Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator

Cho, In Kuk; Kim, Haeryoung; Lee, Jongchan; Kim, Jaihwan; Ahn, Soomin; Park, Hyunjin; Hwang, Jin Hyeok

doi:10.5009/gnl19180

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…Our results align with earlier research, finding more aggressive tumors to have a higher tumor cell proliferation rate [ 17 , 24 , 25 ] and poorer prognosis [ 15 , 17 ]. Other studies have suggested high stroma content and desmoplasia as the primary promoting factor of highly aggressive PDAC [ 8 , 10 , 14 ].…”

Section: Discussionsupporting

confidence: 92%

“…Due to this fact no survival analysis was performed. However, high tumor cell content has been shown to be a negative prognostic marker for overall survival in PDAC patients [ 15 , 17 ]. As this aspect is of high clinical interest, further investigation is required, preferably in a multi-center prospective cohort study.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies identified the massive stroma formation termed desmoplasia typically observed in PDAC, mainly consisting of cancer associated fibroblasts and extracellular matrix, as promoting cancer cell proliferation and metastasis, accelerating epithelial-mesenchymal transition and hindering apoptosis in PDAC cells and have thus suggested it as a possible target for chemotherapy [8][9][10][11][12][13][14]. In other work, high tumor cellularity levels were found to be characteristics of more aggressive PDAC with poorer prognosis [15][16][17].…”

Section: Introductionmentioning

confidence: 94%

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Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging

Jungmann

Kaissis

Ziegelmayer

et al. 2021

Cancers

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Background: PDAC remains a tumor entity with poor prognosis and a 5-year survival rate below 10%. Recent research has revealed invasive biomarkers, such as distinct molecular subtypes, predictive for therapy response and patient survival. Non-invasive prediction of individual patient outcome however remains an unresolved task. Methods: Discrete cellularity regions of PDAC resection specimen (n = 43) were analyzed by routine histopathological work up. Regional tumor cellularity and CT-derived Hounsfield Units (HU, n = 66) as well as iodine concentrations were regionally matched. One-way ANOVA and pairwise t-tests were performed to assess the relationship between different cellularity level in conventional, virtual monoenergetic 40 keV (monoE 40 keV) and iodine map reconstructions. Results: A statistically significant negative correlation between regional tumor cellularity in histopathology and CT-derived HU from corresponding image regions was identified. Radiological differentiation was best possible in monoE 40 keV CT images. However, HU values differed significantly in conventional reconstructions as well, indicating the possibility of a broad clinical application of this finding. Conclusion: In this study we establish a novel method for CT-based prediction of tumor cellularity for in-vivo tumor characterization in PDAC patients.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

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Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging

Jungmann

Kaissis

Ziegelmayer

et al. 2021

Cancers

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“…Using a quantification of the DAPI nuclear staining as a measure of cellularity, cellularity was higher, but not significantly, in the heterogeneous tumors. This result suggests that tumors with clonal heterogeneity proliferate and spread more than others, and it also could provide a basis for a previous observation that high cellularity in PDAC is moderately associated with short survival (26). Thus, heterogeneity is an independent factor of clinical significance that is moderately associated with signal intensity and total cellularity.…”

Section: Heterogeneity In Cluster Types Is Associated With Outcomesupporting

confidence: 67%

Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer

et al. 2023

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IntroductionOutcomes following tumor resection vary dramatically among patients with pancreatic ductal adenocarcinoma (PDAC). A challenge in defining predictive biomarkers is to discern within the complex tumor tissue the specific subpopulations and relationships that drive recurrence. Multiplexed immunofluorescence is valuable for such studies when supplied with markers of relevant subpopulations and analysis methods to sort out the intra-tumor relationships that are informative of tumor behavior. We hypothesized that the glycan biomarkers CA19-9 and STRA, which detect separate subpopulations of cancer cells, define intra-tumoral features associated with recurrence.MethodsWe probed this question using automated signal thresholding and spatial cluster analysis applied to the immunofluorescence images of the STRA and CA19-9 glycan biomarkers in whole-block sections of PDAC tumors collected from curative resections.ResultsThe tumors (N = 22) displayed extreme diversity between them in the amounts of the glycans and in the levels of spatial clustering, but neither the amounts nor the clusters of the individual and combined glycans associated with recurrence. The combined glycans, however, marked divergent types of spatial clusters, alternatively only STRA, only CA19-9, or both. The co-occurrence of more than one cluster type within a tumor associated significantly with disease recurrence, in contrast to the independent occurrence of each type of cluster. In addition, intra-tumoral regions with heterogeneity in biomarker clusters spatially aligned with pathology-confirmed cancer cells, whereas regions with homogeneous biomarker clusters aligned with various non-cancer cells.ConclusionThus, the STRA and CA19-9 glycans are markers of distinct and co-occurring subpopulations of cancer cells that in combination are associated with recurrence. Furthermore, automated signal thresholding and spatial clustering provides a tool for quantifying intra-tumoral subpopulations that are informative of outcome.

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“…Tumor cellularity was also shown to be characteristic of more aggressive subtypes of PDAC in various studies [11][12][13][14], with patients containing high cellularity regions in the primary tumor of PDAC experiencing a significantly shorter OS [14].…”

Section: Introductionmentioning

confidence: 99%

CT Attenuation of Hepatic Pancreatic Cancer Metastases Correlates with Prognostically Detrimental Metastatic Necrosis

Reischl,

Ziegelmayer,

Graf

et al. 2023

JCM

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Percutaneous CT-guided biopsy is a frequently performed procedure for the confirmation and molecular workup of hepatic metastases of pancreatic ductal adenocarcinoma (PDAC). Tumor necrosis of primary PDAC has shown a negative prognostic impact in recent studies. This study aims to examine predictability in CT scans and the prognostic impact of necrosis in hepatic metastases of PDAC. In this tertiary-center retrospective cohort study, we included 36 patients with hepatic metastases of PDAC who underwent CT-guided hepatic biopsies. Normalized attenuation of the biopsied metastasis was determined in venous phase contrast-enhanced planning scans obtained prior to biopsy by automatic, threshold-based 3D segmentation and manual, blinded 2D segmentation. A board-certified pathologist specialized in hepatic pathology histologically quantified the tumor necrosis and cellularity of the biopsy cylinders. We found a significant inverse-linear correlation between normalized attenuation and the fraction of necrosis (Pearson’s r = 0.51, p < 0.001 for automatic 3D segmentation or Pearson’s r = 0.52, p < 0.001 for manual 2D segmentation), whereas no correlation was found with tumor cellularity. Additionally, we discovered that patients with a fraction of necrosis ≥ 20% in metastases had a significantly shorter overall survival (p < 0.035). In summary, tumor necrosis of PDAC metastases can be estimated from contrast-enhanced CT scans, which could help to improve biopsy sample pattern planning. In addition, liver metastatic necrosis may serve as a prognostic biomarker in PDAC.

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Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator

Cited by 6 publications

References 31 publications

Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging

Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging

Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer

CT Attenuation of Hepatic Pancreatic Cancer Metastases Correlates with Prognostically Detrimental Metastatic Necrosis

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