Margriet Kwint

Appendices 174 Summary Over 13,000 patients are yearly diagnosedwith lung cancer in theNetherlands. Surgery is treatment of choice, but only 20% of patients qualify for a curative resection. About 25% of the patients are diagnosed with locally advanced non-small cell lung cancer (LA-NSCLC). The standard treatment of this stage is concurrent chemoradiotherapy (CCRT) with adjuvant immunotherapy in patients without progression after CCRT. This is an intensive treatment and associated with toxicities, such as dysphagia. Despite the curative intent of CCRT for LA-NSCLC patients, overall survival (OS) is still poor. More personalized treatment is needed, in which treatment outcomes can hopefully be improved and toxicity can be more accurately predicted and reduced. The purpose of this thesis was to evaluate strategies to improve the radiotherapy for LA-NSCLC patients. Focus was on different aspects of the treatment. The specific dose prescription for LA-NSCLC patients was optimized by differentiating the dose to the primary tumor and involved mediastinal lymph nodes to improve treatment outcome and to reduce toxicities. Further, the patient selection for the treatment of oligometastatic disease was analyzed. A clear and practical decision support system was introduced in the clinical practice to optimize the workflow for image guided radiotherapy with ConeBeam-CT (CBCT). Besides, the imaging data of tumor volume regression during treatment detected on CBCT was associated with treatment outcome. Finally, the normal tissue complication probability (NTCP) model to predict the risk of acute esophagus toxicity was optimized. Part I Dose prescription and patient selection In the Netherlands Cancer Institute patients with LA-NSCLC are treated with a (mild) hypofractionated radiotherapy schedule (24x2.75 Gy) compared to a conventional schedule of 60 Gy in 30 fractions. This hypofractionated schedule shortens the overall treatment time from 6 till 5 weeks reducing tumor cell repopulation during the course of treatment. Recent studies showed that dose escalation with prolonged overall treatment time might lead to a worse overall survival (OS) and increased toxicity compared to the conventional scheme. Possible causes of this poorer OS are dose to the heart, extended overall treatment time and higher grade ≥3 toxicities (e.g. dysphagia). Concurrent chemoradiation for LA-NSCLC causes severe dysphagia due to the radiation dose to the mediastinal lymphadenopathy and the proximity of the esophagus. Previous research showed that the regional failure rate is lower than