Abstract
PurposeBrain metastases are almost universally lethal with short median survival times. Despite this, they are often potentially curable, with therapy failing only because of local relapse. One key reason relapse occurs is because treatment planning did not delineate metastasis margins sufficiently or accurately, allowing residual tumor to regrow. The aim of this study was to determine the extent to which multimodal magnetic resonance imaging (MRI), with a simple and automated analysis pipeline, could improve upon current clinical practice of single-modality, independent-observer tumor delineation.Methods and MaterialsWe used a single rat model of brain metastasis (ENU1564 breast carcinoma cells in BD-IX rats), with and without radiation therapy. Multimodal MRI data were acquired using sequences either in current clinical use or in clinical trial and included postgadolinium T1-weighted images and maps of blood flow, blood volume, T1 and T2 relaxation times, and apparent diffusion coefficient.ResultsIn all cases, independent observers underestimated the true size of metastases from single-modality gadolinium-enhanced MRI (85 ± 36 μL vs 131 ± 40 μL histologic measurement), although multimodal MRI more accurately delineated tumor volume (132 ± 41 μL). Multimodal MRI offered increased sensitivity compared with independent observer for detecting metastasis (0.82 vs 0.61, respectively), with only a slight decrease in specificity (0.86 vs 0.98). Blood flow maps conferred the greatest improvements in margin detection for late-stage metastases after radiation therapy. Gadolinium-enhanced T1-weighted images conferred the greatest increase in accuracy of detection for smaller metastases.ConclusionsThese findings suggest that multimodal MRI of brain metastases could significantly improve the visualization of brain metastasis margins, beyond current clinical practice, with the potential to decrease relapse rates and increase patient survival. This finding now needs validation in additional tumor models or clinical cohorts.
Highlights
Brain metastasis is one of the most feared diagnoses for patients with cancer
It is becoming increasingly clear that planning may not always encompass the entire tumor volume because many metastases, even those that appear well circumscribed, have an invasive rim.[3,4,5]
To best recapitulate an isolated metastasis surrounded by normal brain, as is common in human patients, a model of brain metastasis induced through intracerebral injection was used
Summary
The conventional view of brain metastases is that they are discrete entities with a clear edge and a noninvasive phenotype. This model suggests that many brain metastases could be potentially cured by either surgical resection or radiation therapy. An incomplete understanding of the tumor extent leads to flawed surgical or radiologic planning, incomplete treatment, and subsequent relapse. Despite this invasive rim, many brain metastases remain potentially curable if tumor extent can be more accurately delineated before treatment planning
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