Publications by authors named "Marius Mayerhoefer"

113 Publications

Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematological Cancers and Identifies Exceptional Responders.

Cancer Discov 2021 Oct 11. Epub 2021 Oct 11.

Platform Austria for Chemical Biology, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences.

Personalized medicine aims to match the right drug with the right patient by utilizing specific features of the individual patients' tumor. However, current strategies of personalized therapy matching only provide treatment opportunities for less than 10% of cancer patients. A promising method may be drug profiling of patient biopsies with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival (PFS) compared to their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude, that therapy matching by scFPM is clinically feasible, and effective in advanced aggressive hematologic cancers.
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http://dx.doi.org/10.1158/2159-8290.CD-21-0538DOI Listing
October 2021

CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line H. pylori eradication.

Blood 2021 Sep 15. Epub 2021 Sep 15.

Medical University of Vienna, Vienna, Austria.

Post-treatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate PET with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow-up biopsies for assessment of residual disease (non-complete remission (CR)) after first-line H. pylori (HP) eradication. Forty-six post-HP eradication [68Ga]Pentixafor-PET/MRI examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard, and showed CR in six cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive value of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up, were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r=0.51 and r=0.52 (P=0.008 and P=0.006). In conclusion, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after HP eradication.
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http://dx.doi.org/10.1182/blood.2021013239DOI Listing
September 2021

Combination of Radiomics and Machine Learning with Diffusion-Weighted MR Imaging for Clinical Outcome Prognostication in Cervical Cancer.

Tomography 2021 08 5;7(3):344-357. Epub 2021 Aug 5.

Department of Radiology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, India.

Objectives: To explore the potential of Radiomics alone and in combination with a diffusion-weighted derived quantitative parameter, namely the apparent diffusion co-efficient (ADC), using supervised classification algorithms in the prediction of outcomes and prognosis.

Materials And Methods: Retrospective evaluation of the imaging was conducted for a study cohort of uterine cervical cancer, candidates for radical treatment with chemo radiation. ADC values were calculated from the darkest part of the tumor, both before (labeled preADC) and post treatment (labeled postADC) with chemo radiation. Post extraction of 851 Radiomics features and feature selection analysis-by taking the union of the features that had Pearson correlation >0.35 for recurrence, >0.49 for lymph node and >0.40 for metastasis-was performed to predict clinical outcomes.

Results: The study enrolled 52 patients who presented with variable FIGO stages in the age range of 28-79 (Median = 53 years) with a median follow-up of 26.5 months (range: 7-76 months). Disease recurrence occurred in 12 patients (23%). Metastasis occurred in 15 patients (28%). A model generated with 24 radiomics features and preADC using a monotone multi-layer perceptron neural network to predict the recurrence yields an AUC of 0.80 and a Kappa value of 0.55 and shows that the addition of radiomics features to ADC values improves the statistical metrics by approximately 40% for AUC and approximately 223% for Kappa. Similarly, the neural network model for prediction of metastasis returns an AUC value of 0.84 and a Kappa value of 0.65, thus exceeding performance expectations by approximately 25% for AUC and approximately 140% for Kappa. There was a significant input of GLSZM features (SALGLE and LGLZE) and GLDM features (SDLGLE and DE) in correlation with clinical outcomes of recurrence and metastasis.

Conclusions: The study is an effort to bridge the unmet need of translational predictive biomarkers in the stratification of uterine cervical cancer patients based on prognosis.
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http://dx.doi.org/10.3390/tomography7030031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396356PMC
August 2021

Single-Cell RNA Sequencing Reveals Tissue Compartment-Specific Plasticity of Mycosis Fungoides Tumor Cells.

Front Immunol 2021 21;12:666935. Epub 2021 Apr 21.

Department of Dermatology, Medical University of Vienna, Vienna, Austria.

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. While initially restricted to the skin, malignant cells can appear in blood, bone marrow and secondary lymphoid organs in later disease stages. However, only little is known about phenotypic and functional properties of malignant T cells in relationship to tissue environments over the course of disease progression. We thus profiled the tumor micromilieu in skin, blood and lymph node in a patient with advanced MF using single-cell RNA sequencing combined with V-D-J T-cell receptor sequencing. In skin, we identified clonally expanded T-cells with characteristic features of tissue-resident memory T-cells (T, ). In blood and lymph node, the malignant clones displayed a transcriptional program reminiscent of a more central memory-like phenotype ( ), while retaining tissue-homing receptors (CLA). The skin tumor microenvironment contained potentially tumor-permissive myeloid cells producing regulatory () and Th2-associated mediators (). Given their expression of and , they might be under direct control by tumor cells. In sum, this study highlights the adaptive phenotypic and functional plasticity of MF tumor cell clones. Thus, the T-like phenotype enables long-term skin residence of MF cells. Their switch to a T-like phenotype with persistent skin homing molecule expression in the circulation might explain the multi-focal nature of MF.
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http://dx.doi.org/10.3389/fimmu.2021.666935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097053PMC
October 2021

F FDG PET/MRI with hepatocyte-specific contrast agent for M staging of rectal cancer: a primary economic evaluation.

