Article

Radioembolization for Metastatic Colorectal Cancer

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The liver is the most common site of metastatic disease in colorectal cancer, and, in the setting of liver-dominant disease, a chief contributor to mortality. Chemotherapy is the backbone of treatment for metastatic colorectal cancer; however, the duration of response is limited and resistance to therapy inevitably develops. Radioembolization represents a targeted treatment to the liver which has been studied in first-line, second-line, and in salvage treatment. Therapeutic rationale, outcomes, and prognostic indicators are presented in this systematic review article.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
Background: Colorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment. Objective: The objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 (90Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy. Methods: EPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90%, and the power to detect the target difference in each end point alone is >80%. Results: Patient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes. Conclusions: The EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver. Trial registration: ClinicalTrials.gov NCT01483027; https://clinicaltrials.gov/ct2/show/NCT01483027 (Archived by WebCite at http://www.webcitation.org/734A6PAYW). International registered report identifier (irrid): RR1-10.2196/11545.
Article
Full-text available
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.
Article
Full-text available
Background: Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival. Methods: FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m(2) oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m(2) bolus fluorouracil followed by a 2400 mg/m(2) continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m(2) oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m(2) bolus fluorouracil followed by a 2400 mg/m(2) continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global). Findings: Between Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6-58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90-1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0-24·5) compared with 23·3 months (21·8-24·7) in the FOLFOX alone group. In the safety population containing patients who received at least one dose of study treatment, as treated, the most common grade 3-4 adverse event was neutropenia (137 [24%] of 571 patients receiving FOLFOX alone vs 186 (37%) of 507 patients receiving FOLFOX plus SIRT). Serious adverse events of any grade occurred in 244 (43%) of 571 patients receiving FOLFOX alone and 274 (54%) of 507 patients receiving FOLFOX plus SIRT. 10 patients in the FOLFOX plus SIRT group and 11 patients in the FOLFOX alone group died due to an adverse event; eight treatment-related deaths occurred in the FOLFOX plus SIRT group and three treatment-related deaths occurred in the FOLFOX alone group. Interpretation: Addition of SIRT to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of SIRT in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of SIRT in metastatic colorectal cancer, careful patient selection and studies investigating the role of SIRT as consolidation therapy after chemotherapy are needed. Funding: Bobby Moore Fund of Cancer Research UK, Sirtex Medical.
Article
Full-text available
Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis.
Article
Full-text available
Colorectal cancer had a low incidence several decades ago. However, it has become a predominant cancer and now accounts for approximately 10% of cancer-related mortality in western countries. The ‘rise’ of colorectal cancer in developed countries can be attributed to the increasingly ageing population, unfavourable modern dietary habits and an increase in risk factors such as smoking, low physical exercise and obesity. New treatments for primary and metastatic colorectal cancer have emerged, providing additional options for patients; these treatments include laparoscopic surgery for primary disease, more-aggressive resection of metastatic disease (such as liver and pulmonary metastases), radiotherapy for rectal cancer and neoadjuvant and palliative chemotherapies. However, these new treatment options have had limited impact on cure rates and long-term survival. For these reasons, and the recognition that colorectal cancer is long preceded by a polypoid precursor, screening programmes have gained momentum. This Primer provides an overview of the current state of art knowledge on the epidemiology and mechanisms of colorectal cancer, as well as on diagnosis and treatment.
