Utilizing Ki67 score to predict optimal liver-directed treatment in patients with metastatic neuroendocrine tumors.

Abstract

370 Background: Patients with metastatic neuroendocrine tumors (NETs) benefit from treatment with yttrium-90 radioembolization (Y-90) or transarterial chemoembolization (TACE), however the criteria for patient selection are not well defined. We sought to determine if the proliferative index (Ki67 score) could be utilized to select patients for one therapy over the other. Methods: A single institution analysis of all patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 scoring, and the data was analyzed using multivariate association for survival outcomes. Results: Amongst 72 patients (M: 39, F: 33; median age, 57 years) included in the study, the most common site of tumor origin was small bowel (n=35, 49%), and the most common histology subtype was carcinoid (n=58, 85%). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) in the TACE group. In Y-90 group, there was a higher concomitant use of sandostatin (94% vs 75%, p=0.023), longer time between diagnosis and treatment (median, 32 vs 11 months, p=<0.001), and less number of total treatments completed (89% vs 46%, p<0.001). There was no significant difference in overall survival (OS) between the groups (median, 69 vs 82 months, respectively; p=0.477); however when adjusted for Ki67 score of 3, patients with Ki67 score >3% were found to have better OS when treated with Y-90 as compared to TACE (HR, 0.083; CI, 0.008-0.854). On the other hand, in patients with Ki67 <3%, OS was better when treated with TACE (HR, 13.5; CI, 1.2-148.8). Further, patients in Y-90 group had higher incidence of carcinoid syndrome (39% vs 21%, p=0.195) and bilobar liver disease (95% vs 89%, p=0.371), whereas hepatic tumor burden >25% was greater in the TACE group (26% vs 20%, p=0.614), but these differences were not significant. Conclusions: In patients with metastatic NETs, Ki-67 score >3% may be predictive of treatment benefit with Y-90 and <3% with TACE. A longer time from diagnosis and an increased number of prior therapies may indicate a need for aggressive therapy; however a prospective validation is warranted.