Pulmonary cystic echinococcosis.

PURPOSE OF REVIEW: The aim of our review is to summarize specific clinical, diagnostic and treatment aspects of pulmonary cystic echinococcosis. The lung is the organ second most affected by cystic echinococcosis with approximately a quarter of cystic echinococcosis cysts. Most cysts are in the liver. Apart from the watch and wait approach for selected inactive cysts [cystic echinococcosis CE4, CE5], the well established WHO cystic echinococcosis cyst classification-based treatment of hepatic cystic echinococcosis cannot be applied to pulmonary cystic echinococcosis cysts. Some standard interventions can even be harmful when applied to pulmonary cystic echinococcosis cysts. RECENT FINDINGS: Cystic echinococcosis is one of the neglected tropical diseases (NTDs). Development of new diagnostics and treatment modalities is hampered by low investment into research and is accordingly slow. SUMMARY: Surgery is the mainstay of treatment for pulmonary cystic echinococcosis cysts. Parenchyma-sparing surgical techniques should be used whenever possible. Albendazole induces decay of the parasitic cyst membrane, opening of cystobronchial fistulas and cyst complications, which can be life threatening. It is strongly recommended to seek advice from expert centres, including differential diagnoses, treatment and a long-term management plan.

Quantification of airway wall contrast enhancement on virtual monoenergetic images from spectral computed tomography.

OBJECTIVES: Quantitative computed tomography (CT) plays an increasingly important role in phenotyping airway diseases. Lung parenchyma and airway inflammation could be quantified by contrast enhancement at CT, but its investigation by multiphasic examinations is limited. We aimed to quantify lung parenchyma and airway wall attenuation in a single contrast-enhanced spectral detector CT acquisition. METHODS: For this cross-sectional retrospective study, 234 lung-healthy patients who underwent spectral CT in four different contrast phases (non-enhanced, pulmonary arterial, systemic arterial, and venous phase) were recruited. Virtual monoenergetic images were reconstructed from 40-160 keV, on which attenuations of segmented lung parenchyma and airway walls combined for 5th-10th subsegmental generations were assessed in Hounsfield Units (HU) by an in-house software. The spectral attenuation curve slope between 40 and 100 keV (λHU) was calculated. RESULTS: Mean lung density was higher at 40 keV compared to that at 100 keV in all groups (p < 0.001). λHU of lung attenuation was significantly higher in the systemic (1.7 HU/keV) and pulmonary arterial phase (1.3 HU/keV) compared to that in the venous phase (0.5 HU/keV) and non-enhanced (0.2 HU/keV) spectral CT (p < 0.001). Wall thickness and wall attenuation were higher at 40 keV compared to those at 100 keV for the pulmonary and systemic arterial phase (p ≤ 0.001). λHU for wall attenuation was significantly higher in the pulmonary arterial (1.8 HU/keV) and systemic arterial (2.0 HU/keV) compared to that in the venous (0.7 HU/keV) and non-enhanced (0.3 HU/keV) phase (p ≤ 0.002). CONCLUSIONS: Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition, and may separate arterial and venous enhancement. Further studies are warranted to analyze spectral CT for inflammatory airway diseases. KEY POINTS: • Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition. • Spectral CT may separate arterial and venous enhancement of lung parenchyma and airway wall. • The contrast enhancement can be quantified by calculating the spectral attenuation curve slope from virtual monoenergetic images.

Balanced steady-state free precession MRCP is a robust alternative to respiration-navigated 3D turbo-spin-echo MRCP.