Article
Full-text available
Background: Hepatic metastases of colorectal carcinoma are a leading cause of cancer-related mortality. The vast majority of colorectal liver metastases become refractory to chemotherapy and biologic agents, at which point the median overall survival declines to 4-5 months. Radioembolization with yttrium-90 has been used in the salvage setting with favorable outcomes. This study reports the survival and safety outcomes of 531 patients treated with glass-based (90)Y microspheres at eight institutions, making it the largest (90)Y study for patients with Patients and METHODS: Data were retrospectively compiled from eight institutions for all (90)Y glass microsphere treatments for colorectal liver metastases. Exposure to chemotherapeutic/biologic agents, prior liver therapies, biochemical parameters prior to and following treatment, radiation dosimetry and complications were recorded. Uni- and multivariate analyses for predictors of survival were performed. Survival outcomes, clinical/biochemical adverse events RESULTS: 531 patients received (90)Y radioembolization for colorectal liver metastases. The most common clinical adverse events were fatigue (55%), abdominal pain (34%) and nausea (19%). Grade 3 or 4 hyperbilirubinemia occurred in 13% of patients at anytime. Median overall survival from first Y90 treatment was 10.6 months (95% CI 8.8-12.4). Performance status, tumor burden ≤25%, no extra-hepatic metastases, albumin >3 g/dL and having received ≤2 chemotherapeutic agents independently predicted better survival outcomes. Conclusion: Multi-institutional review of a large cohort of patients with colorectal liver metastases treated with (90)Y radioembolization using glass microspheres demonstrates promising survival outcomes with low toxicities and side-effects that are reproducible and consistent with prior reports of radioembolization.
Article
Full-text available
To determine in a retrospective study the potential benefit on survival outcomes of radioembolization using yttrium-90 ((90)Y) resin microspheres in a cohort of patients presenting with chemotherapy-refractory liver metastases, primarily from colorectal cancer (CRC). Over 3 years, 249 patients were referred to the authors' center to determine suitability for radioembolization as treatment for hepatic metastases. All patients were defined as salvage, having failed first-line and second-line chemotherapies. These patients were divided into group 1 (CRC) and group 2 (all other cancers, eg, breast, neuroendocrine) and assessed for overall survival (OS) as a whole and according to group. Using (90)Y resin microspheres, 208 patients were treated, undergoing 223 radioembolization treatments. The median OS was 8.3 months for the whole cohort, 7.9 months for group 1, and 8.7 months for group 2. At the 3-month follow-up, there was an overall adverse event rate of 9%. At the end of the data collection period, 62 patients were still alive. Radioembolization shows promise as an effective and safe treatment for patients with chemotherapy-refractory hepatic metastases providing an extension to survival in the salvage setting.
Article
Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population‐based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening‐aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non‐Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steepest among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline‐recommended screening and high‐quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle‐aged adults.
Chapter
Radioembolization is a treatment option for select patients with hepatic metastases from colorectal cancer in the salvage setting. These patients with liver-dominant or liver-only metastatic disease who have failed standard-of-care first- and second-line systemic therapies have clear and consistent objective response rates and survival outcomes from this outpatient procedure. While there is interest in combining systemic and locoregional therapies to benefit from chemoradiation principles as well as treat patients earlier in their disease course, current evidence to support this practice is lacking. Prospective randomized trials employing radioembolization in combination with first-line chemotherapy have been negative to date. Most recently, a clinical trial of second-line chemotherapy with/without radioembolization has completed enrollment in October 2018, and the study results are yet to be published.
Article
Liver metastases are a major cause of death from colorectal cancer. Intraarterial therapy options for colorectal liver metastases include chemoinfusion via a hepatic arterial pump or port, irinotecan-loaded drug-eluting beads, and radioembolization using ⁹⁰Y microspheres. Intraarterial therapy allows the delivery of a high dose of chemotherapy or radiation into liver tumors while minimizing the impact on liver parenchyma and avoiding systemic effects. Specificity in intraarterial therapy can be achieved both through preferential arterial flow to the tumor and through selective catheter positioning. In this review, we discuss indications, contraindications, preprocedure evaluation, activity prescription, follow-up, outcomes, and complications of radioembolization of colorectal liver metastases. Methods for preventing off-target embolization, increasing the specificity of microsphere delivery, and reducing the lung-shunt fraction are discussed. There are 2 types of ⁹⁰Y microspheres: resin and glass. Because glass microspheres have a higher activity per particle, they can deliver a particular radiation dose with fewer particles, likely reducing embolic effects. Glass microspheres thus may be more suitable when early stasis or reflux is a concern, in the setting of hepatocellular carcinoma with portal vein invasion, and for radiation segmentectomy. Because resin microspheres have a lower activity per particle, more particles are needed to deliver a particular radiation dose. Resin microspheres thus may be preferable for larger tumors and those with high arterial flow. In addition, resin microspheres have been approved by the U.S. Food and Drug Administration for colorectal liver metastases, whereas institutional review board approval is required before glass microspheres can be used under a compassionate-use or research protocol. Finally, radiation segmentectomy involves delivering a calculated lobar activity of ⁹⁰Y microspheres selectively to treat a tumor involving 1 or 2 liver segments. This technique administers a very high radiation dose and effectively causes the ablation of tumors that are too large or are in a location considered unsafe for thermal ablation. The selective delivery spares surrounding normal liver, reducing the risk of liver failure. COPYRIGHT © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
Article
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.
