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.

Photon-counting computed tomography - clinical application in oncological, cardiovascular, and pediatric radiology. / Photon-Counting Computertomographie ­ klinische Anwendungen in der onkologischen, kardiovaskulären und pädiatrischen Radiologie.

BACKGROUND: Photon-counting detector computed tomography (PCD-CT) is a promising new technology with the potential to fundamentally change workflows in the daily routine and provide new quantitative imaging information to improve clinical decision-making and patient management. METHOD: The contents of this review are based on an unrestricted literature search of PubMed and Google Scholar using the search terms "photon-counting CT", "photon-counting detector", "spectral CT", "computed tomography" as well as on the authors' own experience. RESULTS: The fundamental difference with respect to the currently established energy-integrating CT detectors is that PCD-CT allows for the counting of every single photon at the detector level. Based on the identified literature, PCD-CT phantom measurements and initial clinical studies have demonstrated that the new technology allows for improved spatial resolution, reduced image noise, and new possibilities for advanced quantitative image postprocessing. CONCLUSION: For clinical practice, the potential benefits include fewer beam hardening artifacts, a radiation dose reduction, and the use of new or combinations of contrast agents. In particular, critical patient groups such as oncological, cardiovascular, lung, and head & neck as well as pediatric patient collectives benefit from the clinical advantages. KEY POINTS: · Photon-counting computed tomography (PCD-CT) is being used for the first time in routine clinical practice, enabling a significant dose reduction in critical patient populations such as oncology, cardiology, and pediatrics.. · Compared to conventional CT, PCD-CT enables a reduction in electronic image noise.. · Due to the spectral data sets, PCD-CT enables fully comprehensive post-processing applications.. CITATION FORMAT: · Hagen F, Soschynski M, Weis M et al. Photon-counting computed tomography - clinical application in oncological, cardiovascular, and pediatric radiology. Fortschr Röntgenstr 2024; 196: 25 - 34.

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.

Myasthenia gravis as initial presentation of a pancreatic neuroendocrine tumor: A case report.

Myasthenia gravis (MG) is a heterogeneous autoimmune disease, which is characterized by a postsynaptic neuromuscular transmission defect, with antibodies directly targeting the acetylcholine receptor (AChR) or other structural proteins of the neuromuscular junction. The majority of MG cases are associated with thymic pathologies, including thymoma, thyroiditis, autoimmune diseases or malignant hematologic neoplasia. The present study reported a rare case of AChR-positive and late-onset ocular MG, which rapidly progressed to a generalized myasthenic syndrome as an initial presentation of a pancreatic neuroendocrine neoplasia (pNEN). Following complete surgical resection of the pNEN, the myasthenic syndrome was improved and the anti-AChR antibody titers were reduced. It has been reported that MG is a paraneoplastic syndrome in thymic neoplasms and less common in hematologic malignancies. However, currently, only few cases of MG as initial presentation of a solid tumor, and more particular of a neuroendocrine neoplasm, have been reported in the literature. In conclusion, surveillance for extrathymic solid malignancies in newly diagnosed patients with MG could promote the early diagnosis of associated tumor diseases.

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome.

Importance: Autoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome. Objective: To test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement. Design, Setting, and Participants: This case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity. Exposure: Prior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion. Main Outcomes and Measures: The patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes. Results: Rapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%). Conclusions and Relevance: CD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

Prediction of Bone Marrow Biopsy Results From MRI in Multiple Myeloma Patients Using Deep Learning and Radiomics.

