Margriet Kwint

Chapter 2 28 Material and methods Patient selection A sequential design cohort study was performed including 308 patients with LA- NSCLC between June 2013 and June 2017. All data were analysed retrospectively. Patient characteristics, treatment data and medical records were also retrospectively retrieved. Standard work-up consisted of a computed tomography (CT)-thorax, a total body 18 Fluorodeoxyglucose positron emission tomography (FDG-PET)-CT-scan (performed within 4-6 weeks before treatment according to the NedPass protocol [16]), a contrast enhanced CT-scan or Magnetic Resonance Imaging (MRI)-scan of the brain and a pulmonary function test. Pathological confirmation of the primary tumour and/or lymph nodes was done. All pre- and post-treatment diagnostic examinations were available for all patients. The Institutional Review Board of our institute approved the study for retrospective data collection according to the European Privacy Law. Radiotherapy preparation Patients were treated with hypofractionated Intensity Modulated Radiotherapy (IMRT) of 66 Gy to the primary tumour and mediastinal lymph nodes in 24 fractions (overall treatment time 32 days), once daily, 5 times per week from June 2013 till June 2015. Following the linear-quadratic model and an α/β-ratio of 10 Gy, an absorbed dose of 66 Gy in 24 fractions is biologically equivalent to 70 Gy in fractions of 2 Gy (EQD2 10 ). From June 2015, the dose to the involved mediastinal lymph nodes was reduced from 66 Gy to 58.08 Gy in 24 fractions, which is equivalent to 60 Gy (EQD2 10 ). Therefore, the dataset was divided in two cohorts: the reference-cohort versus the reduction-cohort. Treatment consisted of sequential chemoradiotherapy (sCRT), cCRT or radiotherapy (RT) only. The concurrent regimen consisted of daily low dose Cisplatin intravenous (6 mg/m², maximum12mg) 1-2 hours before each RT fraction. The chemotherapy in sCRT consisted of Cis- or Carboplatin combined with Gemcitabin, Etoposide or Pemetrexed according to the pathology. A four-dimensional (4D)-CT-scan with intravenous contrast was performed, from which a 3D-midposition-CT-scan (MidP) was reconstructed [17]. The FDG-PET-CT-scan was registered with the MidP to guide the separate delineation of the primary tumour and the involved lymph nodes. The following lymph nodes were considered tumour positive in the absence of pathological evidence: higher FDG-uptake than the mediastinal blood pool on the FDG-PET-CT-scan or growth on