Effect of Radiosurgery Alone vs Radiosurgery with Whole Brain Radiation Therapy on Cognitive Function in Patients with 1 to 3 Brain Metastases

Franklin Reeves, Mercer University College of Pharmacy

According to a review of several clinical trials involving metastatic brain cancer, approximately 20% to 40% of patients with cancer will go on to develop brain metastases. Primary tumor histologies most commonly involved in these cases are non-small cell lung cancer, breast cancer, melanoma, colon cancer, and renal cell carcinoma. The authors add that the median survival of patients following this diagnosis is less than six months.1

Furthermore, the article highlights two treatment options including stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT). It was stated that the identification of WBRT increased overall survival from 1-2 months to 3-6 months and involves the treatment of the entire brain over a period of several weeks. Conversely, SRS is a technique that focuses high-dose radiation at precise intracranial targets to shrink tumor lesions.1

Additionally, while WBRT has been mentioned as the standard of treatment for brain metastases and increased overall survival, it is has been associated with numerous toxic side effects. This has led to the desire for a more optimal approach to metastatic cancer treatment.1

Title: Effect of Radiosurgery Alone vs Radiosurgery with WBRT on Cognitive Function in Patients with 1 to 3 Brain Metastases2
Design Randomized, controlled trial; N = 213
Objective Determine whether there is less cognitive deterioration at 3 months after SRS alone vs. SRS plus WBRT
Study Groups 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102)
Methods Patients randomly assigned to receive SRS alone received 24 Gray units (Gy) in a single fraction if lesions were less than 2.0 cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter. Patients randomly assigned to undergo SRS plus WBRT received 22 Gy in a single fraction if lesions < 2.0 cm or 18 Gy if lesions were 2-2.9 cm in maximum diameter. The dose was prescribed to the highest isodose line encompassing the target, ranging from 50% to 80% of the maximum dose. Patients randomly assigned to SRS plus WBRT received 30 Gy in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Duration February 2002 to December 2013
Primary Outcome Measure Cognitive deterioration > 1 standard deviation (SD) from baseline on at least 1 cognitive test at 3 months
Baseline Characteristics The patient studied were a mean age of 60.6 years (SD, 10.5 years) and 103 (48%) were women.
Results Cognitive deterioration in evaluable patients at 3 months was less frequent after SRS alone than after SRS plus WBRT (40/63 [63.5%] vs 44/48 [91.7%], respectively; difference, −28.2%; 90% CI, −41.9% to −14.4%; P < .001).
Adverse Events Common Adverse Events: Nausea (4.7%) Fatigue (4.2%), Anorexia (3.8%)
Serious Adverse Events: Seizure (2.8%), Arrhythmia (0.5%), Respiratory Distress (0.5%)
Percentage that Discontinued due to Adverse Events: 62/213 (29%)
Study Author Conclusions Among patients with one to three brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. These findings suggest that for patients with one to three brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy.

The results of this study indicate that a treatment strategy of SRS plus WRBT has no benefit in overall survival and worsens cognitive decline, functional status and quality of life compared to SRS alone in patients with brain metastases. To add, radiological treatment, in general, only results in an increase of about 3-6 months in overall survival. Current research as failed to established a correlation of tumor progression decline in cognitive function and overall survival. For these reasons a shift in treatment strategy seems to be on the rise, involving a more targeted, and less aggressive approach, with radiation therapy. In this approach, a comprehensive monitoring program of cognitive decline and functional status would parallel the radiation strategy.


  1. Patil CG, Pricola K, Sarmiento JM, Garg SK, Bryant A, Black KL. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev. 2012;(9):CD006121.
  1. 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):401-9.




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