The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma.

Fibroblast growth factor receptor (FGFR)-2 can be inhibited by FGFR-selective or non-selective tyrosine kinase inhibitors (TKIs). Selective TKIs are approved for cholangiocarcinoma (CCA) with FGFR2 fusions; however, their application is limited by a characteristic pattern of adverse events or evocation of kinase domain mutations. A comprehensive characterization of a patient cohort treated with the non-selective TKI lenvatinib reveals promising efficacy in FGFR2-driven CCA. In a bed-to-bench approach, we investigate FGFR2 fusion proteins bearing critical tumor-relevant point mutations. These mutations confer growth advantage of tumor cells and increased resistance to selective TKIs but remain intriguingly sensitive to lenvatinib. In line with clinical observations, in-silico analyses reveal a more favorable interaction pattern of lenvatinib with FGFR2, including an increased flexibility and ligand efficacy, compared to FGFR-selective TKIs. Finally, the treatment of a patient with progressive disease and a newly developed kinase mutation during therapy with a selective inhibitor results in a striking response to lenvatinib. Our in vitro, in silico, and clinical data suggest that lenvatinib is a promising treatment option for FGFR2-driven CCA, especially when insurmountable adverse reactions of selective TKIs or acquired kinase mutations occur.

Imaging of Pathologies of the Temporal Bone and Middle Ear: Inflammatory Diseases, Their Mimics and Potential Complications-Pictorial Review.

Imaging of the temporal bone and middle ear is challenging for radiologists due to the abundance of distinct anatomical structures and the plethora of possible pathologies. The basis for a precise diagnosis is knowledge of the underlying anatomy as well as the clinical presentation and the individual patient's otological status. In this article, we aimed to summarize the most common inflammatory lesions of the temporal bone and middle ear, describe their specific imaging characteristics, and highlight their differential diagnoses. First, we introduce anatomical and imaging fundamentals. Additionally, a point-to-point comparison of the radiological and histological features of the wide spectrum of inflammatory diseases of the temporal bone and middle ear in context with a review of the current literature and current trends is given.

Reduced versus standard dose contrast volume for contrast-enhanced abdominal CT in overweight and obese patients using photon counting detector technology vs. second-generation dual-source energy integrating detector CT.

PURPOSE: To compare image quality of contrast-enhanced abdominal-CT using 1st-generation Dual Source Photon-Counting Detector CT (DS-PCD-CT) versus 2nd-generation Dual-Source Energy Integrating-Detector CT (DS-EID-CT) in patients with BMI ≥ 25, applying two different contrast agent volumes, vendor proposed protocols and different virtual monoenergetic images (VMI). METHOD: 68 overweight (BMI ≥ 25 kgm2) patients (median age: 65 years; median BMI 33.3 kgm2) who underwent clinically indicated, portal-venous contrast-enhanced abdominal-CT on a commercially available 1st-generation DS-PCD-CT were prospectively included if they already have had a pre-exam on 2nd-generation DS-EID-CT using a standardized exam protocol. Obesity were defined by BMI-calculation (overweight: 25-29.9, obesity grade I: 30-34.9; obesity grade II: 35-39.9; obesity grade III: > 40) and by the absolute weight value. Body weight adapted contrast volume (targeted volume of 1.2 mL/kg for the 1st study and 0.8 mL/kg for the 2nd study) was applied in both groups. Dual Energy mode was used for both the DS-PCD-CT and the DS-EID-CT. Polychromatic images and VMI (40 keV and 70 keV) were reconstructed for both the DS-EID-CT and the DS-PCD-CT data (termed T3D). Two radiologists assessed subjective image quality using a 5-point Likert-scale. Each reader drew ROIs within parenchymatous organs and vascular structures to analyze image noise, contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). RESULTS: Median time interval between scans was 12 months (Min: 6 months; Max: 36 months). BMI classification included overweight (n = 10, 14.7 %), obesity grade I (n = 38, 55.9 %), grade II (n = 13, 19.1 %) and grade III (n = 7, 10.3 %). The SNR achieved with DS-PCD-CT at QIR level 3was 12.61 vs. 11.47 (QIR 2) vs. 10.53 (DS-EID-CT), irrespective of parenchymatous organs. For vessels, the SNR were 16.73 vs. 14.20 (QIR 2) vs. 12.07 (DS-EID-CT). Moreover, the obtained median noise at QIR level 3 was as low as that of the DS-EID-CT (8.65 vs. 8.65). Both radiologists rated the image quality higher for DS-PCD-CT data sets (p < 0.05). The highest CNR was achieved at 40 keV for both scanners. T3D demonstrated significantly higher SNR and lower noise level compared to 40 keV and 70 keV. Median CTDIvol and DLP values for DS-PCD-CT and DS-EID-CT were 10.90 mGy (IQR: 9.31 - 12.50 mGy) vs. 16.55 mGy (IQR: 15.45 - 18.17 mGy) and 589.50 mGy * cm (IQR: 498.50 - 708.25 mGy * cm) vs. 848.75 mGy * cm (IQR: 753.43 - 969.58 mGy * cm) (p < 0.001). CONCLUSION: Image quality can be maintained while significantly reducing the contrast volume and the radiation dose (27% and 34% lower DLP and 31% lower CDTIvol) for abdominal contrast-enhanced CT using a 1st-generation DS-PCD-CT. Moreover, polychromatic reconstruction T3D on a DS-PCD-CT enables sufficient diagnostic image quality for oncological imaging.