International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationMemory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases
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
References (44)
- et al.
The palliation of brain metastases: Final results of the first two studies by the Radiation Therapy Oncology Group
Int J Radiat Oncol Biol Phys
(1980) - et al.
Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials
Int J Radiat Oncol Biol Phys
(1997) - et al.
Neuropsychological outcome after fractionated stereotactic radiotherapy (FSRT) for base of skull meningiomas: A prospective 1-year follow-up
Radiother Oncol
(2003) - et al.
Acute central nervous system (CNS) toxicity of total body irradiation (TBI) measured using neuropsychological testing of attention functions
Int J Radiat Oncol Biol Phys
(1999) - et al.
Prospective evaluation of delayed central nervous system (CNS) toxicity of hyperfractionated total body irradiation (TBI)
Int J Radiat Oncol Biol Phys
(2000) - et al.
Neurobehavioral toxicity of total body irradiation: A follow-up in long-term survivors
Int J Radiat Oncol Biol Phys
(2000) - et al.
Prophylactic cranial irradiation is indicated following complete response to induction therapy in small-cell lung cancer: Results of a multicentre randomised trial
Eur J Cancer
(1997) - et al.
Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation
Int J Radiat Oncol Biol Phys
(1995) - et al.
Follow-up of cognitive functioning in patients with small cell lung cancer
Int J Radiat Oncol Biol Phys
(1995) - et al.
Cognitive deficits in patients with small-cell lung cancer before and after chemotherapy
Lung Cancer
(1995)
Neurocognitive outcome in brain metastasis patients treated with accelerated fractionation vs. accelerated hyperfractionated radiotherapy: An analysis from Radiation Therapy Oncology Group Study 91-04
Int J Radiat Oncol Biol Phys
Mid- to long-term cognitive sequelae in low-grade gliomas: The impact of radiotherapy and other treatment-related factors
Lancet
Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission
N Engl J Med
A randomized trial of prophylactic cranial irradiation (PCI) versus no PCI in extensive disease small cell lung cancer after a response to chemotherapy (EORTC 08993-22993)
J Clin Oncol (Meeting Abstracts)
VLMT-Verbaler Lern- und Merkfähigkeitstest
Medical College of Georgia (MCG) complex figures
Testbatterie zur Aufmerksamkeitsprüfung (TAP)—Test for Attentional Performance, version 1.02c
A test battery for attentional performance
Mehrfachwahl-Wortschatz-Intelligenztest MWT-B (The multiple-choice test of vocabulary knowledge)
HADS-D: Hospital Anxiety and Depression Scale—Deutsche version (German version). Ein Fragebogen zur Erfassung von Angst und Depressivität in der somatischen Medizin
A compendium of neuropsychological tests: Administration, norms, and commentary
Clinical significance: A statistical approach to defining meaningful change in psychotherapy research
J Consult Clin Psychol
Cited by (178)
Stereotactic Radiosurgery for Postoperative Metastatic Surgical Cavities: A Critical Review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines
2021, International Journal of Radiation Oncology Biology PhysicsTumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases
2021, International Journal of Radiation Oncology Biology Physics“A prospective study of assessment of neurocognitive function in illiterate patients with gliomas treated with chemoradiation”: Assessment of neurocognitive function in gliomas
2021, Cancer Treatment and Research CommunicationsFeasibility of hippocampal avoidance whole brain radiation in patients with hippocampal involvement: Data from a prospective study
2021, Medical DosimetryCitation Excerpt :In general, patients with a limited number of brain metastases receive stereotactic radiation delivered in a single session or several sessions, while those with more extensive disease undergo whole brain radiation (WBRT) over 5 to 15 daily treatments. While WBRT treats both visible and subclinical disease in the brain, it can cause irreversible neurocognitive deterioration,5-10 thought to stem from radiation-induced injury of the subgranular zone.11-14 The use of memantine15 and, more recently, hippocampal avoidance in WBRT (HA-WBRT),16-19 have demonstrated improvement in neurocognitive outcomes when compared to conventional WBRT.
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.