross tumor volume and regional lymph nodes starting at 3 CGE x 10 given daily over two weeks (n = 3), to 5 CGE x 5 given daily within 2 weeks (n = 6), to the maximum tolerated dose of 5 CGE x 5 given daily within one week (n = 41). All patients received concurrent and adjuvant capecitabine (825 mg/m2 twice daily) followed by surgery. Calculations of Kendall's tau coefficients were performed to determine correlation of dosimetric parameters of irradiated normal tissue structures including stomach, duodenum, liver, small and large bowels to percent weight loss. We also evaluated potential correlation of clinical factors including gender, BMI, alcohol use, prior history of abdominal surgery, diabetes, and presence of gastric ulcers on endoscopy to percent weight loss. Forty-nine patients had weights recorded both at the start and within seven days of radiation completion and were included in this analysis. Mean percent weight loss at the end of radiation was 1.1%±1.9 (SD). Duodenum maximal dose (Dmax, Kendall's τ coefficient 0.23, p = 0.024), volume of duodenum that received 30 Gy or higher (V30, τ = 0.28, p = 0.017), and volume of large bowel that received 10 Gy or higher (V10, τ = 0.21, p = 0.040) were all directly associated with percent weight loss. Mean duodenal Dmax and V30 were 27.3 Gy (range, 25.9-32.5) and 7.9 Gy (range, 0-100), respectively, while mean large bowel V10 was 13.5% (range, 0-50). On multiple regression analysis, female gender (estimated regression coefficient 1.34, p = 0.033) also predicted higher percent weight loss. Hypofractionated radiation to the duodenum and large bowel, in particular duodenal Dmax and V30 and large bowel V10, are directly associated with percent weight loss during radiation treatment. While these findings require validation, they suggest dosimetric constraints that should be considered to minimize the risk of radiation-induced nausea and vomiting.