Consider Total Volume of Brain Mets When Deciding Rx

DENVER-When physicians are deciding whether to offer stereotactic radiosurgery to patients with multiple brain metastases who have a fairly good functional status, they should consider the total volume of these metastases instead of their number. This was among the key findings of a study presented at the 2005 meeting of the American Society for Therapeutic Radiology and Oncology (abstract 2068).

"Most patients with multiple brain metastases do not receive radiosurgery as a treatment option, given their grim prognoses," Ajay K. Bhat-nagar, MD, a resident physician at the University of Pittsburgh Cancer Institute, said at a poster session. "Typically, patients who have one to three brain metastases are the ones who receive stereotactic radiosurgery in addition to whole-brain radiation ther-apy," he said, but his institution's experience has suggested that radiosurgery confers a survival benefit in at least some patients who have more brain metastases.

John Flickinger, MD, professor of radiation oncology, University of Pittsburgh School of Medicine, was the senior author of the study.

Study Patients

Most of the patients Dr. Bhatnagar and his colleagues studied at their institute had non-small-cell lung cancer (42%), breast cancer (23%), or melanoma (17%), while smaller proportions had renal cell carcinoma (6%), colon cancer (3%), and other or unknown cancers (9%). Sixty-five percent were aged 60 or younger. Importantly, he noted, 85% had a Karnofsky Performance Status score of 70 or higher. By the RTOG recursive partitioning analysis (RPA) classification, 10% fell into class 1, while 75% were in class 2, and 15% in class 3.

The number of brain metastases the patients had ranged widely, from 4 to 18, with a median of 5. Likewise, the total treatment volume varied considerably, from 0.6 to 51.0 cc, with a median of 6.8 cc. Stereotactic radiosurgery, performed in a single session with a gamma knife, was the sole treatment in 17% of patients, was combined with whole-brain radiation therapy in 46%, and was used as salvage therapy after a failure of whole-brain radiation therapy in 38%. The median marginal dose of stereotactic radiation was 16 Gy. Patients had a mean follow-up of 8 months.

Survival Results

As a group, the patients survived a median of 8 months after undergoing stereotactic radiosurgery. When compared with historical controls treated with whole-brain radiation therapy only (42% of whom had solitary brain metastases), the study patients had better or equivalent median overall survival, whether they were in RTOG RPA class 1 (18 vs 7 months), class 2 (9 vs 4 months), or class 3 (3 vs 2 months).

In a multivariate analysis, the independent determinants of survival were total treatment volume, as well as RPA class, age, and marginal dose. In contrast, the number of brain metastases and a variety of other factors (sex, visceral vs nonvisceral metastases, and type of cancer) did not independently influence this outcome.

"It's not necessarily the number of metastases that is important, but actually the volume of metastases," Dr. Bhatnagar said of the findings. "If a patient has three brain metastases but with a total treatment volume of greater than 7 cc, this patient would be . . . typically a candidate for radiosurgery," he said. "However, a patient with six brain metastases but a total treatment volume of only 4 cc normally would not be considered for radiosurgery, even though our analysis shows that the second patient would actually be a much better candidate."

He stressed that the findings do not apply to all patients, but rather only to those who are functioning fairly well to begin with. "Given the fact that the majority of these patients had relatively good performance status," he said, "these patients with multiple metastases warrant aggressive treatment including radiosurgery and should not be denied this treatment despite the number of metastases they have." This issue is becoming increasingly important, Dr. Bhatnagar noted, given the greater sensitivity of contemporary imaging technology. "With improved imaging modalities, such as high-resolution MRI, patients are infrequently being diagnosed with solitary brain metastases," he explained.

In conclusion, Dr. Bhatnagar said, "When oncologists are considering treatment modalities for patients with multiple brain metastases, we hope they will consider additional factors such as the total intracranial tumor volume rather than just the number of metastases."

The study suggests, he said, that stereotactic radiosurgery results in a survival benefit for selected patients, but this needs to be confirmed prospectively. "Clearly, there are still many questions to be answered regarding the management of brain metastases, but the results of this study add more food for thought," Dr. Bhatnagar said.