Eur J Nucl Med Mol Imaging 2021 09 9;48(10):3268-3276. Epub 2021 Mar 9.

Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Purpose: Rectal cancer is one of the most frequent causes of cancer-related morbidity and mortality in the world. Correct identification of the TNM state in primary staging of rectal cancer has critical implications on patient management. Initial evaluations revealed a high sensitivity and specificity for whole-body PET/MRI in the detection of metastases allowing for metastasis-directed therapy regimens. Nevertheless, its cost-effectiveness compared with that of standard-of-care imaging (SCI) using pelvic MRI + chest and abdominopelvic CT is yet to be investigated. Therefore, the aim of this study was to analyze the cost-effectiveness of whole-body F FDG PET/MRI as an alternative imaging method to standard diagnostic workup for initial staging of rectal cancer.

Methods: For estimation of quality-adjusted life years (QALYs) and lifetime costs of diagnostic modalities, a decision model including whole-body F FDG PET/MRI with a hepatocyte-specific contrast agent and pelvic MRI + chest and abdominopelvic CT was created based on Markov simulations. For obtaining model input parameters, review of recent literature was performed. Willingness to pay (WTP) was set to $100,000/QALY. Deterministic sensitivity analysis of diagnostic parameters and costs was applied, and probabilistic sensitivity was determined using Monte Carlo modeling.

Results: In the base-case scenario, the strategy whole-body F FDG PET/MRI resulted in total costs of $52,186 whereas total costs of SCI were at $51,672. Whole-body F FDG PET/MRI resulted in an expected effectiveness of 3.542 QALYs versus 3.535 QALYs for SCI. This resulted in an incremental cost-effectiveness ratio of $70,291 per QALY for PET/MRI. Thus, from an economic point of view, whole-body F FDG PET/MRI was identified as an adequate diagnostic alternative to SCI with high robustness of results to variation of input parameters.

Conclusion: Based on the results of the analysis, use of whole-body F FDG PET/MRI was identified as a feasible diagnostic strategy for initial staging of rectal cancer from a cost-effectiveness perspective.
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http://dx.doi.org/10.1007/s00259-021-05193-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426298PMC
September 2021

Minimal residual disease in multiple myeloma: defining the role of next generation sequencing and flow cytometry in routine diagnostic use.

Pathology 2021 Apr 3;53(3):385-399. Epub 2021 Mar 3.

Haematology Service, Peter MacCallum Cancer Centre, East Melbourne, Vic, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Vic, Australia.

For patients diagnosed with multiple myeloma (MM) there have been significant treatment advances over the past decade, reflected in an increasing proportion of patients achieving durable remissions. Clinical trials repeatedly demonstrate that achieving a deep response to therapy, with a bone marrow assessment proving negative for minimal residual disease (MRD), confers a significant survival advantage. To accurately assess for minute quantities of residual cancer requires highly sensitive methods; either multiparameter flow cytometry or next generation sequencing are currently recommended for MM response assessment. Under optimal conditions, these methods can detect one aberrant cell amongst 1,000,000 normal cells (a sensitivity of 10). Here, we will review the practical use of MRD assays in MM, including challenges in implementation for the routine diagnostic laboratory, standardisation across laboratories and clinical trials, the clinical integration of MRD status assessment into MM management and future directions for ongoing research.
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http://dx.doi.org/10.1016/j.pathol.2021.02.003DOI Listing
April 2021

Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Scientific Expert Panel.

Radiology 2021 08 24;300(2):E323-E327. Epub 2021 Feb 24.

From the Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-704, New York, NY 10065 (A.S.B., R.P.J., M.E.H., K.N.F., K.M.G., A.T.I., R.Y., M.E.M., H.H., H.A.V.); Department of Radiology, Brigham and Women's Hospital, Boston, Mass (S.A.C., A.B.S.); Departments of Imaging (S.A.C., A.B.S.) and Medical Oncology (E.L.M.), Dana-Farber Cancer Institute, Boston, Mass; and Division of Diagnostic Imaging (M.M.C., M.H.) and Department of Head and Neck Surgery (E.Y.H.), MD Anderson Cancer Center, Houston, Tex.

Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (eg, for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information-date(s) administered, injection site(s), laterality, and type of vaccine-should be included in every preimaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams, and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination.
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http://dx.doi.org/10.1148/radiol.2021210436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909071PMC
August 2021

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

Eur J Nucl Med Mol Imaging 2021 05 22;48(5):1522-1537. Epub 2021 Feb 22.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.

Background: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use.

Methods: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered.

Results: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies.

Conclusion: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.
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http://dx.doi.org/10.1007/s00259-021-05198-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240455PMC
May 2021

Incorporating radiomics into clinical trials: expert consensus endorsed by the European Society of Radiology on considerations for data-driven compared to biologically driven quantitative biomarkers.

Eur Radiol 2021 Aug 25;31(8):6001-6012. Epub 2021 Jan 25.

European Imaging Biomarkers Alliance (EIBALL), European Society of Radiology, Vienna, Austria.

