Search

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.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.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 mm2/s, 7 × 10-6 mm2/s, and -58 × 10-6 mm2/s, and the bias between the second reader and the automatic approach was 12 × 10-6 mm2/s, 2 × 10-6 mm2/s, and -66 × 10-6 mm2/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 mm2/s, 8 × 10-6 mm2/s, and 7 × 10-6 mm2/s, and the mean absolute difference between manual readers was 84 × 10-6 mm2/s, 65 × 10-6 mm2/s, and 75 × 10-6 mm2/s. Automatically extracted ADC values significantly correlated with bone marrow plasma cell infiltration (R = 0.36, P = 0.007).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.

Despite the extensive number of publications in the field of radiomics, radiomics algorithms barely enter large-scale clinical application. Supposedly, the low external generalizability of radiomics models is one of the main reasons, which hinders the translation from research to clinical application. The objectives of this study were to investigate reproducibility of radiomics features (RFs) in vivo under variation of patient positioning, magnetic resonance imaging (MRI) sequence, and MRI scanners, and to identify a subgroup of RFs that shows acceptable reproducibility across all different acquisition scenarios.Between November 30, 2020 and February 16, 2021, 55 patients with monoclonal plasma cell disorders were included in this prospective, bi-institutional, single-vendor study. Participants underwent one reference scan at a 1.5 T MRI scanner and several retest scans: once after simple repositioning, once with a second MRI protocol, once at another 1.5 T scanner, and once at a 3 T scanner. Radiomics feature from the bone marrow of the left hip bone were extracted, both from original scans and after different image normalizations. Intraclass correlation coefficient (ICC) was used to assess RF repeatability and reproducibility.Fifty-five participants (mean age, 59 ± 7 years; 36 men) were enrolled. For T1-weighted images after muscle normalization, in the simple test-retest experiment, 110 (37%) of 295 RFs showed an ICC ≥0.8: 54 (61%) of 89 first-order features (FOFs), 35 (95%) of 37 volume and shape features, and 21 (12%) of 169 texture features (TFs). When the retest was performed with different technical settings, even after muscle normalization, the number of FOF/TF with an ICC ≥0.8 declined to 58/13 for the second protocol, 29/7 for the second 1.5 T scanner, and 49/7 for the 3 T scanner, respectively. Twenty-five (28%) of the 89 FOFs and 6 (4%) of the 169 TFs from muscle-normalized T1-weighted images showed an ICC ≥0.8 throughout all repeatability and reproducibility experiments.In vivo, only few RFs are reproducible with different MRI sequences or different MRI scanners, even after application of a simple image normalization. Radiomics features selected by a repeatability experiment only are not necessarily suited to build radiomics models for multicenter clinical application. This study isolated a subset of RFs, which are robust to variations in MRI acquisition observed in scanners from 1 vendor, and therefore are candidates to build reproducible radiomics models for monoclonal plasma cell disorders for multicentric applications, at least when centers are equipped with scanners from this vendor.

Lung cancer screening may provide a favorable opportunity for a spirometry examination, to diagnose participants with undiagnosed lung function impairments, or to improve targeting of computed tomography (CT) screening intensity in view of expected net benefit.Spirometry was performed in the CT screening arm (n=2,029) of the German Lung Cancer Screening Intervention Study (LUSI)-a trial examining the effects of annual CT screening on lung cancer mortality, in 50-69-year-old long-term smokers. Participants were classified as having chronic obstructive pulmonary disease (COPD) [forced expiration in one second (FEVA total of 1,987 screening arm participants (98%) provided interpretable spirometry measurements; of these, 34.3% had spirometric patterns consistent with either COPD (18.6%) or PRISm (15.7%). Two thirds of participants with COPD or PRISm were asymptomatic, and only 23% reported a previous medical diagnosis concordant with COPD. Participants reporting a diagnosis tended to be more often current and heavier smokers, and more often had respiratory symptoms, cardiovascular comorbidities, or more severe lung function impairments. Independently of smoking history, moderate-to-severe (GOLD 2-4) COPD (OR =2.14; 95% CI: 1.54-2.98), and PRISm (OR =2.68; 95% CI: 1.61-4.40), were associated with increased lung cancer risk. Lung cancer patients with PRISm less frequently had adenocarcinomas, and more often squamous cell or small cell tumors, compared to those with normal spirometry (n=45), and both PRISm and COPD were associated with more advanced lung cancer tumor stage for screen-detected cancers. PRISm and COPD, depending on GOLD stage, were also associated with about 2- to 4-fold increases in risk of overall mortality, which to 87 percent had causes other than lung cancer.About one third of smokers eligible for lung cancer screening in Germany have COPD or PRISm. As these conditions were associated with detection of lung cancer, spirometry may help identify populations at high risk for death of lung cancer or other causes, and who might particularly benefit from CT screening.

