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Cognitive functioning and predictors thereof in patients with 1-10 brain metastases selected for stereotactic radiosurgery.

ABSTRACT: PURPOSE:Information on predictive factors of cognitive functioning in patients with (multiple) brain metastases (BM) selected for radiosurgery may allow for more individual care and may play a role in predicting cognitive outcome after radiosurgery. The aim of this study was to evaluate cognitive performance, and predictors thereof, in patients with 1-10 BM before radiosurgery. METHODS:Cognition was measured before radiosurgery using a standardized neuropsychological test battery in patients with 1-10 BM (expected survival?>?3 months; KPS???70; no prior BM treatment). Regression formulae were constructed to calculate sociodemographically corrected z scores. Group and individual cognitive functioning was analyzed. Multivariable regression was used to explore potential predictors. RESULTS:Patients (N?=?92) performed significantly worse than controls (N?=?104) on all 11 test variables (medium-large effect sizes for 8 variables). Percentages of impairment were highest for information processing (55.3%), dexterity (43.2%) and cognitive flexibility (28.7%). 62% and 46% of patients had impairments in at least two, or three test variables, respectively. Models including combinations of clinical and psychological variables were predictive of verbal memory, psychomotor speed, information processing and dexterity. Neither number nor volume of metastases predicted patients' test performance. CONCLUSIONS:Already before radiosurgery, almost half of the patients suffered from severe cognitive deficits in at least three test variables. At group and individual level, information processing, cognitive flexibility, and dexterity were most affected. These cognitive impairments may impair daily functioning and patients' ability to make (shared) treatment decisions. Both clinical (symptomatic BM; timing of BM diagnosis) and psychological (mental fatigue) characteristics influenced cognitive performance. CLINICAL TRIAL INFORMATION:Cognition and Radiation Study A (CAR-Study A; ClinicalTrials.gov Identifier: NCT02953756; Medical Ethics Committee file number: NL53472.028.15/P1515).

SUBMITTER: Schimmel WCM

PROVIDER: S-EPMC6856035 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Cognitive functioning and predictors thereof in patients with 1-10 brain metastases selected for stereotactic radiosurgery.

Schimmel Wietske C M WCM Gehring Karin K Hanssens Patrick E J PEJ Sitskoorn Margriet M MM

Journal of neuro-oncology 20190924 2

<h4>Purpose</h4>Information on predictive factors of cognitive functioning in patients with (multiple) brain metastases (BM) selected for radiosurgery may allow for more individual care and may play a role in predicting cognitive outcome after radiosurgery. The aim of this study was to evaluate cognitive performance, and predictors thereof, in patients with 1-10 BM before radiosurgery.<h4>Methods</h4>Cognition was measured before radiosurgery using a standardized neuropsychological test battery ...[more]

PMID: 31552588

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Project description:Introduction:Due to the neurocognitive side effects of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) is being used with increasing frequency. The use of SRS is expanding for patients with multiple (>4) brain metastases (BM). This study summarizes our institutional experience with single-fraction, linear-accelerator-based SRS for multiple BM. Methods and materials:All patients who were treated between January 1, 2013, and September 30, 2015, with single-fraction SRS for ?4 BM were included in this institutional review board-approved, retrospective, single-institution study. Patients were treated with linear accelerator-based image guided SRS. Results:A total of 59 patients with ?4 BM were treated with single-fraction SRS. The median follow-up was 15.2 months, and the median overall survival for the entire cohort was 5.8 months. The median number of treated lesions per patient was 5 (range, 4-23). Per patient, the median planning target volume (PTV) was 4.8?cc (range, 0.7-28.8?cc). The prescribed dose across all 380 BM for the 59 patients ranged from 7 to 20?Gy. The median of the mean dose to the total PTV was 19.5?Gy. Although the number of treated lesions (4-5 vs ?6) did not influence survival, better survival was noted for a total PTV <10?cc versus ?10?cc (7.1 vs 4.2 months, respectively; P?=?.0001). A mean dose of ?19?Gy to the entire PTV was also associated with increased survival (6.6 vs 5.0 months, respectively; P?=?.0172). Patients receiving a dose of >12?Gy to ?10?cc of normal brain had worse survival (5.1 vs 8.6 months, respectively; P?=?.0028). Conclusion:In single-fraction SRS for patients with multiple BM, smaller total tumor volume, higher total dose, and lower volume of normal brain receiving >12?Gy were associated with increased survival. These data suggest that using SRS for the treatment of multiple BM is efficacious and that outcomes may be affected more by total tumor volume than by the number of lesions.

Project description:Maintenance of quality of life is the primary goal during treatment of brain metastases (BM). This is a protocol of an ongoing phase III randomised multicentre study. This study aims to determine the exact additional palliative value of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with 4-10 BM.The study will include patients with 4-10 BM from solid primary tumours diagnosed on a high-resolution contrast-enhanced MRI scan with a maximum lesional diameter of 2.5 cm in any direction and a maximum cumulative lesional volume of 30 cm3. Patients will be randomised between WBRT in five fractions of 4 Gy to a total dose of 20 Gy (standard arm) and single dose SRS to the BMs (study arm) in the range of 15-24 Gy. The largest BM or a localisation in the brainstem will determine the prescribed SRS dose. The primary endpoint is difference in quality of life (EQ5D EUROQOL score) at 3 months after radiotherapy with regard to baseline. Secondary endpoints are difference in quality of life (EQ5D EUROQOL questionnaire) at 6, 9 and 12 months after radiotherapy with regard to baseline. Other secondary endpoints are at 3, 6, 9 and 12 months after radiotherapy survival, Karnofsky ? 70, WHO performance status, steroid use (mg), toxicity according to CTCAE V4.0 including hair loss, fatigue, brain salvage during follow-up, type of salvage, time to salvage after randomisation and Barthel index. Facultative secondary endpoints are neurocognition with the Hopkins verbal learning test revised, quality of life EORTC QLQ-C30, quality of life EORTC BN20 brain module and fatigue scale EORTC QLQ-FA13.Worldwide, most patients with more than 4 BM will be treated with WBRT. Considering the potential advantages of SRS over WBRT, i.e. limiting radiation doses to uninvolved brain and a high rate of local tumour control by just a single treatment with fewer side effects, such as hair loss and fatigue, compared to WBRT, SRS might be a suitable alternative for patients with 4-10 BM.Trial registration number: NCT02353000 , trial registration date 15th January 2015, open for accrual 1st July 2016, nine patients were enrolled in this trial on 14th April 2017.

Project description:BackgroundStereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases.MethodsPatients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life.DiscussionCurrently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure.Trial registrationClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

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Cognitive functioning and predictors thereof in patients with 1-10 brain metastases selected for stereotactic radiosurgery.

Publications

Cognitive functioning and predictors thereof in patients with 1-10 brain metastases selected for stereotactic radiosurgery.

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