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. KEY POINTS: • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.
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http://dx.doi.org/10.1007/s00330-020-07598-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270834PMC
August 2021

Positive selection as the unifying force for clonal evolution in multiple myeloma.

Leukemia 2021 05 22;35(5):1511-1515. Epub 2021 Jan 22.

Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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http://dx.doi.org/10.1038/s41375-021-01130-7DOI Listing
May 2021

CXCR4 PET imaging of mantle cell lymphoma using [Ga]Pentixafor: comparison with [F]FDG-PET.

Theranostics 2021 1;11(2):567-578. Epub 2021 Jan 1.

Dept. of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Austria.

For PET imaging of mantle cell lymphoma (MCL), [F]FDG (2-deoxy-2-[F]fluoro-D-glucose) is the currently recommended radiotracer, although uptake is variable and bone marrow evaluation is limited. In this prospective study, we evaluated the novel CXCR4 (G-protein-coupled C-X-C chemokine receptor type 4) tracer [Ga]Pentixafor in MCL patients, and compared it to [F]FDG. MCL patients underwent [Ga]Pentixafor-PET/MRI, and, if required for routine purposes, also [F]FDG-PET/MRI, before treatment. PET was evaluated separately for 23 anatomic regions (12 lymph node stations and 11 organs/tissues), using MRI as the main reference standard. Standardized uptake values (SUV and SUV) and tumor-to-background ratios (TBR and TBR) were calculated. General Estimation Equations (GEE) were used to compare [Ga]Pentixafor-PET and [F]FDG-PET sensitivities and positive predictive values (PPV). For bone marrow involvement, where biopsy served as the main reference standard, and splenic involvement, receiver operating characteristic curves were used to determine the optimal SUV and TBR cut-off values, and areas under the curve (AUC) were calculated. Twenty-two MCL patients were included. [Ga]Pentixafor-PET sensitivity (100%) was significantly higher than for [F]FDG-PET (75.2%) (<0.001), and PPV was slightly, but not significantly lower (94.0%.vs. 96.5%; =0.21). SUVs and TBRs were significantly higher for [Ga]Pentixafor-PET than for [F]FDG-PET (<0.001 in all cases); the greatest difference was observed for mean TBR, with 4.9 for [Ga]Pentixafor-PET and 2.0 for [F]FDG-PET. For bone marrow involvement, [Ga]Pentixafor-PET SUV showed an AUC of 0.92; and for splenic involvement, TBR showed an AUC of 0.81. [Ga]Pentixafor-PET may become an alternative to [F]FDG-PET in MCL patients, showing clearly higher detection rates and better tumor-to-background contrast.
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http://dx.doi.org/10.7150/thno.48620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738870PMC
August 2021

PET/MRI for neuroendocrine tumors: a match made in heaven or just another hype?

Clin Transl Imaging 2019 Dec 20;7(6):405-413. Epub 2019 Sep 20.

Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.

Purpose: To evaluate the current literature on technical feasibility and diagnostic value of PET/MRI in management of patients with neuroendocrine tumors (NETs).

Methods: A systematic literature search of the PubMed/MEDLINE database identified studies that evaluated the role of simultaneous PET/MRI for the evaluation of neuroendocrine tumors in human subjects. Exclusion criteria included studies lacking simultaneous PET/MRI, absence of other than attenuation-correction MRI pulse sequences, and case reports. No data-pooling or statistical analysis was performed due to the small number of articles and heterogeneity of the methodologies.

Results: From the 21 identified articles, five were included, which demonstrated successful technical feasibility of simultaneous PET/MRI through various imaging protocols in a total of 105 patients. All articles demonstrated equal or superior detection of liver lesions by PET/MRI over PET/CT. While one study reported superior detection of bone lesions by PET/MRI, two demonstrated favorable detection by PET/CT. Two studies demonstrated superiority of PET/CT in detection of nodal metastases; three studies reported the pitfall of PET/MRI in detection of lung lesion.

Conclusion: The current literature reports successful technical feasibility of PET/MRI for imaging of NETs. While whole-body PET/CT in conjunction with an abdominal MRI may serve as a comprehensive approach for baseline staging, follow up with PET/MRI may be preferred for those with liver-only disease. Another possible role for PET/MRI is to provide a multiparametric approach to follow up of response to treatment. With further advances in MRI imaging acquisitions and post-processing techniques, PET/MRI may become more applicable to a broader group of patients with NETs, and possibly the imaging modality of choice for this patient population.
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http://dx.doi.org/10.1007/s40336-019-00344-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717609PMC
December 2019

Radiomics of high-resolution computed tomography for the differentiation between cholesteatoma and middle ear inflammation: effects of post-reconstruction methods in a dual-center study.

Eur Radiol 2021 Jun 4;31(6):4071-4078. Epub 2020 Dec 4.

Department of Biomedical Imaging and Image-guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Objectives: To evaluate the performance of radiomic features extracted from high-resolution computed tomography (HRCT) for the differentiation between cholesteatoma and middle ear inflammation (MEI), and to investigate the impact of post-reconstruction harmonization and data resampling.