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.

Supplementary Table 1 and Figure 1 from In vitro Drug Sensitivity Predicts Response and Survival after Individualized Sensitivity-Directed Chemotherapy in Metastatic Melanoma: A Multicenter Phase II Trial of the Dermatologic Cooperative Oncology Group

Purpose:In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome.Patients and Methods: The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay.Results: Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine + treosulfan, paclitaxel + cisplatin, paclitaxel + doxorubicin, and gemcitabine + cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P = 0.114); progression arrest (complete response + partial response + stable disease) was 59.1% versus 22.6% (P = 0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P = 0.041).Conclusion:In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.

Disseminated bone marrow (BM) involvement is frequent in multiple myeloma (MM). Whole-body magnetic resonance imaging (wb-MRI) enables to evaluate the whole BM. Reading of such whole-body scans is time-consuming, and yet radiologists can transfer only a small fraction of the information of the imaging data set to the report. This limits the influence that imaging can have on clinical decision-making and in research toward precision oncology. The objective of this feasibility study was to implement a concept for automatic, comprehensive characterization of the BM from wb-MRI, by automatic BM segmentation and subsequent radiomics analysis of 30 different BM spaces (BMS).This retrospective multicentric pilot study used a total of 106 wb-MRI from 102 patients with (smoldering) MM from 8 centers. Fifty wb-MRI from center 1 were used for training of segmentation algorithms (nnU-Nets) and radiomics algorithms. Fifty-six wb-MRI from 8 centers, acquired with a variety of different MRI scanners and protocols, were used for independent testing. Manual segmentations of 2700 BMS from 90 wb-MRI were performed for training and testing of the segmentation algorithms. For each BMS, 296 radiomics features were calculated individually. Dice score was used to assess similarity between automatic segmentations and manual reference segmentations.The "multilabel nnU-Net" segmentation algorithm, which performs segmentation of 30 BMS and labels them individually, reached mean dice scores of 0.88 ± 0.06/0.87 ± 0.06/0.83 ± 0.11 in independent test sets from center 1/center 2/center 3-8 (interrater variability between radiologists, 0.88 ± 0.01). The subset from the multicenter, multivendor test set (center 3-8) that was of high imaging quality was segmented with high precision (mean dice score, 0.87), comparable to the internal test data from center 1. The radiomic BM phenotype consisting of 8880 descriptive parameters per patient, which result from calculation of 296 radiomics features for each of the 30 BMS, was calculated for all patients. Exemplary cases demonstrated connections between typical BM patterns in MM and radiomic signatures of the respective BMS. In plausibility tests, predicted size and weight based on radiomics models of the radiomic BM phenotype significantly correlated with patients' actual size and weight ( P = 0.002 and P = 0.003, respectively).This pilot study demonstrates the feasibility of automatic, objective, comprehensive BM characterization from wb-MRI in multicentric data sets. This concept allows the extraction of high-dimensional phenotypes to capture the complexity of disseminated BM disorders from imaging. Further studies need to assess the clinical potential of this method for automatic staging, therapy response assessment, or prediction of biopsy results.