BACKGROUND: Despite synchronization to respiration, respiration-navigated (RN) 3D turbo-spin-echo MRCP is limited by susceptibility to motion artifacts. The aim of this study was to assess the quality of pancreaticobiliary duct visualization of a non-RN MRCP alternative based on balanced steady-state free precession imaging (BSSFP) with overlapping slices compared with RN-MRCP. METHODS: This is a retrospective study on 50 patients without pancreaticobiliary duct disease receiving MRCP at 1.5 T. We performed an intraindividual comparison of coronal RN-MRCP with combined coronal and transverse BSSFP-MRCP. Image quality was scored by 3 readers for 6 pancreaticobiliary duct segments (3 pancreatic, 3 biliary) using a 6-point scale. A segment score of 3 or lower as assessed by at least 2 of 3 readers was defined as insufficient segment visualization. Nonparametric tests and interrater reliability testing were used for statistical analysis. RESULTS: Overall duct visualization averaged over all readers was scored with 4.5 ± 1.1 for RN-MRCP (pancreatic, 4.1 ± 0.5; biliary, 5.0 ± 0.4) and 4.9 ± 0.9 for combined coronal and transverse BSSFP-MRCP (pancreatic, 4.6 ± 0.6; biliary, 5.1 ± 0.6), respectively (p < 0.001). The number of segments visualized insufficiently was 81/300 for RN-MRCP and 43/300 for BSSFP-MRCP (p < 0.001). Segments visualized insufficiently only in RN-MRCP had a mean score of 4.4 ± 0.8 in BSSFP-MRCP. Overall interrater agreement on superiority of BSSFP-MRCP segment scores over corresponding RN-MRCP was 0.70. Mean acquisition time was 98% longer for RN-MRCP (198.0 ± 98.7 s) than for combined coronal and transverse BSSFP-MRCP (100.2 ± 0.4 s). CONCLUSIONS: Non-RN BSSFP-MRCP with overlapping slices is a fast alternative to RN-MRCP, frequently providing sufficient duct visualization when RN-MRCP fails.

[Skeletal changes in plasma cell dyscrasias]. / Skelettveränderungen bei Plasmazelldyskrasien.

BACKGROUND: Plasma cell dyscrasias are a spectrum of diseases characterized by clonal plasma cell proliferation. Important entities within this group are monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and symptomatic multiple myeloma. PURPOSE: The goal of this review is to illustrate plasma cell dyscrasia imaging findings of bone and bone marrow as seen on whole-body computed tomography (CT) and magnetic resonance imaging (MRI) and to discuss the relevance of imaging for management of patients with plasma cell dyscrasias. MATERIALS AND METHODS: Selective literature search with analysis of dedicated original research articles and reviews and discussion of clinical guidelines. RESULTS: Diagnostic classification of plasma cell dyscrasias is based on the SLiM-CRAB criteria. CT primarily represents imaging of mineralized bone to show osseous end organ damage by detecting osteodestruction. MRI is primarily used for bone marrow imaging to detect diffuse or focal bone marrow infiltration, even in the absence of bone destruction. Different patterns of bone marrow infiltration can be distinguished. Treatment response is associated with characteristic imaging signs of lesion regression. CONCLUSION: Imaging plays a prominent role in treatment stratification of patients with plasma cell dyscrasia at first diagnosis and during follow-up.

Metastatic adult pancreatoblastoma: Multimodal treatment and molecular characterization of a very rare disease.

BACKGROUND: Pancreatoblastoma is a rare malignancy that occurs predominantly in children. Less than 50 adult cases, including 17 patients with metastatic disease, have been published to date. Recent outcome data from children with advanced-stage disease suggest an intensive multimodal treatment approach; however, little is known about the most beneficial therapy in adults. Molecular characterization of pancreatoblastoma is limited to a small number of pediatric cases and revealed few recurrent genetic events without immediate clinical relevance. METHODS: Patients were treated between 2013 and 2018 at a high-volume German university cancer center. Molecular analyses included whole genome, exome, transcriptome, and fusion gene panel sequencing. Molecularly guided treatment recommendations were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER). RESULTS: We identified four adult patients with metastatic pancreatoblastoma. In three patients, local approaches were combined with systemic treatment. Oxaliplatin-containing protocols showed an acceptable tumor control as well as an adequate toxicity profile. Overall survival was 15, 17, 18 and 24 months, respectively. Three tumors harbored genetic alterations involving the FGFR pathway that included an oncogenic FGFR2 fusion. CONCLUSION: Oxaliplatin-containing chemotherapy seems to be a reasonable approach in adult patients with advanced pancreatoblastoma, whereas the benefit of intensified treatment including local ablative techniques or surgical resection remains unclear. Our finding of FGFR alterations in three of four cases indicates a potential role of FGFR signaling in adult pancreatoblastoma whose clinical significance warrants further study.