Methods: One hundred patients were included in this retrospective dual-center study: 48 with histology-proven cholesteatoma (center A: 23; center B: 25) and 52 with MEI (A: 27; B: 25). Radiomic features (co-occurrence and run-length matrix, absolute gradient, autoregressive model, Haar wavelet transform) were extracted from manually defined 2D-ROIs. The ten best features for lesion differentiation were selected using probability of error and average correlation coefficients. A multi-layer perceptron feed-forward artificial neural network (MLP-ANN) was used for radiomics-based classification, with histopathology serving as the reference standard (70% of cases for training, 30% for validation). The analysis was performed five times each on (a) unmodified data and on data that were (b) resampled to the same matrix size, and (c) corrected for acquisition protocol differences using ComBat harmonization.

Results: Using unmodified data, the MLP-ANN classification yielded an overall median area under the receiver operating characteristic curve (AUC) of 0.78 (0.72-0.84). Using original data from center A and resampled data from center B, an overall median AUC of 0.88 (0.82-0.99) was yielded, while using ComBat harmonized data, an overall median AUC of 0.89 (0.79-0.92) was revealed.

Conclusion: Radiomic features extracted from HRCT differentiate between cholesteatoma and MEI. When using multi-centric data obtained with differences in CT acquisition parameters, data resampling and ComBat post-reconstruction harmonization clearly improve radiomics-based lesion classification.

Key Points: • Unenhanced high-resolution CT coupled with radiomics analysis may be useful for the differentiation between cholesteatoma and middle ear inflammation. • Pooling of data extracted from inhomogeneous CT datasets does not appear meaningful without further post-processing. • When using multi-centric CT data obtained with differences in acquisition parameters, post-reconstruction harmonization and data resampling clearly improve radiomics-based soft-tissue differentiation.
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http://dx.doi.org/10.1007/s00330-020-07564-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128805PMC
June 2021

First Line Systemic Treatment for MALT Lymphoma-Do We Still Need Chemotherapy? Real World Data from the Medical University Vienna.

Cancers (Basel) 2020 Nov 26;12(12). Epub 2020 Nov 26.

Department of Medicine I, Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria.

There is no clear therapeutic algorithm for mucosa-associated lymphoid tissue (MALT) lymphoma beyond Helicobacter pylori eradication and while chemotherapy-based regimens are standard for MALT lymphoma patients in need of systemic treatment, it appears of interest to also investigate chemotherapy-free strategies. We have retrospectively assessed MALT lymphoma patients undergoing upfront systemic treatment, classified either as chemotherapy (=classical cytostatic agents +/- rituximab) or immunotherapy (=immunomodulatory agents or single anti-CD20 antibodies) at the Medical University Vienna 1999-2019. The primary endpoint was progression-free survival (PFS). In total, 159 patients were identified with a median follow-up of 67 months. The majority of patients had extragastric disease (80%), but we also identified 32 patients (20%) with Helicobacter pylori negative or disseminated gastric lymphoma. Regarding the type of first line treatment and outcome, 46% (74/159) received a chemotherapy-based regimen and 54% (85/159) immunotherapy including IMiDs lenalidomide/thalidomide (37%), anti-CD20-anitbodies rituximab/ofatumumab (27%), macrolides clarithromycin/azithromycin (27%) and proteasome inhibitor bortezomib (9%). Median PFS was 76 months (95%CI 50-102), and while the overall response (90% vs. 68%, 0.01) and the complete remission rate (75% vs. 43%, 0.01) was significantly higher for chemotherapy, there was no difference in PFS between chemotherapy (median 81 months, 95%CI 47-116) and immunotherapy (76 months, 95%CI 50-103, = 0.57), suggesting comparable long-term outcomes. To conclude, our data show higher response rates with chemo- compared to immunotherapy, but this did not translate into a superior PFS. Given the biological background of MALT lymphoma, and the favorable toxicity profile of novel immunomodulatory treatments, this should be further investigated.
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http://dx.doi.org/10.3390/cancers12123533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761357PMC
November 2020

Assessment of Central Nervous System Lymphoma Based on CXCR4 Expression In Vivo Using 68Ga-Pentixafor PET/MRI.

Clin Nucl Med 2021 Jan;46(1):16-20

From the Division of Oncology, Department of Medicine I.

Purpose Of The Report: F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL.

Materials And Methods: Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests.

Results: Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI).

Conclusions: Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.
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http://dx.doi.org/10.1097/RLU.0000000000003404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385649PMC
January 2021

Accuracy of PET quantification in [Ga]Ga-pentixafor PET/MR imaging of carotid plaques.

J Nucl Cardiol 2020 Jul 21. Epub 2020 Jul 21.

QIMP Team, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Aim: The aim of this study was to evaluate and correct for partial-volume-effects (PVE) on [Ga]Ga-Pentixafor uptake in atherosclerotic plaques of the carotid arteries, and the impact of ignoring bone in MR-based attenuation correction (MR-AC).