COVID-19 is a new viral disease that is associated with inflammatory pulmonary changes which can be detected in computed tomography (CT). So far postmortem CT (PMCT) has not been used as a screening instrument for the evaluation of deaths with and without autopsy. In this respect, its validity has to be proved in comparison to clinical-radiological experiences.Postmortem CT METHODICAL INNOVATIONS: So far, PMCT can be regarded as a methodological innovation that has not yet been sufficiently evaluated for pneumonia.CT in clinical routine has a high sensitivity for pneumonia. However, to what extent postmortem artifacts are relevant to PMCT still has to be determined.There is still no standard procedure for the postmortem radiological diagnosis of COVID-19 disease. Despite postmortem artifacts, PMCT can provide valuable information about the presence of pneumonia with interstitial character, especially without autopsy.PMCT is particularly useful in the assessment of suspected cases of COVID-19 pneumonia for morphological assessment in the context of monitoring deaths in the current pandemic situation.

Over the last decade, a fundamentally new type of computed tomography (CT) detectors has proved its superior capabilities in both physical and preclinical evaluations and is now approaching the stage of clinical practice. These detectors are able to discriminate single photons and quantify their energy and are hence called photon-counting detectors. Among the promising benefits of this technology are improved radiation dose efficiency, increased contrast-to-noise ratio, reduced metal artifacts, improved spatial resolution, simultaneous multi-energy acquisitions, and the prospect of multi-phase imaging within a single acquisition using multiple contrast agents. Taking the conventional energy-integrating detectors as a reference, the authors demonstrate the technical principles of this new technology and provide phantom and patient images acquired by a whole-body photon-counting CT. These images serve as a basis for discussing the potential future of clinical CT.

Background Tumor-associated autoantibodies are considered promising markers for early lung cancer detection; so far, however, their capacity to detect cancer has been tested mostly in a clinical context, but not in population screening settings. This study evaluates the early detection accuracy, in terms of sensitivity and specificity, of EarlyCDT®-Lung-a test panel of seven tumor-associated autoantibodies optimized for lung cancer detection-using blood samples originally collected as part of the German Lung Cancer Screening Intervention Trial. Methods The EarlyCDT®-Lung test was performed for all participants with lung cancer detected via low-dose computed tomography and with available blood samples taken at detection, and for 180 retrospectively selected cancer-free participants at the end of follow-up: 90 randomly selected from among all cancer-free participants (baseline controls) and 90 randomly selected from among cancer-free participants with suspicious imaging findings (suspicious nodules controls). Sensitivity and specificity of lung cancer detection were estimated in the case group and the two control groups, respectively. Results In the case group, the test panel showed a sensitivity of only 13.0% (95% CI: 4.9-26.3%). Specificity was estimated at 88.9% (95% CI: 80.5-94.5%) in the baseline control group, and 91.1% (95% CI: 83.2-96.1%) among controls presenting CT-detected nodules. Conclusions The test panel showed insufficient sensitivity for detecting lung cancer at an equally early stage as with low-dose computed tomography screening.

The definition of multiple myeloma (MM) was updated in 2014, with the intent to enable earlier treatment and thereby avoid appearance of end-organ damage at progression from smouldering multiple myeloma (SMM) to MM. The purpose of this study was to investigate to which extent the development of end-organ damage at progression to MM was reduced under the updated guidelines. In this prospective observational cohort study (ClinicalTrials.gov Identifier: NCT01374412), between 2014 and 2020, 96 SMM patients prospectively underwent whole-body magnetic resonance imaging (wb-MRI) and serological follow-up at baseline and every 6 months thereafter. A total of 22 patients progressed into MM during follow-up, of which seven (32%) showed SLiM-criteria only but no end-organ damage. Four (57%) of the seven patients who progressed by SLiM-criteria only progressed with1 focal lesion (FL) or a growing FL, and three (43%) due to serum free light-chain-ratio ≥100. Fifteen (68%) out of 22 patients who progressed still suffered from end-organ damage at progression. The updated disease definition reduced the proportion of SMM patients suffering from end-organ damage at progression to MM by one third. wb-MRI is an important tool for detection of SMM patients who progress to MM without end-organ damage.

