Radiological and Clinical Efficacy of Intra-Arterial 90Y-DOTATATE in Patients with Unresectable, Progressive, Liver Dominant Neuroendocrine Neoplasms.

This study was performed to determine if intra-arterial (i.a.) administration of 90Y DOTATATE can provide an effective and safe alternative to the accepted standard for i.v. of peptide receptor radionuclide therapy (PRRT) in liver-dominant metastases of gastrointestinal pancreatic neuroendocrine neoplasm (GEP-NEN). A single site, prospective, preliminary case series study included 39 patients with histologically proven liver-dominant NEN. PRRT in the form of 1.15GBq 90Y DOTATATE was given selectively into the liver via radiological catheterization of the hepatic artery, up to four times. The endpoint was radiological response (RECIST). Secondary endpoints assessed clinical well-being post-treatment, progression-free survival (PFS), overall survival (OS), and toxicity. Partial response (PR) was noted in 13% of subjects six weeks post-therapy, increasing to 24% at six months and dropping to 13% at 36 months. Disease progression (DP) was not seen at six weeks, was 5% at six months, and 47% at 36 months. Clinical response based on PS seen in 74% of patients at six weeks, 69% at six months, and 39% at 36 months had PFS and OS, respectively, of 22.7 months and 38.2 months. There was no difference in OS/PFS between those with RECIST PR and SD. One patient had significant toxicity (3%). Use of i.a. PRRT appears to be safe and effective in treating patients with liver-dominant NEN. In addition, the best OS (51 vs. 22 months) was seen when i.a. was used as an upfront treatment of bulky GEP-NEN liver metastases and not after i.v. 90Y DOTATATE. The use of i.a. 90Y DOTATATE PRRT appears to be safe and effective in treating patients with liver-dominant NEN.

Initial study of radiological and clinical efficacy radioembolization using 188Re-human serum albumin (HSA) microspheres in patients with progressive, unresectable primary or secondary liver cancers.

BACKGROUND: The aim of this initial study was to evaluate the clinical and radiological effectiveness of radioembolization (RE) using 188Re-Human Serum Albumin (HSA) microspheres in patients with advanced, progressive, unresectable primary or secondary liver cancers, not suitable to any other form of therapy. MATERIAL/METHODS: Overall, we included 13 patients with 20 therapy sessions. Clinical and radiological responses were assessed at 6 weeks after therapy, and then every 3 months. The objective radiological response was classified according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 by sequential MRI. Adverse events were evaluated using NCI CTCAE v.4.03. RESULTS: There were 4 patients with hepatocellular carcinoma (HCC), 6 with metastatic colorectal cancer (mCRC), 2 with neuroendocrine carcinoma (NEC), and 1 patient with ovarian carcinoma. Mean administered activity of 188Re HSA was 7.24 GBq (range 3.8-12.4) A high microspheres labeling efficacy of over 97±2.1% and low urinary excretion of 188Re (6.5±2.3%) during first 48-h follow-up. Median overall survival (OS) for all patients was 7.1 months (CI 6.2-13.3) and progression-free survival (PFS) was 5.1 months (CI 2.4-9.9). In those patients who had a clinical partial response (PR), stable disease (SD), and disease progression (DP) as assessed 6 weeks after therapy, the median OS was 9/5/4 months, respectively, and PFS was 5/2/0 months, respectively. The treatment adverse events (toxicity) were at an acceptable level. Initially and after 6 weeks, the CTC AE was grade 2, while after 3 months it increased to grade 3 in 4 subjects. This effect was mostly related to rapid cancer progression in this patient subgroup. CONCLUSIONS: The results of this preliminary study indicate that RE using 188Re HSA is feasible and a viable option for palliative therapy in patients with extensive progressive liver cancer. It was well tolerated by most patients, with a low level of toxicity during the 3 months of follow-up.

The clinical value of MRI using single-shot echoplanar DWI to identify liver involvement in patients with advanced gastroenteropancreatic-neuroendocrine tumors (GEP-NETs), compared to FSE T2 and FFE T1 weighted image after i.v. Gd-EOB-DTPA contrast enhancement.

BACKGROUND: To assess the detection rate of liver lesions in patients with advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs) using echo planar (EP) DWI (diffusion weighted imaging) as compared to standard FSE T2 wi and FFE T1 wi with i.v. (Gd-EOB)-DTPA. MATERIAL/METHODS: This prospective single-institution study included 55 patients with liver involvement confirmed by GEP-NETs 1.5T MRI system, using FSE T2, EP DWI and FFE T1 with i.v. (Gd-EOB)-DTPA. The potential differences between detection rates of liver deposits using 3 different MR approaches and between groups of patients were compared. RESULTS: Mean number of liver deposits: FSE T2=20.7, FFE T1=25.7 and tested EP DWI=24.0. No significant difference was found in overall detection rate of liver deposits seen in 3 different techniques. A significant difference in detection rate of liver deposits was noted between male vs. female and secreting vs. non-secreting cancers. There was nearly perfect agreement between both observers, and each of the tested MRI approaches in regards to number of detected liver lesions (Cohen's kappa=0.848-1). CONCLUSIONS: There were no significant differences among the 3 different MRI approaches in detection rates of liver deposits. Perfect agreement with high detection rate of liver deposits provides a rationale for the use of EP DWI in follow-up studies in GEP-NET patients.