Methods: Twenty [Ga]Ga-pentixafor PET/MR examinations including a high-resolution T2-TSE MR of the neck were included in this study. Carotid plaques located at the carotid bifurcation were delineated and the anatomical information was used for partial-volume-correction (PVC). Mean and max tissue-to-background ratios (TBR) of the [Ga]Ga-Pentixafor uptake were compared for standard and PVC-PET images. A potential influence of ignoring bone in MR-AC was assessed in a subset of the data reconstructed after incorporating bone into MR-AC and a subsequent comparison of standardized-uptake values (SUV).

Results: In total, 34 atherosclerotic plaques were identified. Following PVC, mean and max TBR increased by 77 and 95%, respectively, when averaged across lesions. When accounting for bone in the MR-AC, SUV of plaque changed by 0.5%.

Conclusion: Quantitative readings of [Ga]Ga-pentixafor uptake in plaques are strongly affected by PVE, which can be reduced by PVC. Including bone information into the MR-AC yielded no clinically relevant effect on tracer quantification.
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http://dx.doi.org/10.1007/s12350-020-02257-3DOI Listing
July 2020

Functional imaging using radiomic features in assessment of lymphoma.

Methods 2021 04 4;188:105-111. Epub 2020 Jul 4.

Department of Radiology, Memorial Sloan Kettering Cancer Center, NY, USA.

Lymphomas are typically large, well-defined, and relatively homogeneous tumors, and therefore represent ideal targets for the use of radiomics. Of the available functional imaging tests, [18F]FDG-PET for body lymphoma and diffusion-weighted MRI (DWI) for central nervous system (CNS) lymphoma are of particular interest. The current literature suggests that two main applications for radiomics in lymphoma show promise: differentiation of lymphomas from other tumors, and lymphoma treatment response and outcome prognostication. In particular, encouraging results reported in the limited number of presently available studies that utilize functional imaging suggest that (1) MRI-based radiomics enables differentiation of CNS lymphoma from glioblastoma, and (2) baseline [18F]FDG-PET radiomics could be useful for survival prognostication, adding to or even replacing commonly used metrics such as standardized uptake values and metabolic tumor volume. However, due to differences in biological and clinical characteristics of different lymphoma subtypes and an increasing number of treatment options, more data are required to support these findings. Furthermore, a consensus on several critical steps in the radiomics workflow -most importantly, image reconstruction and post processing, lesion segmentation, and choice of classification algorithm- is desirable to ensure comparability of results between research institutions.
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http://dx.doi.org/10.1016/j.ymeth.2020.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349521PMC
April 2021

In Human Visualization of Ibrutinib-Induced CLL Compartment Shift.

Cancer Immunol Res 2020 08 24;8(8):984-989. Epub 2020 Jun 24.

Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Bruton tyrosine kinase inhibitor ibrutinib is effective in treating chronic lymphocytic leukemia (CLL). However, after ibrutinib treatment initiation, patients frequently experience an increase of CLL blood cell count. This phenomenon in clinical practice is thought to reflect a "compartment shift" of CLL cells from lymph nodes to the peripheral blood, but the actual shifting has not yet been demonstrated. Using [Ga]Pentixafor-PET/MRI for CXCR4 visualization, we here provide images of topical changes of CLL cells upon ibrutinib treatment. Within the first month of ibrutinib treatment, mean standardized [Ga]Pentixafor uptake decreased in the bone marrow and lymph nodes, whereas [Ga]Pentixafor uptake increased in the spleen. Leukocytosis rose, as did numbers of CXCR4 (tissue-resident) CLL cells. Volumes of lymph nodes and spleen decreased. Upon longer ibrutinib treatment, leukocytosis decreased, followed by a decrease of [Ga]Pentixafor uptake in the spleen. These results support the preexisting clinical hypothesis of a "compartment shift" of CLL cells from the lymph nodes to the peripheral blood, but also refine the mechanistic model by describing early clearing of the bone marrow and redistribution of CLL cells to the orthotopic splenic cavernous system in response to ibrutinib treatment.
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http://dx.doi.org/10.1158/2326-6066.CIR-19-0880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373313PMC
August 2020

Non-Invasive Assessment of Breast Cancer Molecular Subtypes with Multiparametric Magnetic Resonance Imaging Radiomics.

J Clin Med 2020 Jun 14;9(6). Epub 2020 Jun 14.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

We evaluated the performance of radiomics and artificial intelligence (AI) from multiparametric magnetic resonance imaging (MRI) for the assessment of breast cancer molecular subtypes. Ninety-one breast cancer patients who underwent 3T dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping were included retrospectively. Radiomic features were extracted from manually drawn regions of interest (n = 704 features per lesion) on initial DCE-MRI and ADC maps. The ten best features for subtype separation were selected using probability of error and average correlation coefficients. For pairwise comparisons with >20 patients in each group, a multi-layer perceptron feed-forward artificial neural network (MLP-ANN) was used (70% of cases for training, 30%, for validation, five times each). For all other separations, linear discriminant analysis (LDA) and leave-one-out cross-validation were applied. Histopathology served as the reference standard. MLP-ANN yielded an overall median area under the receiver-operating-characteristic curve (AUC) of 0.86 (0.77-0.92) for the separation of triple negative (TN) from other cancers. The separation of luminal A and TN cancers yielded an overall median AUC of 0.8 (0.75-0.83). Radiomics and AI from multiparametric MRI may aid in the non-invasive differentiation of TN and luminal A breast cancers from other subtypes.
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http://dx.doi.org/10.3390/jcm9061853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356091PMC
June 2020

Particular findings on lung CT in patients undergoing immunotherapy for bronchogenic carcinoma.

