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.].

Fast-Track Registration: A Way to Increase Efficiency in the IR Division.

PURPOSE: To evaluate changes in patient registration process at an academic 2-suite IR Division to determine if moving registration from the waiting room to the vascular holding area decreased amount of time patients spent in the Radiology Department and improved start times. MATERIALS AND METHODS: A data collection sheet was created by evaluating patient-related processes; event timestamps were recorded on the sheet. The control group consisted of 33 patients who registered using the traditional process. The fast-track group consisted of 29 patients who bypassed the traditional registration procedure and were registered by nurses in the vascular holding area. RESULTS: Total time between control and fast-track groups significantly decreased from an average time of 215 minutes to 178 minutes (P = .020). The average start time improved significantly from an average of 63 minutes after scheduled procedure start time for the control group to 33 minutes after the scheduled procedure start time for the fast-track group (P = .009). Start time (P = .022), time spent in recovery area (P = .006), and total time, after correcting for differences in laboratory test turnaround time, (P = .010) decreased in variability after implementation of fast-track registration. CONCLUSIONS: Implementing fast-track registration for outpatient subcutaneous port placement in the IR Division improved start times and decreased total time patients spent in the hospital, while also reducing variability in the process.

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.

Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review.

Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source, thus limiting its effects to the site of delivery. However, the off-target diversion of yttrium-90 microspheres to tissues other than the tumor may lead to complications. The most prominent of these complications include radiation gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radioembolization-induced liver disease, which may occur despite careful pretreatment planning. Thus, selective internal radiation therapy demands an expert multidisciplinary team approach in order to provide comprehensive care for patients. This review provides recommendations to multidisciplinary teams on the optimal medical processes in order to ensure the safe delivery of selective internal radiation therapy. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis, and management of potential radiation injury to the liver and to other organs. (Hepatology 2017;66:969-982).

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.

The development, commercialization, and clinical context of yttrium-90 radiolabeled resin and glass microspheres.

Selective internal radiation therapy has emerged as a well-accepted therapeutic for primary and metastatic hepatic malignancies. This therapeutic modality requires the combined efforts of multiple medical disciplines to ensure the safe delivery of yttrium-90 (90Y)-labeled microspheres. The development of this therapy followed decades of clinical research involving tumor vascularity and microsphere development. Today, it is essential that treating physicians have a thorough understanding of hepatic tumor vascularity and 90Y microsphere characteristics before undertaking this complex intervention. This review explores the contributions of early investigators of this therapy, as well as the development, US Food and Drug Administration approval, manufacturing process, and attributes of the 2 commercially available 90Y radiolabeled microsphere device to clarify the key physical differences between the products.

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.

A novel biliary stent loaded with (125)I seeds in patients with malignant biliary obstruction: preliminary results versus a conventional biliary stent.

BACKGROUND & AIMS: Stenting is a palliative therapy method for relieving malignant biliary obstruction. The aim of this study was to evaluate the safety and effectiveness of an irradiation stent compared to a conventional biliary stent in patients with biliary obstruction caused by both primary and metastatic adenocarcinomas. METHODS: Participants were randomly assigned to receive treatment with a biliary irradiation stent (irradiation stent group) or a conventional biliary stent (control group). After stent implantation, the outcomes were measured in terms of relief of obstructive jaundice, survival time, complications related to the procedure. A p value of less than 0.05 indicated a significant difference. RESULTS: The stents were successfully placed in all the 23 patients. The obstructive jaundice was relieved in all patients except three in the control group. The median and mean overall survivals in the irradiation stent group were higher than those in the control group (7.40 months versus 2.50 months, 8.03 months versus 3.36 months, p=0.006). The patients with stent patent at 3, 6, and 12 months in the irradiation stent group were 11 (91.7%), 7 (58.3%), and 1 (8.3%), respectively. While in the control group, 4 (36.4%), 1 (9.1%), and 0 (0%), respectively. There were no significant differences in the complications related to stent insertion between the two groups. CONCLUSIONS: This interim analysis shows that treatment with the biliary intraluminal irradiation stent in patients with biliary obstruction caused by adenocarcinomas appears safe and technically feasible, has benefits in relieving jaundice, and seems to extend survival when compared to a conventional biliary stent.

