NEW ORLEANSFor certain types of patients with brain metastases, the addition of stereotactic
radiosurgery after whole brain radiation therapy improved survival as well as
local control, performance status, and steroid dependency, according to a phase
III study by the Radiation Therapy Oncology Group (RTOG). Lead investigator
Paul W. Sperduto, MD, of Methodist Hospital, Minneapolis, presented the results
at the 44th Annual Meeting of the American Society for Therapeutic Radiation
and Oncology (abstract plenary 5).
"We consider whole brain radiation therapy plus radiosurgery
to be the new standard of care for patients who fit the eligibility for this
trial," he said.
RTOG 95-08 enrolled 333 cancer patients from 34 institutions
between 1996 and 2001 in a study that evaluated whether stereotactic
radiosurgery improved overall survival in patients with one to three brain
metastases. The study was stratified by the number of brain metastases and the
extent of extracranial metastases. The patients were randomized to receive
whole brain radiation therapy (WBRT) plus stereotactic radiosurgery or WBRT
alone. WBRT was given at 250 cGy/fraction up to 3,750 cGy in 3 weeks. The
stereotactic radiosurgery dose was based on tumor size and was delivered within
1 week of completion of WBRT.
The intention-to-treat analysis of all patients showed
overall survival of 6.5 months for the WBRT plus radiosurgery patients and 5.7
months for WBRT alone (P = .13), Dr. Sperduto reported. For certain
groups of patients, there was a statistically significant improvement in
survival with stereotactic radiosurgery (see Table). These included
patients with a solitary brain metastasis; those with one to three metastases
and age less than 50; those with one to three metastases and non-small-cell
lung cancer (NSCLC); and those with one to three metastases and RTOG RPA class
I. [RPArecursive partitioning analysisclasses are based on Karnofsky
performance status, age, control of primary tumor, and extracranial
For several other groups, the survival benefit approached
significance. These included patients with Karnofsky performance status of 90
to 100 (10.2 vs 7.4 months for WBRT alone), patients with tumor size greater
than 2 cm, and patients with a controlled primary tumor.
Dr. Sperduto speculated that the lack of an overall survival
benefit with the addition of radiosurgery might be due to the high rate of
patients who were randomized to radiosurgery but did not receive it19% overall
and 24% with two to three metastases. Secondly, many patients in the WBRT group
(17%) received salvage radiosurgery.
RPA class I patients (age less than 65, Karnofsky
performance status 70 or higher, controlled primary tumor, and no extracranial
metastases) had the best outcomes, with a 2-year survival of 40%, Dr. Sperduto
said. Multivariate analysis found RPA class to be by far the most significant
predictive factor. Components of the RPA classnamely Karnofsky performance
status, age, and extracranial metastaseswere also significant prognostic
factors, he said.