Preservation of neurocognitive function and local control of 1 to 3 brain metastases treated with surgery and carmustine wafers

Steven Brem, Christina A Meyers, Gary Palmer, Margaret Booth-Jones, Surbhi Jain, Matthew G Ewend, Steven Brem, Christina A Meyers, Gary Palmer, Margaret Booth-Jones, Surbhi Jain, Matthew G Ewend

Abstract

Background: Neurosurgical resection and whole-brain radiation therapy (WBRT) are accepted treatments for single and oligometastatic cancer to the brain. To avoid the decline in neurocognitive function (NCF) linked to WBRT, the authors conducted a prospective, multicenter, phase 2 study to determine whether surgery and carmustine wafers (CW), while deferring WBRT, could preserve NCF and achieve local control (LC).

Methods: NCF and LC were measured in 59 patients who underwent resection and received CW for a single (83%) or dominant (oligometastatic, 2 to 3 lesions) metastasis and received stereotactic radiosurgery (SRS) for tiny nodules not treated with resection plus CW. Preservation of NCF was defined as an improvement or a decline ≤ 1 standard deviation from baseline in 3 domains: memory, executive function, and fine motor skills, evaluated at 2-month intervals.

Results: Significant improvements in executive function and memory occurred throughout the 1-year follow-up. Preservation or improvement of NCF occurred in all 3 domains for the majority of patients at each of the 2-month intervals. NCF declined in only 1 patient. The chemowafers were well tolerated, and serious adverse events were reversible. There was local recurrence in 28% of the patients at 1-year follow-up.

Conclusions: Patients with brain metastases had improvements in their cognitive trajectory, especially memory and executive function, after treatment with resection plus CW. The rate of LC (78%) was comparable to historic rates of surgery with WBRT and superior to reports of WBRT alone. For patients who undergo resection for symptomatic or large-volume metastasis or for tissue diagnosis, the addition of CW can be considered as an option.

Trial registration: ClinicalTrials.gov NCT00525590.

Keywords: brain metastases; carmustine wafers; neurocognitive function; stereotactic radiosurgery; whole brain radiotherapy.

© 2013 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Figures

Figure 1
Figure 1
Preoperative and postoperative magnetic resonance images (MRIs) are shown. A patient with metastatic melanoma developed aphasia and facial weakness. (A) The 3-dimensional preoperative model reveals the tumor (green), the primary motor cortex (red) and arcuate fasciculus (purple), the Broca speech area (yellow), and the corticospinal tract (purple). (B) This preoperative sagittal MRI reveals a single hemorrhagic metastasis (arrows) in the left frontal lobe near the primary motor and the Broca speech areas. (C) This postoperative MRI reveals resection of the tumor and intracavitary placement of the carmustine wafers. Speech, motor, and neurocognitive function returned postoperatively. (D) A follow-up scan shows no tumor recurrence at 34 months.
Figure 2
Figure 2
Participant flow is illustrated. CNS indicates central nervous system; WBRT, whole-brain radiation therapy.
Figure 3
Figure 3
Improvement in neurocognitive function was measured after surgical resection and carmustine wafer placement for brain metastasis using average, standardized Z-scores (indicated as the mean change with 95% confidence interval [CI]). Statistically significant changes were noted in (A) memory (a, P = .001; b, P = .029) and (B) executive function (a, P = .001; b, P = .0007; c [left], P = .041; c [right], P = .018). (C) Fine motor skills.
Figure 4
Figure 4
These are Kaplan-Meier curves for (A) local recurrence and (B) distant recurrence. The median time to distant recurrence was 8.5 months.

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Source: PubMed

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