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Journal Club

Tumor/Skull Base

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

Rapid review note

Journal Club is a rapid, AI-assisted appraisal layer. It highlights study design, effect estimates, and practice relevance, but it is still a briefing, not a replacement for the paper.

For education only. Not medical advice.

Paper snapshot

Rapid study overview

Open paper

DOI

10.1001/jama.2016.9839

PMID

27458945

PICO

Population

Patients with 1 to 3 brain metastases

Intervention

Stereotactic radiosurgery (SRS) alone

Comparator

SRS plus whole brain radiation therapy (WBRT)

Outcomes

Cognitive deterioration at 3 months, time to intracranial failure, quality of life, functional independence, overall survival

Design

Type

Randomized clinical trial

Randomized

Yes

Multicenter

Yes

Blinded

Not reported

Follow-up

Primary endpoint at 3 months; long-term cognitive status assessed up to 12 months

Primary endpoint

Cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test) at 3 months

Secondary endpoints

  • Time to intracranial failure
  • Quality of life
  • Functional independence
  • Long-term cognitive status
  • Overall survival

Practice impact

What this means

This randomized trial compared SRS alone versus SRS+WBRT in patients with 1-3 brain metastases. SRS alone resulted in significantly less cognitive deterioration at 3 months (63.5% vs 91.7%) but had higher intracranial failure (HR 3.6). There was no difference in overall survival. For patients prioritizing cognitive preservation, SRS alone may be preferred despite increased local failure risk.

Bottom line

SRS alone results in less cognitive deterioration at 3 months compared to SRS+WBRT, with no survival difference but higher intracranial failure.

Strength of evidence

high

Recommendation

consider change

Why it matters

  • Randomized trial showing significant cognitive benefit with SRS alone
  • No overall survival difference between groups
  • Higher intracranial failure with SRS alone requires consideration

What would change my mind

  • Long-term survival data showing benefit of WBRT
  • Subgroup analysis identifying patients who benefit from WBRT
  • Improved neurocognitive assessment methods

Critical appraisal

How strong is the paper?

Methods critique

Risk of bias

Randomized multicenter design reduces selection bias; no mention of blinding for cognitive assessments

Confounding

Baseline characteristics balanced; no major confounders identified

Missing data

Primary analysis used completers (111/213 randomized); missing data could affect estimates

Multiplicity

Multiple secondary endpoints tested without explicit adjustment

Notes

  • Primary endpoint analysis limited to patients completing baseline and 3-month assessments
  • Cognitive deterioration defined as >1 SD decline on any test

Stats check

NNT

N/A

Effect sizes

  • HR 3.6 (95% CI 2.2-5.9) for time to intracranial failure
  • HR 1.02 (95% CI 0.75-1.38) for overall survival

Absolute effects

  • 63.5% cognitive deterioration with SRS alone vs 91.7% with SRS+WBRT at 3 months
  • Median overall survival 10.4 months (SRS alone) vs 7.4 months (SRS+WBRT)

Concerns

  • 90% CI used for primary endpoint difference
  • Completer analysis may introduce bias

External validity

Who it applies to

Patients with 1-3 brain metastases amenable to radiosurgery, mean age 60.6 years

Who it does not

Patients with >3 metastases, poor performance status, or leptomeningeal disease

Generalizability notes

  • Multicenter North American trial with 34 institutions
  • WBRT dose was 30 Gy in 12 fractions

Evidence trace

Source trace and metadata

Citations (3)

claim_id

methods_critique.missing_data

locator

p. 5 Results

quote

Primary end point was cognitive deterioration... in participants who completed the baseline and 3-month assessments.

claim_id

stats_check.effect_sizes

locator

p. 5 Results

quote

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).

claim_id

practice_impact.rationale

locator

p. 5 Results

quote

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).

Metadata

Generated at

2026-03-06T13:41:29.251Z

Version

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