The Protégé Nitinol Self-Expanding Stent for the Treatment of Iliofemoral Veno-Occlusive Disease.

PURPOSE: To evaluate the safety and effectiveness of the Protégé nitinol self-expanding stent for the treatment of iliofemoral veno-occlusive disease. MATERIALS AND METHODS: A retrospective review was performed of 376 (284 left, 92 right) Protégé stents in 212 limbs of 183 patients (mean age: 53 ± 17 years, 52% female) treated for iliofemoral veno-occlusive disease between 2011 and 2018. Binary patency was assessed with duplex ultrasound and calculated by Kaplan Meier analysis. Clinical outcomes were evaluated by clinical-etiology-anatomy-pathophysiology (CEAP) classification and Villalta scores. Adverse events were recorded and categorized per Society of Interventional Radiology reporting standards. RESULTS: Of the 212 limbs, 125 presented with acute thrombosis and 28 with chronic thrombosis requiring thrombectomy (n = 44), catheter directed thrombolysis (n = 32), or both (n = 77). Fifty-nine limbs were non-thrombotic. Mean follow-up time was 11.44 ± 11.37 months. Kaplan Meier analysis revealed a primary limb-level patency of 92.3%, 88.6%, 86.9% and 86.9% at 6, 12, 24 and 36 months, respectively. CEAP and Villalta scores improved from a median of C3 (range: 0-6) to C1 (0-5) (p < 0.001) and from a mean of 13.4 ± 7.5 to 5.3 ± 4.9 (p < 0.001), respectively. Nine minor and 2 major adverse events were recorded. CONCLUSIONS: Endovascular treatment of iliofemoral veno-occlusive disease with the Protégé self-expanding stent appears to have good mid-term patency. LEVEL OF EVIDENCE: Level 4, Case Series.

Safety of Therapeutic Anticoagulation with Low-Molecular-Weight Heparin or Unfractionated Heparin Infusion during Catheter-Directed Thrombolysis for Acute Pulmonary Embolism.

PURPOSE: To examine the safety of therapeutic-dose anticoagulation during catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE). MATERIALS AND METHODS: A retrospective review of 156 consecutive cases (age, 56.6 ± 15.4 years; 85 males) of CDT with alteplase for acute PE (symptoms, <14 days) between 2009 and 2019 was performed. All patients received full-dose anticoagulation before, during, and after thrombolysis with low-molecular-weight heparin (LMWH) (n = 45) or unfractionated heparin (n = 111) infusion. Massive PE was diagnosed in 21 of 156 patients at presentation; submassive PE was diagnosed in 135 of 156 patients at presentation. The Simplified Pulmonary Embolism Severity Index was ≥1 in 69 of 156 patients. RESULTS: There were 4 mild (2.6%), 3 moderate (1.9%), and 3 severe (1.9%) hemorrhagic complications (Global Use of Strategies to Open Occluded Arteries), 1 of which (0.6%) was intracranial. No significant differences in hemorrhagic complication rates (P = .3, P = 1.0, and P = .6, respectively) or general complication rates (Society of Interventional Radiology [SIR] minor, P = .2; SIR major, P = .7) were noted between the LMWH and heparin groups. Mean pulmonary arterial pressure for the entire cohort improved from 28.9 ± 7.6 mmHg to 20.4 ± 6.5 mmHg (P < .001), whereas the Miller score improved from 19.3 ± 4.6 to 7.3 ± 3.9 (P < .001). The average infusion duration was 26 ± 11.9 hours over 2.3 ± 0.6 total visits to the angiography lab, during which a mean of 27.85 ± 14.2 mg of tissue plasminogen activator were infused. CONCLUSIONS: Therapeutic anticoagulation during CDT for PE appears to be safe. The current study did not find a significant difference between LMWH and heparin infusion with respect to hemorrhagic and general complication rates.

Baseline hemoglobin and liver function predict tolerability and overall survival of patients receiving radioembolization for chemotherapy-refractory metastatic colorectal cancer.

