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CMET-31. WHOLE BRAIN RADIOTHERAPY VERSUS STEREOTACTIC RADIOSURGERY IN POOR-PROGNOSIS PATIENTS WITH 1 – 10 BRAIN METASTASES: A RANDOMIZED FEASIBILITY STUDY

ABSTRACT: Abstract BACKGROUND The clinical advantage of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with brain metastases and poor prognosis is controversial. To investigate the feasibility of a phase III clinical trial in a population of patients with poor prognosis, we conducted a randomized feasibility study of WBRT versus SRS. METHODS Patients with Karnofsky performance status (KPS) ? 70, life expectancy of 3–6 months, based on both Diagnosis-Specific Graded Prognostic Assessments and attending oncologist opinion, and 1– 10 brain metastases with a diameter ? 4 cm were enrolled at six Canadian cancer centers. Patients were randomly assigned to WBRT (20 Gy in 5 fractions) or SRS (15 Gy in 1 fraction). The primary endpoint was the rate of accrual. A secondary endpoint was the ratio of screened subjects to accrued subjects. This trial is registered with ClinicalTrials.gov (NCT02220491). RESULTS Between January 2015 and November 2017, 210 were screened to enroll 22 patients (9.5 screened/participant) and 20 patients were randomized. The accrual rate was 0.63 patients / month. The most common reasons for exclusion were: estimated median survival outside 3–6 months (n = 40), baseline KPS below 70 (n = 28), and > 10 brain metastases (n = 28). The median survival was 7.0 months. The overall survival was 9.5 months (n = 11) for patients who had subsequent systemic therapy, compared to 3.7 months (n = 9) in patients who had none. In both arms, the cumulative incidence of retreatment with brain radiotherapy was 40%. CONCLUSIONS Accrual was slow and the median survival was longer than expected, but a randomized trial evaluating WBRT vs SRS in patients with poor prognosis would likely be feasible by enrolling only patients with no remaining systemic therapy options.

SUBMITTER: Nichol A

PROVIDER: S-EPMC6847139 | biostudies-literature | 2019 Nov

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: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:BackgroundUntil 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS).MethodsBetween 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data.ResultsAfter a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65-2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively.ConclusionFractionation does not decrease LPFS. Even for small radioresistant brain metastases (< 3 cm), HFSRT, with 3 or 6 fractions, leads to an excellent local control rate of 72% at 1 year with a rate of 7.1% of radionecrosis. HFSRT is a safe and efficient alternative treatment to SRS.

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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CMET-31. WHOLE BRAIN RADIOTHERAPY VERSUS STEREOTACTIC RADIOSURGERY IN POOR-PROGNOSIS PATIENTS WITH 1 – 10 BRAIN METASTASES: A RANDOMIZED FEASIBILITY STUDY

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