ASTRO. US: Cancer patients with limited brain metastases (one to four tumors)
who are ≤50 years old should receive stereotactic radiosurgery (SRS)
without whole brain radiation therapy (WBRT), according to a study
available online, open-access, and published in the March 15, 2015 issue
of the International Journal of Radiation Oncology • Biology • Physics
(Red Journal), the official scientific journal of the American Society
for Radiation Oncology (ASTRO). For patients ≤50 years old who received
SRS alone, survival was improved by 13 percentage points when compared
to those patients ≤50 who received both SRS and WBRT.
This study, “Phase 3 Trials of Stereotactic Radiation Surgery With or
Without Whole-Brain Radiation Therapy For 1 to 4 Brain Metastases:
Individual Patient Data Meta-Analysis,” analyzed patient data from the
three largest randomized clinical trials (RCT) of SRS and WBRT conducted
to-date: the Asian trial (JROSG99-1) by Aoyama et al.1, published in 2006; the North American trial (MDACC NCT00548756) by Chang et al.2, published in 2009; and the European trial (EORTC 22952-26001) by Kocher et al.3,
published in 2011. A total of 364 patients from the three RCTs were
evaluated for this meta-analysis. Of those 364 patients, 51 percent
(186) were treated with SRS alone, and 49 percent (178) received both
SRS and WBRT. Nineteen percent of patients (68) were ≤50 years of age,
and 61 percent (19) of these patients had a single brain metastasis.
Twenty percent of all patients (72) had local brain failure, which is
the occurrence of progression of previously treated brain metastases;
and 43 percent (156) experienced distant brain failure, which is the
occurrence of new brain metastases in areas of the brain outside the
primary tumor site(s).
The impact of age on treatment effectiveness revealed SRS alone
yielded improved overall survival (OS) in patients 50 years old and
younger. Patients ≤50 years old who received SRS alone had a median
survival of 13.6 months after treatment, a 65 percent improvement, as
opposed to 8.2 months for patients ≤50 who were treated with SRS plus
WBRT. Patients >50 years old had a median survival of 10.1 months
when treated with SRS alone, and 8.6 months for those who received SRS
plus WBRT.
“We expected to see a survival advantage favoring combined therapy of
SRS and WBRT. However, these data clearly demonstrate the benefit for
SRS alone to improve survival for our younger patients with limited
brain metastases,” said lead author of the study Arjun Sahgal, MD,
associate professor of radiation oncology and surgery at the University
of Toronto, and a radiation oncologist at the Odette Cancer Centre of
the Sunnybrook Health Sciences Centre in Toronto. “Furthermore, it was
previously thought that the positive effect of whole brain radiation in
reducing the risk of distant brain relapse was generalizable for all
patients. However, we did not observe this effect in patients 50 years
and younger with limited brain metastases. In these patients, the same
rate of distant brain failure was observed despite treatment with whole
brain radiation. This result, together with our survival result, gave
rise to the hypothesis that if patients are treated with whole brain
radiation without realizing the benefits of improving distant brain
control, then survival may be adversely affected. Therefore, our
sub-group meta-analysis has swung the pendulum in favor of SRS alone as
the standard of care. These findings also reinforce ASTRO’s Choosing Wisely® recommendation4 that states that it may not be necessary to add WBRT to SRS, thus improving patients’ quality of life and memory function.”
In addition to being open-access (free to the public), Sahgal et al.’s paper is also available for SA-CME credit.
Drs. Nils D. Arvold and Paul J. Catalano have reviewed Sahgal et
al.’s research. Their editorial, “Local Therapies for Brain Metastases,
Competing Risks, and Overall Survival,” is also published in the March
15, 2015, issue of the Red Journal.
For a copy of the study manuscript and the editorial, contact ASTRO’s Press Office. Learn more about the Red Journal.
[1] Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery
plus whole-brain radiation therapy vs stereotactic radiosurgery alone
for treatment of bone metastases: A randomized controlled trial. JAMA 2006;295:2483-2491.
[2]
Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with
brain metastases treated with radiosurgery or radiosurgery plus
whole-brain irradiation: a randomised controlled trial. Lancet Oncol 2009;10:1037-1044.
[3]
Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain
radiotherapy versus observation after radiosurgery or surgical resection
of one to three cerebral metastases: results of the EORTC 22952-26001
study. J Clin Oncol 2010;29:134-141.
[4] ASTRO’s Choosing Wisely® List. ABIM Foundation. http://www.choosingwisely.org/doctor-patient-lists/american-society-for-radiation-oncology/