• breast cancer
• disease control rate
• glass
• objective response rate
• prognosis
• radioembolization
• resin
• survival

• Humans
• Liver Neoplasms/secondary
• Liver Neoplasms/radiotherapy
• Breast Neoplasms/pathology
• Breast Neoplasms/radiotherapy
• Female
• Embolization, Therapeutic/methods
• Treatment Outcome
• Yttrium Radioisotopes/therapeutic use

• ablation
• breast cancer
• embolization
• interventional radiology
• metastasis

• breast cancer
• chemoembolization
• cryoablation
• locoregional therapy
• microwave ablation
• oligometastatic disease
• radioembolization

• Humans
• Female
• Breast Neoplasms/surgery
• Liver Neoplasms/therapy
• Embolization, Therapeutic
• Brachytherapy
• Catheter Ablation

• BCLM
• Cryoablation
• TACE
• TARE
• percutaneous ablation

• Female
• Humans
• Breast Neoplasms/therapy
• Breast Neoplasms/pathology
• Quality of Life
• Embolization, Therapeutic
• Brachytherapy
• Liver Neoplasms/secondary

• RECIST
• breast cancer
• interventional radiology
• liver metastases
• radioembolization
• yttrium

Our purpose was to retrospectively evaluate the safety and efficacy of transarterial hepatic radioembolization (TARE) treatment with yttrium-90 labeled glass microspheres in patients with chemotherapy-refractory breast cancer with liver-dominant metastatic disease.

This retrospective single-institution study evaluated 31 female patients (mean age of 59.6 ± 13.2 years) who were treated with TARE. All patients received and progressed on systemic chemotherapy before TARE. Twenty-one patients also had extrahepatic metastases, including 13 patients who had metastases in bones only besides the liver. Survival data were analyzed by Kaplan-Meier method and compared using log-rank test. Imaging response to treatment was determined by Response Evaluation Criteria in Solid Tumors.

Median overall survival (OS) from the TARE was 13 months (95% confidence interval, 9.1-16.9 months). The survival probability at 1, 2, and 3 years was 60.1%, 36.7%, and 24.5%, respectively. The median hepatic progression-free survival was 7 months (95% confidence interval, 6.1-7.9 months). There was no 30-day mortality and 3 patients (9.4%) had grade 3 toxicity. Estrogen receptor (ER) positive status predicted prolonged survival (14 months for ER+ vs 9 months for ER-; P = .028). Patients who had bone-only extrahepatic disease had higher OS than patients with extraosseous metastases (23 vs 8 months, P = .02). At the 3-month follow-up the radiographic objective response rate was 46.6% and disease control rate was 70%.

The treatment of patients with liver-dominant chemotherapy-refractory breast cancer metastases with TARE using yttrium-90 labeled glass microspheres is safe and led to promising hepatic disease control and OS especially in patients with ER+ tumors and in patients without extrahepatic extraosseous metastases.

• breast cancer
• freedom from local progression rate
• liver metastasis
• overall survival
• proton beam therapy
• radiotherapy

• hepatic metastasis
• liver-directed therapies
• radioembolization

• Breast neoplasm
• Intra-arterial infusion
• Liver neoplasms
• Meta-analysis
• Systematic review

Breast cancer is the most common malignancy occurring in women worldwide. More than 90% of patients present with localized disease are treated with curative intent; however, recurrence can occur with development of metastatic lesions. Frequently associated with extra-hepatic lesions, localized treatments (surgery or stereotaxic body radiotherapy) are rarely proposed in liver lesions. ⁹⁰Y radioembolization has extensively been evaluated in colorectal cancer, but its role in breast cancer with isolated liver metastases remains largely unknown. Pre-existing liver diseases are known risk factors for ⁹⁰Y induced liver toxicity. Not considered as an excluding factor for this treatment, data are limited regarding its safe use with cholangitis. We report a successful control of liver metastases by ⁹⁰Y radioembolization in a breast cancer patient.

