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Abstract

IMPORTANCE:

Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial.

OBJECTIVE:

To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT.

DESIGN, SETTING, AND PARTICIPANTS:

At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013.

INTERVENTIONS:

The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone.

MAIN OUTCOMES AND MEASURES:

The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival.

RESULTS:

There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, -48.7%; 95% CI, -87.6% to -9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, -34.4%; 95% CI, -74.4% to 5.5%; P = .04).

CONCLUSIONS AND RELEVANCE:

Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00377156.

Comment in

Whole Brain Radiotherapy for Brain Metastases: Is the Debate Over? [JAMA. 2016] 

Author information

Brown PD1, Jaeckle K2, Ballman KV3, Farace E4, Cerhan JH5, Anderson SK3, Carrero XW3, Barker FG 2nd6, Deming R7, Burri SH8, Ménard C9, Chung C10, Stieber VW11, Pollock BE5, Galanis E5, Buckner JC5, Asher AL12.

1University of Texas M. D. Anderson Cancer Center, Houston2Mayo Clinic, Rochester, Minnesota.

2Mayo Clinic, Jacksonville, Florida.

3Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.

4Penn State Hershey Medical Center, Hershey, Pennsylvania.

5Mayo Clinic, Rochester, Minnesota.

6Massachusetts General Hospital, Boston.

7Mercy Medical Center, Des Moines, Iowa.

8Levine Cancer Institute, Carolinas Healthcare System, Charlotte, North Carolina.

9Princess Margaret Cancer Centre, Toronto, Ontario, Canada10Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.

10Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

11Novant Health Forsyth Medical Center, Winston-Salem, North Carolina.

12Levine Cancer Institute, Carolinas Healthcare System, Charlotte, North Carolina12Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina.