In patients with brain metastases, use of stereotactic radiosurgery (SRS) alone compared with SRS plus whole brain radiotherapy (WBRT) is associated with less cognitive deterioration at 3 months, according to data published in JAMA.1
Although the combination therapy has been shown to be more effective for tumor control, its association with cognitive problems has made the therapy more controversial.
To analyze the effects of SRS or SRS and WBRT on cognition, Paul D. Brown, MD, of Mayo Clinic in Rochester, MN and colleagues randomized 213 patients with 1 to 3 brain metastases (less than 3cm diameter) to receive SRS or SRS plus WBRT between February 2002 and December 2013. Patients had a mean age of 60.6 years and 48% (103) were women.
Ultimately, 111 patients were randomized to receive SRS alone (20-24 Gy) and 102 were randomized to receive SRS plus WBRT (30 Gy WBRT in 12 fractions; 18-22 Gy SRS). The rate of cognitive deterioration was less in the SRS alone group (40/63 patients [63.5%]) vs the SRS plus WBRT group at 3 months (44/48 patients [91.7%]; difference, −28.2%; 90% CI, −41.9% to −14.4%; P< .001).
Analysis of secondary endpoints revealed that quality of life at 3 months was greater in the SRS alone group (mean change from baseline, −0.1 vs −12.0 points; mean difference, 11.9; 95%CI, 4.8-19.0 points; P= .001); however time to intracranial failure was significantly shorter in the SRS alone group vs the SRS plus WBRT group (HR, 3.6; 95%CI, 2.2-5.9; P< .001). The authors noted that median overall survival was 10.4 months in the SRS alone group vs 7.4 months in the SRS plus WBRT group (HR, 1.02; 95%CI, 0.75-1.38; P= .92). Thus, despite better intracranial disease control in the SRS plus WBRT group at 3, 6, and 12 months (93.7% vs 75%, 88.4% vs 64%, 85% vs 50%, respectively), this effect did not improve overall survival.
Additionally, no significant difference was observed for functional independence at 3 months between the 2 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).
When the authors examined cognition in long-term survivors, they found that cognitive deterioration in the SRS alone group was still less than the combination therapy group 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 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, −34.4%; 95%CI, −74.4%to 5.5%; P= .04).
“The debate between WBRT and SRS has been resolved for the specific type of patient (with 1-3 metastases) who enrolled in the current study, and there is little role for WBRT for these patients,” commented Kaidar-Person et al, who authored a related editorial.2
“However, both treatment modes have a valid position in clinical practice because many patients do not precisely fit the characteristics for study entry.”
Noting that the characteristics of the study did not account for various physiological and genetic differences in patients, they concluded that “…the study results cannot be extrapolated to infer that SRS is the standard for patients with 4 or more metastases or that WBRT no longer has a role in the treatment of brain metastases.”
- Brown PD, Jaeckle K, Ballman KV, et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016;316(4):401-409. doi:10.1001/jama.2016.9839.
- Kaidar-Person O, Anders CK, Zagar TM. Whole Brain Radiotherapy for Brain Metastases: Is the Debate Over? JAMA. 2016;316(4):393-395. doi:10.1001/jama.2016.8692.