Article
Objectives Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC). Methods We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months. ResultsSurvival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure. Conclusions After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated. Key Points• After multiple chemotherapies, many patients are still eligible for radioembolization (RE).• RE can achieve meaningful survival in patients with chemorefractory liver-predominant metastatic colorectal cancer (mCRC).• Tumour responsiveness to prior systemic treatments is a significant determinant of overall survival (OS) after RE.• Radioembolization in patients with a good performance status is generally well tolerated.
Article
Purpose: SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer. Patients and methods: Chemotherapy-naïve patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm. Results: Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267). Median PFS at any site was 10.2 v 10.7 months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95% CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4% in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8% v 78.7% in control v SIRT; P = .042). Grade ≥ 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT. Conclusion: The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liver-only metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies.
Article
The liver is the most common site for colorectal cancer (CRC) metastases. Radioembolization with yttrium-90 (Y90) represents an alternative approach in the management of unresectable hepatic colorectal metastases. The objective of this study was to evaluate outcomes after treatment with Y90. A retrospective review of patients undergoing Y90 glass microsphere treatment for metastatic CRC from 2009 to 2013 was conducted. Multivariable analysis (MVA) of factors related to overall survival (OS) was performed using the Cox proportional hazard and OS estimates were calculated using the Kaplan-Meier method. We identified 68 patients. Median and 2-year OS were 11.6 months and 34%. For patients with ≤ 25% hepatic burden of disease (HBD) and 1 chemotherapy regimen, 2-year OS was 63%. Median and 2-year OS for patients with ≤ 25% versus > 25% HBD were 19.6 months and 42% versus 3.4 months and 0% (P < .0001). Univariate analysis revealed that higher HBD, ≥ 3 lines of chemotherapy received, and higher carcinoembryonic antigen (CEA) were found to be significant predictors of worse OS. MVA revealed age, > 25% HBD, ≥ 3 lines of chemotherapy, and higher CEA were independently prognostic for increased mortality, and resected status of the primary tumor was associated with decreased mortality. The presence of extrahepatic metastases was not prognostic. Toxicities were mild and only 5 patients experienced Grade 3/4 biochemical toxicity. Yttrium-90 was associated with acceptable OS with minimal morbidity in this series. Minimal exposure to chemotherapy and low HBD were found to be associated with better OS, however, even patients with chemotherapy-refractory disease received a benefit from treatment. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
Purpose:: To report safety and survival outcomes of Yttrium-90 (Y-90) radioembolization when used as salvage therapy for chemotherapy-resistant liver metastases from colorectal cancer. Methods:: In this IRB-approved retrospective study, 45 patients with hepatic metastases from colorectal cancer underwent Y-90 radioembolization after failure of systemic chemotherapy. Toxicities were assessed as per NCI-CTCAE and response based on RECIST and PET. Kaplan-Meier survival analysis was performed to calculate median survival, prognostic factors on univariate analysis, and Cox regression analysis for independent predictors of survival. Results:: Y-90 radioembolization was technically successful in all (100%). Twenty-three patients (51%) had no toxicities, whereas 6 patients (13%) had grade 3 toxicities, and no patients had grade 4 toxicity. Two patients died within 30 days of treatment from renal failure unrelated to the procedure. Per RECIST, 1 patient (2%) had partial response, 34 (71%) had stable disease, and 6 (13%) had progressive disease. PET response was seen in 46% of patients with 2 patients (4%) demonstrating complete and 22 (42%) demonstrating partial metabolic response. The median survival was 186 days (95% CI, 149-277 d). Response on PET was the only independent predictor of superior overall survival. Patients who had response on PET following Y-90 therapy had a median overall survival of 317 days (10.6 mo) (95% CI, 193-564 d), whereas patients with no response on PET had a median overall survival of 163 days (5.4 mo) (95% CI, 64-283 d). Conclusions:: Y-90 radioembolization as a salvage therapy for chemotherapy-resistant hepatic metastases from colon cancer was safe and resulted in disease stability. Response on PET was an independent predictor of superior overall survival.