RSPO2 gene rearrangement: a powerful driver of ß-catenin activation in liver tumours.

OBJECTIVE: We aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC). DESIGN: Large cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed. RESULTS: A roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microdeletion on chromosome 8q23.1 was detected as a new morphomolecular driver of ß-catenin-activated HCA. RSPO2 fusion positive HCA displayed upregulation of RSPO2 protein, nuclear accumulation of ß-catenin and transcriptional activation of ß-catenin-target genes indicating activation of Wingless-Type MMTV Integration Site Family (WNT) signalling. Architectural and cytological atypia as well as interstitial invasion indicated malignant transformation in one of the RSPO2 rearranged b-HCAs. The RSPO2 gene rearrangement was also observed in three ß-catenin-activated HCCs developing in context of chronic liver disease. Mutations of the human telomerase reverse transcriptase promoter-known to drive malignant transformation of CTNNB1-mutated HCA-seem to be dispensable for RSPO2 rearranged HCA and HCC. CONCLUSION: The RSPO2 gene rearrangement leads to oncogenic activation of the WNT signalling pathway in HCA and HCC, represents an alternative mechanism for the development of b-HCA and may drive malignant transformation without additional TERT promoter mutation.

Is MRCP necessary to diagnose pancreas divisum?

BACKGROUND: The purpose of this study is to compare the performance of three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) with non-MRCP T2-weighted magnetic resonance imaging (MRI) sequences for diagnosis of pancreas divisum (PD). METHODS: This is a retrospective study of 342 consecutive patients with abdominal MRI including 3D-MRCP. 3D-MRCP was a coronal respiration-navigated T2-weighted sequence with 1.5 mm slice thickness. Non-MRCP T2-weighted sequences were (1) a coronal inversion recovery sequence (TIRM) with 6 mm slice thickness and (2) a transverse single shot turbo spin echo sequence (HASTE) with 4 mm slice thickness. For 3D-MRCP, TIRM, and HASTE, presence of PD and assessment of evaluability were determined in a randomized manner. A consensus read by two radiologists using 3D-MRCP, non-MRCP T2-weighted sequences, and other available imaging sequences served as reference standard for diagnosis of PD. Statistical analysis included performance analysis of 3D-MRCP, TIRM, and HASTE and testing for noninferiority of non-MRCP T2-weighted sequences compared with 3D-MRCP. RESULTS: Thirty-three of 342 patients (9.7%) were diagnosed with PD using the reference standard. Sensitivity/specificity of 3D-MRCP for detecting PD were 81.2%/69.7% (p < 0.001). Sensitivity/specificity of TIRM and HASTE were 92.5%/93.9 and 98.1%/97.0%, respectively (p < 0.001 each). Grouped sensitivity/specificity of non-MRCP T2-weighted sequences were 99.8%/91.0%. Non-MRCP T2-weighted sequences were non-inferior to 3D-MRCP alone for diagnosis of PD. 20.2, 7.3%, and 2.3% of 3D-MRCP, TIRM, and HASTE, respectively, were not evaluable due to motion artifacts or insufficient duct depiction. CONCLUSIONS: Non-MRCP T2-weighted MRI sequences offer high performance for diagnosis of PD and are noninferior to 3D-MRCP alone. TRIAL REGISTRATION: Not applicable.

Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive marker for clinical response in first-line metastatic colorectal cancer patients: results of the phase II REMOTUX trial.

