Margriet Kwint

General discussion and future perspectives 157 8 out-of-field (4%), respectively. The low incidence (6%) of marginal failures in this trial, supports an adaptive radiotherapy strategy to adjust for primary tumor regression. In chapter 5 tumor volume regression during CCRT was investigated. In more than a third (35%) of the patients objective tumor regression during treatment was observed on CBCT. Three distinct subgroups of tumor volume change trajectories seen on a CBCT during CCRT for LA-NSCLC patients were identified in this study. Previously published studies indicated that tumor volume changes during treatment might be predictive for treatment outcomes (44-46). Surprisingly, no association between these subgroups and treatment outcome was found, whereas baseline volume of the primary tumor was significantly associated with OS. Our results were confirmed by the recent study of Amugongo et al. (47). Similarly to our study, 3 distinct subgroups of tumor volume change trajectories seen on CBCT were reported, but no significant association between these subgroups and OS was found. These findings demonstrate that tumor regression during treatment frequently occurs, and this has led to a new initiative in our institute, to analyze an adaptive radiotherapy re-planning approach based on tumor regression seen on the CBCT compared to non-adaptive radiotherapy for LA-NSCLC. This will be subject of future research in lung cancer patients irradiated with radical intent. Part III Acute esophagus toxicity NTCP-modelling of acute esophagus toxicity As previously mentioned, for patients with LA-NSCLC, the treatment of choice is CCRT (1, 48, 49). The addition of chemotherapy provokes a radiosensitizing effect leading to improved local control and OS, compared to radiotherapy only or sequential chemoradiation. However, this comes at the cost of an increase of acute esophageal toxicity (AET) (50). In chapter 6 , the V50 (volume of the esophagus receiving ≥50 Gy) was identified as an accurate predictor of AET with IMRT for NSCLC patients treated with CCRT. Nowadays, IMRT and Volumetric Modulated Arc Radiotherapy (VMAT) are commonly used techniques. These techniques have the ability to modulate the beam intensity during dose delivery, which leads to an increased dose conformality compared to 3DCRT (51, 52). In a retrospective study (N=188), a higher incidence of AET grade ≥2 was reported with VMAT compared to IMRT (51). This study also reported a not statistically significant higher rate of late pulmonary toxicity in VMAT patients. Since VMAT and IMRT have a different dose delivery and distribution, it is important