Margriet Kwint

Chapter 5 92 Baseline analyses and cox proportional hazard analyses were performed in SPSS version 22.0 for Windows. LCMM was performed in R version 3.4.1. with package LCMM (lcmm function)(31). A p-value of ≤ 0.05 was regarded as statistically significant. Results In this study, 394 patients were included. Patient and tumor characteristics are shown in Table 1. The median follow-up was 63 months (IQR 48-83), median OS was 23 months (IQR 11-67), median PFS was 17 months (IQR 7-66) and the median LRC was 63 months (IQR 17-NA) ( Supplement Figure 1 ). In total, 288 patients died (73.1%) before the end of study of whom 221 (56.1%) had lung cancer related mortality. Progressive disease was observed for 259 patients (66%) of whom 113 (29%) had local or regional infield recurrence. The Pearson correlation coefficient between the manually delineated GTV and the deformable GTV was very high, 0.978 (p=0.001) for the first fraction and 0.951 (p=0.001) for the last CBCT, respectively. The Bland Altman plot ( Supplement Figure 2 ) further showed a good agreement (B-value of 0.008 (p=0.767)) for the first fraction and 0.037 (p=0.393) for the last CBCT, respectively). In general, the majority of patients (93%) had tumor volume reduction of the primary tumor during treatment ( Figure 1 ). Seven percent (N=26) of the patients showed a stable volume or progression during treatment. Using LCMM, 3 subgroups with distinct trajectories of relative GTV-change during CCRT were identified ( Figure 2 ). Addition of a 4th subgroup did not result in an improvement of fit, included a subgroup containing only 12 patients (3%), and was therefore considered clinically irrelevant. The first, and largest subgroup showed limited progression between the MidP-CT and start of treatment and showed limited tumor volume reduction during CCRT (subgroup 1, N=327, 83%), the second subgroup showed more progression between MidP-CT and start of treatment and a more profound tumor reduction during CCRT (subgroup 2, N=39, 10%). The third subgroup showed the most progression between MidP-CT and start, followed by the steepest tumor volume reduction during CCRT (subgroup 3, N=28, 7%). Subgroup 1 and 2 contained significantly more males compared to subgroup 3 (p=0.014) ( Table 1 ). No significant differences in other patient and tumor characteristics were observed. Although not significant, a tendency towards a higher