Long Term Efficacy and Assessment of Tumor Response of Transarterial Chemoembolization in Neuroendocrine Liver Metastases: A 15-Year Monocentric Experience

Abstract

Background: transarterial chemoembolization (TACE) is an established treatment for neuroendocrine tumor (NET) liver metastases. The aim was to evaluate the long-term treatment efficacy of TACE for NET liver metastases, and correlate imaging response with survival. Methods: this IRB-approved, single-center, retrospective study evaluated all TACE procedures performed for NET liver metastases from 2003–2017 for imaging tumor response (RECIST and mRECIST), time to liver progression (TTLP), time to untreatable progression with TACE (TTUP), and overall survival (OS). Patient, tumor, and treatment characteristics were analyzed as prognostic factors. Survival curves according to the Kaplan–Meier method were compared by Log-rank test. Tumor responses according to RECIST and mRECIST were correlated with OS. Results: 555 TACE procedures were performed in 202 NET patients (38% grade 1, 60% grade 2) with primary tumors originating from pancreas, small bowel, and lung (39, 26, and 22% respectively). Median follow-up was 8.2 years (90–139 months). Median TTLP and TTUP were 19.3 months (95%CI 16.3–22.3) and 26.2 months (95%CI 22.3–33.1), respectively. Median OS was 5.3 years (95%CI 4.2–6.7), and was higher among mRECIST responders (80.5 months; 95%CI 64.6–89.8) than in non-responders (39.6 months; 95%CI = 32.8–60.2; p < 0.001). In multivariable analysis, age, tumor grade and liver involvement predicted worse OS, whereas administration of somatostatin analogs correlated with improved OS. Conclusion: TACE for NET liver metastases provides objective response and sustained local disease control rates. RECIST and mRECIST responses correlate with OS.

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

“…The clinical predictive factors for poor response with liver-directed therapy’s efficacy include higher age [ 347 , 348 ] and poorer performance status (≥1) [ 349 , 350 , 351 ]. In terms of biomarkers, elevated pre-treatment levels of serum CgA [ 347 ], pancreastatin [ 342 , 352 ], bilirubin [ 353 ], alkaline phosphatase [ 354 , 355 ], and Child-Pugh score [ 351 , 355 ] are associated with worse OS post liver-directed therapies ( Table 5 ).…”

“…Like the other treatment modalities, patients who experienced a radiological response to liver-directed therapies had better OS than non-responders [ 347 , 348 , 351 , 357 ]. It is also reported that an increasing number of TACE sessions is associated with better survival [ 347 , 352 ], which may be the case since patients with longer PFS are more likely to receive many sessions of TACE.…”

“…The reason for a significant association between the presence of enterobiliary communication and a worse OS with liver-directed therapies can be explained by the poor survival rates in patients undergoing pancreaticoduodenectomy or common bile duct stent insertion caused by a mass located in the pancreatic head or lymph node metastases [ 358 ]. Several studies report that patients who received prior systemic therapy had worse outcomes post liver-directed therapies [ 348 , 353 , 355 , 358 , 359 ]. The concomitant use of SSA correlated with improved OS [ 348 , 356 ], whereas systemic therapy during the follow-up period was associated with worse PFS [ 349 ].…”

“…Several studies report that patients who received prior systemic therapy had worse outcomes post liver-directed therapies [ 348 , 353 , 355 , 358 , 359 ]. The concomitant use of SSA correlated with improved OS [ 348 , 356 ], whereas systemic therapy during the follow-up period was associated with worse PFS [ 349 ]. In one Phase II study [ 360 ] involving 39 patients with NELM, following TAE, they were treated with sunitinib, and a high ORR of 62%, a median PFS of 15.2 mos.…”

“…Several studies showed that patients with higher tumor grade had worse PFS [ 348 , 349 , 356 , 359 ] and OS [ 342 , 347 , 348 , 349 , 351 , 354 , 356 , 357 ] with liver-directed therapies, particularly in patients with G3 tumors [ 342 , 347 , 349 , 357 ]. Pathologic factors predicting worse outcomes with liver-directed therapies include high hepatic tumor burden [ 342 , 347 , 348 , 349 , 352 , 354 , 357 , 358 , 361 , 365 ] ( Table 5 ).…”