254 Chapter 17 contribute to accurately determining the percentages of different tissue reaction compartments (e.g., viable tumor, necrosis, and stromal reaction) in the tumor bed. This subject requires further investigation363 364. In chapter 3, we found that a high expression of PDL-1 and high proliferation activity (marker MIB-1), were related to a worse outcome. Also, in a later study by Vrankar et al., high PD-L1 expression was a negative prognostic factor for PFS and OS after concurrent CRT in locally advanced NSCLC. As only small number of patients had enough tissue for the IHC testing, no firm conclusions could be made57. On the contrary, Zens et al. discovered that PD-L1 expression did not have a significant correlation with longer survival in 53 cases of resected NSCLC after neoadjuvant chemotherapy. Their study demonstrated that after neoadjuvant therapy, PD-L1 expression was lower in 7 out of 53 cases and higher in 12 out of 53 cases. However, the sample size of cases with changed PD-L1 expression was too small to draw conclusions on any prognostic value 365. As these findings may be of value for further refinement of the assessment of pathologic response, more studies are needed, probably also taking other variables (e.g., histologic subtypes and IHC of p53 and PD-L1) into account. Tsao et al. for instance, found in an adjuvant setting lower recurrence free survival in high grade subtypes like solid and micropapillary adenocarcinoma, compared to lepidic and acinar predominant patterns366. The T-descriptor in the pTNM staging In the transition from TNM-7 to TNM-8, a tumour with a diameter larger than 7 cm moved from the T3 to the T4 category, based on follow-up data of the several international researchers, with a major contribution from Japan (79%)79. The IASLC database for the TNM8 staging project did not contain information from Dutch lung cancer patients. Since we had already collected the overview data for the study in chapter 16, and the T-descriptors of T3 in the TNM-7 are quite variable, we investigated in chapter 4 several staging related parameters in a nationwide population of patients with a pT3N0 NSCLC. We demonstrated that following the implementation of TNM-7 and subsequent modifications made in TNM-8 within the Dutch population, while some data remained consistent, there were also findings that did not fully endorse all the alterations made in TNM-8. As a result, we suggest that further refinement may be feasible. To begin with, we observed that the group of patients with tumor diameters larger than 7 cm should not necessarily be reclassified as category pT4. Furthermore, our findings indicate that a “mixed group of two pT3 descriptors”, not previously described, merits migration to pT4. Additionally, in the pT3N0 subcategory of “two or more nodules,” the histologic type is a relevant descriptor. Based on the Dutch population, patients with adenocarcinoma in this subcategory have a more favorable outcome compared to other subtypes and could be reclassified as a pT2 category. This histologic prognostic correlation was supported by Grosu et al., studying patients with stage I NSCLC and found that those with squamous histology have a higher mortality risk than those with adenocarcinoma histology367. Our study suggests that besides using
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