Science Times: Effect of Whole Brain Radiation Therapy on Cognitive Function

Brain metastases (BM) are common and can be detrimental in patients with primary cancers. Lung cancer accounts for over 40% of BM cases and breast cancer is responsible for 10% to 20% of BM. Typically, patients present with oligometastatic disease—1 to 3 intracranial metastases. Stereotactic radiosurgery (SRS) is often used to good effect in treating these tumors. To investigate intracranial tumor progression control, researchers have conducted randomized clinical trials (RCTs) in which whole brain radiotherapy (WBRT) was added to the clinical regimen following SRS. RCTs demonstrated that WBRT did in fact show improvement in intracranial tumor control; however, WBRT does not confer a survival advantage. In fact, previous RCTs have suggested that WBRT may cause deterioration of cognitive function and quality of life (QOL).1-3

Brown et al1 conducted the largest, multi-institutional study utilizing a plethora of cognitive and QOL assessments to determine the effects of WBRT. They enrolled 213 randomized participants with 1 to 3 BM at 34 participating institutions. One group underwent SRS alone and the second group had SRS plus WBRT that began within 14 days of SRS. The WBRT dose regimen was 30 Gy in 12 fractions and the SRS dose was 18 to 22 Gy in the SRS plus WBRT group, and 20 to 24 Gy in SRS alone. Baseline evaluations were made starting at week 6 and subsequently at months 3, 6, 9, and eventually, at month 60. QOL was assessed using the Functional Assessment of Cancer Therapy-Brain. Scores ranged between 0 and 200 where higher scores signified better QOL. The Barthel Index of Activities of Daily Living (ADL Index) was used to determine functional independence where a score of 100 indicated complete independence and a lower score demonstrated the need for supervision and assistance. Seven other assessments were used to evaluate immediate memory, fine motor control, delayed memory, and other cognitive abilities. The primary endpoint was deemed to be cognitive deterioration at 3 months after SRS defined as a decline in any of the cognitive tests. Secondary endpoints included time to intracranial failure, overall survival, QOL, as well as other parameters.

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