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68Ga-Pentixafor PET/MRI for Treatment Response Assessment in Mantle Cell Lymphoma: Comparison Between Changes in Lesion CXCR4 Expression on PET and Lesion Size and Diffusivity on MRI
Mayerhoefer, Marius E; Raderer, Markus; Weber, Michael; Lamm, Wolfgang; Kiesewetter, Barbara; Hacker, Marcus; Nics, Lukas; Schmitl, Stefan; Leithner, Doris; Wester, Hans-Juergen; Haug, Alexander
PURPOSE/OBJECTIVE:The aim of this study was to compare CXCR4 imaging with 68Ga-pentixafor PET to MRI for treatment response assessment in patients with mantle cell lymphoma (MCL). PATIENTS AND METHODS/METHODS:Twenty-two posttreatment 68Ga-pentixafor PET/MRI scans of 16 patients (7 women and 9 men; mean age, 69.9 ± 7.9) with a total of 67 target lesions on baseline PET/MRI were analyzed. Rates of complete remission per lesion and per scan, according to MRI (based on lesion size) and 68Ga-pentixafor PET (based on SUV decrease to lower than liver and blood pool uptake), were compared using McNemar tests. The t tests and Pearson correlation coefficients (r) were used to compare rates of change in lesion diameter products (DPs) on MRI, and standardized uptake values (SUVmax, SUVmean) on PET, relative to baseline. RESULTS:At interim PET/MRI, 18/32 (56.3%) target lesions met CR criteria on 68Ga-pentixafor PET, and 16/32 (50.0%) lesions met size-based MRI criteria for CR (P = 0.63). At end-of-treatment PET/MRI, 40/57 (70.2%) target lesions met 68Ga-pentixafor PET criteria for CR, and 27/57 (47.4%) lesions met size-based MRI criteria for CR (P = 0.021). Complete remission after treatment was observed more frequently on 68Ga-pentixafor PET (11/22 scans, 54.5%) than on MRI (6/22 scans, 27.3%) (P = 0.031). Rates of change did not differ significantly between lesion DP (-69.20% ± 34.62%) and SUVmax (-64.59% ± 50.78%, P = 0.22), or DP and SUVmean (-60.15 ± 64.58, P = 0.064). Correlations were strong between DP and SUVmax (r = 0.71, P < 0.001) and DP and SUVmean (r = 0.73, P < 0.001). CONCLUSIONS:In MCL patients, 68Ga-pentixafor PET may be superior for assessment of complete remission status than anatomic MRI using lesion size criteria, especially at the end of treatment.
PMCID:10247159
PMID: 37272977
ISSN: 1536-0229
CID: 5595882
89Zr-DFO-Isatuximab for CD38-Targeted ImmunoPET Imaging of Multiple Myeloma and Lymphomas
Herrero Alvarez, Natalia; Michel, Alexa L; Viray, Tara D; Mayerhoefer, Marius E; Lewis, Jason S
Multiple myeloma (MM) is the second most prevalent hematological malignancy. It remains incurable despite the availability of novel therapeutic approaches, marking an urgent need for new agents for noninvasive targeted imaging of MM lesions. CD38 has proven to be an excellent biomarker due to its high expression in aberrant lymphoid and myeloid cells relative to normal cell populations. Using isatuximab (Sanofi), the latest FDA-approved CD38-targeting antibody, we have developed Zirconium-89(89Zr)-labeled isatuximab as a novel immunoPET tracer for the in vivo delineation of MM and evaluated the extension of its applicability to lymphomas. In vitro studies validated the high binding affinity and specificity of 89Zr-DFO-isatuximab for CD38. PET imaging demonstrated the high performance of 89Zr-DFO-isatuximab as a targeted imaging agent to delineate tumor burden in disseminated models of MM and Burkitt's lymphoma. Ex vivo biodistribution studies confirmed that high accumulations of the tracer in bone marrow and bone skeleton correspond to specific disease lesions as they are reduced to background in blocking and healthy controls. This work demonstrates the promise of 89Zr-DFO-isatuximab as an immunoPET tracer for CD38-targeted imaging of MM and certain lymphomas. More importantly, its potential as an alternative to 89Zr-DFO-daratumumab holds great clinical relevance.
