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P05.31 Plan quality of stereotactic radiosurgery in a multicenter phase III randomized trial in patients with 4 up to 10 brain metastases

ABSTRACT: 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.

SUBMITTER: Hartgerink D

PROVIDER: S-EPMC6144076 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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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:BackgroundPostoperative stereotactic radiosurgery (SRS) is a standard management option for patients with resected brain metastases. Preoperative SRS may have certain advantages compared to postoperative SRS, including less uncertainty in delineation of the intact tumor compared to the postoperative resection cavity, reduced rate of leptomeningeal dissemination postoperatively, and a lower risk of radiation necrosis. The recently published ASCO-SNO-ASTRO consensus statement provides no recommendation for the preferred sequencing of radiotherapy and surgery for patients receiving both treatments for their brain metastases.MethodsThis multicenter, randomized controlled trial aims to recruit 88 patients with resectable brain metastases over an estimated three-year period. Patients with ten or fewer brain metastases with at least one resectable, fulfilling inclusion criteria will be randomized to postoperative SRS (standard arm) or preoperative SRS (investigational arm) in a 1:1 ratio. Randomization will be stratified by age (< 60 versus ≥60 years), histology (melanoma/renal cell carcinoma/sarcoma versus other), and number of metastases (one versus 2-10). In the standard arm, postoperative SRS will be delivered within 3 weeks of surgery, and all unresected metastases will receive primary SRS. In the investigational arm, enrolled patients will receive SRS of all brain metastases followed by surgery of resectable metastases within one week of SRS. In either arm, single fraction or hypofractionated SRS in three or five fractions is permitted. The primary endpoint is to assess local control at 12 months in both arms. Secondary endpoints include local control at other time points, regional/distant brain recurrence rates, leptomeningeal recurrence rates, overall survival, neurocognitive outcomes, and adverse radiation events including radiation necrosis rates in both arms.DiscussionThis trial addresses the unanswered question of the optimal sequencing of surgery and SRS in the management of patients with resectable brain metastases. No randomized data comparing preoperative and postoperative SRS for patients with brain metastases has been published to date.Trial registrationClinicaltrials.gov , NCT04474925; registered on July 17, 2020. Protocol version 1.0 (January 31, 2020).SponsorAlberta Health Services, Edmonton, Canada (Samir Patel, MD).

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.

Project description:PurposeAs radiation therapy treatment precision increases with advancements in imaging and radiation delivery, dose painting treatment becomes increasingly feasible, where targets receive a nonuniform radiation dose. The high precision of stereotactic radiosurgery (SRS) makes it a good candidate for dose painting treatments, but no suitable metrics to assess dose painting SRS plans exist. Existing dose painting assessment metrics weigh target overdose and underdose equally but are unsuited for SRS plans, which typically avoid target underdose more. Current SRS metrics also prioritize reducing healthy tissue dose through selectivity and dose fall-off, and these metrics assume single prescriptions. We propose a set of metrics for dose painting SRS that would meet clinical needs and are calculated with nonuniform dose painting prescriptions.Methods and materialsSample dose painting SRS prescriptions are first created from Gamma Knife SRS cases, apparent diffusion coefficient magnetic resonance images, and various image-to-prescription functions. Treatment plans are found through semi-infinite linear programming optimization and using clinically determined isocenters, then assessed with existing and proposed metrics. Modified versions of SRS metrics are proposed, including coverage, selectivity, conformity, efficiency, and gradient indices. Quality factor, a current dose painting metric, is applied both without changes and with modifications. A new metric, integral dose ratio, is proposed as a measure of target overdose.ResultsThe merits of existing and modified metrics are demonstrated and discussed. A modified conformity index using mean or minimum prescription dose would be suitable for dose painting SRS with integral or maximum boost methods, respectively. Either modified efficiency index is a suitable replacement for the existing gradient index.ConclusionsThe proposed modified SRS metrics are appropriate measures of plan quality for dose painting SRS plans and have the advantage of giving equal values as the original SRS metrics when applied to single-prescription plans.

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: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).

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P05.31 Plan quality of stereotactic radiosurgery in a multicenter phase III randomized trial in patients with 4 up to 10 brain metastases

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