BACKGROUND: Patients with liver metastatic colorectal cancer (mCRC) often benefit from receiving 90Y-microsphere radioembolization (RE) administered via the hepatic arteries. Prior to delivery of liver-directed radiation, standard laboratory tests may assist in improving outcome by identifying correctable pre-radiation abnormalities. METHODS: A database containing retrospective review of consecutively treated patients of mCRC from July 2002 to December 2011 at 11 US institutions was used. Data collected included background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90Y treatment, subsequent adverse events and survival. Kaplan-Meier estimates compared the survival of patients across lines of chemotherapy. The following values were obtained within 10 days prior to each RE treatment: haemoglobin (HGB), albumin, alkaline phosphatase (Alk phosph), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin and creatinine. Common Terminology Criteria Adverse Events (CTCAEs) 3.0 grade was assigned to each parameter and analysed for impact on survival by line of chemotherapy. Consensus Guidelines were used to categorize the parameter grades as either within or outside guidelines for treatment. RESULTS: A total of 606 patients (370 male; 236 female) were studied with a median follow-up was 8.5 mo. (IQR 4.3-15.6) after RE. Fewer than 11% of patients were treated outside recommended RE guidelines, with albumin being the most common, 10.5% grade 2 (<3-2.0 g/dL) at time of RE. All seven parameters showed statistically significant decreased median survivals with any grade >0 (P<0.001) across all lines of prior chemotherapy. Compared to grade 0, grade 2 albumin decreased overall survival 67%; for grade 2 total bilirubin a 63% drop occurred, and grade 1 HGB resulted in 66% lower median survival. CONCLUSIONS: Review of pre-RE laboratory parameters may aid in improving median survivals if correctable grade >0 values are addressed prior to radiation delivery. HGB <10 g/dL is a well-known negative factor in radiation response and is easily corrected. Improving other parameters is more challenging. These efforts are important in optimizing treatment response to liver radiotherapy.

Hepatopulmonary Shunting: A Prognostic Indicator of Survival in Patients with Metastatic Colorectal Adenocarcinoma Treated with 90Y Radioembolization.

Purpose To determine if high lung shunt fraction (LSF) is an independent prognostic indicator of poor survival in patients who undergo yttrium 90 radioembolization for unresectable liver-dominant metastatic colorectal cancer. Materials and Methods Retrospective data were analyzed from 606 patients (62% men; mean age, 62 years) who underwent radioembolization to treat liver metastases from colorectal adenocarcinoma between July 2002 and December 2011 at 11 U.S. centers. Institutional review board exemptions were granted prior to the collection of data at each site. Overall survival was estimated by using Kaplan-Meier survival and univariate Cox proportional hazards models to examine the effect of LSF on survival and to compare this to other potential prognostic indicators. Multivariate analysis was also performed to determine whether LSF is an independent risk factor for poor survival. Results LSF higher than 10% was predictive of significantly decreased survival (median, 6.9 months vs 10.0 months; hazard ratio, 1.60; P < .001) and demonstrated a mild but significant correlation to serum carcinoembryonic antigen levels and tumor-to-liver volume ratio (Pearson correlation coefficients, 0.105 and 0.113, respectively; P < .05). A progressive decrease in survival was observed as LSF increased from less than 5% to more than 20% (P < .05). LSF did not correlate with the presence of extrahepatic metastases or prior administration of bevacizumab. Conclusion Increased LSF is an independent prognostic indicator of worse survival in patients undergoing radioembolization for liver-dominant metastatic colorectal adenocarcinoma. High LSF correlates poorly to other potential markers of tumor size, such as tumor-to-liver volume ratio or serum carcinoembryonic antigen level, and does not correlate to the presence of extrahepatic metastases. © RSNA, 2016 Online supplemental material is available for this article.

Safety and Efficacy of Radioembolization in Elderly (≥ 70 Years) and Younger Patients With Unresectable Liver-Dominant Colorectal Cancer.

BACKGROUND: The effects of advancing age on clinical outcomes after radioembolization (RE) in patients with unresectable liver-dominant metastatic colorectal cancer (mCRC) are largely unknown. PATIENTS AND METHODS: This study was a retrospective analysis of 160 elderly (≥ 70 years) and 446 younger (< 70 years) consecutive patients from 11 US centers who received RE using ytrrium-90 ((90)Y) resin microspheres ((90)Y radioembolization [(90)Y-RE]) between July 2002 and December 2011. A further analysis was conducted in 98 very elderly patients (≥ 75 years). Statistical analyses of safety, tolerability, and overall survival were conducted. RESULTS: Mean ages (± standard deviation) in the younger (< 70 years), elderly (≥ 70 years), and very elderly (≥ 75 years) cohorts were 55.9 ± 9.4 years, 77.2 ± 4.8 years, and 80.2 ± 3.8 years, respectively. Overall survival was similar between elderly and younger patients: 9.3 months (95% confidence interval [CI], 8.0-12.1) and 9.7 months (95% CI, 9.0-11.4) (P = .335). There were no differences between cohorts for any grade adverse events (P = .433) or grade 3+ events (P = .482). Analysis of patients ≥ 75 years and < 75 years confirmed similar overall survival (median, 9.3 months vs. 9.6 months, respectively; P = .987) and grade 3+ events (P = .398) or any adverse event (P = .158) within 90 days of RE. CONCLUSION: For patients with unresectable liver-dominant mCRC who meet eligibility criteria for RE, (90)Y-RE microspheres appear to be effective and well-tolerated, regardless of age. Criteria for selecting patients for RE should not include age for exclusion from this potentially beneficial intervention.