Breast cancer is the most common malignancy occurring in women worldwide. Metastasis-directed therapies are more and more often offered to patients in order to delay systemic treatments; however, their role in improving survival remains unknown. Trans-arterial radioembolization with ⁹⁰Y appears to be an interesting strategy in breast cancer with isolated liver metastases, even if its survival benefit remains largely unknown. Safety of trans-arterial radioembolization also remains under investigated in patients with previous liver disease. We report a successful control of liver metastases by ⁹⁰Y radioembolization in a breast cancer patient.

• breast cancer
• liver metastases
• metastasis-directed therapies
• trans-arterial radioembolization
• yttrium-90

The liver is the second most common site of breast cancer metastasis. Liver directed therapies including hepatic resection, radiofrequency ablation (RFA), transarterial chemo- and radioembolization (TACE/TARE), and hepatic arterial infusion (HAI) have been scarcely researched for breast cancer liver metastasis (BCLM). The purpose of this review is to present the known body of literature on these therapies for BCLM.

A systematic review was performed with pre-specified search terms using PubMed, MEDLINE, EMBASE, and Cochrane Review resulting in 9,957 results. After review of abstracts and application of exclusion criteria, 51 studies were included in this review.

Hepatic resection afforded the longest median overall survival (mOS) and 5-year survival (45 mo, 41%) across 23 studies. RFA was presented in six studies with pooled mOS and 5-year survival of 38 mo and 11–33%. Disease burden and tumor size was lower amongst hepatic resection and RFA patients. TACE was presented in eight studies with pooled mOS and 1-year survival of 19.6 mo and 32–88.8%. TARE was presented in 10 studies with pooled mOS and 1-year survival of 11.5 mo and 34.5–86%. TACE and TARE populations were selected for chemo-resistant, unresectable disease. Hepatic arterial infusion was presented in five studies with pooled mOS of 11.3 months.

Although further studies are necessary to delineate appropriate usage of liver directed therapies in BCLM, small studies suggest hepatic resection and RFA, in well selected patients, can result in prolonged survival. Longitudinal studies with larger cohorts are warranted to further investigate the effectiveness of each modality.

• breast cancer liver metastasis
• hepatic resection
• liver directed therapies
• radiofrequency ablation
• transarterial chemoembolization
• transarterial radioembolization

• ablation
• breast cancer
• chemoembolization
• hepatic metastasis
• locoregional
• radioembolization

Liver metastases secondary to breast cancer are associated with unfavourable prognosis. Radioembolization with ytrrium-90 is an emerging option for management of liver metastases of breast cancer when other systemic therapies have failed to achieve disease control. However, unlike the case of other liver tumours (colorectal/melanoma metastases/cholangiocarcinoma), its role in the management of breast liver metastases is yet to be elucidated.

The aims of this systematic review were to (1) assess the effect of radioembolization with yttrium-90 on tumour response; and (2) to estimate patient survival post radioembolization.

The review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic literature search was performed using the PubMed and EMBASE databases from January 2007 to December 2018. The initial search yielded 265 reports which were potentially suitable for inclusion in this review. Studies published in English reporting at least one outcome of interest were considered to be suitable for inclusion. Conference abstracts; case reports, animal studies and reports not published in English were excluded from this review. Data was retrieved from each individual report on the name of primary author, year of publication, patient demographics, type of microspheres used, radiation dose delivered to tumour, duration of follow-up, disease control rate (%), tumour response, and overall patient survival.

The final number of studies which met the inclusion criteria was 12 involving 452 patients. There were no randomized controlled trials identified after the literature search. The age of the patients included in this review ranged from 52 to 61 years. The duration of the follow up period post-radioembolization ranged from 6 to 15.7 mo. The total number of patients with breast metastases not confined to the liver was 236 (52.2%). Cumulative analysis revealed that radioembolization with yttrium-90 conferred tumour control rate in 81% of patients. Overall survival post-radioembolization ranged from 3.6 to 20.9 mo with an estimated mean survival of 11.3 mo.

