Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience.
BACKGROUND
Neuroendocrine tumors (NETs) metastatic to the liver are treated with transarterial radioembolization (TARE) using yttrium-90 (Y-90) microspheres or transarterial chemoembolization (TACE). However the criteria for patient selection are not well defined. We sought to determine if Ki67 score could help select patients for one therapy over the other in the management of hepatic neuroendocrine metastases.


METHODS
Single institution analysis of patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 staining. Data were analyzed using multivariate association for survival outcomes.


RESULTS
Amongst 72 patients (male: 39, female: 33, median age: 57 years) with metastatic NET, the most common site of origin was small bowel (n=35, 49%), while pancreas constituted 32% (n=23). 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%) with TACE. Within Y-90 group, there was greater use of Sandostatin (95% vs. 75%, P=0.02) and less number of total treatments completed (89% vs. 46%, P<0.001). There was no significant difference in overall survival (OS) between Y-90 and TACE when used without selection (median, 69 vs. 82 months, P=0.47). When adjusted for Ki67, patients with Ki67 score ≥3% had better OS with Y-90 compared to TACE (HR, 0.1; CI, 0.01-0.9), however for Ki67 <3%, OS was better when treated with TACE compared to Y-90 (HR, 13.5; CI, 1.22-148.87).


CONCLUSIONS
There is significant interaction between Ki-67 score and liver-directed treatment benefit in patients with hepatic neuroendocrine metastases. Ki-67 score ≥3% predicts greater benefit with Y-90 and a Ki-67 score <3% predicts greater benefit with TACE.
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Smit
S
Singla
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Charles M
CM
LeVea
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Venkata K
VK
Pokuri
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Kristopher M
KM
Attwood
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Michael M
MM
Wach
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Garin M
GM
Tomaszewski
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Boris
B
Kuvshinoff
1 Department of Surgical Oncology, 2 Department of Pathology, 3 Department of Medical Oncology, 4 Department of Biostatistics and Bioinformatics, 5 Department of Interventional Radiology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Renuka
R
Iyer
Ki67 score; Neuroendocrine tumors (NETs); liver directed therapy; transarterial chemoembolization (TACE); yttrium-90 (Y-90)