Margriet Kwint

Chapter 8 148 General discussion and future perspectives Main findings and summary of results The aim of this thesis was to explore strategies to optimize radiotherapy for locally advanced non-small cell lung cancer patients (LA-NSCLC). In the first part we investigated if a modified dose prescription resulted in improved treatment outcomes for LA-NSCLC ( Chapter 2 ) and for oligo-metastasized treatment ( Chapter 3 ). In the second part, optimization of the radiotherapy with the use of image guided radiotherapy (IGRT) was studied (Chapter 4 & 5) . In the last part, normal tissue complication probability (NTCP) models for acute esophagus toxicity (AET) in radically treated LA-NSCLC patients were investigated (Chapter 6 & 7) . In this final chapter, the findings of this thesis are discussed and recommendations for future research are presented. Part I Dose prescription and patient selection Optimization of radiotherapy by dose alteration The standard treatment of LA-NSCLC is concurrent chemoradiotherapy (CCRT) (1). In patients without progression, adjuvant immunotherapy is administered afterwards and part of the current standard of care (2, 3). In the past, different treatment strategies have been tested to improve local control and overall survival (OS) for LA- NSCLC patients. One of these strategies is dose escalation. Recently, an unexpected poor OS was associated with dose escalation in two randomized trials (RTOG 0617 and the trial of Hallqvist et.al .) (4, 5). In those studies, dose-escalation with prolonged overall treatment time was given in the experimental arm (74 and 84 Gy versus 60 Gy in 2 Gy). Other factors associated with poor OS in these studies were, tumor location, institution accrual volume, esophagitis, PTV and heart dose (V5). It has been suggested that the extended overall treatment time contributed to the poor OS in the experimental arm. Therefore, new interest is growing in dose-escalation using hypofractionation. In the Netherlands Cancer Institute, patients are treated with a mildly hypofractionated radiotherapy schedule of 24x2.75 Gy, combined with daily low dose Cisplatin, which is different from the international standard of 30x2 Gy and has been shown to have favorable outcomes compared to dose-escalation with extended treatment time (6-8).