Radioembolization with ytrrium-90 appears to confer control of tumour growth rate in most patients, however its effect on patient survival need to be elucidated further. Furthermore, quality evidence in the form of randomized trials is needed in order to assess the effect of radioembolization in more depth.

• Breast cancer
• Liver metastases
• Yttrium-90
• Radioembolization
• Survival

• Breast cancer
• Liver metastasis
• PET/CT imaging
• Radioembolization

Radiation is a widely used therapeutic method for treating breast cancer. N-dihydrogalactochitosan (GC), a biocompatible immunostimulant, is known to enhance the effects of various treatment modalities in different tumor types. However, whether GC can enhance the radiosensitivity of cancer cells remains to be explored. In this study, triple-negative murine 4T1 breast cancer cells transduced with multi-reporter genes were implanted in immunocompetent Balb/C mice to track, dissect, and identify liver-metastatic 4T1 cells. These cells expressed cancer stem cell (CSC) -related characteristics, including the ability to form spheroids, the expression of the CD44 marker, and the increase of protein stability. We then ex vivo investigated the potential effect of GC on the radiosensitivity of the liver-metastatic 4T1 breast cancer cells and compared the results to those of parental 4T1 cells subjected to the same treatment. The cells were irradiated with increased doses of X-rays with or without GC treatment. Colony formation assays were then performed to determine the survival fractions and radiosensitivity of these cells. We found that GC preferably increased the radiosensitivity of liver-metastatic 4T1 breast cancer cells rather than that of the parental cells. Additionally, the single-cell DNA electrophoresis assay (SCDEA) and γ-H2AX foci assay were performed to assess the level of double-stranded DNA breaks (DSBs). Compared to the parental cells, DNA damage was significantly increased in liver-metastatic 4T1 cells after they were treated with GC plus radiation. Further studies on apoptosis showed that this combination treatment increased the sub-G1 population of cells, but not caspase-3 cleavage, in liver-metastatic breast cancer cells. Taken together, the current data suggest that the synergistic effects of GC and irradiation might be used to enhance the efficacy of radiotherapy in treating metastatic tumors.

• N-dihydrogalactochitosan (GC), metastatic tumors
• cancer stem cells
• radiosensitivity
• triple-negative breast cancer

• Animals
• Apoptosis/drug effects
• Apoptosis/radiation effects
• Cell Line, Tumor
• Cell Separation
• Cell Survival/drug effects
• Cell Survival/radiation effects
• Cell Tracking
• Chitosan/pharmacology
• DNA Damage
• Female
• Histones/metabolism
• Liver Neoplasms/pathology
• Liver Neoplasms/radiotherapy
• Liver Neoplasms/secondary
• Mammary Neoplasms, Animal/pathology
• Mice, Inbred BALB C
• Molecular Imaging
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/pathology
• Neoplastic Stem Cells/radiation effects
• Radiation Tolerance/drug effects
• Radiation Tolerance/radiation effects
• Radiation, Ionizing
• X-Rays

• P20 GM103447 NIGMS NIH HHS

Breast cancer represents a leading cause of death worldwide. Despite the advances in systemic therapies, the prognosis for patients with breast cancer liver metastasis (BCLM) remains poor. Especially in case of failure or cessation of systemic treatments, surgical resection for BCLMs has been considered as the treatment standard despite a lack of robust evidence of benefit. However, due to the extent and location of disease and physical condition, the number of patients with BCLM who are eligible for surgery is limited. Palliative locoregional treatments of liver metastases (LM) include transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiotherapy (SIRT). Percutaneous thermal ablation methods, such as radiofrequency ablation (RFA) and microwave ablation (MWA), are considered potentially curative local treatment options. They are less invasive, less expensive and have fewer contraindications and complication rates than surgery. Because conventional ultrasound- and computed tomography-guided single-probe thermal ablation is limited by tumor size, multi-probe stereotactic radiofrequency ablation (SRFA) with intraoperative image fusion for immediate, reliable judgment has been developed in order to treat large and multiple tumors within one session. This review focuses on the different minimally invasive local and locoregional treatment options for BCLM and attempts to describe their current and future role in the multidisciplinary treatment setting.