OBJECTIVES: In multiple myeloma and its precursor stages, plasma cell infiltration (PCI) and cytogenetic aberrations are important for staging, risk stratification, and response assessment. However, invasive bone marrow (BM) biopsies cannot be performed frequently and multifocally to assess the spatially heterogenous tumor tissue. Therefore, the goal of this study was to establish an automated framework to predict local BM biopsy results from magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective multicentric study used data from center 1 for algorithm training and internal testing, and data from center 2 to 8 for external testing. An nnU-Net was trained for automated segmentation of pelvic BM from T1-weighted whole-body MRI. Radiomics features were extracted from these segmentations, and random forest models were trained to predict PCI and the presence or absence of cytogenetic aberrations. Pearson correlation coefficient and the area under the receiver operating characteristic were used to evaluate the prediction performance for PCI and cytogenetic aberrations, respectively. RESULTS: A total of 672 MRIs from 512 patients (median age, 61 years; interquartile range, 53-67 years; 307 men) from 8 centers and 370 corresponding BM biopsies were included. The predicted PCI from the best model was significantly correlated ( P ≤ 0.01) to the actual PCI from biopsy in all internal and external test sets (internal test set: r = 0.71 [0.51, 0.83]; center 2, high-quality test set: r = 0.45 [0.12, 0.69]; center 2, other test set: r = 0.30 [0.07, 0.49]; multicenter test set: r = 0.57 [0.30, 0.76]). The areas under the receiver operating characteristic of the prediction models for the different cytogenetic aberrations ranged from 0.57 to 0.76 for the internal test set, but no model generalized well to all 3 external test sets. CONCLUSIONS: The automated image analysis framework established in this study allows for noninvasive prediction of a surrogate parameter for PCI, which is significantly correlated to the actual PCI from BM biopsy.

Is There Still a Role for Two-Phase Contrast-Enhanced CT and Virtual Monoenergetic Images in the Era of Photon-Counting Detector CT?

BACKGROUND: To compare the diagnostic characteristics between arterial phase imaging versus portal venous phase imaging, applying polychromatic T3D images and low keV virtual monochromatic images using a 1st generation photon-counting CT detector, of CT in patients with hepatocellular carcinoma (HCC). METHODS: Consecutive patients with HCC, with a clinical indication for CT imaging, were prospectively enrolled. Virtual monoenergetic images (VMI) were reconstructed at 40 to 70 keV for the PCD-CT. Two independent, blinded radiologists counted all hepatic lesions and quantified their size. The lesion-to-background ratio was quantified for both phases. SNR and CNR were determined for T3D and low VMI images; non-parametric statistics were used. RESULTS: Among 49 oncologic patients (mean age 66.9 ± 11.2 years, eight females), HCC was detected in both arterial and portal venous scans. The signal-to-noise ratio, the CNR liver-to-muscle, the CNR tumor-to-liver, and CNR tumor-to-muscle were 6.58 ± 2.86, 1.40 ± 0.42, 1.13 ± 0.49, and 1.53 ± 0.76 in the arterial phase and 5.93 ± 2.97, 1.73 ± 0.38, 0.79 ± 0.30, and 1.36 ± 0.60 in the portal venous phase with PCD-CT, respectively. There was no significant difference in SNR between the arterial and portal venous phases, including between "T3D" and low keV images (p > 0.05). CNRtumor-to-liver differed significantly between arterial and portal venous contrast phases (p < 0.005) for both "T3D" and all reconstructed keV levels. CNRliver-to-muscle and CNRtumor-to-muscle did not differ in either the arterial or portal venous contrast phases. CNRtumor-to-liver increased in the arterial contrast phase with lower keV in addition to SD. In the portal venous contrast phase, CNRtumor-to-liver decreased with lower keV; whereas, CNRtumor-to-muscle increased with lower keV in both arterial and portal venous contrast phases. CTDI and DLP mean values for the arterial upper abdomen phase were 9.03 ± 3.59 and 275 ± 133, respectively. CTDI and DLP mean values for the abdominal portal venous phase were 8.75 ± 2.99 and 448 ± 157 with PCD-CT, respectively. No statistically significant differences were found concerning the inter-reader agreement for any of the (calculated) keV levels in either the arterial or portal-venous contrast phases. CONCLUSIONS: The arterial contrast phase imaging provides higher lesion-to-background ratios of HCC lesions using a PCD-CT; especially, at 40 keV. However, the difference was not subjectively perceived as significant.

Radiation Dose Reduction in Contrast-Enhanced Abdominal CT: Comparison of Photon-Counting Detector CT with 2nd Generation Dual-Source Dual-Energy CT in an oncologic cohort.

