Phase I trial of selective internal radiation therapy for chemorefractory colorectal cancer liver metastases progressing after hepatic arterial pump and systemic chemotherapy.

INTRODUCTION: This prospective study assessed the safety and outcomes of selective internal radiation therapy (SIRT) using yttrium-90 ((90)Y) resin microspheres as a salvage therapy for liver-predominant metastases of colorectal cancer in patients with documented progression after hepatic arterial chemotherapy (HAC) and systemic chemotherapy. PATIENTS AND METHODS: We recruited 19 patients who had received a mean of 2.9 prior lines of chemotherapy and ≥ 1 line of HAC. Dose-limiting toxicities (grade 3 or higher) were catalogued using Common Terminology Criteria for Adverse Events version 3.0. At 4 to 8 weeks and 3 to 4 months post SIRT, responses were assessed by carcinoembryonic antigen (CEA), and quantitative imaging using Response Evaluation Criteria in Solid Tumors (RECIST) and PET Response Criteria in Solid Tumors (PERCIST). Liver progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were calculated using Kaplan-Meier methodology. RESULTS: Median follow-up was 31.2 months after SIRT. Within 6 weeks of SIRT, 3 patients (15.8%) experienced grade 3 toxicity. There was no incidence of radiation-induced liver disease. Responses by RECIST, PERCIST, and CEA were, respectively, 0%, 20%, and 32% at 4 to 8 weeks and 5%, 33%, and 21% at 3 to 4 months post SIRT; 53% of patients had stable disease (by RECIST) at 3 to 4 months. Of 19 patients, 4 (21.1%) had liver ablation, 9 (47%) received additional HAC, and 17 (89%) received systemic chemotherapy after SIRT. Median LPFS, PFS, and OS after SIRT were 5.2 months, 2.0 months, and 14.9 months, respectively. CONCLUSION: SIRT was well tolerated and did not prohibit subsequent treatment, resulting in a median OS of 14.9 months in this heavily pretreated population.

Margin size is an independent predictor of local tumor progression after ablation of colon cancer liver metastases.

PURPOSE: This study was designed to evaluate the relationship between the minimal margin size and local tumor progression (LTP) following CT-guided radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLM). METHODS: An institutional review board-approved, HIPPA-compliant review identified 73 patients with 94 previously untreated CLM that underwent RFA between March 2003 and May 2010, resulting in an ablation zone completely covering the tumor 4-8 weeks after RFA dynamic CT. Comparing the pre- with the post-RFA CT, the minimal margin size was categorized to 0, 1-5, 6-10, and 11-15 mm. Follow-up included CT every 2-4 months. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the effect of the minimal margin size, tumor location, size, and proximity to a vessel on LTP. RESULTS: Forty-five of 94 (47.9 %) CLM progressed locally. Median LTP-free survival (LPFS) was 16 months. Two-year LPFS rates for ablated CLM with minimal margin of 0, 1-5 mm, 6-10 mm, 11-15 mm were 26, 46, 74, and 80 % (p < 0.011). Minimal margin (p = 0.002) and tumor size (p = 0.028) were independent risk factors for LTP. The risk for LTP decreased by 46 % for each 5-mm increase in minimal margin size, whereas each additional 5-mm increase in tumor size increased the risk of LTP by 22 %. CONCLUSIONS: An ablation zone with a minimal margin uniformly larger than 5 mm 4-8 weeks postablation CT is associated with the best local tumor control.

Perfusion CT improves diagnostic accuracy for hyperacute ischemic stroke in the 3-hour window: study of 100 patients with diffusion MRI confirmation.

PURPOSE: Conventional noncontrast CT (NCCT) is insensitive to hyperacute cerebral infarction in the first 3 h. Our aim was to determine if CT perfusion (CTP) can improve diagnostic accuracy over NCCT for patients presenting with stroke symptoms in the 3-hour window. METHODS: Consecutive patients presenting to our emergency department with symptoms of ischemic stroke <3 h old and receiving NCCT and CTP as part of their triage evaluation were retrospectively reviewed. Patients with follow-up diffusion-weighted MRI (DWI) <7 days from ictus were included. Two readers rated the NCCT and CTP for evidence of acute infarct and its vascular territory. CTP selectively covered 24 mm of brain centered at the basal ganglia with low relative cerebral blood volume in a region of low cerebral blood flow or elevated time to peak as the operational definition for infarction. A third reader rated all follow-up DWI for acute infarct and its vascular territory as the reference standard. Sensitivity, specificity, and predictive values were calculated. An exact McNemar test and generalized estimating equations from a binary logistic regression model were used to assess the difference in detection rates between modalities. A two-sided p value <0.05 was considered significant. RESULTS: 100 patients were included. Sixty-five (65%) patients had follow-up DWI confirmation of acute infarct. NCCT revealed 17 (26.2%) acute infarcts without false positives. CTP revealed 42 (64.6%) acute infarcts with one false positive. Of the 23 infarcts missed on CTP, 10 (43.5%) were outside the volume of coverage while the remaining 13 (56.5%) were small cortical or lacunar type infarcts (

Correlation of volumetric mismatch and mismatch of Alberta Stroke Program Early CT Scores on CT perfusion maps.

INTRODUCTION: We aimed to determine if volumetric mismatch between tissue at risk and tissue destined to infarct on computed tomography perfusion (CTP) can be described by the mismatch of Alberta Stroke Program Early CT Score (ASPECTS). MATERIALS AND METHODS: Forty patients with nonlacunar middle cerebral artery infarct <6 h old who had CTP on admission were retrospectively reviewed. Two raters segmented the lesion volume on mean transit time (MTT) and cerebral blood volume (CBV) maps using thresholds of >6 s and <2.0 mL per 100 g, respectively. Two other raters assigned ASPECTS to the same MTT and CBV maps while blinded to the volumetric data. Volumetric mismatch was deemed present if >or=20%. ASPECTS mismatch (=CBV ASPECTS - MTT ASPECTS) was deemed present if >or=1. Correlation between the two types of mismatches was assessed by Spearman's coefficient (rho). ROC curve analyses were performed to determine the optimal ASPECTS mismatch cut point for volumetric mismatch >or=20%, >or=50%, >or=100%, and >or=150%. RESULTS: Median volumetric mismatch was 130% (range 10.9-2,031%) with 31 (77.5%) being >or=20%. Median ASPECTS mismatch was 2 (range 0-6) with 26 (65%) being >or=1. ASPECTS mismatch correlated strongly with volumetric mismatch with rho = 0.763 [95% CI 0.585-0.870], p < 0.0001. Sensitivity and specificity for volumetric mismatch >or=20% was 83.9% [95% CI 65.5-93.5] and 100% [95% CI 65.9-100], respectively, using ASPECTS mismatch >or=1. Volumetric mismatch >or=50%, >or=100%, and >or=150% were optimally identified using ASPECTS mismatch >or=1, >or=2, and >or=2, respectively. CONCLUSION: On CTP, ASPECTS mismatch showed strong correlation to volumetric mismatch. ASPECTS mismatch >or=1 was the optimal cut point for volumetric mismatch >or=20%.