• breast cancer
• image fusion
• liver metastasis
• local recurrence
• metastasectomy
• resection
• stereotactic radiofrequency ablation (SRFA), stereotaxy
• survival
• thermal ablation

18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (FDG-PET/CT) and contrast-enhanced computed tomography (CT) can be used for response evaluation in metastatic breast cancer (MBC). In this study, we aimed to review literature comparing the PET Response Criteria in Solid Tumors (PERCIST) with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with MBC. We made a systematic search in Embase, PubMed/Medline, and Cochrane Library using a modified PICO model. The population was MBC patients and the intervention was PERCIST or RECIST. Quality assessment was performed using the QUADAS-2 checklist. A total of 1975 articles were identified. After screening by title/abstract, 78 articles were selected for further analysis of which 2 duplicates and 33 abstracts/out of focus articles were excluded. The remaining 43 articles provided useful information, but only one met the inclusion and none of the exclusion criteria. This was a retrospective study of 65 patients with MBC showing one-year progression-free survival for responders versus non-responders to be 59% vs. 27% (p = 0.2) by RECIST compared to 64% vs. 0% (p = 0.0001) by PERCIST. This systematic literature review identified a lack of studies comparing the use of RECIST (with CE-CT) and PERCIST (with FDG-PET/CT) for response evaluation in metastatic breast cancer. The available sparse literature suggests that PERCIST might be more appropriate than RECIST for predicting prognosis in patients with MBC.

• CE-CT
• FDG-PET/CT
• PERCIST
• RECIST
• metastatic breast cancer
• response evaluation

• breast cancer
• cholangiocarcinoma, melanoma
• hepatic-arterial therapy
• liver metastases
• melanoma
• neuroendocrine
• radioembolization
• selective internal radiation therapy

• Female
• Humans
• Breast Neoplasms/pathology
• Breast Neoplasms/radiotherapy
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/radiotherapy
• Embolization, Therapeutic/methods
• Liver Neoplasms/pathology
• Liver Neoplasms/radiotherapy
• Melanoma/pathology
• Melanoma/radiotherapy
• Microspheres
• Neuroendocrine Tumors/pathology
• Neuroendocrine Tumors/radiotherapy
• Radiography, Interventional
• Yttrium Radioisotopes/therapeutic use

• Liver-directed therapy
• SIRT
• Selective internal radiation therapy
• Transarterial radioembolization

• breast cancer
• chemoembolization
• gynecologic malignancies
• interventional radiology
• liver metastases
• radioembolization

• Selective internal radiation therapy (SIRT)
• consensus
• cytotoxins
• liver neoplasms

• 8971 Cancer Research UK

• chemoembolization
• interventional radiology
• liver metastases
• locoregional therapy
• radioembolization
• thermal ablation

• chemoembolization
• hepatic artery infusion chemotherapy
• interventional radiology
• liver metastases
• radioembolization

To evaluate prognostic values of clinical and diffusion-weighted magnetic resonance imaging-derived intravoxel incoherent motion (IVIM) parameters in patients undergoing primary radioembolization for metastatic breast cancer liver metastases.