RATIONAL AND OBJECTIVES: Comparison of radiation dose and image quality in routine abdominal and pelvic contrast-enhanced computed tomography (CECT) between a photon-counting detector CT (PCD-CT) and a dual energy dual source CT (DSCT). MATERIALS AND METHODS: 70 oncologic patients (mean age 66 ± 12 years, 29 females) were prospectively enrolled between November 2021 and February 2022. Abdominal CECT were clinically indicated and performed first on a 2nd-generation DSCT and at follow-up on a 1st-generation dual-source PCD-CT. The same contrast media (Imeron 350, Bracco imaging) and pump protocol was used for both scans. For both scanners, polychromatic images were reconstructed with 3mm slice thickness and comparable kernel (I30f[DSCT] and Br40f[PCD-CT]); for PCD-CT data from all counted events above the lowest energy threshold at 20 keV ("T3D") were used. Results were compared in terms of radiation dose metrics of CT dose index (CTDIvol), dose length product (DLP) and size-specific dose estimation (SSDE), objective and subjective measurements of image quality were scored by two emergency radiologists including lesion conspicuity. RESULTS: Median time interval between the scans was 4 months (IQR: 3-6). CNRvessel and SNRvessel of T3D reconstructions from PCD-CT were significantly higher than those of DSCT (all, p < 0.05). Qualitative image noise analysis from PCD-CT and DSCT yielded a mean of 4 each. Lesion conspicuity was rated significantly higher in PCD-CT (Q3 strength) compared to DSCT images. CTDI, DLP and SSDE mean values for PCD-CT and DSCT were 7.98 ± 2.56 mGy vs. 14.11 ± 2.92 mGy, 393.13 ± 153.55 mGy*cm vs. 693.61 ± 185.76 mGy*cm and 9.98 ± 2.41 vs. 14.63 ± 1.63, respectively, translating to a dose reduction of around 32% (SSDE). CONCLUSION: PCD-CT enables oncologic abdominal CT with a significantly reduced dose while keeping image quality similar to 2nd-generation DSCT.

Deep Learning for Automatic Bone Marrow Apparent Diffusion Coefficient Measurements From Whole-Body Magnetic Resonance Imaging in Patients With Multiple Myeloma: A Retrospective Multicenter Study.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging (MRI) is increasingly important in patients with multiple myeloma (MM). The objective of this study was to train and test an algorithm for automatic pelvic bone marrow analysis from whole-body apparent diffusion coefficient (ADC) maps in patients with MM, which automatically segments pelvic bones and subsequently extracts objective, representative ADC measurements from each bone. MATERIALS AND METHODS: In this retrospective multicentric study, 180 MRIs from 54 patients were annotated (semi)manually and used to train an nnU-Net for automatic, individual segmentation of the right hip bone, the left hip bone, and the sacral bone. The quality of the automatic segmentation was evaluated on 15 manually segmented whole-body MRIs from 3 centers using the dice score. In 3 independent test sets from 3 centers, which comprised a total of 312 whole-body MRIs, agreement between automatically extracted mean ADC values from the nnU-Net segmentation and manual ADC measurements from 2 independent radiologists was evaluated. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. In 56 patients with newly diagnosed MM who had undergone bone marrow biopsy, ADC measurements were correlated with biopsy results using Spearman correlation. RESULTS: The ADC-nnU-Net achieved automatic segmentations with mean dice scores of 0.92, 0.93, and 0.85 for the right pelvis, the left pelvis, and the sacral bone, whereas the interrater experiment gave mean dice scores of 0.86, 0.86, and 0.77, respectively. The agreement between radiologists' manual ADC measurements and automatic ADC measurements was as follows: the bias between the first reader and the automatic approach was 49 × 10 -6 mm 2 /s, 7 × 10 -6 mm 2 /s, and -58 × 10 -6 mm 2 /s, and the bias between the second reader and the automatic approach was 12 × 10 -6 mm 2 /s, 2 × 10 -6 mm 2 /s, and -66 × 10 -6 mm 2 /s for the right pelvis, the left pelvis, and the sacral bone, respectively. The bias between reader 1 and reader 2 was 40 × 10 -6 mm 2 /s, 8 × 10 -6 mm 2 /s, and 7 × 10 -6 mm 2 /s, and the mean absolute difference between manual readers was 84 × 10 -6 mm 2 /s, 65 × 10 -6 mm 2 /s, and 75 × 10 -6 mm 2 /s. Automatically extracted ADC values significantly correlated with bone marrow plasma cell infiltration ( R = 0.36, P = 0.007). CONCLUSIONS: In this study, a nnU-Net was trained that can automatically segment pelvic bone marrow from whole-body ADC maps in multicentric data sets with a quality comparable to manual segmentations. This approach allows automatic, objective bone marrow ADC measurements, which agree well with manual ADC measurements and can help to overcome interrater variability or nonrepresentative measurements. Automatically extracted ADC values significantly correlate with bone marrow plasma cell infiltration and might be of value for automatic staging, risk stratification, or therapy response assessment.

