Clinical Investigation
Use of Yttrium-90 Microspheres in the Treatment of Unresectable Hepatic Metastases From Breast Cancer

https://doi.org/10.1016/j.ijrobp.2007.03.056Get rights and content

Purpose

Therapy for patients with unresectable liver metastases from breast cancer that were refractory to multiple treatment regimens was performed using radioactive microspheres. High doses of radiation were delivered to tumors from these permanently implanted yttrium-90 (90Y) microspheres, delivered through the hepatic arterial vessels.

Methods and Materials

Women from three institutions were selected for treatment, after screening that demonstrated vascular access to all tumors and after imaging confirmed that microspheres would be implanted only in the liver tumors. All patients were followed with laboratory and imaging studies at regular intervals until death. Toxicities, both acute and late were recorded, and actuarial survival determined.

Results

A total of 44 women were treated from April 2002 to April 2005. Median follow-up of these women was 14 months (1–42 months). No treatment-related procedure deaths or radiation related veno-occlusive liver failures were found. Computed tomographic imaging partial response was 47% and positron emission tomographic response 95%.

Conclusion

In this group of heavily pretreated patients, radioactive microspheres produced an encouraging median survival, with acceptable toxicity and a significant objective response rate, suggesting that further investigation of this approach is warranted.

Introduction

In the United States in 2006, breast cancer is expected to be diagnosed in an estimated 213,000 patients (1). The percentage of patients who will eventually develop metastatic disease in the liver is less well known but is believed to be at least 60%, or 127,000 individuals (2). Tumors in the liver are approachable by potentially curative surgery in only a select group of these patients who do not have other sites of metastatic disease. However, the disease in the liver is the lifespan-limiting site of disease in most cases, whereas metastases to the brain account for the death of many of the remaining patients. Among those who do undergo curative liver resection, 5-year survival rates range from 25% to 38%; but 60% to 90% of these patients will ultimately develop recurrent liver metastases. Chemotherapy, which for decades was mostly limited to doxorubicin, resulted in poor response and survival rates when used alone for metastatic disease in the liver. The introduction of taxanes and herceptin now offers a dramatic and long hoped-for improvement against advanced metastatic breast cancer 3, 4, 5. Yet despite these significant gains, metastatic breast cancer is almost always fatal, with up to 60% of patients dying of liver failure caused by local effects of hepatic tumors. Surveillance, Epidemiology, and End Results (SEER) data reveal that, once breast cancer is metastasized, the median survival of patients with this disease is 18.5 months, compared with 7.5 months for colorectal cancer and 24.5 months for prostate cancer (6).

A number of liver-directed therapies are now available including radiofrequency or microwave ablation, cryotherapy, and direct chemical injection. These techniques are effective only in patients who have a limited number of tumors. For patients with larger numbers, particularly of small tumors, the hepatic arterial therapies of hepatic arterial embolization and chemoembolization may be more effective. However, no controlled studies have been performed with these modalities. In addition, in the opinion of the current investigators, these modalities are variably effective, given the nature of the procedure, because they are so operator sensitive and are effective in palliation of symptoms only.

Radiotherapy has become more effective in destroying breast tumors, typically with combined chemotherapy (usually 5-fluorouracil [5FU] at doses >50 Gy) because of the technologic advances in treatment planning and delivery. However, three-dimensional radiotherapy, intensity-modulated radiotherapy, and stereotactic radiotherapy are limited by the tolerance of normal liver parenchyma to radiation. The maximum acceptable dose to the whole liver of 35 Gy is far below that required to destroy adenocarcinoma metastases, estimated at ≥70 Gy. An alternate approach is implantation of radiation sources into the tumor, i.e., brachytherapy, using yttrium-90 (90Y) microspheres 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. This report presents a review of our institutions' experience, and represents the largest number and longest follow-up of patients treated with 90Y microspheres in liver brachytherapy for metastatic breast cancer.

Section snippets

Patient selection

Several reports in abstract form have been published regarding delivery of microspheres for colorectal hepatic metastases 11, 12, 13, 14, 17, 18, 19, 20, 21. This report is limited to resin microspheres that are fully cleared by the Food and Drug Administration (FDA), indicated for colorectal cancer, and used in an off-label fashion, with data collected retrospectively without the institutions following a prescribed protocol. Approval from the institutional review board was obtained for

Patients

A total of 44 women were treated in this study. Their mean age was 58 years (range, 42–71 years). All had documented metastatic breast cancer in their liver that was symptomatic. Symptoms of hepatic metastases included right upper quadrant pain, hepatomegaly, lethargy, and mass effect from the enlarged liver. In all, 29 patients (66%) had disease elsewhere, in either the nodes or bone, but none had brain metastases. Of the patients with extrahepatic metastases, 20 had nodal metastases and 16

Discussion

Treatment of hepatic metastases predominantly from gastrointestinal tumors has a long history of using brachytherapy. There are early reports using implanted isotopes from a number of sources but, only recently, has the treatment begun to rely more on the intra-arterial delivery of the particles or spheres. Early data demonstrated the safety of using 90Y as the treating agent, with more recent data obtained from reports written in the last 5 years 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21. The

Conclusion

In conclusion, this small series demonstrates the efficacy of this therapy when applied to breast cancer metastases, both in chemotherapy-refractory disease and during a treatment hiatus, and warrants further investigation.

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    Dr. Coldwell is currently affiliated with Coldwell Associates, Dallas, TX.

    Conflict of interest: D. M. Coldwell, A. S. Kennedy, and C. W. Nutting have received honoraria for lectures and training provided on microsphere therapy from Sirtex, Inc., which is the manufacturer of the microspheres used in the patients in this report. They do not have any other financial arrangements with Sirtex.

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