BACKGROUND: To assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC). METHODS: In this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. Primary endpoint was the predictive significance of ΔSUV for ECR. Secondary endpoints were PFS (progression free survival), OS and the influence of ΔSUV on survival. RESULTS: Forty pts were enroled and 33 pts were evaluable for the primary endpoint. The CT response rate was 57.6%. For responders, ΔSUV was significantly higher (p = 0.0092). A significant association of ΔSUV with ECR was found (p = 0.02). Median PFS was 11.7 months and median OS was 33.5 months with a 1-year survival rate of 87.9%. ΔSUV was found to significantly impact the hazard for OS (p = 0.045). CONCLUSIONS: We demonstrate that cetuximab induces metabolic responses in mCRC pts. The study endpoint was met with the ΔSUV discriminating between responders and non-responders. However, these data should be validated in larger patient cohorts.

Performance of Magnetic Resonance Susceptibility-Weighted Imaging for Detection of Calcifications in Patients With Hepatic Echinococcosis.

OBJECTIVE: We evaluated the performance of susceptibility-weighted imaging (SWI) for identification of hepatic calcifications in alveolar echinococcosis and cystic echinococcosis. METHODS: The SWI images of 58 lesions in 40 patients (age, 49 ± 14 y) with alveolar echinococcosis (n = 22) or cystic echinococcosis (n = 18) were reviewed for calcifications. First, calcifications were suggested by visual assessment. Second, ratios of minimum intralesional intensity and mean lumbar muscle intensity were recorded. Computed tomography (CT) served as the criterion standard. RESULTS: Thirty-seven lesions showed calcifications on CT. Susceptibility-weighted imaging provided a sensitivity of 89.2% (95% confidence interval [CI], 50.1-75.7) and a specificity of 57.1% (95% CI, 34.4-77.4) for calcifications detected by visual assessment. Receiver operating characteristic curves demonstrated a sensitivity of 67.6% and a specificity of 85.0% for an intensity ratio of 0.61. A specificity of 100% (95% CI, 80.8-100) and a sensitivity of 84.5% (95% CI, 67.3-93.2) were achieved by SWI for calcifications with a density greater than 184 HU in CT. CONCLUSIONS: Identification of hepatic calcifications is possible with SWI. Susceptibility-weighted imaging offers the potential to reduce the need for of CT imaging for evaluation of echinococcosis.

Gadoxetic Acid-Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for Delineation of Focal Nodular Hyperplasia: Superiority of High-Flip-Angle Imaging.

OBJECTIVE: The aim of this study was to investigate whether hepatobiliary-phase (HBP) flip-angle (FA) increase to 25° improves conspicuity of focal nodular hyperplasia (FNH) and enables HBP delay reduction. METHODS: This was a retrospective study of 23 patients with 46 FNHs. In each patient, HBP was performed with reduced-delay high FA (early/high), standard-delay high FA (late/high), and standard-delay standard FA (standard). Relative enhancement of liver and FNH periphery, FNH periphery-to-liver contrast ratio, and FNH periphery-to-central scar contrast ratio were compared between each HBP. RESULTS: Early/high, late/high, and standard HBPs were performed after 13.00 ± 2.12, 19.12 ± 3.10, and 19.68 ± 3.22 minutes, respectively. Liver and FNH periphery relative enhancement, FNH periphery-to-liver contrast ratio, and FNH periphery-to-central scar contrast ratio were higher for early/high and late/high than for standard HBP (P < 0.001 to P = 0.0048). CONCLUSIONS: Increasing FA to 25° improves delineation of FNHs in HBP. Combining FA increase with delay reduction is superior to standard HBP and is sufficient for FNH characterization.

Echinococcoses - A Primer for Radiologists. / Die Echinokokkosen aus Sicht der Radiologie.

