Clinical Investigation
Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

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Purpose

To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases.

Methods and Materials

Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6–8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast.

Results

Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT.

Conclusions

The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6–8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.

Introduction

Whole brain radiotherapy (WBRT) is the standard treatment for patients with brain metastases, especially with multiple lesions. It results in a median survival of 4–6 months and improves neurologic function in about one-half of the patients 1, 2. Prophylactic WBRT provides a survival benefit in patients with limited and extensive small-cell lung cancer 3, 4.

The acute side effects of WBRT can include alopecia, fatigue, and dermatitis; these are generally temporary. However, potential acute and subacute neurocognitive dysfunction in these patients has been widely discussed and is poorly understood. We have previously reported impaired performance in the verbal memory domain after the first fraction and 6–8 weeks after completion of fractionated stereotactic RT in patients with base of skull meningioma (5). In contrast, patients undergoing hyperfractionated total body irradiation before autologous bone marrow/peripheral blood stem cell transplantation showed no verbal memory impairment 6, 7.

The objective of the present study was to systematically evaluate the timing, intensity, and specificity of neurocognitive changes during and immediately after WBRT completion in patients with and without brain metastases, with special emphasis on verbal memory function. The results were compared with those from control patients undergoing RT to the breast.

Section snippets

Patients

A total of 44 patients were prospectively enrolled (Table 1 [8, 9, 10, 11, 12]), of whom 13 were small-cell lung cancer patients (prophylactic cranial irradiation [PCI] group). The therapeutic cranial irradiation (TCI) group (n = 16) consisted of 11 patients with non–small-cell lung cancer, 3 patients with breast cancer, and 2 patients with gastrointestinal cancer. The control group consisted of 15 patients with breast cancer.

The eligibility criteria included age ≥18 years, no previous cranial

Study population

The demographic and treatment-related characteristics of the patient groups are listed in Table 2, Table 3. The three groups differed in age (F = 8.2, p = 0.001), Karnofsky performance status (F = 3.7, p = 0.034), and chemotherapy status (chi-square = 13.0, p = 0.006), with almost all PCI patients pretreated with chemotherapy in the previous 3 months.

In all patient groups, a premorbid intelligence level in the normal range was observed. The mean scores for anxiety and depression and the rate of

Discussion

We investigated cognitive function during and after WBRT in patients with and without brain metastases compared with control patients receiving RT for breast cancer. A neuropsychological test battery that took ≤45 min was performed to obtain the acute and subacute effects of WBRT.

First, even before the start of WBRT, the performance of the PCI and TCI patients—who had average educational and intelligence levels—ranged below the test norms for almost all test scores. Patients treated with PCI

Conclusions

Our data have shown that cognitive functioning after WBRT is influenced by both pretreatment cognitive status and, to a lesser extent, WBRT. Cognitive dysfunction after WBRT is restricted to verbal memory. Visual memory and attention functions were not influenced by WBRT. Because brain metastases can cause multiple, severe, neurologic, neurocognitive, and emotional difficulties and a concomitant reduction in quality of life (18), we believe it is important that patients do not avoid palliative

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    Supported by a grant from the Dietmar-Hopp Foundation.

    Presented at the 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), October 28–November 1, 2007, Los Angeles, CA.

    Conflict of interest: none.

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