This article is more than 5 years old. Information may no longer be current.
Radiosurgery alone lessens cognitive decline for patients with limited brain metastases
Click Here to Manage Email Alerts
The use of stereotactic radiosurgery without adjuvant whole-brain radiation lessened cognitive deterioration at 3 months among patients with one to three brain metastases, according to the results of multicenter, randomized trial.
However, OS did not differ between patients who received stereotactic radiosurgery (SRS) alone or with whole-brain radiotherapy (WBRT).
“SRS is an effective and commonly used treatment for brain metastases, but intracranial tumor progression is frequent after SRS alone, primarily because of the development of new metastatic lesions,” Paul D. Brown, MD, radiation oncologist at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “Additionally, central to this issue is whether tumor progression anywhere in the brain is more detrimental to a patient’s well-being than the potential deterioration of cognitive function and quality of life associated with WBRT. Because more than 200,000 individuals in the United States alone are estimated to receive WBRT each year, it is important that the potential benefits and risks of adjuvant WBRT be clearly defined.”
Brown and colleagues evaluated whether SRS alone could lessen cognitive deterioration at 3 months. They randomly assigned 213 patients with one to three brain metastases between February 2002 and December 2013 to receive SRS alone (n = 111; mean age, 59.8 years; 51.4% women) or with adjuvant WBRT (n = 102; mean age, 61.4 years; 45.5% female). The primary tumor site was lung in 72.1% of patients in the SRS arm and 65.4% of patients on the SRS plus WBRT arm.
Patients assigned SRS alone received 20 to 24 Gy. Patients assigned the combination received 18 to 22 Gy of SRS and 12 fractions of 30 Gy of WBRT within 14 days of SRS.
Cognitive deterioration — defined as more than one standard deviation decline from baseline on at least one cognitive test at 3 months — served as the study’s primary endpoint.
Secondary endpoints included time to intracranial failure, quality of life, functional independence, long-term cognitive status and OS.
Researchers repeated all baseline evaluations at 6 weeks, and at 3, 6, 9, 12, 16, 24, 36, 48 and 60 months.
Based on a 73.5% overall testing completion rate, 63 patients in the SRS arm and 48 from the combination arm were evaluable. Median follow-up for these patients was 11.6 months (95% CI, 2.7-62.5).
Overall, 63.5% of patients in the SRS arm experienced cognitive decline compared with 91.7% of patients in the combination arm (difference, –28.2%; 90% CI, –41.9% to –14.4%).
Eighty-seven patients from the SRS arm and 69 from the combination arm had quality-of-life data recorded at baseline and at a subsequent time point. Mean change from baseline in overall quality-of-life scores was –0.1 in the SRS arm compared with –12 in the combination arm (mean difference, 11.9; 95% CI, 4.8-19). Functional well-being also had greater declines in the combination arm (mean change from baseline, 2.5 vs. –22.3; mean difference, 24.7 points; 95% CI, 7.2-42.2). There was no significant difference in functional independence at 3 months between the two groups.
However, patients in the SRS group experienced a significantly shorter time to intracranial failure (HR = 3.6; 95% CI, 2.2-5.9). A greater proportion of patients in the SRS plus WBRT group achieved 3-month intracranial tumor control (93.7% vs. 75.3%; difference, 18.4%; 95% CI, 7.8-29).
Survival appeared comparable in both groups, despite the higher intracranial tumor control rate in the WBRT arm (median OS for SRS alone, 10.4 months; SRS plus WBRT, 7.4 months; HR = 1.02; 95% CI, 0.75-1.38).
Among patients who survived at least 12 months following randomization (SRS, n = 19; control, n = 15), fewer patients in the SRS arm experienced cognitive deterioration at 3 months (45.5%vs. 94.1%; P = .007) and 12 months (60% vs. 94.4%; P = .04).
Incidence of grade 3 or worse adverse events occurred in similar proportions of patients on each arm.
These results may be limited since researchers did not attempt to enrich for primary cancers other than lung cancer.
“In the absence of a difference in OS, these findings suggest that for patients with one to three brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy,” Brown and colleagues wrote.
These results do not imply that WBRT no longer has a role in the treatment of brain metastases, Orit Kaidar-Person, MD, clinical fellow in the department of radiation oncology at University of North Carolina at Chapel Hill, and colleagues wrote in an accompanying editorial.
“The debate between WBRT and SRS has been resolved for the specific type of patient (those with one to three brain metastases) who enrolled in the current study, and there is little role for WBRT for these patients,” they wrote. “However, both treatment modes have a valid position in clinical practice because many patients do not precisely fit the characteristics for study entry. ... the study results cannot be extrapolated to infer that SRS is the standard for patients with four or more metastases or that WBRT no longer has a role in the treatment of brain metastases.” – by Nick Andrews
Disclosure: Brown reports no relevant financial disclosures. One researcher reports an advisory board role with Orbus Therapeutics, as well as data and safety monitoring membership with and travel reimbursement and honoraria from Bristol-Myers Squibb. Kaidar-Person reports no relevant financial disclosures. Please see the accompanying editorial for a list of all other authors’ relevant financial disclosures.
Click Here to Manage Email Alerts