for those with brain mets--WBRT,cyberknife,or both?

[Lani]

No Survival Advantage, Less Recurrence With Whole-Brain Radiation Plus Radiosurgery for Brain Metastases

Susan Jeffrey

Medscape Daily News Email
June 7, 2006 — Results of a randomized trial suggest that the addition of whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the treatment of brain metastases does not improve survival, but intracranial relapse requiring salvage treatment was more common when WBRT was not used in first-line management.

"Our findings demonstrate that SRS alone without up-front WBRT was associated with increased brain tumor recurrence; however, it did not result in either worsening neurologic function or increased risk of neurologic death," the researchers, with first author Hidefumi Aoyama MD, PhD, from the Hokkaido University Graduate School of Medicine, Sapporo, Japan, conclude.

"With respect to patient survival, the control of systemic cancer might outweigh the frequent recurrence of brain tumors," they write. "Therefore, SRS alone could be a treatment option, provided that frequent monitoring of brain tumor status is conducted."

Their report appears in the June 7, 2006 issue of the Journal of the American Medical Association.

Metastatic "Seeding" Questioned

Metastatic spread to the brain, often from primary tumors in lung or breast or from melanoma, is commonly hematogenous, the researchers note, "and it is therefore presumed that the entire brain is 'seeded' with micrometastatic disease, even when only a single intracranial lesion is detected." However, recently that assumption has been challenged, and because of the neurologic toxicity associated with WBRT, treatments using the more focal approach of SRS alone are being used with increasing frequency, they point out.

In this study, Aoyama et al conducted a multicenter, randomized, controlled trial of SRS with or without WBRT in 132 patients with limited brain metastases, defined as 1 to 4 lesions, each less than 3 mm in diameter. The primary end point was overall survival, with secondary end points assessing brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.

At the last follow-up, in April 2005, the authors report, 57 of the WBRT-plus-SRS group had died, compared with 62 patients receiving SRS alone. Death was attributed to neurologic causes in 13 patients (22.8%) in the combination-therapy group vs 12 patients (19.3%) in the SRS-alone group ( P = .64).

Median survival time was higher in the SRS-alone group, a finding that was discordant with the 1-year actuarial survival, which was higher, although not significantly so, in the WBRT-plus-SRS group, they note. The discordant findings were due to a crossing of the 2 survival curves at about 12 months of follow-up, they point out.

Median survival time and 1-year actuarial survival by treatment group
End point
WBRT + SRS
SRS alone
P
Median survival time, mo
7.5
8.0
—
1-year actuarial survival, % (95% CI)
38.5 (26.7-50.3)
28.4 (17.6-39.2)
.42

The 12-month brain tumor recurrence rate was significantly higher with SRS alone, they note, and salvage brain treatment was required significantly less often when WBRT was also used.

Tumor recurrence and requirement for brain salvage treatment by treatment group
End point
WBRT + SRS
SRS alone
P
12-month brain tumor recurrence rate, %
46.8
76.4
<.001
Salvage brain treatment required, n
10
29
<.001

There were no significant differences in systemic and neurologic functional preservation or in the toxic effects of radiation, Aoyama et al note.

Commenting on their findings for Medscape Neurology/Oncology, Dr. Aoyama said in an email communication that standard treatment is WBRT with or without SRS, given the significantly higher frequency of brain tumor recurrence when up-front WBRT is omitted. However, Dr. Aoyama said, "I cannot stop feeling that this answer would be too straightforward when I'm faced with the patient whose quality of life has been deteriorating because of a toxic event resulting from WBRT."

Standard treatment is not the only approach, Dr. Aoyama said. If patients are remote from the hospital and cannot be followed closely, for example, WBRT should be included in their initial management. "On the other hand, if the patient cares about hair loss and the potential risk of neurocognitive deterioration with WBRT and is willing to receive frequent MRI follow-up, SRS alone can be a treatment option."

In this study, they found patients with a single metastasis, stable systemic disease, and good performance status had a lower risk for tumor recurrence, Dr. Aoyama added. "Therefore, I personally think that those patients are good candidates for SRS alone as an initial brain treatment, although further investigation should be conducted to find an optimal group of patients who have a really very low risk of brain tumor recurrence."

Either, or Both . . .

In an editorial accompanying the paper, Jeffrey Raizer, MD, from the Feinberg School of Medicine, Northwestern University, Chicago, Illinois, suggests that, on the basis of the current findings, along with other reports in the literature, patients with more than 4 metastases should continue to be treated with WBRT, but for those with 4 or fewer metastases, the addition of SRS to WBRT improves local brain control but does not affect survival.

"Therefore, either mode is a reasonable first choice; the exception is for patients with a single brain metastasis, non–small cell lung cancer, or RPA class 1 patients, for whom stereotactic radiosurgery should be added to WBRT."

The current paper confirms that "withholding stereotactic radiosurgery does not influence how patients die of their disease," Dr. Raizer concludes. "Whether overall quality of life is positively or negatively affected is unknown, but for patients who might be cured of their cancer, omitting WBRT could avoid long-term neurotoxic effects."

The authors report no relevant financial relationships.

JAMA. 2006;295:2483-2491, 2535-2536.