Myeloma bone disease imaging on a 1st-generation clinical photon-counting detector CT vs. 2nd-generation dual-source dual-energy CT.

OBJECTIVE: Subjective and objective image quality comparison of bone microstructure and disease-related abnormalities in multiple myeloma patients using a 1st-generation dual-source photon-counting detector CT(DS-PCD-CT) and a 2nd-generation dual-source dual-energy (energy-integrating detector) CT (DS-EID-CT). METHODS: Fifty multiple myeloma patients (mean age 67.7 ± 10.9 years,16 females) were prospectively enrolled. Unenhanced whole-body CTs were clinically indicated and performed on DS-EID-CT and DS-PCD-CT (median time difference: 12 months). DS-PCD-CT was performed in Quantumplus UHR mode and DS-EID-CT was performed using dual-energy mode. DS-PCD-CT kernel was set at Br64 with Quantum iterative reconstruction strength Q1; for DS-EID-CT a comparable I70f kernel with SAFIRE iterative reconstruction strength 1 was used. Two independent radiologists assessed image quality subjectively using a 5-point Likert scale considering delineation and sharpness of trabecular bone and lytic bone lesions in the spine and pelvic bones. Additionally, ImageJ was used for quantification of bony septa inside the cancellous bone and through or the edges of osteolysis. RESULTS: Overall quality as well as detectability and sharpness in the delineation of lytic bone lesions were superior for DS-PCD-CT compared with DS-EID-CT (p < 0.0001). The inter-reader agreement for subjective image quality readings showed excellent consistency(α = 94.2-98.8). CTDI and DLP mean values for DS-PCD-CT and DS-EID-CT were 1107.4 ± 247.6 mGy*cm and 8.2 ± 1.8 mGy vs. 1344.3 ± 204.6 mGy*cm and 10.1 ± 1.9 mGy. The quantitative metric for bone microstructure in the femoral head showed significantly better visualization of trabeculae in DS-PCD-CT compared with DS-EID-CT (p < 0.0001). Quantitative analyses of edge sharpness of osteolysis showed significant steeper edges for DS-PCD-CT (p < 0.0001). CONCLUSION: DS-PCD-CT significantly improves spatial resolution of bony microstructure and lytic bone lesions compared to DS-EID-CT. KEY POINTS: • Application of photon-counting detector CT is superior to dual-source dual-energy integrating detector in clinical workup of multiple myeloma patients. • Compared to energy integrating detectors, photon-counting detectors significantly increase the spatial resolution of bone microstructure including disease-related lytic bone lesions in patients with multiple myeloma.

Effects of different virtual monoenergetic CT image data on chest wall post-processing "unfolded ribs" and proposal of an algorithm improvement.

