Chemoembolization using streptozotocin versus embolization in metastatic NETs

Locoregional therapies are a standard treatment for neuroendocrine tumors (NET) with predominant liver metastases. The efficacy of transarterial chemoembolization (TACE) using streptozotocin (STZ) has been poorly compared to transarterial embolization (TAE). Predictive biomarkers of TACE efficacy have never been explored. We studied all patients with pancreatic (panNET) or small intestine (siNET) NET and liver metastases treated between 2006 and 2022 using a standardized protocol of TACE-STZ (1,500 mg/m 2 ) or TAE. The primary endpoint was the RECIST1.1-defined objective response rate (ORR). The variables associated with ORR were explored using a propensity score to account for confounding factors. Secondary endpoints included the impact of tumor expression of O6-methylguanine-methyltransferase (MGMT), alkylpurine–DNA–N–glycosylase (APNG), and carbonic anhydrase IX (CAIX), and progression-free survival (PFS). Among 116 patients, 58 received TACE (15 siNET and 43 panNET) and 58 received TAE (42 siNET and 16 panNET). TACE was associated with a higher ORR than TAE (43% vs. 22%, p=0.045), which remained statistically significant on propensity-adjusted multivariable analysis (OR 2.71, 95% CI [1.08-7.17], p=0.038). TACE provided longer PFS than TAE in panNET patients (12.9 vs. 6.4 months, p=0.026), but not in siNET patients (16.1 vs. 15.1 months, p=0.47). Low APNG expression was predictive of higher ORR with TACE (70% vs. 16%, p<0.001), while the expression of MGMT and CAIX had no impact. TACE-STZ provided a higher ORR than TAE, although yielded longer PFS only in patients with panNET . Low tumor expression of APNG might help select the best candidates for TACE-STZ, although this result was only exploratory.