BACKGROUND: Cystic (CE) and alveolar (AE) echinococcoses are zoonotic parasitoses that may pose diagnostic problems due to their relative rarity in Middle Europe. METHODS: Based on a recent literature search and the observation of casuistics from a national echinococcosis treatment center, epidemiological, radiological, and therapeutic fundamentals are presented and important differences between AE and CE are discussed. RESULTS AND CONCLUSION: AE and CE must be regarded as completely different diseases, which differ from each other in every significant aspect. This applies not only to the epidemiological background of the patients but also to the biology of the diseases and their respective imaging features. KEY POINTS: · AE and CE are very distinct from one another and must be considered separately.. · AE is endemic in Middle Europe and is known as malignant parasitosis due to its destructive growth form.. · CE is primarily seen in Middle Europe in individuals with migration background and has a rather benign character.. CITATION FORMAT: · Weber TF, Mokry T, Stojkovic M. Die Echinokokkosen - Einblicke aus Sicht der Radiologie. Fortschr Röntgenstr 2023; 195: 1106 - 1121.

Pattern and time point of relapse in locally advanced esophagogastric adenocarcinoma after multimodal treatment: implications for a useful structured follow-up.

PURPOSE: Despite improvements in multimodal treatment of locally advanced esophagogastric adenocarcinoma, the majority of patients still relapses. The impact of structured follow-up for early detection of recurrence is unclear and controversially discussed. METHODS: Patients with locally advanced esophagogastric adenocarcinoma having received neoadjuvant/perioperative chemotherapy followed by tumor resection between 2009 and 2021, underwent a structured follow-up including three-monthly imaging during the first 2 years, followed by semiannual and annual examinations in year 3-4 and 5, respectively. Clinical outcome including pattern and time point of relapse was analyzed. RESULTS: Two hundred fifty-seven patients were included in this analysis. In 50.2% (n = 129) of patients, recurrent disease was diagnosed, with the majority (94.6%) relapsing within the first 2 years. The most common site of relapse were lymph node metastases followed by peritoneal carcinomatosis and hepatic and pulmonary metastases. 52.7% of patients presented with symptoms at the time of relapse. Cumulative risk and time point of relapse differed significantly between patient with a node-positive tumor (ypN+) after neoadjuvant treatment (high-risk group) and patients with node-negative primary tumor (ypN0) (low-risk group). High-risk patients had a significantly inferior disease-free survival (DFS) and overall survival (OS) with 11.1 and 29.0 months, respectively, whereas median DFS and OS were not reached for the low-risk group. CONCLUSIONS: The risk of relapse differs significantly between high- and low-risk patients. Only a part of relapses is associated with clinical symptoms. An individualized follow-up strategy is recommended for high- and low-risk patients considering the individual risk of relapse.

Test-retest, inter- and intra-rater reproducibility of size measurements of focal bone marrow lesions in MRI in patients with multiple myeloma.

OBJECTIVE: To investigate the reproducibility of size measurements of focal bone marrow lesions (FL) in MRI in patients with monoclonal plasma cell disorders under variation of patient positioning and observer. METHODS: A data set from a prospective test-retest study was used, in which 37 patients with a total of 140 FL had undergone 2 MRI scans with identical parameters after patient repositioning. Two readers measured long and short axis diameter on the initial scan in T1 weighted, T2 weighted short tau inversion recovery and diffusion-weighted imaging sequences. The first reader additionally measured FL on the retest-scan. The Bland-Altman method was used to assess limits of agreement (LoA), and the frequencies of absolute size changes were calculated. RESULTS: In the simple test-retest experiment with one identical reader, a deviation of ≥1 mm / ≥2 mm / ≥3 mm for the long axis diameter in T1 weighted images was observed in 66% / 25% / 8% of cases. When comparing measurements of one reader on the first scan to the measurement of the other reader on the retest scan, a change of ≥1 mm / ≥3 mm / ≥5 mm for the long axis diameter in T1 weighted images was observed in 78% / 21% / 5% of cases. CONCLUSION: Small deviations in FL size are common and probably due to variation in patient positioning or inter-rater variability alone, without any actual biological change of the FL. Knowledge of the uncertainty associated with size measurements of FLs is critical for radiologists and oncologists when interpreting changes in FL size in clinical practice and in clinical trials. ADVANCES IN KNOWLEDGE: According to the MY-RADs criteria, size measurements of focal lesions in MRI are now of relevance for response assessment in patients with monoclonal plasma cell disorders.Size changes of 1 or 2 mm are frequently observed due to uncertainty of the measurement only, while the actual focal lesion has not undergone any biological change.Size changes of at least 6 mm or more in T1 weighted or T2 weighted short tau inversion recovery sequences occur in only 5% or less of cases when the focal lesion has not undergone any biological change.

