Radioembolization for colorectal liver metastases

Journal of Gastrointestinal Oncology, 2017

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 90 Y-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: 90 Y-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 90 Y-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 90 Y-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 90 Y-RE. Overall, our updated analysis confirms that 90 Y-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.

American Journal of Clinical Oncology, 2012

Clinical decisions regarding the treatment of metastatic colorectal cancer require consideration of current and evolving modalities to best achieve prolonged patient survival. Clinical trials have established that for first-line treatment of patients with or without extrahepatic metastases, radioembolization augments the response produced by chemotherapy in patients with unresectable liver metastases. This includes progression-free and overall survivals that compare favorably with phase II to III data of current chemotherapy regimens. The increased response rate with radioembolization and first-line chemotherapy may improve the likelihood for potentially curative hepatic lesion resection or ablation. Application of an innovative multidisciplinary treatment approach that integrates radioembolization and local ablative therapy may enable the benefits of curative hepatic resection to be extended to a broader group of patients.

European Journal of Nuclear Medicine and Molecular Imaging, 2014

The aim of this study was to analyze the safety, treatment characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for unresectable colorectal carcinoma (CRC) liver metastases refractory to standard of care therapy. Methods A total of 214 patients with CRC metastases were treated with Y90 radioembolization over 12 years. Toxicity was assessed using National Cancer Institute common terminology criteria. Overall survival was analyzed from date of diagnosis of primary cancer, hepatic metastases and from the first Y90. Uni/multivariate analyses were performed. Substratification by era of chemotherapeutics was performed. Results Most patients were male (60 %) and <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3 lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11 %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP toxicities were observed in 5 % and 3 % of patients, respectively. Median overall survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary cancer, hepatic metastases and first Y90, respectively. Survival was significantly longer in patients: (1) who received ≤2 cytotoxic drugs (n=104) than those who received 3 (n=110) (15.2 vs. 7.5 months, p= 0.0001); and (2) who received no biologic agents (n=52) compared with those that did (n=162) (18.6 vs. 9.4 months, p=0.0001). Multivariate analyses identified ≤2 cytotoxic agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of extrahepatic disease and albumin >3 g/dL as independent predictors of survival. Conclusion In this largest metastatic CRC series published to date, Y90 radioembolization was found to be safe; survival varied by prior therapy. Further studies are required to further refine the role of Y90 in metastatic CRC.

Journal of Cancer Research and Clinical Oncology, 2014

ranged from 11 to 100 % (median 40.5 %). Most cases of acute toxicity were mild (Grade I or II) (median 39 %; range 7-100 %) which resolved without intervention. The number of previous lines of chemotherapy (≥3), poor radiological response to treatment, extra-hepatic disease and extensive liver disease (≥25 %) were the factors most commonly associated with poorer overall survival. Conclusion Y90 radioembolization is a safe and effective treatment of CRCLM in the salvage setting and should be more widely utilized.

Journal of Vascular and Interventional Radiology, 2011

Purpose: To report clinical experience with radioembolization (RE) plus systemic chemotherapy as a first-line treatment for liver metastases from colorectal cancer (CRC). Materials and Methods: Clinical outcomes were evaluated retrospectively among 19 patients with unresectable liver metastases from CRC who had a good performance status and a low burden of extrahepatic disease (EHD) and were eligible for RE. Most (74%) had disease confined to the liver. Concurrent treatment with 5-fluorourail/leucovorin (n ϭ 7) or 5-fluorourail/leucovorin/oxaliplatin (FOLFOX; n ϭ 12) was started 3-4 days before single treatment with RE. Results: Overall response rate according to the Response Evaluation Criteria in Solid Tumors was 84% (two complete responses and 14 partial responses). Median progression-free survival (PFS) time was 10.4 months and median overall survival (OS) time was 29.4 months. For patients with disease confined to the liver, PFS improved (10.7 mo vs 3.6 mo; P ϭ .09), with significant prolongation of OS (median, 37.8 mo vs 13.4 mo; P ϭ .03) compared with those who had EHD. Nine patients, including three long-term (Ͼ 3 y) survivors, remained alive after a median follow-up of 18.6 months. Serious treatment-related toxicities included febrile neutropenia with concurrent FOLFOX treatment, a perforated duodenal ulcer, and one death from hepatic toxicity. Conclusions: The present findings confirm the effectiveness of RE plus systemic chemotherapy for metastatic CRC. Patients with liver-confined disease derived the greatest benefit, with median survival times beyond 36 months. Larger datasets from ongoing phase III trials are needed to further define the safety and efficacy of RE in the first-line setting. ABBREVIATIONS CRC ϭ colorectal cancer, EHD ϭ extrahepatic disease, FOLFOX ϭ 5-fluorouracil/leucovorin/oxaliplatin, GDA ϭ gastroduodenal artery, OS ϭ overall survival, PFS ϭ progression-free survival, RE ϭ radioembolization, RECIST ϭ Response Evaluation Criteria in Solid Tumors, RGA ϭ right gastric artery From BioGrid Australia (S.K.,

