TP53-altered chronic lymphocytic leukemia treated with firstline Bruton's tyrosine kinase inhibitor-based therapy: A retrospective analysis.

Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients had del(17p). TP53-m was noted in 89/110 (81%) patients tested; there were 101 unique TP53-m with an available VAF. The 4-year progression-free survival (PFS) and overall survival (OS) rates were 72.9% and 83.6%. No baseline characteristics including IGHV mutation status and number of TP53 alterations were associated with significant differences in PFS or OS, though a trend toward shorter PFS with increasing karyotypic complexity (hazard ratio 1.08, p = .066) was observed. Del(17p) was identified in <25% of cells in 26/104 (25%) of patients, and 28/101 (28%) of TP53-m were low-burden with a VAF of <10%; outcomes of these patients were similar to those with high-burden lesions. This study suggests that low-burden TP53 alterations should not be ignored when assessing genomic risk in CLL in the era of targeted therapy.

Adult Primary Peripheral PNET/Ewing's Sarcoma of the Cervical and Thoracic Spine.

This case report describes a patient with a rare occurrence of primary spinal intramedullary Ewing's sarcoma (ES) in the cervical and thoracic spine. The older age of disease occurrence, uncommon location in the cervical and thoracic spine, and EWSR1 gene fusion as the basis of diagnosis are unique features of this case. There is no clear protocol for treatment of primary extraskeletal ES of the spine, with controversy between evidence for pursuing surgery versus a combination of radiation and chemotherapy. Our patient was treated with temozolomide chemotherapy for recurrent metastatic disease of primary ES of the spine.

Multi-compartment mesenchymal tissue segmentation in pelvic MRI examinations of women: Anthropomorphic and clinical correlations.

AIM: To investigate the reliability of multicompartmental volumetric mesenchymal segmentations on MRI and their correlations with anthropomorphic and clinical parameters. MATERIALS AND METHODS: A consecutive series of middle-age (35-50 year old) female volunteers with variable body mass index (BMI) and MRI scans performed as a part of the Dallas Heart Study were included. A semi-automatic segmentation tool was used to partition different mesenchymal tissues- fat, muscle, and bone on MRI of pelvis. Total volumes of each compartment were calculated and compared between overweight/obese (BMI> = 25 kg/m2) and non-obese (BMI < 25 kg/m2) groups, and with physical performance measurements, i.e. mean activity counts per minute (MVPA) and cardiorespiratory fitness (CRF) estimated by submaximal treadmill test (TT). Kruskal Wallis, Mann-Whitney U test, intraclass correlation coefficient (ICC) and Spearman correlations were used. P value <0.05 was considered statistically significant. RESULTS: There were statistically significant positive correlations between fat volume and BMI (p < 0.0001), muscle volume and height (p = 0.03), and bone volume and height (p < 0.0001). Significant inverse correlations were found between bone volume and BMI (p = 0.002). Fair to good interobserver reliability was seen with muscle and fat volumes (ICC = 0.43-0.64) and excellent reliability was seen with bone volumes (ICC = 0.78-0.79). Statistically significant inverse correlations were found between MVPA and age (p = 0.01), and TT with BMI and weight (p = 0.01, 0.03). CONCLUSION: Multi-compartment mesenchymal tissue volume quantification on pelvic MRI is reliable in females. Inverse correlation of bone volume with BMI has potential implications for future risk of fracture.

Sciatic neurosteatosis: Relationship with age, gender, obesity and height.

AIM: To evaluate inter-reader performance for cross-sectional area and fat quantification of bilateral sciatic nerves on MRI and assess correlations with anthropometrics. METHODS: In this IRB-approved, HIPPA-compliant study, three readers performed a cross-sectional analysis of 3T lumbosacral plexus MRIs over an 18-month period. Image slices were evaluated at two levels (A and B). The sciatic nerve was outlined using a free hand region of interest tool on PACS. Proton-density fat fraction (FF) and cross-sectional areas were recorded. Inter-reader agreement was assessed using intra-class correlation coefficient (ICC). Spearman correlation coefficients were used for correlations with age, BMI and height and Wilcoxon rank sum test was used to assess gender differences. RESULTS: A total of 67 patients were included in this study with male to female ratio of 1:1. Inter-reader agreement was good to excellent for FF measurements at both levels (ICC=0.71-0.90) and poor for sciatic nerve areas (ICC=0.08-0.27). Positive correlations of sciatic FF and area were seen with age (p value<0.05). Males had significantly higher sciatic intraneural fat than females (p<0.05). CONCLUSION: Fat quantification MRI is highly reproducible with significant positive correlations of sciatic FF and area with age, which may have implications for MRI diagnosis of sciatic neuropathy. KEY POINTS: • MR proton density fat fraction is highly reproducible at multiple levels. • Sciatic intraneural fat is positively correlated with increasing age (p < 0.05). • Positive correlations exist between bilateral sciatic nerve areas and age (p < 0.05). • Males had significantly higher sciatic intraneural fat than females (p < 0.05).