Risk factors affecting prognosis in metachronous liver metastases from WHO classification G1 and G2 gastroenteropancreatic neuroendocrine tumors after initial R0 surgical resection

Abstract

Background Here we describe the treatments and prognosis for metachronous metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) after initial R0 surgical resection at a large center in China. Methods The clinicopathological data and survival outcomes for 108 patients (median age, 54.0 years) with metachronous hepatic metastatic GEP-NETs disease who were initially treated using R0 surgical resection between August 2003 and July 2014 were analyzed using one-way comparisons, survival analysis, and a predictive nomogram. Results Fifty-five (50.9%) patients had pancreatic NETs and 92 (85.2%) had G2 primary tumors. For treatment of the hepatic metastases, 48 (44.4%) patients received liver-directed local treatment (metastasectomy, radiofrequency ablation, transcatheter arterial chemoembolization, etc.), 15 (13.9%) received systemic treatment (interferon, somatostatin analogs, etc.), and 45 (41.7%) received both treatments. Multivariable analyses revealed that OS was associated with hepatic tumor number ( P < 0.001), treatment modality ( P = 0.045), and elevated Ki-67 index between the metastatic and primary lesions ( P = 0.027). The predictive nomogram C-index was 0.63. Conclusions A higher Ki-67 index in metastases compared to primary tumor was an independent factor for poor prognosis. Local treatment was associated with prolonged survival of hepatic metastatic GEP-NET patients. Optimal treatment strategies based on clinicopathological characteristics should be developed.

The overriding role of surgery and tumor grade for long‐term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population‐based cohort study

“…20 Moreover, the finding of a higher grade (i.e., WHO grade 3) in metachronous liver metastases in GEP-NEN patients compared with a low-grade primary tumor will further add prognostic value by indicating a poor prognosis. 36,37 T A B L E 3 (Continued) F I G U R E 4 Overall survival (OS) and relative survival of the patient cohort. Notably, the two curves have a similar pattern, particularly during the early time period of 2-3 years…”

“… 20 Moreover, the finding of a higher grade (i.e., WHO grade 3) in metachronous liver metastases in GEP‐NEN patients compared with a low‐grade primary tumor will further add prognostic value by indicating a poor prognosis. 36 , 37 …”

Development and validation of a nomogram for predicting the overall survival of patients with gastroenteropancreatic neuroendocrine neoplasms

“…The criteria for evaluating prognosis for GEP-NENs differ for distinct pathological differentiation statuses and clinical systems. There have been previous reports show the favorable predictive ability of nomograms for NENs with stomach, [ 24 ] liver metastases, [ 25 ] small intestine [ 26 ] and pancreas. [ 27 ] These results verify that a consistent and specific nomogram could be clinically applied to effectively and accurately predict the prognosis of patients with NENs.…”

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

“…Pancreatic NENs also show differences in prognosis depending on disease distribution, with worse prognosis if > 25% of the liver and bone metastases are present. In particular, liver metastases at diagnosis significantly decrease survival in most GEP NETs [ 59 ].…”