Document Detail


Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.
MedLine Citation:
PMID:  19801201     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction.
METHODS: Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756.
FINDINGS: After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis.
INTERPRETATION: Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.
Authors:
Eric L Chang; Jeffrey S Wefel; Kenneth R Hess; Pamela K Allen; Frederick F Lang; David G Kornguth; Rebecca B Arbuckle; J Michael Swint; Almon S Shiu; Moshe H Maor; Christina A Meyers
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial     Date:  2009-10-02
Journal Detail:
Title:  The Lancet. Oncology     Volume:  10     ISSN:  1474-5488     ISO Abbreviation:  Lancet Oncol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-02     Completed Date:  2009-11-23     Revised Date:  2014-08-18    
Medline Journal Info:
Nlm Unique ID:  100957246     Medline TA:  Lancet Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1037-44     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00548756
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Bayes Theorem
Brain Neoplasms / mortality,  psychology,  radiotherapy*,  secondary,  surgery*
Cognition / radiation effects*
Cranial Irradiation / adverse effects*
Female
Humans
Kaplan-Meier Estimate
Male
Memory / radiation effects*
Middle Aged
Neuropsychological Tests
Patient Selection
Proportional Hazards Models
Radiation Injuries / etiology*,  psychology
Radiosurgery*
Radiotherapy, Adjuvant / adverse effects
Risk Assessment
Salvage Therapy
Time Factors
Treatment Outcome
Verbal Learning / radiation effects*
Comments/Corrections
Comment In:
Lancet Oncol. 2010 Jan;11(1):13; author reply 13-4   [PMID:  20129127 ]
Lancet Oncol. 2010 Mar;11(3):221-2; author reply 223   [PMID:  20202606 ]
Lancet Oncol. 2010 Mar;11(3):220-1   [PMID:  20202605 ]
Lancet Oncol. 2009 Nov;10(11):1024   [PMID:  19880055 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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