Whole Brain Radiation May be Postponed in Cancer Patients with Limited Metastasis to the BrainKey Words
Brain metastases, stereotactic radiosurgery, whole brain radiation therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Patients who received stereotactic radiosurgery for four or fewer contained metastases to the brain lived as long, and had comparable radiation side effects and mental functioning, as patients who were also treated with whole brain radiation. However, the radiosurgery-only patients had higher recurrence in their brain and were more likely to require salvage treatment.
Source
Journal of the American Medical Association, June 7, 2006 (see the journal abstract)
(JAMA, 2006 June 7;295(21): 2583-91)
Background
Each year in the United States, more than 170,000 patients experience cancer that metastasizes (spreads) to the brain from other parts of their body, an event that can prove fatal. The standard treatment has been radiation therapy directed to the whole brain – a choice that carries the risk of neurocognitive (mental function) changes and threatens the quality of life. In rare cases, a single metastatic brain tumor that’s small enough might be removed by surgery, which is then usually followed by whole brain radiation therapy to kill any remaining cancer cells.
In the 1990s, a technique known as stereotactic radiosurgery was developed, where radiation beams are focused more precisely at the tumor(s) in hopes of minimizing damage to healthy brain cells and avoiding invasive physical surgery. The more focused approach is also a one-day procedure, while whole brain radiation therapy can take weeks. Studies suggest, however, that more than 50 percent of patients treated with stereotactic radiosurgery will see their brain tumors return.
Further research is needed to determine which radiotherapy approach works best for which cases of metastatic brain tumors, and when a combination of approaches might be preferable.
The Study
This study is the first phase III trial designed to see whether patients with a limited number of brain metastases lived just as long with stereotactic radiosurgery alone compared to those receiving a combination of stereotactic radiosurgery and whole brain radiation therapy.
Between October 1999 and December 2003, 132 patients in 11 hospitals throughout Japan were randomly assigned to one of the two groups. Every patient had cancer that had metastasized to the brain, with between one and four tumors no larger than 3 centimeters. The patients' primary cancers included breast, lung, colorectal, and kidney cancers, among a few others. (Brain metastases from these types of cancer are not the same thing as brain cancer.) All patients had roughly comparable mental performance at the beginning of the trial and were otherwise in similar condition.
Sixty-seven patients received stereotactic radiosurgery alone; 65 had whole brain radiation therapy followed by stereotactic radiosurgery. Patients in both groups were evaluated for tumor recurrence, mental function, and side effects at one month, three months, and every three months thereafter. In the case of recurrence, patients received whatever further treatment their doctors’ deemed best.
The study was led by Hidefumi Aoyama, M.D., Ph.D., from Hokkaido University in Sapporo, Japan.
Results
Ninety-two percent of the patients completed their assigned treatment. At a median follow-up time of 7.8 months after the start of treatment, researchers found no statistically significant difference in overall survival or median survival between the two groups.
Those receiving stereotactic surgery alone survived a median of eight months, compared to 7.5 months in the whole brain radiation therapy group. By the end of the trial, 62 of the stereotactic radiosurgery-only group and 57 of the combination group had died. The study was stopped early when it became apparent that not enough patients could be enrolled to detect a meaningful difference in survival if there were one.
Contrary to expectations, there were also no significant differences observed between the groups either in mental functioning or toxic side effects from radiation. That is, those receiving stereotactic radiosurgery alone were just as likely to suffer toxic effects as those treated with both approaches.
Meaningful differences were seen, however, in whether brain tumors recurred. The 12-month rate of recurrence for stereotactic surgery alone was 76.4 percent, compared to 46.8 percent for those who also received whole brain radiation. This represents a 68 percent reduction in the risk of recurrence by adding whole brain radiation.
Salvage treatment for progression of brain tumors was required in 29 patients who received stereotactic radiosurgery alone, compared to only ten patients who also received whole brain radiation.
Comments
This study is consistent with other findings demonstrating that whole brain radiation therapy “can be delayed without compromising patient survival,” said Jeffrey Raizer, M.D., from the Feinberg School of Medicine at Northwestern University, in an editorial accompanying the published results.
Up to 60 percent of patients diagnosed with brain metastases have one to four tumors that are contained and stable, as did the patients in this study. “These results show that [such patients] have a decision to make,” explained Anurag Singh, M.D., from the Radiation Oncology Branch in the Center for Cancer Research at the National Cancer Institute. “If they understand that their brain tumors may return sooner because they decide to forego whole brain radiotherapy, ideally they and their doctors will be vigilant about looking for those recurrences and will quickly address them with salvage treatments.”
Whether such surveillance is feasible should be an important part of the decision, he said, because patients in many community settings are usually not followed as closely as they might be in large urban cancer centers.
Limitations
While it’s possible that stereotactic radiosurgery alone could be a treatment option for some patients, said lead author Aoyama and his colleagues, the results from studies conducted thus far, including their own, do not provide a consistent picture about overall survival with or without whole brain radiation, how much radiation should be used in the various approaches, and whether the higher recurrence rates with stereotactic surgery might also lead to “neurologic deterioration.”
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