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Selective internal radiation therapy (SIRT): a new modality for treating patients with colorectal liver metastases.

ABSTRACT: BACKGROUND: Selective internal radiation therapy (SIRT) is a new and developing modality for treating non-resectable liver tumours. Evidence is emerging that it is very efficacious in patients with hepatocellular cancer and colorectal liver metastases. DISCUSSION: SIRT generally involves a single delivery of (90)yttrium micro-spheres into the hepatic artery. Preferential uptake is achieved into liver tumours, because of their predominant hepatic arterial blood supply. Average tumour doses of radiation in excess of 200 Gy are achieved. The treatment is generally well tolerated and has been documented by a number of groups internationally to achieve response rates of around 90% in patients with extensive colorectal cancer (CRC) liver metastases. Since the product obtained FDA approval in the USA in 2002, it is being more widely employed and investigated. Unlike other ablative therapies being applied to non-resectable liver tumours, SIRT is indicated even in patients with an extensive burden of liver tumour. Indications, dosing schedules and expected outcomes will become better defined as more groups take up the treatment.

SUBMITTER: Stubbs RS

PROVIDER: S-EPMC2020675 | biostudies-other | 2004

REPOSITORIES: biostudies-other

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Project description:Background: This Phase II, open-label, study examined the safety of regorafenib followed by selective internal radiation therapy (SIRT) with regorafenib re-initiation in the treatment of metastatic colorectal cancer (mCRC) patients with liver metastases who are not surgical candidates. Methods: Patients received 160 mg regorafenib daily on a 21-day course followed by a 1 week washout prior to SIRT. Liver function was evaluated at 2 and 4 weeks after SIRT, and regorafenib re-initiated if liver function was normal. Patients were evaluated for safety, and restaged at weeks 6 and 12 following SIRT. In addition, protein and cytokine assays of blood were performed to identify candidate molecular biomarkers associated with outcomes. Individual patient voxel-based dosimetry assessment was performed post-SIRT. Results: Twenty-Five patients were enrolled and received a median 11 weeks regorafenib. Three patients received regorafenib, but not SIRT due to disease progression. The remaining 22 patients received SIRT with a median activity delivered to the liver of 38 mCi, mean normal liver dose of 14.98 Gy and tumor mean dose of 29.0 Gy with a tumor to normal ratio mean of 2.42. There were four treatment-related serious AEs and no treatment-related deaths. Median progression-free survival was 3.7 months and the median overall survival was 12.1 months. The relative densities of several biomolecules changed significantly during the course of treatment, most notably post-treatment increases in levels of sex-hormone binding globulin (SHBG) and decreased levels of the cytokine MIG (CXL9). Decreases in von Willebrand factor (VWF), the ankyrin repeat domain (ANKRD26), and MIG were associated with improved survival times. Post-treatment increases in alpha-2-macroglobulin (A2M) and the cytokine intercellular adhesion molecule (ICAM-1) were associated with reduced overall survival time, while increases in Eotaxin (CCL14) predicted longer overall survival times. Conclusions: The treatment of mCRC patients with liver metastases using regorafenib followed by SIRT was tolerable in this patient population. Further efficacy analysis of this treatment schema and analysis of potential molecular biomarkers using larger sample sizes is merited.