Wien Klin Wochenschr 2020 Aug 20;132(15-16):467-474. Epub 2020 May 20.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: Immune checkpoint inhibitors have become a valuable tool in the therapeutic strategy against metastasized non-small cell lung cancer (NSCLC) as they represent an effective and safe treatment option for many patients; however, the treatment response and side effects of this class of drugs can considerably differ compared to classical chemotherapeutics. The aim of this study was to highlight specific radiological pulmonary findings of NSCLC patients treated with immune checkpoint inhibitors.

Methods And Results: Medical records and images of prospectively collected data from 70 patients with advanced NSCLC, treated with immune checkpoint inhibitors, were reviewed. Of the patients two experienced an initial increase in tumor size, followed by a decrease in tumor size that was described as pseudoprogression. Another patient developed a sarcoid-like reaction accompanied by clinical improvements and radiological treatment response. A further two patients developed immune checkpoint-associated pulmonary injury that was clinically and radiologically classified as pneumonitis, which responded well to anti-inflammatory treatment.

Conclusion: Management of patients with NSCLC using immune checkpoint inhibitors requires a knowledge of specific clinical and radiological findings. Both oncologists and radiologists have to be aware of the most common types, including atypical response patterns, such as a sarcoid-like reaction and pseudoprogression as well as of the pulmonary side effects that can encompass pneumonitis.
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http://dx.doi.org/10.1007/s00508-020-01667-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445205PMC
August 2020

[18F]FDG-PET/CT Radiomics for Prediction of Bone Marrow Involvement in Mantle Cell Lymphoma: A Retrospective Study in 97 Patients.

Cancers (Basel) 2020 05 2;12(5). Epub 2020 May 2.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Biopsy is the standard for assessment of bone marrow involvement in mantle cell lymphoma (MCL). We investigated whether [18F]FDG-PET radiomic texture features can improve prediction of bone marrow involvement in MCL, compared to standardized uptake values (SUV), and whether combination with laboratory data improves results. Ninety-seven MCL patients were retrospectively included. SUVmax, SUVmean, SUVpeak and 16 co-occurrence matrix texture features were extracted from pelvic bones on [18F]FDG-PET/CT. A multi-layer perceptron neural network was used to compare three combinations for prediction of bone marrow involvement-the SUVs, a radiomic signature based on SUVs and texture features, and the radiomic signature combined with laboratory parameters. This step was repeated using two cut-off values for relative bone marrow involvement: REL > 5% (>5% of red/cellular bone marrow); and REL > 10%. Biopsy demonstrated bone marrow involvement in 67/97 patients (69.1%). SUVs, the radiomic signature, and the radiomic signature with laboratory data showed AUCs of up to 0.66, 0.73, and 0.81 for involved vs. uninvolved bone marrow; 0.68, 0.84, and 0.84 for REL ≤ 5% vs. REL > 5%; and 0.69, 0.85, and 0.87 for REL ≤ 10% vs. REL > 10%. In conclusion, [18F]FDG-PET texture features improve SUV-based prediction of bone marrow involvement in MCL. The results may be further improved by combination with laboratory parameters.
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http://dx.doi.org/10.3390/cancers12051138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281173PMC
May 2020

Depth of Remission Following First-Line Treatment Is an Independent Prognostic Marker for Progression-Free Survival in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

Cancers (Basel) 2020 Feb 20;12(2). Epub 2020 Feb 20.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma responding to upfront treatment has an excellent outcome and no further therapy is recommended, even in the presence of residual disease. However, no data exist on the influence of initial depth of remission on progression-free survival (PFS). : We investigated a correlation between PFS and depth of response, categorizing them as complete remission (CR), partial remission (PR) and stable disease (SD) in 137 consecutive patients at the Medical University Vienna. : All patients with ()-positive, localized disease received eradication (70%, 96/137), while the remaining patients were treated with various modalities. The response rate was 67% for the entire collective and 58% for eradication only, with corresponding CR-rates of 48% and 38%. At a median follow-up of 56.2 months, the estimated PFS for the entire cohort was 34.2 months (95% Confidence Interval 16.0-52.4). Responding patients (=CR/PR) had a significantly longer PFS compared to SD (68.3 vs. 17.3 months, < 0.001). This was also applicable to the eradication only cohort (49.0 vs. 17.3 months, < 0.001) and remained significant after correction for MALT-IPI. Furthermore, CR significantly prolonged PFS over PR ( = 0.007 entire cohort, = 0.020 eradication). Remission status correlated significantly with PFS, suggesting depth of remission as prognostic marker for long-term relapse-free survival.
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http://dx.doi.org/10.3390/cancers12020492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072189PMC
February 2020

Introduction to Radiomics.

J Nucl Med 2020 04 14;61(4):488-495. Epub 2020 Feb 14.

