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

Abstract

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.

Figure 1

An example of a contrast-enhanced CT (A) and fused CT and bremsstrahlung image (B) of a 52-year-old male with neuroendocrine carcinoma. NEC G3 (WHO 2010). The patient was after primary tumor surgery, currently with liver metastasis and chemotherapy refractory disease. RECIST DP (liver metastasis), not suitable for ⁹⁰Y Sir-spheres, due to high bilirubin level (>1.5 xULN). RE using ¹⁸⁸Re HSA microspheres (segment 4 hepatic artery administration of 4.8 GBq of ¹⁸⁸Re HSA microspheres.

Figure 2

The zoomed transaxial slices of SPECT images pertaining to the same patient are presented. The reconstructions with different time points upper row 9 h after therapy and lower row 20 h after therapy. First column: no correction, second column correction for bremsstrahlung and resolution loss, and third column correction for bremsstrahlung, resolution loss, attenuation and scatter correction as well. There is limited corrections (columns 1 and 2) compare to all corrections (column 3). The most advanced reconstruction technique resulted in high-quality representation of the biodistribution of microspheres in spite of the low abundance (15%) of the ¹⁸⁸Re photopeak and high bremsstrahlung background.

Figure 3

The maximum percent change in the sum of the longest diameters of target lesions evaluated using RECIST v.1.0 and volumetric analysis in the sum of the biggest volume of the same target lesions, evaluated from baseline and after 3 months post-therapy using sequential MRI in all 13 patients.

Figure 4

Cumulative proportion surviving (Kaplan-Mayer) for patients (N=13) after RE of liver tumor. Median overall survival – OS 7.1 months (CI±95% 6.2–13.3 months) and median progression-free survival – PFS 5.1 months (CI±95% 2.4–9.9M).