Neurocognitive Function and Quality of Life After Multifraction Radiosurgery for Large Resected and Intact Brain...

Stereotactic radiosurgery (SRS) is the standard of care for brain metastases, providing effective local tumor control while avoiding the neurocognitive effects of whole-brain radiation therapy. However, large brain metastases have been excluded from the randomized studies of single-fraction SRS, and there are limited data regarding neurocognitive outcomes with multifraction radiosurgery approaches for large intact or resected brain metastases.

We performed a prospective phase 1 dose-escalation study of multifraction SRS for intact or resected brain metastases 3 to 6 cm in diameter from 2012 to 2021. Patients longitudinally completed the Hopkins Verbal Learning Test (HVLT), Mini-Mental State Examination, Functional Assessment of Cancer Therapy-Brain, and Medical Outcomes Cognitive Scale. Reliable Change Index is used to assess HVLT change from baseline to 4 months. Significance is defined as greater than 1 SD change. Analysis of variance comparisons were performed for clinicodemographic characteristics associated with neurocognitive outcomes or quality-of-life metrics.

Of the 24 patients treated in the trial, 15 completed both baseline and 4-month neurocognitive assessments. For the 15 patients with neurocognitive assessments, median age was 57 years (range, 37-74 years), median baseline Karnofsky Performance Status was 80 (range, 70-90), and median volume of radiation target was 15.9 cm³ (range, 7.7-57.2 cm³). At 4 months, 20% of patients had a significant decline in HVLT Total Recall scores, 33% had no significant change, and 47% had significant improvement. Mean neurocognitive function and quality-of-life scores were either stable or improved over time up to the last evaluation at 25 months. There were no clinical or treatment characteristics significantly associated with changes in neurocognitive function or quality-of-life scores.

Of the evaluable patients with large brain metastases treated with dose-escalated, multifraction SRS, the majority of patients demonstrated stable or improved neurocognitive function and quality of life in follow-up.