Journal of Vascular and Interventional Radiology

To retrospectively evaluate the safety and survival of patients with chemotherapy-refractory liver metastases treated with yttrium-90 ( 90 Y) resin microspheres, and to compare survival in this patient group versus survival after standard/supportive care to assess whether radioembolization contributes to survival gains in the salvage setting.

European Journal of Cancer, 2013

To investigate the safety, response rate, progression-free and overall survival of patients with liver metastases treated with (90)Y (glass) radioembolisation in a prospective, multicenter phase II study. 151 patients with liver metastases (colorectal n=61, neuroendocrine n=43 and other tumour types n=47) refractory to standard of care therapies were enrolled in this prospective, multicenter, phase II study under an investigational device exemption. Clinical/laboratory/imaging follow-up were obtained at 30 days followed by 3-month intervals for 1 year and every 6 months thereafter. The primary end-point was progression-free survival (PFS); secondary end-points included safety, hepatic progression-free survival (HPFS), response rate and overall survival. Median age was 66 (range 25-88). Grade 3/4 adverse events included pain (12.8%), elevated alkaline phospatase (8.1%), hyperbilirubinemia (5.3%), lymphopaenia (4.1%), ascites (3.4%) and vomiting (3.4%). Treatment parameters including dose delivery were reproducible among centers. Disease control rates were 59%, 93% and 63% for colorectal, neuroendocrine and other primaries, respectively. Median PFS was 2.9 and 2.8 months for colorectal and other primaries, respectively. PFS was not achieved in the neuroendocrine group. Median survival from (90)Y treatment was 8.8 months for colorectal and 10.4 months for other primaries. Median survival for neuroendocrine patients has not been reached. Patients with liver metastases can be safely treated with (90)Y microspheres. This study is the first to demonstrate technical and dose reproducibility of (90)Y glass microspheres between centers in a prospective setting. Based on these promising data, three international, multicenter, randomised phase III studies in colorectal and hepatocellular carcinoma have been initiated.

American Journal of Clinical Oncology, 2014

Objectives: To assess patterns of failure and factors affecting recurrence patterns in colorectal cancer patients treated with 90 Y-labeled resin microspheres for metastatic liver disease. Methods: We retrospectively reviewed 30 colorectal patients treated with Yttrium-90 radioembolization and assessed follow-up computed tomography scans and positron emission tomography scans to determine disease outcomes. All patients were included in survival analysis. Twenty-six patients with hepatic metastases were assessed for patterns of failure after radioembolization treatment and grouped into 3 patterns: (1) hepatic; (2) extrahepatic; and (3) intrahepatic and extrahepatic. Results: The median overall survival and progression-free survival for all colorectal patients treated with radioembolization was 9.4 and 3.2 months, respectively. Overall survival and progression-free survival were not significantly different between patterns of failure (P = 0.43 and 0.26, respectively). Logistic regression analysis demonstrated a trend toward the predictive value of tumor volume in determining patterns of failure. Smaller tumor volumes had a higher predictive probability for extrahepatic failure than larger tumor volumes (P = 0.057). Tumor volumes <300 mL were predictive for extrahepatic failure patterns compared with hepatic recurrence (P = 0.046). Conclusions: Radioembolization with 90 Y-labeled resin microspheres continues to be an effective salvage treatment for colorectal liver metastases. Analysis of patterns of radiologic failure demonstrated that patients treated by radioembolization develop a greater proportion of extrahepatic failure. Tumor volumes >300 mL were predictive for hepatic recurrence, suggesting that increased dosing or retreatment of these lesions may lead to improved hepatic control of disease and better patient outcomes.

Current Colorectal Cancer Reports, 2009

Colorectal cancer remains a significant cause of morbidity and mortality. Treatment options and therapeutic interventions for patients who have disease progression despite treatment with systemic therapies have not been clearly established. However, yttrium-90 radioembolization may be useful as a minimally invasive liver-directed therapy. Although there are no large randomized controlled studies that specifically establish the role of radioembolization in this

Clinical Colorectal Cancer, 2015