PURPOSE: To find out if the use of different virtual monoenergetic data sets enabled by DECT technology might have a negative impact on post-processing applications, specifically in case of the "unfolded ribs" algorithm. Metal or beam hardening artifacts are suspected to generate image artifacts and thus reduce diagnostic accuracy. This paper tries to find out how the generation of "unfolded rib" CT image reformates is influenced by different virtual monoenergetic CT images and looks for possible improvement of the post-processing tool. MATERIAL AND METHODS: Between March 2021 and April 2021, thin-slice dual-energy CT image data of the chest were used creating "unfolded rib" reformates. The same data sets were analyzed in three steps: first the gold standard with the original algorithm on mixed image data sets followed by the original algorithm on different keV levels (40-120 keV) and finally using a modified algorithm which in the first step used segmentation based on mixed image data sets, followed by segmentation based on different keV levels. Image quality (presence of artifacts), lesion and fracture detectability were assessed for all series. RESULTS: Both, the original and the modified algorithm resulted in more artifact-free image data sets compared to the gold standard. The modified algorithm resulted in significantly more artifact-free image data sets at the keV-edges (40-120 keV) compared the original algorithm. Especially "black artifacts" and pseudo-lesions, potentially inducing false positive findings, could be reduced in all keV level with the modified algorithm. Detection of focal sclerotic, lytic or mixed (k = 0.990-1.000) lesions was very good for all keV levels. The Fleiss-kappa test for detection of fresh and old rib fractures was ≥ 0.997. CONCLUSION: The use of different virtual monoenergetic keVs for the "unfolded rib" algorithm is generating different artifacts. Segmentation-based artifacts could be eliminated by the proposed new algorithm, showing the best results at 70-80 keV.

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.

Case report: Immunovirotherapy as a novel add-on treatment in a patient with thoracic NUT carcinoma.

NUT carcinoma (NC) is a rare and extremely aggressive form of cancer, usually presenting with intrathoracic or neck manifestations in adolescents and young adults. With no established standard therapy regimen and a median overall survival of only 6.5 months, there is a huge need for innovative treatment options. As NC is genetically driven by a single aberrant fusion oncoprotein, it is generally characterized by a low tumor mutational burden, thus making it immunologically cold and insusceptible to conventional immunotherapy. Recently, we have demonstrated that oncolytic viruses (OVs) are able to specifically infect and lyse NC cells, thereby turning an immunologically cold tumor microenvironment into a hot one. Here, we report an intensive multimodal treatment approach employing for the first time an OV (talimogene laherparepvec (T-VEC); IMLYGIC®) together with the immune checkpoint inhibitor pembrolizumab as an add-on to a basic NC therapy (cytostatic chemotherapy, radiation therapy, epigenetic therapy) in a patient suffering from a large thoracic NC tumor which exhibits an aberrant, unique BRD3:NUTM1 fusion. This case demonstrates for the first time the feasibility of this innovative add-on immunovirotherapy regimen with a profound, repetitive and durable replication of T-VEC that is instrumental in achieving tumor stabilization and improvement in the patient´s quality of life. Further, a previously unknown BRD3:NUTM1 fusion gene was discovered that lacks the extraterminal domain of BRD3.

NUT Carcinoma-An Underdiagnosed Malignancy.

NUT carcinoma (NC) is a rare and highly aggressive malignancy with a dismal prognosis and a median survival of 6-9 months only. Although very few cases of NC are reported each year, the true prevalence is estimated to be much higher, with NC potentially widely underdiagnosed due to the lack of awareness. NC primarily occurs in midline structures including thorax, head, and neck; however, other sites such as pancreas and kidney are also affected, albeit at lower frequencies. NC is characterized by a single translocation involving the NUTM1 (NUT midline carcinoma family member 1) gene and different partner genes. The resulting fusion proteins initiate tumorigenesis through a mechanism involving BET (bromo-domain and extra-terminal motif) proteins such as Bromodomain-containing protein 4 (BRD4) and inordinate acetylation of chromatin, leading to the dysregulation of growth and differentiation genes. While no clinical characteristics are specific for NC, some histologic features can be indicative; therefore, patients with these tumor characteristics should be routinely tested for NUTM1. The diagnosis of NC using immunohistochemistry with a highly specific antibody is straightforward. There are currently no standard-of-care treatment options for patients with NC. However, novel therapies specifically addressing the unique tumorigenic mechanism are under investigation, including BET inhibitors. This review aims to raise awareness of this underdiagnosed cancer entity and provide all patients the opportunity to be properly diagnosed and referred to a clinical study.