Margriet Kwint

Summary 175 local failure, due to the lower tumor volume of the involved mediastinal lymph nodes. Reducing the dose to themediastinummight reduce these severe toxicity rates. Due to improved position verificationmethods with image guidance radiotherapy techniques, the margins for the primary tumor and involved lymph nodes were reduced in our institute, which can also decrease the toxicity. In chapter 2 an observational study is described where dose-reduction to the lymph nodes as well as a margin reduction in 2 consecutive cohorts of LA-NSCLC patients treated with (chemo) radiotherapy were analyzed. The reference-cohort (N=170) received the same dose of 70 Gy (24x2.75Gy, EQD2 10 ) to the involved lymph nodes and primary tumor, while the reduction-cohort (N=138) received 24x2.42Gy (which is 60Gy; EQD2 10 ) to the involved lymph nodes. With 60 Gy instead of 70 Gy to the involved mediastinal lymph nodes, the acute grade 3 dysphagia and grade 3 pulmonary toxicity decreased significantly from 12.9% to 3.6% and 4.1% versus 0%, respectively. The regional failure rates were comparable. The median OS was significantly different: 26 months for the reference-cohort versus 35 months for the dose reduction-cohort. The conclusions of this study were that a differentiated dose to primary tumour and lymph nodes using a hypofractionated regimen is a safe treatment strategy with very low toxicity for LA-NSCLC patients. Nowadays these inhomogeneous dose prescriptions for the primary tumor and lymph nodes, as well as the reduced margins due to the daily online CBCT position verification, are standard care in current clinical practice in the Netherlands Cancer Institute. In current practice patients with ≤ 5 metastases are considered as having oligometastatic disease. Evidence is growing that a radical treatment of the primary tumor as well all the metastases, leads to an improved progression free survival (PFS) and OS for these oligometastatic NSCLC patients. In chapter 3 the PFS and OS is described of a cohort study of 91 patients with synchronous oligometastatic NSCLC who were treated with a radical intent. The PFS of this cohort was 14 months and the OS 32 months. The 1- and 2-year OS rates were 85% and 58% and the 1- and 2-year PFS rates were 55% and 27%, respectively. The conclusion of this study was that a radical local treatment of a selected group of NSCLC patients with good performance status presenting with synchronous oligometastatic disease resulted in favorable long-term PFS and OS. In current clinical practice in our institute, patients with oligometastatic disease are discussed in a multidisciplinary tumor board, and when feasible, a radical treatment is advised.