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Quality of Automated Stereotactic Radiosurgery Plans in Patients with 4 to 10 Brain Metastases.

ABSTRACT: The purpose was to compare linac-based stereotactic radiosurgery and hypofractionated radiotherapy plan quality of automated planning, intensity modulated radiotherapy (IMRT) and manual dynamic conformal arc (DCA) plans as well as single- and multiple-isocenter techniques for multiple brain metastases (BM). For twelve patients with four to ten BM, seven non-coplanar linac-based plans were created: a manually planned DCA plan with a separate isocenter for each metastasis, a single-isocenter dynamic IMRT plan, an automatically generated single-isocenter volumetric modulated arc radiotherapy (VMAT) plan, four automatically generated single-isocenter DCA plans with three or five couch angles, with high or low sparing of normal tissue. Paddick conformity index, gradient index (GI), mean dose, total V_12Gy and V_5Gy of uninvolved brain, number of monitor units (MUs), irradiation time and pass rate were compared. The GI was significantly higher for VMAT than for separate-isocenter, IMRT, and all automatically generated plans. The number of MUs was lowest for VMAT, followed by automatically generated DCA and IMRT plans and highest for manual DCA plans. Irradiation time was the shortest for automatically planned DCA plans. Automatically generated linac-based single-isocenter plans for multiple BM reduce the number of MUs and irradiation time with at least comparable GI and V_5Gy relative to the reference separate-isocenter DCA plans.

SUBMITTER: Petoukhova A

PROVIDER: S-EPMC8307043 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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).

Project description:Abstract Background Stereotactic radiosurgery is a promising treatment option for patients with multiple brain metastases (BM). A multicenter randomized phase III trial (NCT02353000) is ongoing in patients with 4 up to 10 BM to determine the palliative value of SRS compared to whole brain radiotherapy (WBRT). Optimal SRS plan quality is essential to minimize the risk of radionecrosis (RN) and thereby maintenance of quality of life. This study evaluates the possible differences in the plan quality of the participating radiotherapy centers. Material and Methods An anonymized planning-CT with three BM scenarios was sent to the participating centers to contour targets and make clinical SRS treatment plans. The first, second, and third scenario consisted of 7, 5, and 10 BM, 1x21 Gy, 1x18Gy, and 1x18Gy respectively. Planning Target Volume coverage should be V100?99%. The maximum allowed gross tumor volume (GTV) to PTV margin was 2 mm. To assess SRS plan quality, the primary endpoint for this study was the Paddick gradient index (ratio of the volume of half the prescription isodose to the volume of the prescription isodose). Several secondary endpoints were calculated, such as the V12Gy of the largest BM (e.g. volume of healthy brain tissue which received 12 Gy or more). For all the endpoints the median and corresponding range were calculated. Results Data was available for nine centers for the first two scenarios and for eight centers for the third scenario. Eight centers used Volumetric Modulated Arc Therapy (VMAT) as their SRS technique and one center Cyberknife. Only once center used three fractions instead of a single fraction SRS. In the three scenario’s, the median Paddick gradient ranged from 3.5 up to 4.6, the poorest Paddick gradient index from 5.9 up to 7.4 and the optimal Paddick gradient index from 2.6 up to 3.1. Also variation was seen on other endpoints, such as the V12Gy of the largest BM. Conclusion Clinical relevant variation is seen in SRS plan quality in the participating centers, expressed by the variation in the Paddick gradient index, V12 Gy and the mean PTV dose. A Paddick gradient of less than 3.0 generally reflects a favorable SRS plan quality. Centers are encouraged to further optimize SRS plan quality.

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.

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Quality of Automated Stereotactic Radiosurgery Plans in Patients with 4 to 10 Brain Metastases.

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