Use of yttrium-90 microspheres in the treatment of unresectable hepatic metastases from breast cancer.

PURPOSE: Therapy for patients with unresectable liver metastases from breast cancer that were refractory to multiple treatment regimens was performed using radioactive microspheres. High doses of radiation were delivered to tumors from these permanently implanted yttrium-90 ((90)Y) microspheres, delivered through the hepatic arterial vessels. METHODS AND MATERIALS: Women from three institutions were selected for treatment, after screening that demonstrated vascular access to all tumors and after imaging confirmed that microspheres would be implanted only in the liver tumors. All patients were followed with laboratory and imaging studies at regular intervals until death. Toxicities, both acute and late were recorded, and actuarial survival determined. RESULTS: A total of 44 women were treated from April 2002 to April 2005. Median follow-up of these women was 14 months (1-42 months). No treatment-related procedure deaths or radiation related veno-occlusive liver failures were found. Computed tomographic imaging partial response was 47% and positron emission tomographic response 95%. CONCLUSION: In this group of heavily pretreated patients, radioactive microspheres produced an encouraging median survival, with acceptable toxicity and a significant objective response rate, suggesting that further investigation of this approach is warranted.

Gastrointestinal complications associated with hepatic arterial Yttrium-90 microsphere therapy.

Hepatic arterial therapy with yttrium-90 microspheres exploits the avenue provided by the neoplastic microvasculature to deliver high-energy, low-penetrating therapeutic doses of radiation. Variant hepatic arterial anatomy, collateral vessels, and changes in flow dynamics during treatment can affect particle dispersion and lead to nontarget particle distribution and subsequent gastrointestinal morbidity. Awareness of these variances and techniques to prevent gastrointestinal tract microsphere delivery is essential in mitigating this serious complication. Our aim is to increase the understanding of the role of various imaging and preventative techniques in minimizing this undesired effect.

Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications.

Management of hepatic malignancies is a ubiquitous medical problem. Surgical resection of primary or metastatic liver cancer, with or without adjuvant chemotherapy, is the most effective method for enhancing survival; however, hepatic malignancies in the vast majority of patients are unresectable both at initial manifestation and at recurrence. In these patients, palliative cytoreductive therapies may help to retard tumor progression and therefore favorably alter the course of the disease. Since hepatic neoplasms are principally supplied by the hepatic artery, various arterially delivered cytotoxic agents have been developed to achieve these objectives. Recently, the Food and Drug Administration approved the transarterial administration of yttrium-90 microspheres for liver-directed therapy. Effective use of these devices requires knowledge of the accumulated clinical experience and a dedicated multidisciplinary effort to ensure optimal outcomes and avoid therapy-specific life-threatening complications.

The expanding role of interventional radiology in the supportive care of the oncology patient: from diagnosis to therapy.

Interventional radiology (IR) plays an increasing role in the supportive care of the cancer patient from the placement of catheters to treating the offending tumor via image-guided methods. These methods entail the use of both local and regional means, with thermal ablative technology comprising the former and intra-arterial embolization with radioactive particles the latter. Direct placement of the radiofrequency or cryotherapy probes into tumors that are accessible using computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI) guidance provides reliable symptomatic relief of single or multiple tumors in liver, kidney, lung, bone, or soft tissue. Combined with systemic chemotherapy, these techniques increase patient survival. Intra-arterial delivery of radioactive particles to unresectable tumors both provides symptomatic relief and extends survival when combined with current systemic chemotherapy. These new approaches allow IR to provide crucial therapy for cancer patients.