Evaluation of radiological prognostic factors of hepatic metastases in patients with non-functional pancreatic neuroendocrine tumors
Introduction
Neuroendocrine neoplasms (NEN) are a rare and heterogeneous group of malignancies that can arise from neuroendcrine cells of various locations in mostly the gastrointestinal tract, pancreas, and lung. Poorly differentiated NEN (G3) are referred to as neuroendocrine carcinomas (NEC) whilst well to moderately differentiated tumors (G1 and G2) are referred to as neuroendocrine tumors (NET) [1]. They can cause symptoms due to mass effects and due to hormonal secretion. The pancreas is amongst the more common sites of primary tumors with an annual incidence of about 0.32/100,000 [2]. Many patients present with metastatic disease at time of initial diagnosis and the presence of hepatic metastases is a negative prognostic factor [2], [3], [4].
Treatment recommendations depend mainly on tumor differentiation and extent of disease as well as on functional activity. In non-functional well to moderately differentiated (G1 and G2) pancreatic neuroendocrine tumors (pNET) surgical resection of hepatic metastases and primary tumor with curative intent is recommended where feasible. Since pNET have a variable natural course watchful waiting is a well established approach if metastases are unresectable, especially in G1 pNET. Somatostatin analogs (SSA) are considered optional in non-functional tumors. They were found to have disease stabilizing effects [5], [6], [7] but data from a placebo controlled trial in pNET are still pending (CLARINET study). It remains unclear if an early initiation of such treatment leads to an improved overall prognosis. Systemic chemotherapy should be initiated upon tumor progression [4]. As it is unpredictable whether a newly diagnosed patient will experience progressive disease (PD) in short term or remain stable, close surveillance by means of imaging is obligatory. Predictors of the individual course of the disease would be desirable in order to identify patients who might profit from early treatment initiation or intensification.
Goal of this study was to evaluate imaging features as potential prognostic factors predicting early tumor progression within twelve months in patients newly diagnosed with non-functional G1 and G2 pNET metastasized to the liver.
Section snippets
Total patient cohort
From the institutional database we identified patients who were newly diagnosed with hepatic metastases of non-functional G1 and G2 pNET between 2001 and 2011 and who had received no prior antiproliferative treatment other than SSA. Further inclusion criteria were the availability of CT or MR imaging with at least arterial and venous contrast phase performed at the initial time of diagnosis of hepatic metastases as well as close follow-up imaging valid for analysis according to the response
Patients and treatment
Forty-four patients newly diagnosed with hepatic metastases of non-functional pNET and without prior antiproliferative treatment other than SSA were included in this study. Twenty-three patients were female. The age range was 30–80 years. In 34 patients hepatic metastases were present at the initial time of diagnosis of the pNET. Ten patients had metachronous hepatic metastases occurring after 4.5 years on average (range, 0.6–7.3 years). Twenty-nine patients had lymphatic metastases, 10
Discussion
In this retrospective study of patients with non-functional G1 and G2 pNET with unresectable hepatic metastases, treatment with SSA was found to be associated with a prolonged TTP. Our study was not designed to analyze the effectiveness of treatment with SSA and therefore no treatment recommendations can be deduced from these results. However, this finding is consistent with previous studies describing mild antiproliferative effects of SSA in well differentiated NET leading to disease
Conclusion
In conclusion we found that in treatment-naive patients with non-functional pNET and unresectable hepatic metastases hypoenhancement of the metastases during early contrast phases is a negative prognostic factor for early tumor progression. Enhancement is probably associated with tumor vascularization and differentiation. The finding of hypoenhancement might encourage considering repeated biopsy of metastases, especially if histology is not recent or taken from the primary tumor. In addition
Disclosures
T.D. has acted as a speaker for Novartis. B.W. and M.P. have acted as speakers and advisers for Novartis. Both have received research funding by Novartis. The other authors have no conflicts of interest to disclose.
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These authors contributed equally to this work.