Quantitative comparison of yttrium-90 (90Y)-microspheres and technetium-99m (99mTc)-macroaggregated albumin SPECT images for planning 90Y therapy of liver cancer.

Yttrium-90 ((90)Y)-microspheres administered via the hepatic artery has been used for the treatment of unresectable primary or metastatic cancer in the liver. Prior to (90)Y therapy, however, the (90)Y administered activity and the percent shunting to lungs must be determined, most commonly by gamma camera imaging of technetium-99m ((99m)Tc)-macroaggregated albumin (MAA). The purpose of the current study was to identify and evaluate an objective measure of the correlation of (90)Y and MAA activity distributions and thus assess the reliability of MAA imaging for evaluation of (90)Y administered activity and tumor and liver radiation doses. The MAA study consisted of two acquisitions. After administration of 185 MBq of MAA, a partial-body or so-called breakthrough scan was performed in order to determine the percent shunting to lungs. Immediately after a breakthrough scan, a combined single-photon emission computed tomography (SPECT)/transmission computed tomography (CT) scanner was used to image MAA distribution in order to derived the prescribed (90)Y administered activity based on tumor and liver dosimetry. (90)Y SPECT/CT was performed 2-4 weeks later and activities used were in the range of 777-2,442 MBq. In order to compare (90)Y and MAA SPECT images, first the respective CT image sets were registered using a transform based on normalized mutual information. The transform thus derived was used to align the 90Y and MAA SPECT image sets, and the Spearman's (rho) rank correlation as well as image distance (L2-norm) between the registered SPECT images were then calculated. The Spearman's rank correlation values ranged from 0.451 to 0.818 and the L2 distances from 0.626 to 2.889. Based on visual inspection, the registration of the (90)Y and MAA SPECT images appeared reasonably accurate. The regression coefficient (r) between visual scoring and the Spearman's rank correlation was 0.65 and between visual scoring and L2 distance 0.61. The Spearman's rank correlation thus appears to be more reliable than the image distance for assessing the correlation of the (90)Y and MAA images.

Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival.

PURPOSE: Alpha-fetoprotein (AFP) is considered to be an indicator of tumor activity in hepatocellular carcinoma (HCC). We present a novel correlation of AFP response to radiologic response, time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) in patients treated with locoregional therapies. PATIENTS AND METHODS: Four hundred sixty-three patients with HCC were treated with chemoembolization or radioembolization at our institution. One hundred twenty-five patients with baseline AFP higher than 200 ng/mL were studied for this analysis. AFP response was defined as more than 50% decrease from baseline. One hundred nineteen patients with follow-up imaging were studied for the AFP imaging correlation analysis. AFP response was correlated to radiologic response, TTP, PFS, and OS. Multivariate analyses were performed. RESULTS: Eighty-one patients (65%) showed AFP response. AFP response was seen in 26 (55%) of 47 and 55 (70%) of 78 of patients treated with chemoembolization and radioembolization, respectively (P = .12). WHO response was seen in 41 (53%) of 77 and 10 (24%) of 42 of AFP responders and nonresponders, respectively (P = .002). The hazard ratio (HR) for TTP in AFP nonresponders compared with responders was 2.8 (95% CI, 1.5 to 5.1). The HR for PFS was 4.2 (95% CI, 2.4 to 7.2) in AFP nonresponders compared with responders. The HR for OS in AFP nonresponders compared with responders was 5.5 (95% CI, 3.1 to 9.9) and 2.7 (95% CI, 1.6 to 4.6) on univariate and multivariate analyses, respectively. CONCLUSION: The data presented support the use of AFP response seen after locoregional therapy as an ancillary method of assessing tumor response and survival, as well as an early objective screening tool for progression by imaging.

Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy.

PURPOSE: Liver metastases are the principal cause of death in patients with advanced colorectal cancer (CRC). Irinotecan is a chemotherapeutic agent used in the treatment of CRC and has demonstrated synergistic potential when used with radiation. Radioembolization with yttrium-90 microspheres has demonstrated increased response and survival rates when given with fluorouracil chemotherapy. This study's goal was to evaluate the maximum-tolerated dose of concomitant irinotecan and radioembolization in fluorouracil-refractory patients with CRC hepatic metastases. PATIENTS AND METHODS: Twenty-five irinotecan-naive patients who had experienced relapse after previous chemotherapy were enrolled onto three dose-escalating groups. Irinotecan was administered at 50, 75, or 100 mg/m(2) on days 1 and 8 of a 3-week cycle for the first two cycles, and full irinotecan doses (ie, 100 mg/m(2)) were administered during cycles 3 to 9. Radioembolization was administered during the first chemotherapy cycle. RESULTS: Most patients experienced acute, self-limiting abdominal pain and nausea. Mild lethargy and anorexia were common. Grades 3 to 4 events were seen in three of six patients at 50 mg/m(2) (obstructive jaundice, thrombocytopenia, diarrhea), in five of 13 patients at 75 mg/m(2) (neutropenia, leukopenia, thrombocytopenia, elevated alkaline phosphatase, abdominal pain, ascites, fatigue) and in four of six patients at 100 mg/m(2) (diarrhea, deep vein thrombosis, constipation, leukopenia). Eleven (48%) of 23 patients had a partial response, and nine patients (39%) had stable disease. The median progression-free survival was 6.0 months; the median survival was 12.2 months. CONCLUSION: Concomitant use of radioembolization plus irinotecan did not reach a maximum-tolerated dose. The recommended dose of irinotecan in this setting is 100 mg/m(2) on days 1 and 8 of a 3-week cycle.