Trials in the USA and Europe have convincingly demonstrated the efficacy of screening by low-dose computed tomography (LDCT) as a means to lower lung cancer mortality, but also document potential harms related to radiation, psychosocial stress, and invasive examinations triggered by false-positive screening tests and overdiagnosis. To ensure that benefits (lung cancer deaths averted; life years gained) outweigh the risk of harm, lung cancer screening should be targeted exclusively to individuals who have an elevated risk of lung cancer, plus sufficient residual life expectancy. Overall, randomized screening trials show an approximate 20 % reduction in lung cancer mortality by LDCT screening. In view of declining residual life expectancy, especially among continuing long-term smokers, risk of being over-diagnosed is likely to increase rapidly above the age of 75. In contrast, before age 50, the incidence of LC may be generally too low for screening to provide a positive balance of benefits to harms and financial costs. Concise criteria as used in the NLST or NELSON trials may provide a basic guideline for screening eligibility. An alternative would be the use of risk prediction models based on smoking history, sex, and age as a continuous risk factor. Compared to concise criteria, such models have been found to identify a 10 % to 20 % larger number of LC patients for an equivalent number of individuals to be screened, and additionally may help provide security that screening participants will all have a high-enough LC risk to balance out harm potentially caused by radiation or false-positive screening tests. · LDCT screening can significantly reduce lung cancer mortality. · Screening until the age of 80 was shown to be efficient in terms of cancer deaths averted; in terms of LYG relative to overdiagnosis, stopping at a younger age (e. g. 75) may have greater efficiency. · Risk models may improve the overall net benefit of lung cancer screening.· Kaaks R, Delorme S. Lung Cancer Screening by Low-Dose Computed Tomography - Part 1: Expected Benefits, Possible Harms, and Criteria for Eligibility and Population Targeting. Fortschr Röntgenstr 2021; 193: 527 - 536. Zahlreiche Studien in den USA und Europa haben zeigen können, dass durch Screening mit Niedrigdosis-Computertomografie (Low-Dose-CT, LDCT) der Lunge die Sterblichkeit an Lungenkrebs gesenkt werden kann, haben aber auch damit verbundene Risiken aufgezeigt, die sich durch ionisierende Strahlung, emotionalen Stress, Eingriffe infolge falsch positiver Befunde oder Überdiagnose ergeben. Um zu gewährleisten, dass die Risiken durch den möglichen Nutzen (abgewendeter Tod durch Lungenkrebs, Gewinn an Lebensjahren) aufgewogen werden, sollte Lungenkrebs-Screening auf Personen zielen, deren Lungenkrebsrisiko erhöht ist und deren verbleibende Lebenserwartung ausreichend hoch ist. Im Ganzen beträgt die Senkung der Lungenkrebssterblichkeit durch LDCT-Screening ca. 20 %. In Anbetracht der mit dem Alter abnehmenden Lebenserwartung, insbesondere bei langjährigen aktiven Rauchern, nimmt das Risiko der Überdiagnose jenseits des 75. Lebensjahres deutlich zu. Vor dem 50. Lebensjahr ist die Lungenkrebsinzidenz hingegen zu gering, als dass Risiken und auch Kosten ein angemessener Nutzen gegenübersteht. Konzise Kriterien, wie in den NLST- und NELSON-Studien angewendet, stellen einen grundlegenden Anhalt für geeignete Einschlusskriterien dar. Ihnen stehen Modelle zur Risikoprädiktion gegenüber, die neben dem Geschlecht das Alter und die Rauchanamnese als kontinuierliche Variablen verwenden. Verglichen mit konzisen Kriterien konnten mithilfe dieser Modelle 10–20 % mehr Patienten mit Lungenkrebs bei gleicher Gesamtzahl gescreenter Personen identifiziert werden. Zugleich können sie zu einer größeren Sicherheit beitragen, dass die Screening-Teilnehmer ein ausreichend hohes Lungenkrebsrisiko haben, sodass die Risiken aufgrund von Strahlung und den Folgen falsch positiver Screening-Ergebnisse aufgewogen werden. · Durch LDCT-Screening kann die Lungenkrebssterblichkeit signifikant gesenkt werden.. · Um Überdiagnose zu beschränken, sollte nach dem 75. Lebensjahr kein LDCT-Screening mehr erfolgen.. · Durch den Einsatz von Risikomodellen kann der Nettonutzen des Lungenkrebs-Screenings verbessert werden..

