Clinical Study Offers Definitive Local Treatment of Bone Metastases from Breast Cancer
By Bryan Tutt
Metastatic breast cancer carries a poor prognosis, and most systemic treatments for metastatic disease aim to slow its progression rather than to cure it. In a select group of patients, however, systemic treatment combined with definitive local treatment of the metastatic tumors can offer long-term progression-free survival—and perhaps a cure.
“For several years, we’ve been prescribing aggressive treatment for a select group of patients—those with breast cancer and 1–3 bone metastases,” said Eric A. Strom, M.D., a professor in the Department of Radiation Oncology at The University of Texas MD Anderson Cancer Center.
Dr. Strom said some of his patients have no evidence of disease more than 15 years after such treatment. Although he and many colleagues at MD Anderson were convinced that aggressive treatment of bone metastases was effective, no prospective study had been done to confirm this belief.
Six years ago, MD Anderson physicians opened a phase I clinical trial in which women with breast cancer and skeletal metastases at 1–3 sites receive standard systemic treatment plus definitive treatment of their bone metastases with surgery or radiation. Patients with more than 3 metastases or with metastases to distant organs are excluded from the study.
Dr. Strom, the study’s principal investigator, said patients enrolled in the study receive initial systemic therapy—which may include chemotherapy, targeted therapy, and/or hormonal therapy, depending on the characteristics of the tumors. After 3–9 months of systemic treatment, patients are reassessed. Patients whose disease has progressed are removed from the study, and their treatment plan is reassessed by their physicians; patients whose disease does not progress will receive definitive local therapy to each metastasis.
The metastases are treated with radiation therapy or surgical excision depending on the site. For example, Dr. Strom said, lesions on the spine are difficult to remove surgically but can be effectively treated with radiation. Other sites, such as a rib or the skull, are very amenable to surgery. Dr. Strom said it is not uncommon for a patient to have one metastasis removed surgically and another treated with radiation.
The radiation modality most often used in the study is intensity-modulated radiation therapy, which allows the delivery of high doses of radiation to the tumor with much lower doses to the surrounding tissue. “The dose to the metastatic tumor is 66–72 Gy, which is high enough to kill the tumor,” Dr. Strom said.
The study’s primary endpoint is 3-year progression-free survival. Each patient has follow-up visits every 3 months for the first year after the completion of treatment and every 6 months for the next 2 years.
Dr. Strom and his colleagues conducted an interim analysis of the study in August 2013. At a median follow-up of 2.25 years, 13 of 24 patients had no evidence of disease, 10 patients had metastatic disease in sites other than those treated in the study, and 1 patient had died of a cause unrelated to her cancer. No patient has had recurrent disease at a site where a metastasis was removed surgically or treated with radiation.
“Metastatic breast cancer is usually not curable. The fact that we have a number of patients with no evidence of disease is very compelling,” Dr. Strom said. “At the very least, local treatment of the metastases is good palliation. Even if these patients later develop metastases in other sites, they have a period where they’re free from symptoms and free from detectable cancer. Their quality of life is very high.”
Dr. Strom added that there have been no adverse events of grade 3 or higher from any treatments given in the study. “The radiation is incredibly well tolerated,” he said.
Most of the patients enrolled in the study had metastases arise 1 or more years after their breast cancer was initially treated. However, some patients enter the study while receiving treatment for their primary tumors, and their treatment in the study is tailored accordingly.
“When a patient is diagnosed with metastatic disease at the same time as her primary tumor, we watch how the metastases respond to her initial chemotherapy and then we develop a comprehensive plan that includes the breast tumor and regional lymph nodes as well as the metastatic sites,” Dr. Strom said. In one patient, Dr. Strom delivered postoperative radiation therapy to the chest wall and regional lymph nodes and the metastatic sites concurrently.
Dr. Strom acknowledged that it is rare to find patients with the precise disease characteristics required by the study’s protocol. He added that this study is the only one of its kind for patients with those characteristics.
“Selected patients with metastatic breast cancer may in fact be curable,” Dr. Strom said. “We have an open study where we’re treating patients with 1–3 bone metastases, and we’d really like to see these patients.”
For more information, contact Dr. Eric Strom at 713-563-2300. To learn more about the ongoing clinical trial of definitive local treatment of bone metastases from breast cancer, view the trial summary: No. 2008-0319.
OncoLog, August 2014, Volume 59, Issue 8
©The University of Texas MD Anderson Cancer Center