Cancer Imaging Department, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom; and.

Radiomics is a rapidly evolving field of research concerned with the extraction of quantitative metrics-the so-called radiomic features-within medical images. Radiomic features capture tissue and lesion characteristics such as heterogeneity and shape and may, alone or in combination with demographic, histologic, genomic, or proteomic data, be used for clinical problem solving. The goal of this continuing education article is to provide an introduction to the field, covering the basic radiomics workflow: feature calculation and selection, dimensionality reduction, and data processing. Potential clinical applications in nuclear medicine that include PET radiomics-based prediction of treatment response and survival will be discussed. Current limitations of radiomics, such as sensitivity to acquisition parameter variations, and common pitfalls will also be covered.
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http://dx.doi.org/10.2967/jnumed.118.222893DOI Listing
April 2020

RECIL versus Lugano for Treatment Response Assessment in FDG-Avid Non-Hodgkin Lymphomas: A Head-to-Head Comparison in 54 Patients.

Cancers (Basel) 2019 Dec 18;12(1). Epub 2019 Dec 18.

Department of Biomedical Imaging and Image-guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, 1090 Vienna, Austria.

The response evaluation criteria in lymphoma (RECIL) classification for lymphoma treatment response assessment was introduced in 2017, but it has not yet been compared to the established Lugano classification. Also, the value of the provisional "minor response" (MiR) category of RECIL is unclear. In 54 patients with FDG-avid non-Hodgkin lymphomas (41 diffuse large B-cell lymphomas (DLBCL) and 13 follicular lymphomas), [F]FDG-PET/CT-based response according to RECIL and Lugano was determined at interim and end-of-treatment (EOT) restaging. Rates of agreement and Cohen's kappa (κ) coefficients were calculated. The relationship between RECIL and Lugano responses and 2-year complete remission (CR) status of DLBCL patients was determined. At interim restaging, MiR was observed in 14.8%, and at EOT, in 5.6% of patients. When MiR was recoded as partial remission, agreement between RECIL and Lugano was 83.3% at interim restaging (κ = 0.69), and 90.7% at EOT (κ = 0.79). 85.4%, of DLBCL patients with responding disease at interim restaging according to both RECIL and Lugano achieved 2-year CR status; whereas, at EOT, 82.9% of patients with responding disease according to Lugano, and 85.4% of patients with responding disease according to RECIL, achieved 2-year CR status. Thus, RECIL and Lugano classifications show comparable performance for treatment response assessment, and a similar association with 2-year CR status in FDG-avid lymphomas.
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http://dx.doi.org/10.3390/cancers12010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016710PMC
December 2019

Visceral Pleural Invasion in Pulmonary Adenocarcinoma: Differences in CT Patterns between Solid and Subsolid Cancers.

Radiol Cardiothorac Imaging 2019 Aug 29;1(3):e190071. Epub 2019 Aug 29.

Departments of Radiology (B.H.H., U.S.N., C.d.M.M., A.C.M.F., A.A.B.) and Pathology (K.R.A., Y.C., P.A.V.), Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215; Department of Biomedical Imaging and Image-guided Therapy, Vienna General Hospital, Medical University of Vienna, Austria (B.H.H., U.S.N., M.E.M.); and Seacoast Pathology/Aurora Diagnostics, Exeter, NH (K.R.A.).

Purpose: To analyze the incidence and CT patterns of visceral pleural invasion (VPI) in adenocarcinomas on the basis of their CT presentation as solid or subsolid nodules.

Materials And Methods: A total of 286 adenocarcinomas in direct contact with a pleural surface, resected at an institution between 2005 and 2016, were included in this retrospective, institutional review board-approved study. CT size and longest contact length with a pleural surface were measured and their ratios computed. Pleural deviation, pleural thickening, spiculations, different pleural tag types, pleural effusion, and the CT appearance of transgression into an adjacent lobe or infiltration of surrounding tissue were evaluated. Fisher exact tests and simple and multiple logistic regression models were used.

Results: Of the 286 nodules, 179 of 286 (62.6%) were solid and 107 of 286 (37.4%) were subsolid. VPI was present in 49 of 286 (17.1%) nodules and was significantly more frequent in solid (44 of 179; 24.6%) than in subsolid nodules (five of 107; 4.7%; < .001). In solid nodules, multiple regression analysis showed an association of higher contact length-to-size ratio (adjusted odds ratio [OR], 1.02; = .007) and the presence of multiple pleural tag types (adjusted OR, 5.88; = .002) with VPI. In subsolid nodules, longer pleural contact length of the solid nodular component (adjusted OR, 1.27; = .017) and the CT appearance of transgression or infiltration (adjusted OR, 10.75; = .037) were associated with VPI.

Conclusion: During preoperative evaluation of adenocarcinomas for the likelihood of VPI, whether a tumor manifests as a solid or a subsolid nodule is important to consider because the incidence of VPI is significantly higher in solid than in subsolid nodules. In addition, this study showed that the CT patterns associated with VPI differ between solid and subsolid nodules.© RSNA, 2019See also the commentary by Elicker in this issue.
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http://dx.doi.org/10.1148/ryct.2019190071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977962PMC
August 2019

PET/MRI versus PET/CT in oncology: a prospective single-center study of 330 examinations focusing on implications for patient management and cost considerations.

