Immunohistochemical pattern of liver metastases and paired sample analysis in patients with metastatic pancreatic cancer: Pronounced CDX2 expression and loss of SMAD4 indicate poor survival

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S107
Author(s):  
Thomas Held ◽  
Caroline S. Verbeke ◽  
Oliver Strobel ◽  
Wiktor Rutkowski ◽  
Christina Villard ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastases ◽  
Metastatic Pancreatic Cancer ◽  
Sample Analysis ◽  
Poor Survival ◽  
Paired Sample ◽  
Cdx2 Expression

scholarly journals Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study

2019 ◽  
Vol 12 ◽  
pp. 175628481987866 ◽  
Author(s):  
Nicolas Williet ◽  
Angélique Saint ◽  
Anne-Laure Pointet ◽  
David Tougeron ◽  
Simon Pernot ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Propensity Score ◽  
Liver Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Reverse Sequence ◽  
Metastatic Sites

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

scholarly journals Readily available biomarkers predict poor survival in metastatic pancreatic cancer

Biomarkers ◽  
2021 ◽  
pp. 1-15
Author(s):  
Marin Strijker ◽  
Eran van Veldhuisen ◽  
Lydia G van der Geest ◽  
Olivier R Busch ◽  
Maarten F Bijlsma ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Poor Survival

The role of selective internal radiation therapy for liver metastases from pancreatic adenocarcinoma after progression on prior chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16272-e16272
Author(s):  
Jonathan O Hackett ◽  
Rebecca S Crothers ◽  
Emma Shaughnessy ◽  
Giuseppe Cardaci ◽  
Alaar Kaard ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Liver Metastases ◽  
Metastatic Pancreatic Cancer ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Prior Chemotherapy ◽  
Selective Internal Radiation ◽  
Internal Radiation Therapy ◽  
Adenocarcinoma Of The Pancreas

e16272 Background: Selective internal radiation therapy (SIRT) has established benefit for liver metastases in colorectal cancer. Very little data exists on the use of SIRT for liver dominant metastatic pancreatic cancer. A 2015 phase II trial by Gibbs et al suggested that SIRT at diagnosis may be beneficial in liver metastases in pancreatic cancer, particularly in those who have had a previous primary resection. Methods: In this single-institute retrospective audit we identified eleven patients who had liver predominant metastatic adenocarcinoma of the pancreas who received SIRT at any stage of their treatment. Data was analysed from our electronic patient databases. Results: 11 patients with adenocarcinoma of the pancreas, who had SIRT following progression on chemotherapy were identified. 3 had a primary surgical resection. All patients had received a minimum of one line of chemotherapy and had ECOG performance status of 2 or less. The median time from diagnosis to SIRT was 13 months (range 5-24 months). Patients received Yttrium-90 microspheres with a median activity of 2.1GBq with all eleven receiving concurrent infusional 5-FU 225mg/m2/day for 7 days prior and 14 days after. The median survival after SIRT therapy was 6 months (range 2-19 months). The median overall survival from diagnosis was 20 months (range 12-31 months). SIRT appeared safe and well-tolerated with no associated 30 day all-cause mortality. One patient developed radiation induced asymptomatic portal hypertension and liver cirrhosis. Conclusions: This is the first report of the use of SIRT with radiosensitising concurrent infusional 5FU for metastatic pancreatic cancer after failure of prior chemotherapy. We conclude that SIRT with concurrent infusional 5FU offers an additional treatment option for patients with liver dominant metastatic pancreatic cancer, who maintain a good PS who have progressed on prior lines of chemotherapy. This can provide a durable treatment response and requires further exploration.

scholarly journals Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis

Gut ◽  
2022 ◽  
pp. gutjnl-2021-325272
Author(s):  
Gaia Bellomo ◽  
Carolyn Rainer ◽  
Valeria Quaranta ◽  
Yuliana Astuti ◽  
Meirion Raymant ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastases ◽  
Disease Progression ◽  
Metastatic Disease ◽  
Ex Vivo ◽  
Receptor Activation ◽  
Tumour Cells ◽  
Metastatic Pancreatic Cancer ◽  
Metastatic Tumour ◽  
Metastatic Liver

ObjectivePancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease and cytotoxic chemotherapy is the standard of care treatment for patients with advanced disease. Here, we investigate how the microenvironment in PDAC liver metastases reacts to chemotherapy and its role in metastatic disease progression post-treatment, an area which is poorly understood.DesignThe impact of chemotherapy on metastatic disease progression and immune cell infiltrates was characterised using flow and mass cytometry combined with transcriptional and histopathological analysis in experimental PDAC liver metastases mouse models. Findings were validated in patient derived liver metastases and in an autochthonous PDAC mouse model. Human and murine primary cell cocultures and ex vivo patient-derived liver explants were deployed to gain mechanistical insights on whether and how chemotherapy affects the metastatic tumour microenvironment.ResultsWe show that in vivo, chemotherapy induces an initial infiltration of proinflammatory macrophages into the liver and activates cytotoxic T cells, leading only to a temporary restraining of metastatic disease progression. However, after stopping treatment, neutrophils are recruited to the metastatic liver via CXCL1 and 2 secretion by metastatic tumour cells. These neutrophils express growth arrest specific 6 (Gas6) which leads to AXL receptor activation on tumour cells enabling their regrowth. Disruption of neutrophil infiltration or inhibition of the Gas6/AXL signalling axis in combination with chemotherapy inhibits metastatic growth. Chemotherapy increases Gas6 expression in circulating neutrophils from patients with metastatic pancreatic cancer and recombinant Gas6 is sufficient to promote tumour cell proliferation ex vivo, in patient-derived metastatic liver explants.ConclusionCombining chemotherapy with Gas6/AXL or neutrophil targeted therapy could provide a therapeutic benefit for patients with metastatic pancreatic cancer.

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