Overdiagnosis is a major potential harm of lung cancer screening; knowing its potential magnitude helps to optimize screening eligibility criteria. The German Lung Screening Intervention Trial ("LUSI") is a randomized trial among 4052 long-term smokers (2622 men), 50.3 to 71.9 years of age from the general population around Heidelberg, Germany, comparing five annual rounds of low-dose computed tomography (n = 2029) with a control arm without intervention (n = 2023). After a median follow-up of 9.77 years postrandomization and 5.73 years since last screening, 74 participants were diagnosed with lung cancer in the control arm and 90 in the screening arm: 69 during the active screening period; of which 63 screen-detected and 6 interval cancers. The excess cumulative incidence in the screening arm (N = 16) represented 25.4% (95% confidence interval: -11.3, 64.3] of screen-detected cancer cases (N = 63). Analyzed by histologic subtype, excess incidence in the screening arm appeared largely driven by adenocarcinomas. Statistical modeling yielded an estimated mean preclinical sojourn time (MPST) of 5.38 (4.76, 5.88) years and a screen-test sensitivity of 81.6 (74.4%, 88.8%) for lung cancer overall, all histologic subtypes combined. Based on modeling, we further estimated that about 48% (47.5% [43.2%, 50.7%]) of screen-detected tumors have a lead time ≥4 years, whereas about 33% (32.8% [28.4%, 36.1%]) have a lead time ≥6 years, 23% (22.6% [18.6%, 25.7%]) ≥8 years, 16% (15.6% [12.2%, 18.3%]) ≥10 years and 11% (10.7% [8.0%, 13.0%]) ≥12 years. The high proportions of tumors with relatively long lead times suggest a major risk of overdiagnosis for individuals with comparatively short remaining life expectancies.

Background/objectives Apparent diffusion coefficient (ADC) and signal intensity (SI) measurements play an increasing role in magnetic resonance imaging (MRI) of monoclonal plasma cell disorders. The purpose of this study was to assess interrater variability, repeatability, and reproducibility of ADC and SI measurements from bone marrow (BM) under variation of MRI protocols and scanners. Patients and methods Fifty-five patients with suspected or confirmed monoclonal plasma cell disorder were prospectively included in this institutional review board-approved study and underwent several measurements after the standard clinical whole-body MR scan, including repeated scan after repositioning, scan with a second MRI protocol, scan at a second 1.5 T scanner with a harmonized MRI protocol, and scan at a 3 T scanner. For T1-weighted, T2-weighted STIR, B800 images, and ADC maps, regions of interest were placed in the BM of the iliac crest and sacral bone, and in muscle tissue for image normalization. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. Results Interrater variability and repeatability experiments showed a maximal relative bias of -0.077 and a maximal coefficient of variation of 16.2% for all sequences. Although the deviations at the second 1.5 T scanner with harmonized MRI protocol to the first 1.5 T scanner showed a maximal relative bias of 0.124 for all sequences, the variation of the MRI protocol and scan at the 3 T scanner led to large relative biases of up to -0.357 and -0.526, respectively. When comparing the 3 T scanner to the 1.5 T scanner, normalization to muscle reduced the bias of T1-weighted and T2-weighted sequences, but not of ADC maps. Conclusions The MRI scanners with identical field strength and harmonized MRI protocols can provide relatively stable quantitative measurements of BM ADC and SI. Deviations in MRI field strength and MRI protocol should be avoided when applying ADC cutoff values, which were established at other scanners or when performing multicentric imaging trials.

Background Single-site carcinoma of unknown primary (CUP) is recognised as a distinct favourable subtype in the European Society of Medical Oncology (ESMO) classification. There is broad consensus that these patients are candidates for local ablative treatment strategies with surgery and/or radiotherapy, but data on their outcomes are scarce. Patients and methods In this study, we have addressed the prospects of cure and prognostic factors in a retrospective cohort of 63 patients who were eligible for local treatment at our centre. Results Median event-free (EFS) and overall survival (OS) were 15.6 months and 52.5 months, respectively. Of 61 patients who received local treatment, 20 (32.8%) remained event-free over a median follow-up of 28 months. Baseline clinical parameters including affected organ, number, volume and histology of metastases had no significant impact on prognosis, whereas deleterious TP53 mutations and DNA copy number loss emerged as independent adverse risk factors with respect to EFS. Surgical treatment was associated with improved OS as compared to radiation-based therapy. Conclusion Our study advocates to pursue localised treatment with surgery and/or radiotherapy whenever feasible and implies that genetic parameters might additionally determine the clinical course of single-site CUP patients.

