Exploring new prognostic biomarkers in Mantle Cell Lymphoma: a comparison of the circSCORE and the MCL35 score.

Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous disease, emphasizing the need for prognostic biomarkers. In this study we aimed at comparing the prognostic value of two RNA-based risk scores, circSCORE and MCL35, in 149 patients from the MCL2 (ISRCTN87866680) and MCL3 (NCT00514475) patient cohorts. Both risk scores provided significant stratification of high versus low risk for progression free survival (PFS) and overall survival (OS). The circSCORE retained significant prognostic value in adjusted multivariable Cox regressions for PFS, but not for OS. Furthermore, circSCORE added significant prognostic value to MIPI in the pooled cohort (MCL2 and MCL3) for PFS and OS, and for PFS in MCL3 alone, outperforming Ki67 and MCL35. We suggest a new, combined MIPI-circSCORE with improved prognostic value, and with potential for future clinical implementation, if validated in a larger, independent cohort.

Characteristic muscle signatures assessed by quantitative MRI in patients with Bethlem myopathy.

Using MRI, the main aim was to (1) map the pattern of muscle involvement by assessing fat fraction and (2) investigate frequency of target and sandwich signs in 42 muscles of patients with Bethlem myopathy (BM). Fifteen BM patients were included. Results were compared to findings in 8 healthy controls and 50 patients with four other types of muscular dystrophies. All muscles, except one, showed higher fat fraction in BM patients vs healthy controls (p < 0.05) with an overall proximal muscle affection, resembling a limb girdle-like pattern. In moderate patients, the specificity was 90% for the sandwich sign and 98% for the target sign. Sensitivity for both signs was 100%. Twelve BM patients had sandwich sign in other muscles than the vastus lateralis. Muscle strength correlated with fat fraction. Mean fat fraction in the psoas major was 39% in BM patients, which was considerably higher than in 3 of the 4 muscular dystrophy control diseases. The presence of signs in conjunction with severe affection of the psoas major muscle can serve as a diagnostic tool in BM. The high level of STIR lesions in muscles of BM patients warrants further investigations.

A quantitative method to assess muscle edema using short TI inversion recovery MRI.

Muscle inflammation is an important component of disease pathophysiology in several muscular dystrophies. Hyperintensities on MRI sequences with short TI inversion recovery (STIR) reflect edema, or inflammation (STIR+). Conventionally, STIR evaluation has been done by visual inspection. In this study, we developed a quantitative STIR method, and tested its ability to identify STIR+ lesions in healthy controls and patients with Facioscapulohumeral muscular dystrophy and compared the results with visual STIR evaluation and quantitative T2 relaxation time mapping. The method was based on pixel-by-pixel histograms of the distribution of signal intensities from muscles. Signal intensities from healthy control muscles were averaged and used to define an upper reference limit. Muscles with >2.5% pixels above the limit were defined as being STIR+. The new method showed agreement with T2 relaxation time mapping in 95% of muscles. The visual STIR method only showed agreement with the quantitative STIR method and T2 relaxation time mapping in 88 and 84%, respectively. STIR sequences are available on most MR scanners and the post-processing used in the new quantitative method can be performed using free software. We therefore believe that the new method can play an important role in identifying STIR+ lesions in patients with neuromuscular diseases.