Article
Surgically directed therapy for liver metastases from colorectal cancer (CRC) has received substantial attention in the literature as a major focus of treatment for metastatic CRC. It is presumed, but not proven, that liver metastases are a major threat to life. This study examined the course of a cohort of consecutive patients who died with CRC to determine the role played by the presence of liver metastases. This is single-institution retrospective observational study involved all patients who died of CRC. Records were examined and imaging studies reviewed to determine the extent of liver and extrahepatic metastases in these patients. Overall survival in patients with and without liver metastases and those in whom liver metastases were thought to contribute to death was determined. After patient exclusions, the study population totaled 121 patients. There were 75 patients (62 %) with liver metastases at death. In 40 of 75 (53 %) patients, the liver metastases contributed to the patients' death. In 46 of 121 patients (38 %), metastatic disease did not include liver metastases. Overall survival in patients with and without liver metastases (median survival 12 vs. 8.5 months, p = 0.089) and in those whose liver metastases did or did not contribute to death (median survival 11.5 vs. 14 months, p = 0.361) was not significant. The presence of liver metastases seemed to contribute to death in approximately half of the study patients, although there did not appear to be a survival disadvantage in these patients.
Article
To present data for radioembolization with yttrium-90 ((90)Y) resin microspheres in patients with colorectal cancer liver metastases in whom currently available therapies had failed. Retrospective review was conducted of case files of patients with colorectal cancer liver metastases in whom chemotherapy had failed, prompting hepatic (90)Y radioembolization administered as a single-session, whole-liver treatment. Imaging and laboratory follow-up results were available for 36 patients. Response and toxicity were assessed by computed tomography/magnetic resonance imaging with the Response Evaluation Criteria in Solid Tumors and the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Forty-one patients (mean age, 61 years; 30 men) received hepatic (90)Y radioembolization with resin microspheres (mean activity, 1.9 GBq). At a median interval of 2.9 months after radioembolization, partial response, stable disease, and progressive disease were demonstrated in seven, 25, and four patients, respectively. Median overall survival was 10.5 months, with improved survival for patients with a decrease in carcinoembryonic antigen level (19.1 months vs 5.4 months) and imaging response (29.3 months vs 4.3 months; P = .0001). Except for one instance of treatment-associated cholecystitis (grade 4 toxicity) and two gastric ulcers (grade 2 toxicity), no severe toxicities were observed. Hepatic (90)Y radioembolization can be performed with manageable toxicity in patients with colorectal cancer liver metastases whose disease is refractory to chemotherapy. The antitumoral effect is supported by imaging and tumor marker responses. Further investigation is warranted to determine the optimal use of this emerging therapeutic modality.