PMCID:10308590
PMID: 37396228
ISSN: 2470-1343
CID: 5595962
Proposal of early CT morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors: Alternatives to RECIST
de Mestier, Louis; Resche-Rigon, Matthieu; Dromain, Clarisse; Lamarca, Angela; La Salvia, Anna; de Baker, Lesley; Fehrenbach, Uli; Pusceddu, Sara; Colao, Annamaria; Borbath, Ivan; de Haas, Robbert; Rinzivillo, Maria; Zerbi, Alessandro; Funicelli, Luigi; de Herder, Wouter W; Selberherr, Andreas; Wagner, Anna Dorothea; Manoharan, Prakash; De Cima, Andrea; Lybaert, Willem; Jann, Henning; Prinzi, Natalie; Faggiano, Antongiulio; Annet, Laurence; Walenkamp, Annemiek; Panzuto, Francesco; Pedicini, Vittorio; Pitoni, Maria Giovanna; Siebenhuener, Alexander; Mayerhoefer, Marius E; Ruszniewski, Philippe; Vullierme, Marie-Pierre
RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06-3.40; p = .03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p = .91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy. CLINICAL TRIAL REGISTRATION: Registered at CNIL-CERB, Assistance publique hopitaux de Paris as "E-NETNET-L-E-CT" July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.
PMID: 37345276
ISSN: 1365-2826
CID: 5595942
Baseline 18F-FDG PET/CT Radiomics in Classical Hodgkin's Lymphoma: The Predictive Role of the Largest and the Hottest Lesions
Triumbari, Elizabeth Katherine Anna; Gatta, Roberto; Maiolo, Elena; De Summa, Marco; Boldrini, Luca; Mayerhoefer, Marius E; Hohaus, Stefan; Nardo, Lorenzo; Morland, David; Annunziata, Salvatore
This study investigated the predictive role of baseline 18F-FDG PET/CT (bPET/CT) radiomics from two distinct target lesions in patients with classical Hodgkin's lymphoma (cHL). cHL patients examined with bPET/CT and interim PET/CT between 2010 and 2019 were retrospectively included. Two bPET/CT target lesions were selected for radiomic feature extraction: Lesion_A, with the largest axial diameter, and Lesion_B, with the highest SUVmax. Deauville score at interim PET/CT (DS) and 24-month progression-free-survival (PFS) were recorded. Mann-Whitney test identified the most promising image features (p < 0.05) from both lesions with regards to DS and PFS; all possible radiomic bivariate models were then built through a logistic regression analysis and trained/tested with a cross-fold validation test. The best bivariate models were selected based on their mean area under curve (mAUC). A total of 227 cHL patients were included. The best models for DS prediction had 0.78 ± 0.05 maximum mAUC, with a predominant contribution of Lesion_A features to the combinations. The best models for 24-month PFS prediction reached 0.74 ± 0.12 mAUC and mainly depended on Lesion_B features. bFDG-PET/CT radiomic features from the largest and hottest lesions in patients with cHL may provide relevant information in terms of early response-to-treatment and prognosis, thus representing an earlier and stronger decision-making support for therapeutic strategies. External validations of the proposed model are planned.