A total of 21 females (mean age 54 years, range 43–72 years) with liver-dominant metastatic breast cancer underwent standard liver magnetic resonance imaging (1.5 T, diffusion-weighted imaging with b-values of 0, 50, and 800 s/mm²) before and 4–6 weeks after radioembolization. The IVIM model-derived estimated diffusion coefficient D’ and the perfusion fraction f’ were evaluated by averaging the values of the two largest treated metastases in each patient. Kaplan–Meier and Cox regression analyses for overall survival (OS) were performed. Investigated parameters were changes in f’- and D’-values after therapy, age, sex, Eastern Cooperative Oncology Group (ECOG) status, grading of primary tumor, hepatic tumor burden, presence of extrahepatic disease, baseline bilirubin, previous bevacizumab therapy, early stasis during radioembolization, chemotherapy after radioembolization, repeated radioembolization and Response Evaluation Criteria in Solid Tumors (RECIST) response at 6-week follow-up.

Median OS after radioembolization was 6 (range 1.5–54.9) months. In patients with therapy-induced decreasing or stable f’-values, median OS was significantly longer than in those with increased f’-values (7.6 [range 2.6–54.9] vs 2.6 [range 1.5–17.4] months, P<0.0001). Longer median OS was also seen in patients with increased D’-values (6 [range 1.6–54.9] vs 2.8 [range 1.5–17.4] months, P=0.008). Patients with remission or stable disease (responders) according to RECIST survived longer than nonresponders (7.2 [range 2.6–54.9] vs 2.6 [range 1.5–17.4] months, P<0.0001). An ECOG status ≤1 resulted in longer median OS than >1 (7.6 [range 2.6–54.9] vs 1.7 [range 1.5–4.5] months, P<0.0001). Pretreatment IVIM parameters and the other clinical characteristics were not associated with OS. Classification by f’-value changes and ECOG status remained as independent predictors of OS on multivariate analysis, while RECIST response and D’-value changes did not predict survival.

Following radioembolization of breast cancer liver metastases, early changes in the IVIM model-derived perfusion fraction f’ and baseline ECOG score were predictive of patient outcome, and may thus help to guide treatment strategy.

• DWI
• IVIM
• MRI
• breast cancer
• radioembolization
• selective internal radiation therapy

Unresectable primary and secondary liver malignancies present a major problem in the treatment of solid tumors. Transarterial radioembolization (TARE) is an increasingly used technique for treating various types of malignant liver tumors. This approach is appealing, as the mechanism of action is independent from other loco-regional treatments and potentially complementary to systemic therapies. There are two commercially available products in use for TARE: ⁹⁰Y-resin and ⁹⁰Y-glass microspheres. Currently available data indicates TARE so be safe and effective in hepatocellular carcinoma (HCC) and metastatic liver disease. In HCC the results compare well with chemoembolization, while the role of TARE in combination with kinase inhibitors has yet to be established. Current data on TARE in metastatic liver disease is promising, but there is a strong need for prospective randomized trials comparing TARE and modern chemotherapeutic regimen to support the growing role of TARE in metastatic liver disease.

• Hepatocellular carcinoma
• Selective internal radiation therapy
• Radioembolization
• Liver
• Neoplasm
• Metastasis

• Selective internal radiation therapy (SIRT)
• liver cancer
• radioembolization
• selective internal radiation-sphere (SIR-sphere)

Patients with hepatic metastases who are candidates for Y90-radioembolization (Y90-RE) usually have advanced tumor stages with involvement of both liver lobes. Per current guidelines, these patients have usually undergone several cycles of potentially hepatotoxic systemic chemotherapy before Y90-RE is at all considered, requiring split (lobar) treatment sessions to reduce hepatic toxicity. Assessing response to Y90-RE early, that is, already after the first lobar session, would be helpful to avoid an ineffective and potentially hepatotoxic second lobar treatment. We investigated the accuracy with which diffusion- weighted magnetic resonance imaging (DWI-MRI) and positron emission tomography/computed tomography (PET/CT) can provide this information.

