28 Chapter 2 Histological tumour type was not associated (p>0.05) with any of the scored items. The smaller the tumour diameter and the lower the number of tumour blocks taken for histological exam, the higher chance of pCR (Spearman’s correlation r=-0.33, p=0.03 and r=0.31, p=0.04, respectively). In other words, from larger tumors more blocks were examined and residual tumour was more likely to be found. The numbers of blocks examined per patient varied from three to 15 with a mean of 6,8 blocks. In cases of residual tumour, most (20/26) had less than 50% vital tumour cells. These vital cells were more frequently found in the periphery than in the center of the pathologic lesion (16/20) (p<0.001). The cytonuclear atypia of tumour cells was more prominent in cases with necrosis compared to cases with mainly fibrosis (r=0.58, p=0.002). A high amount of dyselastosis was associated with a smaller tumour diameter (r=-0.38, p=0.009), as well as with more fibrosis than necrosis (r=-0.52 p<0.001). Dyselastosis was also correlated with chronic vascular changes (i.e., from intimal fibrosis to complete luminal obstruction, r=0.41, p=0.005). In addition, cases with chronic vascular changes frequently occurred together with acute vasculitis-like changes (r=0.33, p=0.03). More type II pneumocytic cytonuclear atypia was found in lung parenchyma that showed more reactive changes (r=0.48, p=0.001). No correlation was found between vascular changes and histological tumour regression. When threshold levels of significance were adjusted for multiple comparisons by the Bonferroni’s correction, none of the stromal related correlations showed p-values < 0.05 36 . The tumour-lung boundary was predominantly sharp in nearly all cases (44/46) and no tumour foci were found outside this boundary. Treatment response Tumour response after CRT and before surgery could be determined on CT scans and/or MRI’s in all but 3 cases. The median time between pre- and post-CRT response evaluation was 2.0 months (range 0-12 months). The median time between end of induction CRT and surgical resection was 4.0 weeks (range 0-26 weeks). Data for the pairwise comparisons using clinical RECIST criteria for pre-treatment, post-CRT and pathological tumour sizes are shown in Table 4. More partial responses were found when the RECIST criteria were applied to pre-treatment imaging and pathological gross specimen tumour size than to pre- and post-treatment imaging (p<0.005). Pathological complete response (pCR) was more frequently found in cases with clinical partial response compared to clinical stable disease and progressive disease (p=0.001). Other histological changes were not associated with the extent of response.
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