Abstract
Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens.Materials and Methods: Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.4 Gy in 28 daily fractions, over 5.5 weeks). The following parameter estimates were assessed in the whole tumor volume at baseline and following radiotherapy: apparent diffusion coefficient (ADC), parameters of the intra-voxel incoherent motion model of diffusion-weighted MRI (D, f, D*), transverse relaxation rate, fat fraction, and enhancing fraction after gadolinium-based contrast injection. Correlation was evaluated between pre-operative quantitative parameters and histopathological assessments of cellularity and fat fraction in post-surgical specimens (ClinicalTrials.gov, registration number NCT01902667).Results: Upper and lower 95% limits of agreement were 7.1 and −6.6%, respectively for median ADC at baseline. Median ADC increased significantly post-radiotherapy. Pre-operative ADC and D were negatively correlated with cellularity (r = −0.42, p = 0.01, 95% confidence interval (CI) −0.22 to −0.59 for ADC; r = −0.45, p = 0.005, 95% CI −0.25 to −0.62 for D), and fat fraction from Dixon MRI showed strong correlation with histopathological assessment of fat fraction (r = 0.79, p = 10−7, 95% CI 0.69–0.86).Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas.
Highlights
Soft-tissue sarcomas are often highly heterogeneous tumors with variable components that can include cellular tumor, fat, necrosis, and cystic change
Where systemic therapies alone are administered in non-resectable disease [3] or where radiotherapy with systemic therapies are used as an alternative to surgery [4], sensitive and reliable non-invasive methods for response assessment are needed
Wide ranges of each fitted parameter were observed across the cohort (Table 1), with median apparent diffusion coefficient (ADC) estimates between 0.95 × 10−3 and 2.77 × 10−3 mm2 s−1 and a similar range of median D estimates (0.99 × 10−3 to 2.71 × 10−3 mm2 s−1); median R2∗ estimates ranged from 5.19 to 58.27 s−1
Summary
Soft-tissue sarcomas are often highly heterogeneous tumors with variable components that can include cellular tumor, fat, necrosis, and cystic change. In many soft-tissue sarcoma sub-types, post-treatment changes often cannot be described by standard size criteria (response evaluation criteria in solid tumors, RECIST 1.1), as components within responding tumors may not shrink, or may increase in size, after radiotherapy [1, 2]. Diffusion-weighted MRI (DW-MRI) assessment of tumor cellularity and dynamic contrast-enhanced MRI (DCE-MRI) assessment of tumor vascularity have been shown to increase sensitivity of MRI in response assessment to neoadjuvant treatment in soft-tissue sarcomas [5]. There is a need, for assessment of the technical performance and clinical utility of quantitative MRI techniques in soft-tissue sarcomas in order to inform protocol development and selection of summary statistics for reporting. Optimization of quantitative imaging protocols requires knowledge of tumor properties, for example selection of diffusion-weightings (bvalues) for estimation of apparent diffusion coefficients (ADCs)
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