Risk factors and management of biliary leakage after Endocystectomy for hepatic cystic echinococcosis.

BACKGROUND: Endocystectomy is a conservative surgical approach to managing cystic echinococcosis. Bile leakage is the main complication of this technique. The aim of this study was to evaluate the factors associated with bile leakage and to assess the outcomes and cost efficiency of strategies used to treat bile leakage. METHODOLOGY/PRINCIPAL FINDINGS: Patients who underwent endocystectomy between 2005 and 2020 were included. The preoperative characteristics, intra- and postoperative outcomes, hospital costs, and cost efficiency (the Diagnosis-Related Group reimbursement minus the overall cost) were evaluated prospectively. A total of eighty patients with 142 cysts were included. Postoperative complications occurred in 17 patients (21%), including 11 patients with bile leakage (type A: 1, type B: 6 and type C: 4 patients, total 13%). Bile leakage was more frequent in patients with preoperative MRI signs of cysto-biliary fistulas or intraoperative visible cysto-biliary fistulas (p = 0.03 and p = 0.04, respectively) and in patients with cysts larger than 8 cm (p = 0.03). Patients with bile leakage who underwent reoperation (type C) had significantly shorter hospital stays (9 vs. 16 days, p<0.01) and better cost efficiency than those who received radiologic or endocscopic interventions (€2,072 vs. -€2,097 p = 0.01). No mortality was observed, and recurrence was seen in two patients. CONCLUSIONS/SIGNIFICANCE: Endocystectomy is a safe and efficient technique. Preoperative and intraoperative cysto-biliary fistulas and a cyst diameter larger than 8 cm are correlated to postoperative bile leakage. Early operative management of bile leakage reduces hospital stay and improves cost efficiency compared with radiologic or endoscopic treatments.

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.

A phase II study for metabolic in vivo response monitoring with sequential 18FDG-PET-CT during treatment with the EGFR-monoclonal-antibody cetuximab in metastatic colorectal cancer: the Heidelberg REMOTUX trial.

BACKGROUND: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor metabolism is of clinical importance since there may be a substantial influence on choice and sequence of drug combinations. Early signals of response to cetuximab may prove useful to identify patients having a relevant clinical treatment benefit. The objective of this trial is to evaluate the predictive relevance of the relative change in (18)F-Fluorodeoxyglucose tumor uptake for early clinical response during short-term single agent treatment with cetuximab. Early clinical response will be routinely measured according to the response evaluation criteria in solid tumors. Accompanying research includes cytokine immune monitoring and analysis of tumor proteins and tumor genes. METHODS/DESIGN: The REMOTUX trial is an investigator-initiated, prospective, open-label, single-arm, single-center early exploratory predictive study. The first (18)F-FDG PET-CT is conducted at baseline followed by the run-in phase with cetuximab at days 1 and 8. At day 14, the second (18)F-FDG PET-CT is performed. Subsequently, patients are treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma. At day 56, clinical response is evaluated with a CT-scan compared to the baseline analysis. Tracer uptake is assessed using standardized uptake values (SUVs). The main hypothesis to be tested in the primary analysis is whether or not the relative change in the SUV from baseline to day 14 has any predictive relevance for early clinical response determined at day 56. Patients are followed until death from any cause or until 24 months after the last patient has ended trial treatment. DISCUSSION: The aim of this trial is to evaluate metabolic changes in metastatic colorectal cancer during short-term single agent treatment with cetuximab and to analyse their potential of predicting early clinical response. This could be helpful to answer the question if early identification of patients not responding to cetuximab is possible. TRIAL REGISTRATION: ClinicalTrials.gov NCT200811021020; EudraCT 200901327923.

