SRS Reduces Cognitive Decline in Those With Brain Metastases

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Findings from a secondary analysis of a phase 3 trial support stereotactic radiosurgery as a standard of care for those with brain metastases, although whole-brain radiotherapy may yield more local and distant control.

Our data support the use of SRS alone after surgical resection as the standard of care, as was previously reported; however, our data suggest that the additional local and distant control gained by the use of WBRT may be important if the long-term toxic effects of WBRT are mitigated," according to the study authors.

Our data support the use of SRS alone after surgical resection as the standard of care, as was previously reported; however, our data suggest that the additional local and distant control gained by the use of WBRT may be important if the long-term toxic effects of WBRT are mitigated," according to the study authors.

The use of stereotactic radiosurgery (SRS) correlated with less cognitive decline compared with postoperative whole-brain radiotherapy (WBRT) in patients with cancer and brain metastases, although the latter resulted in an improvement in intracranial tumor control, according to findings from a secondary analysis of the phase 3 N107C/CEC.3 trial (NCT01372774).

The 3-month rates of cognitive deterioration were 37.0% in the SRS group compared with 88.9% in the WBRT group. The 12-month rates in each respective group were 62.5% vs 91.3%. In the SRS and WBRT groups, respectively, a 1.5 standard deviation (SD) decline in at least 1 cognitive test was less probable in the former at 3 months (30% vs 74%), 6 months (35% vs 77%), 12 months (50% vs 83%), and 16 months (43% vs 74%). Additionally, the likelihood of a 2 SD decline in a minimum of 1 cognitive test was lower in the SRS group at 3 months (22% vs 70%), 6 months (20% vs 46%), and 9 months (20% vs 50%).

The overall rates of intracranial control rates in the SRS and WBRT groups, respectively, were 88.9% vs 100% at 3 months, 70.4% vs 92.6% at 6 months, and 40.7% vs 81.5% at 12 months (P = .003). There were no instances of leptomeningeal disease in either treatment arm.

“Our data support the use of SRS alone after surgical resection as the standard of care, as was previously reported; however, our data suggest that the additional local and distant control gained by the use of WBRT may be important if the long-term toxic effects of WBRT are mitigated,” the study authors wrote.

In the N107C/CEC.3 trial, patients were randomly assigned to receive SRS or WBRT. Investigators administered WBRT at 3000 cGy in 10 fractions or 3750 cGy in 15 fractions, and the radiosurgery dose to the surgical cavity in the SRS arm was dependent on the volume of the cavity. The secondary analysis assessed how SRS or WBRT impacted intracranial tumor control, cognitive deterioration, quality of life (QOL), and cognitive outcomes in evaluable patients who were alive at a year following randomization.

Patients with 1 to 4 brain metastases following surgical resection of 1 metastasis were able to enroll on the study. Other eligibility criteria included having an ECOG performance status of 0 to 2, a brain metastasis resection with a cavity no larger than 5 cm, and no more than 3 unresected brain metastases.

The secondary analysis included 54 long-term survivors from the phase 3 trial, with 27 who underwent treatment with SRS and 27 who received WBRT. The median patient age across the entire population was 60 years (IQR, 52-64). Most patients in the SRS and WBRT arms, respectively, had 1 brain metastasis (78% vs 74%), lung cancer histology (70% vs 59%), and an ECOG performance status of 1 (59% vs 56%).

Compared with the WBRT group, those who received SRS had lower mean QOL scores for physical wellbeing by –10 points (95% CI, –20.0 to –0.3), emotional wellbeing by –9.6 points (95% CI, –18.0 to –0.84), and general scores by –7.3 points (95% CI, –14.0 to –0.16). Additionally, a minimum of 2 cognitive measures with at least 2.0 SD declines correlated with lower mean QOL scores for emotional wellbeing by –10 points (95% CI, –20.0 to –0.30), functional wellbeing by –16 points (95% CI, –27.0 to –3.9), general scores by –8.9 points (95% CI, –17.0 to –0.70), additional concerns by –11 points (95% CI, –18.0 to –4.5), and total score by –12 points (95% CI, –19.0 to –4.5).

Any-grade adverse effects (AEs) affected 26 patients in the WBRT group and 22 of those who were treated with SRS. Additionally, grade 3 or higher AEs occurred in 8 and 5 patients in each respective arm.

Reference

Palmer JD, Klamer BG, Ballman KV, et al. Association of long-term outcomes with stereotactic radiosurgery vs whole-brain radiotherapy for resected brain metastasis: a secondary analysis of the N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group) randomized clinical trial. JAMA Oncol. 2022;8(12):1809-1815. doi:10.1001/jamaoncol.2022.5049

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