Yttrium-90 microsphere-selective internal radiation therapy with chemotherapy (chemo-SIRT) for colorectal cancer liver metastases: an in vivo double-arm-controlled phase II trial.

OBJECTIVES: Selective internal radiation therapy (SIRT) with yttrium-90 (Y) microspheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio for treatment of colorectal cancer liver metastases. The aim of this study was to investigate the objective responses obtained by Y microsphere treatment when combined with contemporary chemotherapy in the front-line (first or second line) setting in patients with CRCLM. METHODS: This study used an in vivo comparison between the right and left liver lobes; systemic chemotherapy was supplied to both liver lobes by virtue of systemic administration, whereas SIRT was administered selectively to the target liver lobe only. Response to treatment was evaluated by serial fludeoxyglucose positron emission tomography computed tomography performed at 4 weeks, 2 to 4 months, and 6 to 8 months. Standard uptake value, anatomic volume, functional tumor volume, and total lesion glycolysis (TLG) calculations were obtained at each time point. RESULTS: A decrease in TLG on fludeoxyglucose positron emission tomography computed tomography imaging was seen in 19 of the 20 patients. The mean decrease in TLG values in the tumors receiving chemo-SIRT and chemo-only treatment were 86.26%±18.57% and 31.74%±80.99% (P<0.01), 93.13%±11.81% and 40.80%±73.32% (P=0.01), and 90.55%±19.75% and 54.91%±38.55% (P<0.01) at 4 weeks, 2 to 4 months, 6 to 8 months posttreatment, respectively. Functional and anatomic tumor volume changes were in concordance with the TLG changes. CONCLUSIONS: The study demonstrated that, under near identical conditions in terms of patient and tumor characteristics, the chemo-SIRT combination produced superior objective responses compared with chemo-only treatment in a front-line treatment setting in patients with colorectal cancer liver metastases.

A 3-D liver segmentation method with parallel computing for selective internal radiation therapy.

This study describes a new 3-D liver segmentation method in support of the selective internal radiation treatment as a treatment for liver tumors. This 3-D segmentation is based on coupling a modified k-means segmentation method with a special localized contouring algorithm. In the segmentation process, five separate regions are identified on the computerized tomography image frames. The merit of the proposed method lays in its potential to provide fast and accurate liver segmentation and 3-D rendering as well as in delineating tumor region(s), all with minimal user interaction. Leveraging of multicore platforms is shown to speed up the processing of medical images considerably, making this method more suitable in clinical settings. Experiments were performed to assess the effect of parallelization using up to 442 slices. Empirical results, using a single workstation, show a reduction in processing time from 4.5 h to almost 1 h for a 78% gain. Most important is the accuracy achieved in estimating the volumes of the liver and tumor region(s), yielding an average error of less than 2% in volume estimation over volumes generated on the basis of the current manually guided segmentation processes. Results were assessed using the analysis of variance statistical analysis.

The prognostic value of functional tumor volume and total lesion glycolysis in patients with colorectal cancer liver metastases undergoing 90Y selective internal radiation therapy plus chemotherapy.

PURPOSE: Functional tumor volume (FTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images. These parameters could potentially have clinical value in response to treatment evaluation and disease prognostication. The objectives of this study were to investigate the relationship between functional tumor parameters (FTV and TLG) and clinical outcomes in patients with colorectal cancer liver metastases (CRCLM) undergoing (90)Y-resin microsphere selective internal radiation therapy (SIRT) (SIR-Spheres®, Sirtex Medical Limited, Lane Cove, NSW, Australia). METHODS: FDG PET/CT studies of 20 patients with unresectable CRCLM who underwent (90)Y SIRT under a phase II clinical trial were analyzed. FTV and TLG were calculated using PET VCAR (GE Healthcare, Milwaukee, WI, USA) on pretreatment and 4-week posttreatment scans. The effects of pretreatment and posttreatment functional tumor activity on patient survival were evaluated using Kaplan-Meier survival curves. RESULTS: The median survival in the study group was 14.8 months (range 2.0-27.7 months). The median survival for patients with pretreatment FTV values of above and below 200 cc were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment FTV values of above and below 30 cc were 10.9 and 26.9 months, respectively (p < 0.05). The median survival for patients with pretreatment TLG values of above and below 600 g were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment TLG values of above and below 100 g were 10.9 and 26.9 months, respectively (p < 0.05). CONCLUSION: Pretreatment and posttreatment FTV and TLG showed very strong association with survival. These values can be useful quantitative criteria for patient selection and disease prognostication when (90)Y SIRT is contemplated in patients with CRCLM.