CA extern

In 2014, the diagnostic criteria for multiple myeloma were updated, leading to revised recommendations for imaging modalities and definition of therapy response. This review provides an overview of the current definitions of monoclonal plasma cell disease, diagnostic options, and changes relevant to radiologists. A pubmed search regarding the multiple myeloma guidelines was conducted, and results were filtered considering publications of international associations and expert reviews. Recommendations by the International Myeloma Working Group (IMWG), the National Comprehensive Cancer Network (NCCN, USA), the European Society for Medical Oncology (ESMO), and the European Myeloma Network are acknowledged. Conventional skeletal survey is to be replaced by cross-sectional imaging techniques. For initial diagnostics of bone lesions or bone marrow involvement defining multiple myeloma, whole-body low-dose CT and whole-body MRI are recommended. Two or more focal bone marrow lesions suspicious for myeloma on MRI will now define symptomatic disease even in the case of intact mineralized bone. Follow-up imaging is not clearly specified so far. New guidelines concerning the definitions of minimal residual disease include the assessment of focal lesions before and after treatment using · Whole-body low-dose CT is recommended by international reference organizations for detecting lytic bone lesions.. · Focal myeloma lesions detected on whole-body MRI will indicate symptomatic multiple myeloma requiring therapy, even in the absence of damage to mineralized bone.. · The IMWG recommends using cross-sectional imaging in the initial work-up: whole-body low-dose CT, MRI, or PET/CT, depending on availability and resources.. · The diagnostic potential of 18F-FDG-PET/CT is highlighted by its inclusion in the definition of minimal residual disease after therapy; implementation in Germany is uncertain due to limited access in the daily routine..· Mosebach J, Thierjung H, Schlemmer H et al. Multiple Myeloma Guidelines and Their Recent Updates: Implications for Imaging. Fortschr Röntgenstr 2019; 191: 998 - 1009. Seit 2014 haben sich die diagnostischen Kriterien für das multiple Myelom und seine nicht therapiepflichtigen Vorstufen geändert. Zudem wurden neue Empfehlungen zur Modalität der Bildgebung und zum Therapieansprechen vorgeschlagen. Dieser Übersichtsartikel soll einen Überblick über aktuelle Definitionen, diagnostische Optionen und neue, für den Radiologen relevante Empfehlungen zum Vorgehen bei Plasmazellerkrankungen bieten. Eine Pubmed-Suche bezüglich Leitlinien zum multiplen Myelom wurde durchgeführt und hinsichtlich der aktuellsten Veröffentlichungen internationaler Fachgesellschaften und Expertenreviews gefiltert. Die Empfehlungen der „International Myeloma Working Group“ (IMWG), des „National Comprehensive Cancer Networks“ (NCCN, USA), der Europäischen Gesellschaft für Medizinische Onkologie (ESMO) sowie des Europäischen Myelom-Netzwerks (EMN) wurden zusammengefasst. Der konventionelle Skelettstatus nach dem „Pariser Schema“ sollte zunehmend durch die Schnittbildgebung ersetzt werden. Zur Differenzierung eines durch Osteolysen oder Knochenmarkbeteiligung therapiepflichtigen multiplen Myeloms von seinen Vorstufen wird eine initiale Diagnostik mittels Ganzkörper-Niedrigdosis-CT und ggf. Ganzkörper-MRT empfohlen. 2 oder mehr fokale Myelom-verdächtige Herdbefunde zeigen nun auch bei intaktem mineralisiertem Knochen ein symptomatisches Myelom an. Zur Verlaufsbeurteilung gibt es bisher keine klare Empfehlung. Die Beurteilung eines fokalen Befalls vor und nach Therapie mittels · Die Ganzkörper-Niedrigdosis-CT wird als neuer Standard zur Detektion von Osteolysen durch internationale Fachgesellschaften befürwortet.. · Fokale Läsionen in der MRT zeigen auch bei intaktem mineralisiertem Knochen ein therapiepflichtiges Myelom an.. · Die IMWG empfiehlt mindestens eine Schnittbildgebung in der initialen Diagnostik: Ganzkörper-Niedrigdosis-CT, MRT oder PET/CT je nach Verfügbarkeit und Finanzierungsmöglichkeiten.. · Das diagnostische Potenzial der 18F-FDG-PET/CT beim Follow-Up wird i. R. der Definition einer minimalen Resterkrankung nach Therapie unterstrichen; die Umsetzung in Deutschland ist wegen ihres eingeschränkten Einsatzes in der Routine unsicher..· Mosebach J, Thierjung H, Schlemmer H et al. Multiple Myeloma Guidelines and Their Recent Updates: Implications for Imaging. Fortschr Röntgenstr 2019; 191: 998 – 1009.