Hepatic imaging response to radioembolization with yttrium-90-labeled resin microspheres for tumor progression during systemic chemotherapy in patients with colorectal liver metastases.

BACKGROUND: To assess response and the impact of imaging artifacts following radioembolization with yttrium-90-labeled resin microspheres ((90)Y-RE) based on the findings from a central independent review of patients with liver-dominant metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC who received (90)Y-RE (SIR-Spheres(®); Sirtex Medical, Sydney, Australia) at nine US institutions between July 2002 and December 2011 were included in the analysis. Tumor response was assessed at baseline and 3 months using either the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or 1.1. For each lesion, known artifacts affecting the interpretation of response (peri-tumoral edema and necrosis) were documented. Survivals (Kaplan-Meier analyses) were compared in responders [partial response (PR)] and non-responders [stable (SD) or progressive disease (PD)]. RESULTS: Overall, 195 patients (mean age 62 years) received (90)Y-RE after a median of 2 (range, 1-6) lines of prior chemotherapy. Using RECIST 1.0 and RECIST 1.1, 7.6% and 6.9% of patients were partial responders, 47.3% and 48.1% had SD, and 55.0% and 55.0% PD, respectively. RECIST 1.0 and RECIST 1.1 showed excellent agreement {Kappa =0.915 [95% confidence interval (CI): 0.856-0.975]}. Peri-tumoral edema was documented in 32.8%, necrosis in 48.1% and both in 57.3% of cases (using RECIST 1.0). Although baseline characteristics were similar in responders and non-responders (P>0.05), responders survived significantly longer in an analysis according to RECIST 1.0: PR median (95% CI) 25.2 (range, 9.2-49.4) months vs. SD 15.8 (range, 9.3-21.1) months vs. PD 7.1 (range, 6.0-9.5) months (P<0.0001). CONCLUSIONS: RECIST 1.0 and RECIST 1.1 imaging responses provide equivalent interpretations in the assessment of hepatic tumors following (90)Y-RE. Radiologic lesion responses at 3 months must be interpreted with caution due to the significant proportion of patients with peri-tumoral edema and necrosis, which may lead to an under-estimation of PR/SD. Nevertheless, 3-month radiologic responses were predictive of prolonged survival.

Multicenter evaluation of the safety and efficacy of radioembolization in patients with unresectable colorectal liver metastases selected as candidates for (90)Y resin microspheres.

BACKGROUND: Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) was an investigator-initiated case-control study to assess the experience of 11 US centers who treated liver-dominant metastases from colorectal cancer (mCRC) using radioembolization [selective internal radiation therapy (SIRT)] with yttrium-90-((90)Y)-labeled resin microspheres. METHODS: Data from 606 consecutive patients who received radioembolization between July 2002 and December 2011 were collected by an independent research organization. Adverse events (AEs) and survival were compared across lines of treatment using Fisher's exact test and Kaplan-Meier estimates, respectively. RESULTS: Patients received a median of 2 (range, 0-6) lines of prior chemotherapy; 35.1% had limited extrahepatic metastases. Median tumor-to-liver ratio and -activity administered at first procedure were 15% and 1.17 GBq, respectively. Hospital stay was <24 hours in 97.8% cases. Common grade ≥3 AEs over 184 days follow-up were: abdominal pain (6.1%), fatigue (5.5%), hyperbilirubinemia (5.4%), ascites (3.6%) and gastrointestinal ulceration (1.7%). There was no statistical difference in AEs across treatment lines (P>0.05). Median survivals [95% confidence interval (CI)] following radioembolization as a 2(nd)-line, 3(rd)-line, or 4(th)-plus line were 13.0 (range, 10.5-14.6), 9.0 (range, 7.8-11.0), and 8.1 (range, 6.4-9.3) months, respectively; and significantly prolonged in patients with ECOG 0 vs. ≥1 (P=0.009). Statistically significant independent variables for survival at radioembolization were: disease stage [extrahepatic metastases, extent of liver involvement (tumor-to-treated-liver ratio)], liver function (uncontrolled ascites, albumin, alkaline phosphatase, aspartate transaminase), leukocytes, and prior chemotherapy. CONCLUSIONS: Radioembolization appears to have a favorable risk/benefit profile, even among mCRC patients who had received ≥3 prior lines of chemotherapy.