Article
To review the evidence about the efficacy and utility of radiofrequency ablation (RFA) for hepatic metastases from colorectal cancer (CRHM). The American Society of Clinical Oncology (ASCO) convened a panel to conduct and analyze a comprehensive systematic review of the RFA literature from Medline and the Cochrane Collaboration Library. Because data were considered insufficient to form the basis of a practice guideline, ASCO has instead published a clinical evidence review. The evidence is from single-arm, retrospective, and prospective trials. No randomized controlled trials have been included. The following three clinical issues were considered by the panel: the efficacy of surgical hepatic resection versus RFA for resectable tumors; the utility of RFA for unresectable tumors; and RFA approaches (open, laparoscopic, or percutaneous). Evidence suggests that hepatic resection improves overall survival (OS), particularly for patients with resectable tumors without extrahepatic disease. Careful patient and tumor selection is discussed at length in the literature. RFA investigators report a wide variability in the 5-year survival rate (14% to 55%) and local tumor recurrence rate (3.6% to 60%). The reported mortality rate was low (0% to 2%), and the major complications rate was commonly reported to be between 6% and 9%. RFA is currently performed with all three approaches. There is a compelling need for more research to determine the efficacy and utility of RFA to increase local recurrence-free, progression-free, and disease-free survival as well as OS for patients with CRHM. Clinical trials have established that hepatic resection can improve OS for patients with resectable CRHM.
Article
The purpose of this study was to evaluate the effectiveness of colorectal cancer (CRC) liver metastasis radioembolization with yttrium-90 (Y90), assessing toxicity and survival rates in patients with no response to chemotherapy through our 3-year experience. From February 2005 to January 2008, we treated 41 patients affected by CRC from a cohort of selective internal radiation therapy patients treated at our institution. All patients examined showed disease progression and arrived for our observation with an abdominal CT, a body PET, and a hepatic angiography followed by gastroduodenal artery coiling previously performed by us. We excluded patients with a bilirubin level>1.8 mg/dl and pulmonary shunt>20% but not patients with minor extrahepatic metastases. On treatment day, under fluoroscopic guidance, we implanted a dose of Y90 microspheres calculated on the basis of liver tumoral involvement and the body surface area formula. All patients were discharged the day after treatment. We obtained, according to Response Evaluation Criteria on Solid Tumors, a complete response in 2 patients, a partial response in 17 patients, stable disease in 14 patients, and progressive disease in 8 patients. In all cases, we obtained a carcinoembryonic antigen level decrease, especially in the week 8 evaluation. Technical success rate was 98% and technical effectiveness estimated at 3 months after treatment was 80.5%. Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, two grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated by Kaplan-Meier analysis were 354 and 279 days, respectively. In conclusion, according to our 3-year experience, Y90 SIR-Spheres radioembolization is a feasible and safe method to treat CRC liver metastases, with an acceptable level of complications and a good response rate.
Article
: The objective of the current study was to determine the safety and efficacy of Yttrium-90 (Y90) microsphere treatment in patients with liver-dominant colorectal metastases. : Seventy-two patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 120 Gray (Gy). Safety and toxicity were assessed using version 3 of the National Cancer Institute Common Terminology Criteria. Response was assessed by anatomic imaging and positron emission tomography (PET). Survival from the diagnosis of hepatic metastases and first treatment were estimated using the Kaplan-Meier method. Substratification analyses were performed. : The median dose delivered was 118 Gy. Treatment-related toxicities included fatigue (61%), nausea (21%), and abdominal pain (25%). Grade 3 and 4 bilirubin toxicities were observed in 9 of 72 patients (12.6%). The tumor response rate was 40.3%. The median time to hepatic progression was 15.4 months, and the median response duration was 15 months. The PET response rate was 77%. Overall survival from the first Y90 treatment was 14.5 months. Tumor replacement (< or =25% vs >25%) was associated with significantly greater median survival (18.7 months vs 5.2 months). The presence of extrahepatic disease was associated negatively with overall survival (7.9 months vs 21 months). Overall survival from the date of initial hepatic metastases was 34.6 months. A subset analysis of patients who had an Eastern Cooperative Oncology Group performance status of 0 demonstrated a median survival of 42.8 months and 23.5 months from the time of hepatic metastases and Y90 treatment, respectively. : Y90 liver therapy appears to provide sustained disease stabilization with acceptable toxicity. Asymptomatic patients with preserved liver function at the time of Y90 appeared to benefit most from treatment. Cancer 2009. (c) 2009 American Cancer Society.