Background The value of cerebral susceptibility-weighted imaging (SWI) in malignant melanoma (MM) patients remains controversial and the effect of melanin on SWI is not well understood. Purpose To systematically analyze the spectrum of intracerebral findings in MM brain metastases (BM) on SWI and to determine the diagnostic value of SWI. Study type Retrospective. Population/subjects In all, 100 patients with melanoma BM (69 having received radiotherapy [RT] and 31 RT-naive) and a control group of 100 melanoma patients without BM were included. For detailed analysis of signal characteristics, 175 metastases were studied. Field strength/sequence Gradient echo SWI sequence at 1.5, 3.0, and 9.4 T. Assessment Signal characteristics from melanotic and amelanotic BMs on SWI with a focus on blooming artifacts were analyzed, as well as the presence and longitudinal dynamics of isolated SWI blooming artifacts in patients with and without BM. Statistical tests Chi-squared and Student's t-test were used for contingency table measures and group data of signal and clinical characteristics, respectively. Results Melanotic and amelanotic metastases did not show significant differences of SWI blooming artifacts (38% vs. 43%, P = 0.61). Most metastases without an initial SWI artifact developed a signal dropout during follow-up (80%; 65/81). Isolated SWI artifacts were detected more frequently in patients with BM (20 vs. 9, P = 0.03), of which the majority were found in patients who had received RT (17 vs. 3, P = 0.08). None of these isolated SWI blooming artifacts turned into overt metastases over time (median follow-up: 8.5 months). Similar findings persisted as remnants of successfully treated metastases (88%; 7/8). Data conclusion We conclude that SWI provides little additional diagnostic benefit over standard T1 -weighted imaging, as melanin content alone does not cause diagnostically relevant SWI blooming. Signal transition of SWI may rather indicate secondary phenomena like microbleeding and/or metal scavenging. Our results suggest that isolated SWI artifacts do not constitute vital tumor tissue but represent unspecific microbleedings, RT-related parenchymal changes or posttherapeutic remnants of former metastatic lesions. Level of evidence 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1251-1259.

