Baseline modern medical management in the BEST-CLI trial.

OBJECTIVES: The use of optimal medical therapy (OMT) in patients with chronic limb-threatening ischemia (CLTI) has not been well-studied. The Best Endovascular vs Best Surgical Therapy in Patients with CLTI study (BEST-CLI) is a multicenter, randomized, controlled trial sponsored by the National Institutes of Health comparing revascularization strategies in patients with CLTI. We evaluated the use of guideline-based OMT among patients with CLTI at the time of their enrollment into the trial. METHODS: A multidisciplinary committee defined OMT criteria related to blood pressure and diabetic management, lipid-lowering and antiplatelet medication use, and smoking status for patients enrolled in BEST-CLI. Status reports indicating adherence to OMT were provided to participating sites at regular intervals. Baseline demographic characteristics, comorbid medical conditions, and use of OMT at trial entry were evaluated for all randomized patients. A linear regression model was used to identify the relationship of predictors to the use of OMT. RESULTS: At the time of randomization (n = 1830 total enrolled), 87% of patients in BEST-CLI had hypertension, 69% had diabetes, 73% had hyperlipidemia, and 35% were currently smoking. Adherence to four OMT components (controlled blood pressure, not currently smoking, use of one lipid-lowering medication, and use of an antiplatelet agent) was modest. Only 25% of patients met all four OMT criteria; 38% met three, 24% met two, 11% met only one, and 2% met none. Age ≥80 years, coronary artery disease, diabetes, and Hispanic ethnicity were positively associated, whereas Black race was negatively associated, with the use of OMT. CONCLUSIONS: A significant proportion of patients in BEST-CLI did not meet OMT guideline-based recommendations at time of entry. These data suggest a persistent major gap in the medical management of patients with advanced peripheral atherosclerosis and CLTI. Changes in OMT adherence over the course of the trial and their impact on clinical outcomes and quality of life will be assessed in future analyses.

Erratum to updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

[This corrects the article DOI: 10.21037/jgo.2017.03.10.].

Updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

BACKGROUND: The Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) study was a retrospective analysis of 606 patients with unresectable colorectal liver metastases treated with radioembolization (RE) using 90Y-labeled resin microspheres. The first analysis of this study was completed with a last patient follow-up of 77.7 months. We now provide an updated survival analysis through September 15, 2016, with a last patient follow-up of 125 months. METHODS: 90Y-RE was considered for patients with advanced liver-only or liver-dominant metastatic colorectal cancer which was deemed not suitable for surgery, ablation, or systemic therapy, and which had progressed or become refractory to at least one line of systemic therapy. All patients with a diagnosis of metastatic colorectal cancer who had received at least 1 RE treatment and 1 follow-up visit were included in the analysis. Patients were treated between July 2002 and December 2011 at one of 11 U.S. tertiary care centers. Data were collected at baseline, on the day of the first 90Y-RE treatment (day 0), and at all subsequent visits or until death. Patient medical charts and/or public records were accessed to obtain dates of death. RESULTS: Dates of death were obtained for 574 out of a total of 606 patients, and overall survival (OS) data analyzed. Updated median OS was 10.0 months (95% CI: 9.2-11.8 months) at a median follow-up of 9.5 months versus the originally reported median OS of 9.6 months (95% CI: 9.0-11.1 months) at a follow-up of 8.6 months in the first MORE analysis. Patients received a median (range) of 2 (0 to 6) lines of chemotherapy. Baseline characteristics and factors significantly associated with patient survival (P<0.01) are consistent with those reported in the first safety analysis of the MORE study. These factors include poor ECOG performance status, markers of advanced disease such as increased extent of tumor-to-target liver involvement, poor baseline liver function, pre-treatment anemia, lung shunt fraction, and number of lines of prior chemotherapy. Patient age did not significantly affect survival outcomes. CONCLUSIONS: Long-term follow-up confirms that 90Y-RE treatment offers favorable survival benefits for patients with unresectable metastatic colorectal cancer, even among patients who received 3 or more prior lines of chemotherapy. Our analysis also supports earlier reported prognostic factors for survival after 90Y-RE. Overall, our updated analysis confirms that 90Y-RE treatment provided a meaningful response and survival advantage for MORE patients across all ages and across diverse community and academic centers in the U.S.

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.

Technical success and safety of retrieval of the G2 filter in a prospective, multicenter study.

PURPOSE: To assess the technical success and safety for retrieval of the G2 filter. MATERIALS AND METHODS: The authors performed a prospective, multicenter study of 100 patients with temporary indication for caval interruption. Patients were enrolled consecutively between December 2005 and July 2006. There were 67 men and 33 women with a mean age of 52.1 years (range, 19-82 years). Indications for filter placement were trauma (n = 56), perioperative risk (n = 16), and medical indications (n = 28). Forty-two patients had venous thromboembolism at filter placement. Fifty-eight filters were placed prophylactically. RESULTS: Retrieval was attempted in 61 patients. Fifty-eight of the 61 filters (95%) were successfully retrieved after a mean dwell time of 140 days (range, 5-300 days). In all failed retrievals, the filter tip was against the caval wall. There was no difference in dwell times between successful and unsuccessful retrievals. Although there were no cases of cranial migration, caudal migrations were observed in 12% of cases (10 of 85 patients with a complete data set). Other device-related complications included filter fracture (1/85, 1.2%), filter tilt of more than 15 degrees (15/85, 18%), and leg penetration (16/61, 26%). The recurrent pulmonary embolism (PE) rate was 2%, with no PE in the 30-day period after filter retrieval. CONCLUSIONS: Retrieval of the Recovery G2 filter was safe and successful in most patients. Caudal migration was observed as an unexpected phenomenon.

Special communication: mandate for creation of a national peripheral arterial disease public awareness program: an opportunity to improve cardiovascular health.

BACKGROUND: There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect. FORMAT: To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1) provides the rationale for creation of a national PAD public education program; (2) reviews the development and success of national hypertension, hypercholesterolemia, and Women's Heart Health public education programs as models of educational efficacy; (3) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4) provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5) outlines the "next steps" required to accomplish these goals. OUTCOME: This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort. CONCLUSION: Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education messages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States.

Mandate for creation of a national peripheral arterial disease public awareness program: an opportunity to improve cardiovascular health.

BACKGROUND: There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect. FORMAT: To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1) provides the rationale for creation of a national PAD public education program; (2) reviews the development and success of national hypertension, hypercholesterolemia, and Women's Heart Health public education programs as models of educational efficacy; (3) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4) provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5) outlines the "next steps" required to accomplish these goals. OUTCOME: This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort. CONCLUSION: Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education messages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States.

Mandate for creation of a national peripheral arterial disease public awareness program: an opportunity to improve cardiovascular health.

BACKGROUND: There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect. FORMAT: To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1). provides the rationale for creation of a national PAD public education program; (2). reviews the development and success of national hypertension, hypercholesterolemia, and Women's Heart Health public education programs as models of educational efficacy; (3). elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4). provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5). outlines the "next steps" required to accomplish these goals. OUTCOME: This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort. CONCLUSION: Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education massages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States.