Tumor heterogenitet
While tumour heterogeneity is known to be extensive and common in pancreatic cancer and deemed to be a significant cause of chemoresistance, it has been hardly investigated at the morphological level.
The aim of this work package is therefore to
- Characterize morphological inter- and intratumour heterogeneity, both regarding the cancer cell population and the nonneoplastic tumour stroma
- Correlate morphological heterogeneity with functional diversity in terms of metabolic activity, chemoresistance, and detection on PET-CT (in collaboration with work packages “Metabolomics” and “Surgery”, NorPACT-3 study)
- Correlate morphological heterogeneity with diversity at the RNA-level in different microanatomic tumour compartments with the help of spatial transcriptomics (in collaboration with work package “Omics and biomarkers”)
- Investigate morphological heterogeneity of both the tumour and the non-neoplastic pancreatic parenchyma in patients with germline mutations that increase the risk for developing pancreatic cancer (in collaboration with work package “Medical genetics”, PREPAIRD study)
- Investigate the impact of morphological heterogeneity on the effect of neoadjuvant chemotherapy and the morphological evaluation of treatment-induced tumour regression.
Improved diagnostics for pancreatic cancer
In recent years, diagnostic reporting on surgical specimens with pancreatic cancer has become more standardized. However, despite this progress, some of the pathology data items that are key to patient management are still examined in a suboptimal and non-standardized way.
This work package aims at improving the following aspects of pathology examination:
- Evaluation of the effect of neoadjuvant treatment: treatment effect is clinically important information that is taken into consideration when planning further patient management. Moreover, evaluation of treatment effect is key to clinical studies that aim at comparing different neoadjuvant treatment regimes. In international collaborative projects, the challenges and shortcomings of the current approach - so-called tumour regression grading - are analyzed. Furthermore, a new approach to the pathology evaluation of treatment effect is being explored.
- Evaluation of the margin status: the margins of a surgical resection specimen with pancreatic cancer are examined to find out whether cancer cells may have been left behind in the surgical bed. While this is fairly well established in routine diagnostics, several aspects remain unexplored. This work package is particularly interested in a quantitative approach to margin evaluation.
- Measurement of tumour size: the size of the primary tumour is an important data item, because it forms the basis for the attribution of T-stage, which is key to patient stratification and management. While measurement of tumour size may seem straightforward, different approaches are currently being used, which lead to highly divergent results and, consequently, differences in T-stage classification. This work package analyses the impact of various measurement techniques on T-stage classification.
- Assessment of lymph node status: metastasis to the regional lymph nodes - represented by the N-stage - is the tumour feature with the largest prognostic impact. So far, the total number of lymph nodes that are examined - the so-called lymph node yield - has been investigated as an important determinant of the quality of the assessment of lymph node status. In this work package, a more refined assessment of the lymph nodes is being tested.
