Efficacy and safety of magnetic resonance-guided focused ultrasound for the treatment of painful bone metastases: a systematic review and meta-analysis.

OBJECTIVE: To report the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of painful bone metastases through a systematic review and meta-analysis of pain scores before and after MRgFUS treatment and post-treatment adverse events. MATERIALS AND METHODS: A comprehensive literature search of PubMed and Embase databases was performed for studies evaluating the efficacy and/or safety of MRgFUS. The mean difference of pain scores (10-point visual analogue scale or numerical rating scale) between baseline and 1-month/3-month pain scores was collected and analyzed in a pooled meta-analysis. Post-treatment adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) grading were recorded and the pooled prevalence was calculated. RESULTS: A total of 33 studies published between 2007 and 2019 were collected, resulting in a total sample size of 1082 patients. The majority of the studies were prospective with a reported follow-up period of 3 months. The pooled proportion of patients that achieved pain relief from MRgFUS (complete response or partial response [≥ 2-point improvement of pain score]) was 79% (95% CI 73-83%). The pooled 1-month and 3-month mean difference in pain score were - 3.8 (95% CI - 4.3; - 3.3) and - 4.4 (95% CI - 5.0; - 3.7), respectively. The overall rate of high-grade (CTCAE grade 3 or higher) and low-grade (CTCAE grade 2 or lower) MRgFUS-related adverse events were 0.9% and 5.9%, respectively. CONCLUSION: MRgFUS is an effective procedure that is able to provide significant pain palliation for patients with symptomatic bone metastases with a favorable safety profile.

Efficacy and Safety of Stereotactic Radiosurgery for Brainstem Metastases: A Systematic Review and Meta-analysis.

IMPORTANCE: Owing to the proximity to critical neurologic structures, treatment options for brainstem metastases (BSM) are limited, and BSM growth can cause acute morbidity or death. Stereotactic radiosurgery (SRS) is the only local therapy for BSM, but efficacy and safety of this approach are incompletely understood because patients with BSM are excluded from most clinical trials. OBJECTIVE: To perform a systematic review and comparative meta-analysis of SRS studies for BSM in the context of prospective trials of SRS or molecular therapy for nonbrainstem brain metastases (BM). DATA SOURCES: A comprehensive search of Pubmed/MEDLINE and Embase was performed on December 6, 2019. STUDY SELECTION: English-language studies of SRS for BSM with at least 10 patients and reporting 1 or more outcomes of interest were included. Duplicate studies or studies with overlapping data sets were excluded. Studies were independently evaluated by 2 reviewers, and discrepancies were resolved by consensus. A total of 32 retrospective studies published between 1999 and 2019 were included in the analysis. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify studies. Study quality was assessed using Methodological Index for Non-Randomized Studies criteria. Fixed and random-effects meta-analyses and meta-regressions were performed for the outcomes of interest. MAIN OUTCOMES AND MEASURES: Primary study outcomes included 1-year and 2-year local control and overall survival, objective response rate, symptom response rate, neurological death rate, and rate of grade 3 to 5 toxic effects as described in Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The 32 retrospective studies included in the analysis comprised 1446 patients with 1590 BSM that were treated with SRS (median [range] dose, 16 [11-39] Gy; median [range] fractions, 1 [1-13]). Local control at 1 year was 86% (95% CI, 83%-88%; I2 = 38%) in 1410 patients across 31 studies, objective response rate was 59% (95% CI, 47%-71%; I2 = 88%) in 642 patients across 17 studies, and symptom improvement was 55% (95% CI, 47%-63%; I2 = 41%) in 323 patients across 13 studies. Deaths from BSM progression after SRS were rare (19 of 703 [2.7%] deaths across 19 studies), and the neurologic death rate in patients with BSM (24%; 95% CI, 19%-31%; I2 = 62%) was equivalent to the neurologic death rate in patients with BM who were treated on prospective trials. The rate of treatment-related grade 3 to 5 toxic effects was 2.4% (95% CI, 1.5%-3.7%; I2 = 33%) in 1421 patients across 31 studies. These results compared favorably to trials of targeted or immunotherapy for BM, which had a wide objective response rate range from 17% to 56%. CONCLUSIONS AND RELEVANCE: Results of this systematic review and meta-analysis show that SRS for BSM was associated with effectiveness and safety and was comparable to SRS for nonbrainstem BM, suggesting that patients with BSM should be eligible for clinical trials of SRS. In this analysis, patients treated with SRS for BSM rarely died from BSM progression and often experienced symptomatic improvement. Given the apparent safety and efficacy of SRS for BSM in the context of acute morbidity or death from BSM growth, consideration of SRS at the time of enrollment on emerging trials of targeted therapy for BM should be considered.