Dual-Layer Spectral CTA for TAVI Planning Using a Split-Phase Protocol and Low-keV Virtual Monoenergetic Images: Improved Image Quality in Comparison with Single-Phase Conventional CTA.

PURPOSE: Adaptation of computed tomography protocols for transcatheter aortic valve implantation (TAVI) planning is required when a first-generation dual-layer spectral CT scanner (DLCT) is used. The purpose of this study was to evaluate the objective image quality of aortic CT angiography (CTA) for TAVI planning using a split-phase technique with reconstruction of 40 keV virtual monoenergetic images (40 keV-VMI) obtained with a DLCT scanner. CT angiography obtained with a single-phase protocol of a conventional single-detector CT (SLCT) was used for comparison. MATERIALS AND METHODS: 75 CTA scans from DLCT were retrospectively compared to 75 CTA scans from SLCT. For DLCT, spiral CTA without ECG-synchronization was performed immediately after a retrospectively ECG-gated acquisition covering the heart and aortic arch. For SLCT, spiral CTA with retrospective ECG-gating was performed to capture the heart and the access route simultaneously in one scan. Objective image quality was compared at different levels of the arterial access route. RESULTS: 40 keV virtual monoenergetic images of DLCT showed a significantly higher mean vessel attenuation, SNR, and CNR at all levels of the arterial access route. With 40 keV-VMI of DLCT, the overall mean aortic attenuation of all six measured regions was 589.6 ±â€Š243 HU compared to 492.7 ±â€Š209 HU of SLCT (p < 0.01). A similar trend could be observed for SNR (23.6 ±â€Š18 vs. 18.6 ±â€Š9; p < 0.01) and CNR (21.1 ±â€Š18 vs. 16.4 ±â€Š8; p < 0.01). No deterioration was observed for vascular noise (27.8 ±â€Š9 HU vs. 28.1 ±â€Š8 HU; p = 0.599). CONCLUSION: Using a DLCT scanner with a split-phase protocol and 40 keV-VMI for TAVI planning, higher objective image quality can be obtained compared to a single-phase protocol of a conventional CT scanner. KEY POINTS: · Adaption of TAVI planning CT protocols may be required when using a first-generation dual-layer CT scanner.. · Reconstruction of virtual monoenergetic images at 40 keV improves image quality.. · With a split-phase protocol, the radiation dose is lower compared to a single-phase ECG-gated CT acquisition.. CITATION FORMAT: · Mangold D, Salatzki J, Riffel J et al. Dual-Layer Spectral CTA for TAVI Planning Using a Split-Phase Protocol and Low-keV Virtual Monoenergetic Images: Improved Image Quality in Comparison with Single-Phase Conventional CTA. Fortschr Röntgenstr 2022; 194: 652 - 659.

Dual-Layer Spectral Detector CT in Comparison with FDG-PET/CT for the Assessment of Lymphoma Activity.