Eur J Nucl Med Mol Imaging 2020 01 13;47(1):51-60. Epub 2019 Aug 13.

Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.

Purpose: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI.

Methods: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [F]FDG, [Ga]Ga-DOTANOC, or [F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated.

Results: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients.

Conclusions: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.
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http://dx.doi.org/10.1007/s00259-019-04452-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885019PMC
January 2020

Whole-Body [F]FDG-PET/MRI vs. [F]FDG-PET/CT in Malignant Melanoma.

Mol Imaging Biol 2020 06;22(3):739-744

Department of Biomedical Imaging and Image-guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Vienna, Austria.

Purpose: To assess the diagnostic performance of simultaneous whole-body 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) compared to [F]FDG PET/x-ray computed tomography (CT) for detection of distant metastatic disease in patients with malignant melanoma.

Procedures: We included patients with malignant melanoma who underwent a single injection [F]FDG dual-imaging protocol that included whole-body PET/CT and subsequent whole-body PET/MRI for staging or restaging purposes in a prospective setting. Images from both modalities were analyzed by two rater teams for the presence of metastatic lesions. PET/CT-PET/MRI overall agreement as well as region-based accuracies, sensitivities (Se), and specificities (Sp) were computed.

Results: Between July 2014 and December 2018, 22 patients were enrolled. Interrater agreement and overall accuracy (consensus reading) were 78.8 % (95 % CI 71-84.9) and 96.1 % (95 % CI 92.3-98) for PET/MRI and 78 % (70.2-84.3) and 97.4 % (95 % CI 93.7-98.9) for PET/CT, respectively (P = 0.42). PET/MRI reached a region-based Se of 89.1 % (95 % CI 79.4-94.5) and a Sp of 100 %, whereas PET/CT showed a region-based Se of 92.7 % (95 % CI 84-96.9) and a Sp of 100 % for the detection of metastatic disease in malignant melanoma.

Conclusions: Whole-body [F]FDG-PET/MRI appears to be comparable to [F]FDG-PET/CT for lesion detection in patients with malignant melanoma.
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http://dx.doi.org/10.1007/s11307-019-01413-7DOI Listing
June 2020

Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia.

Blood 2019 10 10;134(14):1132-1143. Epub 2019 Jul 10.

The Royal Marsden Hospital, NHS Foundation Trust, London, United Kingdom.

T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of patients with T-PLL, it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG) set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL, and will thus support clinical decision making, as well as the approval of new therapeutics by healthcare authorities.
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http://dx.doi.org/10.1182/blood.2019000402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042666PMC
October 2019

Radiomic features of glucose metabolism enable prediction of outcome in mantle cell lymphoma.

Eur J Nucl Med Mol Imaging 2019 Dec 8;46(13):2760-2769. Epub 2019 Jul 8.

Department of Radiology, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center New York, 1275 York Ave, New York, NY, 10065, USA.

Purpose: To determine whether [F]FDG PET/CT-derived radiomic features alone or in combination with clinical, laboratory and biological parameters are predictive of 2-year progression-free survival (PFS) in patients with mantle cell lymphoma (MCL), and whether they enable outcome prognostication.

Methods: Included in this retrospective study were 107 treatment-naive MCL patients scheduled to receive CD20 antibody-based immuno(chemo)therapy. Standardized uptake values (SUV), total lesion glycolysis, and 16 co-occurrence matrix radiomic features were extracted from metabolic tumour volumes on pretherapy [F]FDG PET/CT scans. A multilayer perceptron neural network in combination with logistic regression analyses for feature selection was used for prediction of 2-year PFS. International prognostic indices for MCL (MIPI and MIPI-b) were calculated and combined with the radiomic data. Kaplan-Meier estimates with log-rank tests were used for PFS prognostication.

Results: SUVmean (OR 1.272, P = 0.013) and Entropy (heterogeneity of glucose metabolism; OR 1.131, P = 0.027) were significantly predictive of 2-year PFS: median areas under the curve were 0.72 based on the two radiomic features alone, and 0.82 with the addition of clinical/laboratory/biological data. Higher SUVmean in combination with higher Entropy (SUVmean >3.55 and entropy >3.5), reflecting high "metabolic risk", was associated with a poorer prognosis (median PFS 20.3 vs. 39.4 months, HR 2.285, P = 0.005). The best PFS prognostication was achieved using the MIPI-bm (MIPI-b and metabolic risk combined): median PFS 43.2, 38.2 and 20.3 months in the low-risk, intermediate-risk and high-risk groups respectively (P = 0.005).

Conclusion: In MCL, the [F]FDG PET/CT-derived radiomic features SUVmean and Entropy may improve prediction of 2-year PFS and PFS prognostication. The best results may be achieved using a combination of metabolic, clinical, laboratory and biological parameters.
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http://dx.doi.org/10.1007/s00259-019-04420-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879438PMC
December 2019
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