RESUMEN
BACKGROUND AND PURPOSE: In pancreatic radiotherapy, residual tumor motion during treatment increases the risk of toxicity. Cine imaging acquired during magnetic resonance guided radiotherapy (MRgRT) enables real-time treatment gating in response to anatomical motion, which can reduce this risk; however, treatment gating can negatively impact the efficiency of treatment. This study aimed to quantify the extent of residual tumor motion during breath hold and evaluate the appropriateness of the treatment gating margins used in current clinical practice. MATERIALS AND METHODS: Cine imaging acquired during pancreatic MRgRT of 11 patients on the ViewRay MRIdian was analyzed. The total duration of treatment analyzed was 12 h 13 min. Improved methods for processing and analyzing cine imaging were developed: breath holds were systematically separated with frequency analysis, residual motion was measured with consideration of both the tracking structure contour and centroid, and residual motion measurements were supported by phantom measurements of image scaling, resolution, and noise. Residual motion was measured at angles 0°, 45°, 90°, and 135° to the superior-inferior (SI) direction. Total residual motion was measured by combining directional measurements. RESULTS: The minimum tracking structure displacement resolvable through cine imaging was found to be 1.5 mm; therefore, residual motion analysis was limited to 1.5 mm spatial resolution. Total residual motion was contained within margins Δ = $\Delta =\, $ ±1.5, ±3, and ±4.5mm with mean percentage frequencies of 97.0%, 91.1%, and 67.8%. Most residual motion was observed in the SI direction, and significantly more residual motion was measured for the tracking structure contour than the centroid. CONCLUSION: The results demonstrate that patients are largely able to maintain breath hold positions to within a 3 mm margin, thus provide evidence that supports the use of a 3mm gating margin in clinical practice. Residual motion frequently exceeded 1.5 mm so a reduction in gating margin would have an undesirable impact on treatment efficiency.
RESUMEN
The Centers for Medicare & Medicaid Services (CMS) established a class-based National Coverage Determination (NCD) for monoclonal antibodies directed against amyloid for Alzheimer's disease (AD) with patient access through Coverage with Evidence Development (CED) based on three questions. This review, focused on donanemab, answers each of these CED questions with quality evidence. TRAILBLAZER-ALZ registration trials are presented with supporting literature and real-world data to answer CED questions for donanemab. TRAILBLAZER-ALZ registration trials demonstrated that donanemab significantly slowed cognitive and functional decline in amyloid-positive early symptomatic AD participants, and lowered their risk of disease progression while key safety risks occurred primarily within the first 6 months and then declined. Donanemab meaningfully improved health outcomes with a manageable safety profile in an early symptomatic AD population, representative of Medicare populations across diverse practice settings. The donanemab data provide the necessary level of evidence for CMS to open a reconsideration of their NCD. HIGHLIGHTS: Donanemab meaningfully improved outcomes in trial participants with early symptomatic Alzheimer's disease. Comorbidities in trial participants were consistent with the Medicare population. Co-medications in trial participants were consistent with the Medicare population. Risks associated with treatment tended to occur in the first 6 months. Risks of amyloid-related imaging abnormalities were managed with careful observation and magnetic resonance imaging monitoring.