Image-Guided Percutaneous Ablation of Adrenal Metastases: A Meta-Analysis of Efficacy and Safety.

PURPOSE: To evaluate the efficacy and safety of percutaneous ablation of adrenal metastases through a meta-analysis of various image-guided percutaneous ablation techniques. MATERIALS AND METHODS: A comprehensive literature search of PubMed and Embase databases was performed for studies evaluating the efficacy and/or safety of image-guided percutaneous ablation of adrenal metastases. A total of 37 studies published between 2009 and 2020 were analyzed, comprising a sample size of 959 patients. Proportion estimates of overall survival, local control, and toxicity were analyzed in a pooled meta-analysis. The pooled prevalence of adverse events after ablation was calculated based on common terminology criteria for adverse events (CTCAE) grading. RESULTS: Of the 959 included patients, 320 (33.3%) underwent radiofrequency ablation, 72 (7.5%) microwave ablation, 95 (9.9%) cryoablation, and 46 (4.8%) ethanol injections for treatment of adrenal metastases. The remaining 426 (44.4%) patients were from studies involving a mixture of the 4 listed percutaneous ablation techniques. The pooled 1-year local control rate was 80% (95% confidence interval [CI], 76%-83%). The pooled 1-year overall survival rate was 77% (95% CI, 70%-83%). The overall rate of severe adverse events after ablation (CTCAE grade 3 or higher) was 16.1%. The overall rate of low-grade adverse events after ablation (CTCAE grade 2 or lower) was 32.6%. Approximately 21.9% (n = 203) of patients experienced intraprocedural hypertensive crises, the majority of which were reversed with antihypertensive medications. CONCLUSIONS: This study demonstrates that image-guided percutaneous ablation can be effective in achieving acceptable short- to mid-term local tumor control and overall survival with a moderate safety profile.

Stereotactic Body Radiation Therapy of Adrenal Metastases: A Pooled Meta-Analysis and Systematic Review of 39 Studies with 1006 Patients.

PURPOSE: To perform a systematic review and pooled meta-analysis of adrenal metastasis stereotactic body radiation therapy (SBRT) outcomes, treatment characteristics, and toxicity to define the efficacy and propose guidelines for intervention. METHODS AND MATERIALS: We performed a comprehensive literature search of the Embase and PubMed databases of studies reporting outcome or toxicity data for photon-based SBRT of adrenal metastases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We then conducted a meta-analysis to estimate pooled overall response, local control (LC), and overall survival and analyzed these outcomes in the context of dosimetric parameters and toxicity using metaregression. RESULTS: Thirty-nine studies published between 2009 and 2019 reporting outcomes on 1006 patients were included. The median follow-up was 12 months, and the median biological equivalent dose (BED10, alpha/beta = 10) was 67 Gy. The pooled overall response was 54.6% (95% confidence interval [CI], 46.5%-62.5%). The pooled 1- and 2-year rates of LC were 82% (95% CI, 74%-88%) and 63% (95% CI, 50%-74%), respectively, and the pooled 1- and 2-year overall survival rates were 66% (95% CI, 57%-74%) and 42% (95% CI, 31%-53%), respectively. There was a strong positive association between SBRT dose and 1- and 2-year LC (P < .0001, P = .0002) and an association with 2-year OS (P = .03). Based on a metaregression of dose and LC, BED10 of 60 Gy, 80 Gy, and 100 Gy predicted 1-year LC of 70.5%, 84.8%, and 92.9% and 2-year LC of 47.8%, 70.1%, and 85.6%, respectively. The overall rate of grade 3 or higher toxicity was 1.8%. CONCLUSIONS: SBRT of adrenal metastases provides good 1-year LC with an excellent safety profile, and dose escalation may be associated with improved LC. Prospective studies are needed to validate these findings and determine whether there are subsets of patients for whom adrenal metastasis-directed SBRT may confer a survival advantage.

Glucagon Receptor Antagonism Ameliorates Progression of Heart Failure.

Mice were treated with a fully human monoclonal glucagon receptor antagonistic antibody REMD2.59 following myocardial infarction or pressure overload. REMD2.59 treatment blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfunction at 4 weeks after myocardial infarction. In addition, REMD2.59 treatment at the onset of pressure overload significantly suppressed cardiac hypertrophy and chamber dilation with marked preservation of cardiac systolic and diastolic function. Initiation of REMD2.59 treatment 2 weeks after pressure overload significantly blunted the progression of cardiac pathology. These results provide the first in vivo proof-of-concept evidence that glucagon receptor antagonism is a potentially efficacious therapy to ameliorate both onset and progression of heart failure.