Project description:Aim:Radiation therapy has been proven “safe and effective” in the management of colorectal cancer liver metastases, especially for oligometastases. However, to date, there is no consensus on optimal prescribed doses or dose fraction schemes. The current study was conducted to investigate the effectiveness and safety of 2 different radiation therapy methods, conventional conformal radiation therapy and stereotactic body radiation therapy, in the treatment of limited colorectal cancer liver metastases.Methods:From December 2011 to December 2016, twenty-six patients with colorectal cancer having postoperative liver metastases (?3) who were being treated with radiation therapy, either conventional conformal radiation therapy (50 Gy in 25 fractions) or stereotactic body radiation therapy (50 Gy in 10 fractions), were selected for this study. Overall survival and local control survival were analyzed by log-rank and Cox regression methods.Results:Radiation therapy delivered to each of the 26 patients with a total of 50 liver lesions. Conformal radiation therapy was delivered to 32 lesions in a total of 15 patients. Stereotactic body radiation therapy was delivered to 18 lesions in a total of 11 patients. Median follow-up was 13 months. Three-year overall survival and local control survival were 0% and 38.5%, 20.5%, and 53.0%, respectively, for the conformal radiation therapy and stereotactic body radiation therapy groups. The slightly better overall survival and local control survival in the stereotactic body radiation therapy group in comparison to the conformal radiation therapy group (P = .323 and .297) is insignificant. There were no differences in grade 3 hepatic toxicity between the 2 groups. Eastern Cooperative Oncology Group performance status and the number of liver lesions were significant prognostic factors in both univariate and multivariate analyses.Conclusions:Noninvasive radiation therapy provides satisfactory survival benefit for limited colorectal cancer liver metastases without intolerable toxicity and is therefore especially suitable for those elderly patients with poor performance status. Furthermore, stereotactic body radiation therapy with a higher biological equivalent dose and an abbreviated course of treatment has been shown to provide a better outcome than conventional conformal radiation therapy.

Project description:IntroductionThe aim of this study is to conduct a meta-analysis to assess the efficacy of yttrium-90 selective internal radiation therapy (SIRT) in treating patients with breast cancer with hepatic metastasis.MethodPubMed and The Cochrane Library were queried from establishment to January 2021. The following keywords were implemented: "breast", "yttrium", and "radioembolization". The following variables and outcomes were collected: publication year, region, sample size, study design, presence of extrahepatic disease, tumor burden, infused radioactivity, breast cancer subtype, previous treatment, median survival time (MST), length of follow-up, adverse events, and radiographical response such as Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST).ResultsA total of 24 studies from 14 institutions were included in the present meta-analysis. On the basis of the data from 412 patients, post-embolization MST was 9.8 [95% confidence interval (CI): 9.0-11.6] months. Patients with additional extrahepatic metastasis had a poorer survival rate compared with those with localized hepatic metastasis only (MST: 5.3 vs. 15 months, p < 0.0001). Patients with <25% liver tumor burden exhibited more promising survival than those with >25% (MST: 10.5 vs. 6.8 months, p < 0.0139). On the basis of RECIST, mRECIST, and PERCIST criteria, tumor response rate was 36% (95% CI: 26%-47%), 49% (95% CI: 34%-65%), and 47% (95% CI: 17%-78%), respectively, whereas tumor control rate was 85% (95% CI: 76%-93%), 73% (95% CI: 59%-85%), and 97% (95% CI: 91%-100%), respectively.ConclusionOn the basis of the available published evidence, SIRT is feasible and effective in treating patients with breast cancer with liver metastasis. Patients with lower hepatic tumor burden and without extrahepatic metastasis demonstrated more survival benefit. Future randomized controlled trials are warranted.

Project description:Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments): local parenchymal tumor destruction therapy. The expert panel proposed new nomenclature for 3 distinct disease categories of liver-dominant metastatic colorectal cancer that is consistent with other tumor types: (I) surgically treatable (resectable); (II) surgically untreatable (borderline resectable); (III) advanced surgically untreatable (unresectable) disease. Patients may present at any point in the algorithm and move between categories depending on their response to therapy. The broad intent of therapy is to transition patients toward individualized treatments where possible, given the survival advantage that resection offers in the context of a comprehensive treatment plan. This article reviews what is known about the role of SIRT with Y-90 as neoadjuvant, definitive, or palliative therapy in these different clinical situations and provides insight into when treatment with SIRT with Y-90 may be appropriate and useful, organized into distinct treatment algorithm steps.

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Selective internal radiation therapy (SIRT): a new modality for treating patients with colorectal liver metastases.

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