Assessing the Relationship between Radiotherapy Dosimetric Characteristics and Post-operative Pulmonary Complications in Trimodality Esophageal Cancer Therapy

Abstract

Trimodality therapy (preoperative chemoradiotherapy followed by surgery) for esophageal cancer patients provides superior outcomes when compared to surgery alone, but is associated with increased toxicities. Radiation dose to the lung, in particular the volume of lung receiving low doses of radiation (V5) and the volume of lung spared from radiation (VS), have been reported to correlate with the risk of pulmonary toxicity. Post-operative pulmonary complications are expected to occur in 10-40% of patients treated with esophagectomy alone. The objective of this study was to examine the relationship between pulmonary radiotherapy dosimetric characteristics and post-operative pulmonary complication risk in trimodality therapy. Esophageal cancer patients treated with trimodality therapy on two research ethics board approved phase II protocols (2002-2009), who completed induction and concurrent chemotherapy (irinotecan and cisplatin) and radiotherapy (50 Gy in 25Fr/5 week, 4-6 field conformal) followed by esophagectomy, were included. Primary outcome was the post-operative pulmonary complication rate, including pneumonia and/or respiratory failure requiring ventilation. Pulmonary dosimetric data, including mean lung dose, relative and absolute lung volumes treated in 5 Gy intervals (V5-V45) and volume of lung spared from threshold doses in 5 Gy intervals (e.g., VS5 = lung volume receiving ≤ 5 Gy), were extracted. Logistic regression analysis was used to assess the relationship between dosimetric factors and pulmonary complications. Sixty-four patients completed trimodality therapy and were eligible for analysis. Post-operative pulmonary complications occurred in 16 patients (25%), including 6 (9%) with respiratory failure requiring ventilation. Two (3%) died from respiratory complications. The mean PTV was 547 cc (SD 278) and the mean PTV dose was 49.6 Gy (SD 3.4). The only dosimetric parameter associated with toxicity was absolute V20 (median with complications 583 cc vs. 418 cc without, p = 0.03). Absolute V5-15 and V25-45 were not statistically significant. There was no significant difference in pulmonary complication risk when comparing relative lung volumes (V5-45) treated (e.g., V20 18% vs. 12% p = 0.10, V5 60% vs. 55% p = 0.48), mean lung dose (9.9 Gy vs. 9 Gy; p = 0.71), or spared lung volumes (VS5-VS45) (e.g., VS5 1445 cc vs. 1456 cc; p = 0.79). Trimodality therapy is associated with an acceptable post-operative pulmonary complication rate. Absolute V20 volume was the only dosimetric parameter statistically related to post-operative pulmonary toxicity in our population.