Dataset Information

Radiosurgery for brainstem metastases with and without whole brain radiotherapy: clinical series and literature review.

ABSTRACT:

Objective

The objective of this study was to investigate outcomes for patients with brainstem metastases treated with stereotactic radiosurgery (SRS).

Methods

Patients with brainstem metastases treated with SRS between April 2006 and June 2012 were identified from a prospective database. Patient and treatment-related factors were recorded. Kaplan-Meier analysis was used to calculate survival and freedom from local and distant brain progression. Univariate and multivariate Cox regression was used to identify factors important for overall survival.

Results

In total, 44 patients received SRS for 48 brainstem metastases of whom 33 (75 %) also received whole brain radiotherapy (WBRT): 23 patients (52 %) WBRT prior to SRS, 6 (13.6 %) WBRT concurrently with SRS and 4 (9.0 %) WBRT after SRS. Eight patients received a second course of WBRT at further progression. Median target volume was 1.33 cc (range 0.04-12.17) and median prescribed marginal dose was 15 Gy (range 10-22). There were four cases of local failure, and 6-month and 1-year freedom from local failure was 84.6 and 76.9 %, respectively. Median overall survival (OS) was 5.4 months. There were four cases of radionecrosis, 2 (4.8 %) of which were symptomatic. The absence of external beam brain radiotherapy (predominantly WBRT) showed a trend towards improved OS on univariate analysis. Neither local nor distant brain failure significantly impacted OS.

Conclusion

This retrospective series of patients treated with SRS for brainstem metastases, largely in combination with at least one course of WBRT, demonstrates that this approach is safe and results in good local control. In this cohort, no variables significantly impacted OS, including intracranial control.

SUBMITTER: Murray L

PROVIDER: S-EPMC5357261 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Radiosurgery for brainstem metastases with and without whole brain radiotherapy: clinical series and literature review.

Murray Louise L Menard Cynthia C Zadeh Gelareh G Au Karolyn K Bernstein Mark M Millar Barbara-Ann BA Laperriere Normand N Chung Caroline C

Journal of radiation oncology 20161027 1

<h4>Objective</h4>The objective of this study was to investigate outcomes for patients with brainstem metastases treated with stereotactic radiosurgery (SRS).<h4>Methods</h4>Patients with brainstem metastases treated with SRS between April 2006 and June 2012 were identified from a prospective database. Patient and treatment-related factors were recorded. Kaplan-Meier analysis was used to calculate survival and freedom from local and distant brain progression. Univariate and multivariate Cox regr ...[more]

PMID: 28367275

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Project description:BackgroundThe benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear.ObjectivesTo compare the efficacy and safety of surgery or SRS plus WBRT with that of surgery or SRS alone for treatment of brain metastases in patients with systemic cancer.Search methodsWe searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL) up to May 2013 and annual meeting proceedings of ASCO and ASTRO up to September 2012 for relevant studies.Selection criteriaRandomised controlled trials (RCTs) comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases.Data collection and analysisTwo review authors undertook the quality assessment and data extraction. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), health related quality of life (HRQL) and neurological adverse events. Hazard ratios (HR), risk ratio (RR), confidence intervals (CI), P-values (P) were estimated with random effects models using Revman 5.1 MAIN RESULTS: We identified five RCTs including 663 patients with one to four brain metastases. The risk of bias associated with lack of blinding was high and impacted to a greater or lesser extent on the quality of evidence for all of the outcomes. Adding upfront WBRT decreased the relative risk of any intracranial disease progression at one year by 53% (RR 0.47, 95% CI 0.34 to 0.66, P value < 0.0001, I(2) =34%, Chi(2) P value = 0.21, low quality evidence) but there was no clear evidence of a difference in OS (HR 1.11, 95% CI 0.83 to 1.48, P value = 0.47, I(2) = 52%, Chi(2) P value = 0.08, low quality evidence) and PFS (HR 0.76, 95% CI 0.53 to 1.10, P value = 0.14, I(2) = 16%, Chi(2) P value = 0.28, low quality evidence). Subgroup analyses showed that the effects on overall survival were similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The evaluation of the impact of upfront WBRT on NF, HRQL and neurological adverse events was limited by the unclear and high risk of reporting, performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.Authors' conclusionsThere is low quality evidence that adding upfront WBRT to surgery or SRS decreases any intracranial disease progression at one year. There was no clear evidence of an effect on overall and progression free survival. The impact of upfront WBRT on neurocognitive function, health related quality of life and neurological adverse events was undetermined due to the high risk of performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.