An institutional review board–approved prospective intraindividual comparison trial on 35 patients who underwent fluorodeoxyglucose PET/CT and DWI-MRI within 6 weeks before and 6 weeks after Y90-RE to treat secondary-progressive liver metastases from solid cancers (20 colorectal, 13 breast, 2 other) was performed. An increase of minimal apparent diffusion coefficient (ADCmin) or decrease of maximum standard uptake value (SUVmax) by at least 30% was regarded as positive response. Long-term clinical and imaging follow-up was used to distinguish true- from false-response classifications.

On the basis of long-term follow-up, 23 (66%) of 35 patients responded to the Y90 treatment. No significant changes of metastases size or contrast enhancement were observable on pretreatment versus posttreatment CT or magnetic resonance images.However, overall SUVmax decreased from 8.0 ± 3.9 to 5.5 ± 2.2 (P < 0.0001), and ADCmin increased from 0.53 ± 0.13 × 10⁻³ mm²/s to 0.77 ± 0.26 × 10⁻³ mm²/s (P < 0.0001). Pretherapeutic versus posttherapeutic changes of ADCmin and SUVmax correlated moderately (r = −0.53). In 4 of the 35 patients (11%), metastases were fluorodeoxyglucose-negative such that no response assessment was possible by PET. In 25 (71%) of the 35 patients, response classification by PET and DWI-MRI was concordant; in 6 (17%) of the 35, it was discordant. In 5 of the 6 patients with discordant classifications, follow-up confirmed diagnoses made by DWI. The positive predictive value to predict response was 22 (96%) of 23 for MRI and 15 (88%) of 17 for PET. The negative predictive value to predict absence was 11 (92%) of 12 for MRI and 10 (56%) of 18 for PET. Sensitivity for detecting response was significantly higher for MRI (96%; 22/23) than for PET (65%; 15/23) (P < 0.02).

Diffusion-weighted magnetic resonance imaging appears superior to PET/CT for early response assessment in patients with hepatic metastases of common solid tumors. It may be used in between lobar treatment sessions to guide further management of patients who undergo Y90-RE for hepatic metastases.

• breast cancer
• hepatic metastases
• radioembolization
• survival

• Breast cancer
• Embolization
• Intra-arterial therapy
• Liver
• Melanoma
• Neuroendocrine

• 90Y-radioembolization
• FDG-PET
• breast cancer
• liver metastases
• total lesion glycolysis

The role of 18-fluorodeoxyglucose positron emission tomography CT (¹⁸FDG PET/CT), as a prognostic factor for survival in colorectal cancer patients with liver metastases, is still controversial. We sought to perform a meta-analysis of the literature to address this issue.

A systematic literature search was performed to identify the studies that associated ¹⁸FDG PET/CT to clinical survival outcomes of patients with liver metastases. Methodological qualities of the included studies were also assessed. The summarized hazard ratio (HR) was estimated by using fixed- or random-effect model according to heterogeneity between trails.

By analyzing a total of 867 patients from 15 studies, we found that PET/CT for metabolic response to the therapy was capable of predicting event-free survival (EFS) and overall survival (OS) with statistical significance, and the HR was 0.45 (95 % confidence interval [CI], 0.26–0.78) and 0.36 (95 % CI, 0.18–0.71), respectively. Furthermore, pre-treatment ¹⁸FDG PET/CT with high standardized uptake value (SUV) was also significantly associated with poorer OS HR, 1.24; (95 % CI, 1.06–1.45). However, we did not find a statistically significant effect of post-treatment SUV for predicting OS HR, 1.68; (95 % CI, 0.63–4.52).

The present meta-analysis confirms that ¹⁸FDG PET/CT is a useful tool to help predict survival outcomes in patients with liver metastases.

The online version of this article (doi:10.1186/s40644-015-0055-z) contains supplementary material, which is available to authorized users.

• Arterially directed therapies
• Hepatic malignancy
• SIRT
• Selective internal radiation therapy
• Yttrium-90

• FDG
• PET
• hyperthermia
• soft-tissue sarcoma
• survival

• 18F-FDG PET
• HCC
• SIRT
• radioembolization