Pretherapeutic Assessment of Pancreatic Cancer: Comparison of FDG PET/CT Plus Delayed PET/MR and Contrast-Enhanced CT/MR

PurposeThis study aims to determine the diagnostic performance of whole-body FDG PET/CT plus delayed abdomen PET/MR imaging in the pretherapeutic assessment of pancreatic cancer in comparison with that of contrast-enhanced (CE)-CT/MR imaging.Materials and MethodsForty patients with pancreatic cancer underwent nonenhanced whole-body FDG PET/CT, delayed abdomen PET/MR imaging, and CE-CT/MR imaging. Two nuclear medicine physicians independently reviewed these images and discussed to reach a consensus, determining tumor resectability according to a 5-point scale, N stage (N0 or N positive), and M stage (M0 or M1). With use of clinical-surgical-pathologic findings as the reference standard, diagnostic performances of the two imaging sets were compared by using the McNemar test.ResultsThe diagnostic performance of FDG PET/CT plus delayed PET/MR imaging was not significantly different from that of CE-CT/MR imaging in the assessment of tumor resectability [area under the receiver operating characteristic curve: 0.927 vs. 0.925 (p = 0.975)], N stage (accuracy: 80% (16 of 20 patients) vs. 55% (11 of 20 patients), p = 0.125), and M stage (accuracy: 100% (40 of 40 patients) vs. 93% (37 of 40 patients), p = 0.250). Moreover, 14 of 40 patients had liver metastases. The number of liver metastases detected by CE-CT/MR imaging, PET/CT, and PET/MR imaging were 33, 18, and 61, respectively. Compared with CE-CT/MR imaging, PET/MR imaging resulted in additional findings of more liver metastases in 9/14 patients, of which 3 patients were upstaged. Compared with PET/CT, PET/MR imaging resulted in additional findings of more liver metastases in 12/14 patients, of which 6 patients were upstaged.ConclusionsAlthough FDG PET/CT plus delayed PET/MR imaging showed a diagnostic performance similar to that of CE-CT/MR imaging in the pretherapeutic assessment of the resectability and staging of pancreatic tumors, it still has potential as the more efficient and reasonable work-up approach for the additional value of metastatic information provided by delayed PET/MR imaging.

Prospective evaluation of percutaneous hepatic perfusion with melphalan as a treatment for unresectable liver metastases from colorectal cancer

Purpose Percutaneous hepatic perfusion with melphalan (M-PHP) is increasingly used in patients with liver metastases from various primary tumors, yet data on colorectal liver metastases (CRLM) are limited. The aim of this study was to prospectively evaluate the efficacy and safety of M-PHP in patients with CRLM. Materials and methods Prospective, single-center, single-arm phase II study of M-PHP with hemofiltration in patients with unresectable CRLM. Proven, extrahepatic metastatic disease was one of the exclusion criteria. Primary outcomes were overall response rate (ORR) and best overall response (BOR). Secondary outcomes were overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. Results A total of 14 M-PHP procedures were performed in eight patients between March 2014 and December 2015. All patients (median age 56 years, ranging from 46 to 68) had received (extensive) systemic chemotherapy before entering the study. The ORR was 25.0%, with two out of eight patients showing partial response as BOR. Median OS was 17.3 months (ranging from 2.6 to 30.9) with a one-year OS of 50.0%. Median PFS and hPFS were 4.4 and 4.5 months, respectively. No serious adverse events occurred. Grade 3/4 hematologic adverse events were observed in the majority of patients, though all were transient and well-manageable. Conclusion M-PHP is a safe procedure with only limited efficacy in patients with unresectable CRLM who already showed progression of disease after receiving one or more systemic treatment regimens.

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

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.