PURPOSE: In patients with malignant lymphoma, disease activity is recommended to be assessed by FDG-PET/CT and the Deauville five-point scale (5-PS). The purpose of this study was to explore the potential of iodine concentration measured in contrast-enhanced dual-layer spectral detector CT (SDCT) as an alternative surrogate parameter for lymphoma disease activity by investigating its correlation with maximum standardized uptake values (SUVmax) and 5-PS. MATERIALS AND METHODS: 25 patients were retrospectively analyzed. Contrast-enhanced SDCT and FDG-PET/CT were performed in the same treatment interval within at most 3 months. CT attenuation values (AV), absolute iodine concentrations (aIC), and normalized iodine concentrations (nIC) of lymphoma lesions were correlated with SUVmax using Spearman's rank correlation coefficient. The performance of aIC and nIC to detect lymphoma activity (defined as 5-PS > 3) was determined using ROC curves. RESULTS: 60 lesions were analyzed, and 31 lesions were considered active. AV, aIC, and nIC all correlated significantly with SUVmax. The strongest correlation (Spearman ρ = 0.71; p < 0.001) and highest area under the ROC curve (AUROC) for detecting lymphoma activity were observed for nIC normalized to inferior vena cava enhancement (AUROC = 0.866). The latter provided sensitivity, specificity, and diagnostic accuracy of 87 %, 75 %, and 80 %, respectively, at a threshold of 0.20. ROC analysis for AV (AUROC = 0.834) and aIC (AUROC = 0.853) yielded similar results. CONCLUSION: In malignant lymphomas, there is a significant correlation between metabolic activity as assessed by FDG-PET/CT and iodine concentration as assessed by SDCT. Iodine concentration shows promising diagnostic performance for detecting lymphoma activity and may represent a potential imaging biomarker. KEY POINTS: · Iodine concentration correlates significantly with SUVmax in lymphoma patients. · Iodine concentration may represent a potential imaging biomarker for detecting lymphoma activity. · Normalization of iodine concentration improves diagnostic performance of iodine concentration. CITATION FORMAT: · Gehling K, Mokry T, Do TD et al. Dual-Layer Spectral Detector CT in Comparison with FDG-PET/CT for the Assessment of Lymphoma Activity. Fortschr Röntgenstr 2022; 194: 747 - 754.

Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment : Longitudinal Assessment by Computed Tomography.

PURPOSE: Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose. METHODS: For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1-t4) with the following median and ranges in months: 3.1 (0.4-4.9), 6.2 (5.3-7.8), 10.4 (8.2-11.9), and 18.4 (12.8-49.8). RESULTS: DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p < 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p < 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08). CONCLUSION: CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker.

Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer - The PICCASSO phase I trial.

BACKGROUND: PD-1/PD-L1 inhibitors do not show activity in mismatch repair proficient (MMRp) colorectal cancer. Inhibition of C-C motif chemokine receptor 5 (CCR5) leads to an antitumoral activation of macrophages, affecting immune cell infiltrates. PICCASSO is a phase I trial exploring safety and efficacy of pembrolizumab and maraviroc in refractory MMRp CRC. METHODS: Twenty patients received pembrolizumab and maraviroc (core period, eight cycles), followed by pembrolizumab monotherapy. Primary endpoint was the feasibility rate (patients without treatment-related grade ≥3 immune-related adverse events, treatment-related grade ≥4 adverse events, or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Optional biopsies of liver metastases were performed for analyses of the micromilieu. RESULTS: The feasibility rate was 94.7% [90% CI 77.4-99.7%], with one grade 4 hyperglycemia and no additional ≥ grade 3 treatment-related toxicities. ORR according to RECIST was 5.3%. Median PFS according to RECIST was 2.10 months [95%CI 1.68-2.30], median OS 9.83 months [95% CI, 5.59-20.02]. Disease control rate of poststudy salvage treatment was >70%. Translational analyses showed an increase of antitumoral chemokines during treatment; eotaxin, a chemokine involved in chemotaxis, was identified as a biomarker linked to OS. CONCLUSIONS: Therapy with pembrolizumab and maraviroc was feasible and showed a beneficial toxicity pattern. Clinical activity in MMRp CRC patients was limited with prolonged disease stabilizations observed in single patients. Efficacy of poststudy salvage treatment and OS was higher than expected in this heavily pretreated population. THIS TRIAL IS REGISTERED AT CLINICALTRIALS.GOV: NCT03274804.