Margriet Kwint

Acute esophagus toxicity after IMRT and concurrent chemoradiation 115 6 Introduction Concurrent chemoradiotherapy (CCRT) has become the treatment of choice in locally advanced non-small cell lung cancer (NSCLC). A recent meta-analysis showed that for patients with NSCLC, treatment with CCRT significantly improved local control and survival compared to sequential chemoradiotherapy (SCRT) [1]. However, this is at the cost of more side-effects; CCRT results in more acute esophagus toxicity (AET) than RT-only or SCRT [2-7]. A part of the esophagus is often irradiated due to overlap with the planning target volume because of involvement of mediastinal lymph nodes or mediastinal tumor invasion. The mucosal layer of the esophagus is sensitive to irradiation induced damage [2-7]. Patients with insufficient intake due to radiation esophagitis are at risk for premature discontinuation of therapy. Predicting the risk of AET makes it possible to take appropriate precautions, such as individualized patient information, dietary guidance, hydration or tube feeding. Identifying the low-risk patients of AET gives the opportunity to escalate the dose of radiotherapy to improve tumor control. IntensityModulatedRadiotherapy (IMRT) facilitates amore conformal dose distribution leading to increased organ sparing compared to 3D-conformal-radiotherapy (3DCRT) [8-10]. In a previous study, with mainly RT-only and SCRT treatments, we reported the V35 (relative volume of the esophagus receiving more than 35 Gy), as the best predictor of AET grade ≥2 after radical 3DCRT-treatment [2]. The treatment-planning esophagus constraint for 3DCRT at that time was length of the esophagus ≤12 cm and elective nodal irradiation was given [2]. In this historical dataset the incidence of grade 2 (54%) and grade 3 (27%) AET was higher in a subset of 37 patients treated with CCRT [2]. The derived V35 model was therefore scaled to cover the higher incidence of AET for CCRT, but due to the small sample size, evaluation of the best predictor for AET in CCRT was not feasible. Other studies revealed several dose-volume-parameters to predict AET [2-7]. One specific dose-volume-parameter was not designated yet as most reliable predictor of AET. All studies were based on 3DCRT. However, with IMRT dose-distributions and dose-volume-parameters for the esophagus have changed, which might reveal other predictors for AET. The purpose of this study is to investigate the dose-effect-relation between acute esophagus toxicity and dose-volume-parameters of the esophagus after IMRT and concurrent chemoradiation for NSCLC patients.