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:ImportanceAlthough stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited.ObjectiveTo characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT.Design, setting, and participantsFIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019.InterventionsSRS and WBRT for small cell lung cancer brain metastases.Main outcomes and measuresOverall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses.ResultsIn total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results.Conclusions and relevanceResults of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.

Project description:PurposeWe aimed to compare Australian health system costs at 12 months for adjuvant whole-brain radiotherapy (WBRT) treatment after stereotactic radiosurgery (SRS) and/or surgery versus observation among adults with one to three melanoma brain metastases. We hypothesized that treatment with adjuvant WBRT and subsequent healthcare would be more expensive than SRS/surgery alone.MethodsThe analysis was conducted alongside a multicentre, randomized phase III trial. A bespoke cost questionnaire was used to measure healthcare use, including hospitalizations, specialist and primary care visits, imaging, and medicines over 12 months. Mean per-patient costs were calculated based on the quantity of resources used and unit costs, reported in Australian dollars ($AU), year 2018 values. Skewness of cost data was determined using normality tests and censor-adjusted costs reported using the Kaplan-Meier sample average method. The analysis of difference in mean costs at each 2-month time point and at 12 months was performed and checked using Kruskal-Wallis, generalized linear models with gamma distribution and log link, modified Park test, ordinary least squares, and non-parametric bootstrapping.ResultsIn total, 89 patients with similar characteristics at baseline were included in the cost analysis (n = 43 WBRT; n = 46 observation). Hospitalization cost was the main cost, ranging from 63 to 89% of total healthcare costs. The unadjusted 12-monthly cost for WBRT was $AU71,138 ± standard deviation 41,475 and for observation $AU69,848 ± 33,233; p = 0.7426. The censor-adjusted 12-monthly cost for WBRT was $AU90,277 ± 36,274 and $AU82,080 ± 34,411 for observation. There was no significant difference in 2-monthly costs between groups (p > 0.30 for all models).ConclusionsMost costs were related to inpatient hospitalizations associated with disease recurrence. Adding WBRT after local SRS/surgery for patients with one to three melanoma brain metastases did not significantly increase health system costs during the first 12 months.Trial registrationACTRN12607000512426, prospectively registered 14 September 2007.

Project description:BackgroundIn patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. In this meta-analysis, we sought to compare the efficacy of each post-operative radiation modality with respect to tumor recurrence and survival.MethodsPubmed, Embase and Cochrane databases were searched through June 2016 for cohort studies reporting outcomes of SRS or WBRT after metastasis resection. Pooled effect estimates were calculated using fixed-effect and random-effect models for local recurrence, distant recurrence, and overall survival.ResultsEight retrospective cohort studies with 646 patients (238 with SRS versus 408 with WBRT) were included in the analysis. Comparing SRS to WBRT, the overall crude risk ratio using the fixed-effect model was 0.59 for local recurrence (95%-CI: 0.32-1.09, I2: 3.35%, P-heterogeneity = 0.36, 3 studies), 1.09 for distant recurrence (95%-CI: 0.74-1.60, I2: 50.5%, P-heterogeneity = 0.13; 3 studies), and 2.99 for leptomeningeal disease (95% CI 1.55-5.76; I2: 14.4% p-heterogeneity: 0.28; 2 studies). For the same comparison, the risk ratio for median overall survival was 0.47 (95% CI: 0.41-0.54; I2: 79.1%, P-heterogeneity < 0.01; 4 studies) in a fixed-effect model, but was no longer significant (0.63; 95%-CI: 0.40-1.00) in a random-effect model. SRS was associated with a lower risk of leukoencephalopathy (RR: 0.15, 95% CI: 0.07-0.33, 1 study), yet with a higher risk of radiation-necrosis (RR: 19.4, 95% CI: 1.21-310, 1 study).ConclusionBased on retrospective cohort studies, the results of this study suggest that SRS of the resection cavity may offer comparable survival and similar local and distant control as adjuvant WBRT, yet may be associated with a higher risk for developing leptomeningeal disease. Future research on SRS should focus on achieving a better understanding of the various factors that may favor SRS over WBRT.

Dataset Information

Radiosurgery for brainstem metastases with and without whole brain radiotherapy: clinical series and literature review.

Objective

Methods

Results

Conclusion

Publications

Radiosurgery for brainstem metastases with and without whole brain radiotherapy: clinical series and literature review.

Similar Datasets

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