A Multi-institutional Analysis of Dosimetric Predictors of Toxicity Following Trimodality Therapy for Esophageal Cancer

Abstract PURPOSE AND OBJECTIVES: This multi-institutional review explores associations between radiation dose-volume histogram (DVH) parameters and cardiopulmonary toxicities with trimodality therapy for esophageal cancer. MATERIALS AND METHODS We reviewed 465 consecutive esophageal cancer patients treated with chemoradiotherapy (CRT) followed by surgery at two tertiary care institutions between 2007 and 2013. Using logistic regression, we assessed associations between lung and heart DVH parameters and cardiopulmonary toxicities and survival. Statistically significant variables were subsequently included in multivariable models, which incorporated age, smoking history, previous history of heart disease, and type of chemotherapy. RESULTS The median age was 61 years (IQR 54-68) and 86% were male. At baseline, 60% of patients had known cardiac risk factors, 64% were current or former smokers and 10% had other pulmonary comorbidities. Most patients had stage II-III (96%) adenocarcinoma (94%) of the distal esophagus. The RT modalities used were 3D conformal RT (38%), intensity modulated RT (41%) and proton therapy (20%). Increased heart dose was associated with increased risk of cardiac toxicity on univariable analysis (V20 Gy: OR 1.20, 95% CI 1.08-1.33, p = 0.001; V30 Gy: OR 1.24, 95% CI 1.11-1.38, p CONCLUSIONS We observed an association of heart dose and cardiac toxicity for esophagus cancer. The risk of cardiac toxicity is 5%, 10% and 15% when the heart V30 Gy is 14%, 20%, and 30%, respectively. For every increase in V30 Gy by 10% there is a corresponding 24% relative increase risk in cardiac toxicity.