Article
A retrospective analysis of 113 patients with liver metastases from primary colorectal cancer was performed. Survival was related to the extent of liver involvement with tumour. Patients with widespread liver metastases have a poor prognosis whereas patients with solitary metastases or metastases localized to a single liver lobe have a relatively better prognosis. This is an important consideration in the management of these patients and in assessing the results of various forms of treatment for liver metastases.
Article
One hundred fifty-five patients, laparotomized because of colorectal cancer, were retrospectively evaluated with special attention given to the natural course of untreated synchronous liver metastases. The median survival time for patients with synchronous liver metastases was 4.5 months. The survival time was mainly influenced by the extent of tumor involvement in the liver. Patients with elevated levels of serum-alkaline phosphatase at the time of operation had a significantly shorter survival time than those with normal values. Serum alkaline phosphatase levels are a good indication of prognosis. The incidence of synchronous liver metastases was 16 percent. This low rate is partly explained by the development of metachronous liver metastases in five patients within 1 year. Comparison with previous reports, often more than 10 years old, reveals that the poor prognosis of patients with untreated liver metastases from colorectal cancer has remained unchanged.
Article
The purpose of this phase II study was to determine the safety and efficacy of TheraSphere treatment (90Y microspheres) in patients with liver-dominant colorectal metastases in whom standard therapies had failed or were judged to be inappropriate. Twenty-seven patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 135-150 Gy. Safety and toxicity were assessed according to the National Cancer Institute's Common Toxicity Criteria, version 3.0. Response was assessed with use of computed tomography (CT) and was correlated with response on [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Survival from first treatment was estimated with use of the Kaplan-Meier method. Tumor response measured by FDG PET imaging exceeded that measured by CT imaging for the first (88% vs 35%) and second (73% vs 36%) treated lobes. Tumor replacement of 25% or less (vs >25%) was associated with a statistically significant increase in median survival (339 days vs 162 days; P = .002). Treatment-related toxicities included mild fatigue (n = 13; 48%), nausea (n = 4; 15%), and vague abdominal pain (n = 5; 19%). There was one case of radiation-induced gastritis from inadvertent deposition of microspheres to the gastrointestinal tract (n = 1; 4%). Three patients (11%) experienced ascites/pleural effusion after treatment with TheraSphere as a consequence of liver failure in advanced-stage metastatic disease. With the exception of these three patients whose sequelae were not considered to be related to treatment, all observed toxicities were transient and resolved without medical intervention. TheraSphere administration appears to provide stabilization of liver disease with minimal toxicity in patients in whom standard systemic chemotherapy regimens have failed.
Article
Salvage therapy for patients with unresectable colorectal liver metastases that were refractory to oxaliplatin and irinotecan was performed via radioactive microspheres. High doses of radiation were delivered to tumors from permanently implanted 90Y microspheres, delivered through the hepatic arterial vessels. Patients from 7 institutions were selected for treatment after screening-defined vascular access to all the tumors, and imaging-confirmed 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. A total of 208 patients were treated from April 2002 to April 2005. Median follow-up of the 129 men and 79 women is 13 months (range, 1-42 months). Median survival is 10.5 months for responders but only 4.5 months in nonresponders. No treatment-related procedure deaths or radiation-related venoocclusive liver failures were found. Computed tomography partial response was 35%; positron emission tomography response of 91% and reduction in carcinoembryonic antigen of 70% were achieved. In this group of heavily pretreated patients, radioactive microspheres produced an encouraging median survival, with acceptable toxicity, and a significant objective response rate, which suggests that further investigation of this approach is warranted.
  • E J Kuipers
  • W M Grady
  • D Lieberman
Kuipers EJ, Grady WM, Lieberman D, et al. Colorectal cancer. Nat Rev Dis Primers 2015;1:15065