Margriet Kwint

Chapter 1 12 opinion that dose escalation with prolonged overall treatment time is not effective. Therefore, hypofractionation should be used in further studies focusing on dose- escalation. In our institute a mildly hypofractionated radiotherapy schedule is used of 24x2.75 Gy, once daily, 5 times a week (17). Compared to the conventional schedule of 60 Gy in 30 fractions, this hypofractionated schedule results in a reduction of more than one-week overall treatment time; 32 days versus 40 days. Besides, a higher biological effective dose is given, with the expectation of improved local control. The type of chemotherapy administered for concurrent chemotherapy varies across centers in the Netherlands (21). Due to the advantageous toxicity profile, daily low dose Cisplatin is preferred in the Netherlands Cancer Institute. Several studies (10, 17, 18, 20, 22) reported a high local control and a low toxicity of this CCRT-regime. It is well known that local control is associated with OS in lung cancer. Van Diessen et.al (22) investigated the pattern of local and regional failure in LA-NSCLC patients treated with CCRT. The incidence of local and regional failure as site of first failure was 16% and 6%, respectively. This difference was significantly associated with the difference in volume of the primary tumor and lymph nodes. The risk of severe pulmonary, cardiac and esophageal toxicities induced by CCRT, are mainly determined by the involvement of the mediastinal lymph nodes, the size and location of the primary tumor and the total radiation dose. Since involved mediastinal lymph nodes have generally a smaller volume compared to the primary tumor in the majority of patients, an appealing strategy is to prescribe a differentiated dose to the lymph nodes and primary tumor to reduce acute and late toxicities in LA-NSCLC patients treated with CCRT. Patient selection for oligometastatic disease When a NSCLC patient is diagnosed with metastases, from a historical point of view, the treatment aim is palliative; to prolong PFS or to improve quality of life. In 1995, the term ‘oligometastasis’ was introduced by Hellman andWeichselbach (23). This concept implies that patients with a limited number of metastases might still achieve long term OS if all these metastases are treated with a radical schedule (24-26). With more systemic treatment options for NSCLC patients (e.g. molecular targeted therapies and immune checkpoint inhibitors) (27), there is an increasing interest in a more radical approach for oligometastatic disease (28-30). SABR is a highly advanced radiotherapy technique, which is able to deliver very precisely a high biologically effective dose to a small tumor (31). SABR is a very effective treatment with few side effects, to treat