Background Current guidelines for lung cancer screening via low-dose computed tomography recommend annual screening for all candidates meeting basic eligibility criteria. However, lung cancer risk of eligible screening participants can vary widely, and further risk stratification could be used to individually optimize screening intervals in view of expected benefits, possible harms and financial costs. To this effect, models have been developed in the US National Lung Screening Trial based on self-reported lung cancer risk factors and imaging data. We evaluated these models using data from an independent screening trial in Germany. Methods We examined the Polynomial model by Schreuder et al., the Lung Cancer Risk Assessment Tool extended by CT characteristics (LCRAT + CT) by Robbins et al., and a criterion of presence vs. absence of pulmonary nodules ≥4 mm (Patz et al.), applied to sub-sets of screening participants according to eligibility criteria. Discrimination was evaluated via the receiver operating characteristic curve. Delayed diagnoses and false positive results were calculated at various thresholds of predicted risk. Model calibration was assessed by comparing mean predicted risk versus observed incidence. Results One thousand five hundred and six participants were eligible for the validation of the LCRAT + CT model, and 1,889 for the validation of the Polynomial model and Patz criterion, yielding areas under the receiver operating characteristic curve of 0.73 (95% CI: 0.63, 0.82), 0.75 (0.67, 0.83), and 0.56 (0.53, 0.72) respectively. Skipping 50% annual screenings (participants within the 5 lowest risk deciles by LCRAT + CT in any round or by the Polynomial model; baseline screening round), would have avoided 75% (21.9%, 98.7%) and 40% (21.8%, 61.1%) false positive screen tests and delayed 10% (1.8%, 33.1%) or no (0%, 32.1%) diagnoses, respectively. Using the Patz criterion, referring 63.2% (61.0% to 65.4%) of participants to biennial screening would have avoided 4% (0.2% to 22.3%) of false positive screen tests but delayed 55% (24.6% to 81.9%) diagnoses. Conclusions In this German trial, the LCRAT + CT and Polynomial models showed useful discrimination of screening participants for one-year lung cancer risk following CT examination. Our results illustrate the remaining heterogeneity in risk within screening-eligible subjects and the trade-off between a low-frequency screening approach and delayed detection.

Background Whole-body magnetic resonance imaging (wb-MRI) is an important diagnostic tool for staging, risk assessment and response evaluation in myeloma. Wb-MRIs contain approximately 110 million voxels per sequence, and only a limited amount of this information can be processed and reported by radiologists to date. Deep learning has brought striking advances in biomedical image segmentation in recent years. The goal of this work was to establish an automatic whole-body bone marrow (BM) segmentation algorithm for T1-weighted MRI sequence, and to use these segmentations for comprehensive MRI-phenotypic characterization of the BM by subsequent radiomics analysis, bone by bone. Methods For 66 patients with smoldering multiple myeloma (SMM), BM was manually segmented on T1-w images. Thirty different BM compartments were individually labelled: right and left humerus, second to seventh vertebral bodies of the cervical spine (C2-C7), all vertebral bodies of the thoracic (T1-T12) and lumbar (L1-L5) spine, sacrum, right and left hip bone and right and left femur. Data was split by date by a 3:1 ratio into training-set and independent test-set. A nnU-Net, which is state of the art deep learning framework for medical image segmentation, was trained on the 52 training cases for segmentation of BM compartments, and postprocessing was used to distinguish sides of paired bones (humeri, hip bones, femora). Mean Dice scores report accuracy of automatic segmentations on the test-cases and interrater variability between two radiologists. This study was approved by the institutional review board. Results The mean Dice scores of the nnU-Net segmentation on the 14 test-cases for BM of right and left humerus, C2-C7, T1-T12, L1-L5, sacrum, right and left hip bone, right and left femur were 0.95, 0.94, 0.87, 0.86, 0.84, 0.80, 0.82, 0.84, 0.86, 0.87, 0.88, 0.91, 0.85, 0.85, 0.83, 0.83, 0.87, 0.91, 0.93, 0.93, 0.89, 0.85, 0.85, 0.81, 0.76, 0.88, 0.93, 0.93, 0.97 and 0.97, respectively. The mean Dice scores between segmentations from 2 radiologists on 2 cases for these BM compartments in the same order were 0.94, 0.95, 0.79, 0.86, 0.88, 0.81, 0.78, 0.79, 0.84, 0.81, 0.91, 0.85, 0.89, 0.90, 0.91, 0.91, 0.92, 0.90, 0.90, 0.89, 0.88, 0.92, 0.93, 0.88, 0.88, 0.81, 0.89, 0.89, 0.95, 0.94, respectively. On a descriptive level, we found differences in radiomics signatures between vertebrae with physiological bone marrow, vertebrae with focal lesions and vertebrae with diffuse infiltration in exemplary cases. Conclusion We established automatic, bone by bone BM segmentation in SMM patients with accuracy only slightly worse compared to the interrater variability of radiologists, mostly due to lumbosacral transitional vertebra. In exemplary cases we found different radiomics-signatures between physiological BM and different pathologies, indicating that such BM segmentations can be used for in depth BM characterization from wb-MRI when combined with subsequent radiomics analysis.