Margriet Kwint

General introduction and outline of thesis 1 15 to radiotherapy only or sequential chemoradiation (7). However, this comes at the cost of radiotherapy induced pulmonary, cardiac and esophageal toxicities. Toxicity in radiotherapy can be divided in acute (≤ 90 days after end of treatment) or late toxicity (> 90 days after end of treatment). A common radiotherapy induced toxicity is acute esophagus toxicity (AET) (51). This leads to decreased intake, weight loss, malnutrition and retrosternal pain, requiring analgesics, intravenous hydration, tube feeding, dietary supplements, hospitalization or a combination of these. To inform a patient thoroughly about the risk on toxicities before start of treatment, it is important that the normal tissue complication probability models (NTCP-models) clinically used to predict the risk on toxicities, are accurate. Several NTCP-models are used in clinical practice to predict the risk of AET (51-56). However, many of these models are based on 3D-conformal radiotherapy (3D-CRT) techniques. With the introduction of newer radiotherapy techniques like Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT), a more conformal dose distribution can be achieved (57, 58). These techniques give the opportunity to irradiate larger tumor volumes and increase organ sparing compared to 3D-CRT (59-61). However, this might result in dose inhomogeneity, which can lead to e.g. high dose areas in organs at risk, which are situated inside the PTV such as the esophagus. In addition, an increase of larger low dose areas in healthy tissue is frequently seen with IMRT and/or VMAT. This is due to the use of segments and greater amount of beam directions compared to 3D-CRT. Hence, patients who were not eligible for a radical radiotherapy schedule because of large tumor volumes in the 3D-CRT era, benefit due to IMRT and VMAT, and may be able to receive radiotherapy with a curative intent. These improvements in radiation dose characteristics have influence on the predictive performance of dose limiting toxicities, such as AET, of NTCP models. Therefore, the development of these new radiotherapy techniques and schedules requires a constant validation and update of the existing NTCP-models. Purpose and outline of thesis The primary aim of this thesis is to optimize radiotherapy for LA-NSCLC patients further. This aim is achieved by focusing on different aspects of the radiation treatment. The first part focused on the effect of margin reduction and dose de- escalation of the dose on the mediastinal lymph nodes on toxicity and treatment outcome. Furthermore, we analyzed patients with oligo metastasized NSCLC that qualified for a radical treatment. The second part focused on imaging data of intra