PMCID:10137254
PMID: 37189492
ISSN: 2075-4418
CID: 5595852
Detecting CXCR4 Expression in Meningioma on 68Ga-Pentixafor PET/MRI
Krebs, Simone; Schwartz, Jazmin; Grommes, Christian; Young, Robert J; Schöder, Heiko; Mayerhoefer, Marius E
PMCID:10071788
PMID: 36357178
ISSN: 1535-5667
CID: 5595812
Attitudes and perceptions of radiologists towards online (virtual) oncologic multidisciplinary team meetings during the COVID-19 pandemic-a survey of the European Society of Oncologic Imaging (ESOI)
Bonanno, Nathania; Cioni, Dania; Caruso, Damiano; Cyran, Clemens C; Dinkel, Julien; Fournier, Laure; Gourtsoyianni, Sofia; Hoffmann, Ralf-Thorsten; Laghi, Andrea; Martincich, Laura; Mayerhoefer, Marius E; Zamboni, Giulia A; Sala, Evis; Schlemmer, Heinz-Peter; Neri, Emanuele; D'Anastasi, Melvin
OBJECTIVES/OBJECTIVE:To explore radiologists' opinions regarding the shift from in-person oncologic multidisciplinary team meetings (MDTMs) to online MDTMs. To assess the perceived impact of online MDTMs, and to evaluate clinical and technical aspects of online meetings. METHODS:An online questionnaire including 24 questions was e-mailed to all European Society of Oncologic Imaging (ESOI) members. Questions targeted the structure and efficacy of online MDTMs, including benefits and limitations. RESULTS:A total of 204 radiologists responded to the survey. Responses were evaluated using descriptive statistical analysis. The majority (157/204; 77%) reported a shift to online MDTMs at the start of the pandemic. For the most part, this transition had a positive effect on maintaining and improving attendance. The majority of participants reported that online MDTMs provide the same clinical standard as in-person meetings, and that interdisciplinary discussion and review of imaging data were not hindered. Seventy three of 204 (35.8%) participants favour reverting to in-person MDTs, once safe to do so, while 7/204 (3.4%) prefer a continuation of online MDTMs. The majority (124/204, 60.8%) prefer a combination of physical and online MDTMs. CONCLUSIONS:Online MDTMs are a viable alternative to in-person meetings enabling continued timely high-quality provision of care with maintained coordination between specialties. They were accepted by the majority of surveyed radiologists who also favoured their continuation after the pandemic, preferably in combination with in-person meetings. An awareness of communication issues particular to online meetings is important. Training, improved software, and availability of support are essential to overcome technical and IT difficulties reported by participants. KEY POINTS/CONCLUSIONS:• Majority of surveyed radiologists reported shift from in-person to online oncologic MDT meetings during the COVID-19 pandemic. • The shift to online MDTMs was feasible and generally accepted by the radiologists surveyed with the majority reporting that online MDTMs provide the same clinical standard as in-person meetings. • Most would favour the return to in-person MDTMs but would also accept the continued use of online MDTMs following the end of the current pandemic.
PMCID:9391636
PMID: 35986772
ISSN: 1432-1084
CID: 5595282
Added value of quantitative, multiparametric 18F-FDG PET/MRI in the locoregional staging of rectal cancer
Herold, Alexander; Wassipaul, Christian; Weber, Michael; Lindenlaub, Florian; Rasul, Sazan; Stift, Anton; Stift, Judith; Mayerhoefer, Marius E; Hacker, Marcus; Ba-Ssalamah, Ahmed; Haug, Alexander R; Tamandl, Dietmar
PURPOSE:The purpose of this study was to determine whether multiparametric positron emission tomography/magnetic resonance imaging (mpPET/MRI) can improve locoregional staging of rectal cancer (RC) and to assess its prognostic value after resection. METHODS:In this retrospective study, 46 patients with primary RC, who underwent multiparametric 18F-fluorodeoxyglucose (FDG) PET/MRI, followed by surgical resection without chemoradiotherapy, were included. Two readers reviewed T- and N- stage, mesorectal involvement, sphincter infiltration, tumor length, and distance from anal verge. In addition, diffusion-weighted imaging (DWI) and PET parameters were extracted from the multiparametric protocol and were compared to radiological staging as well as to the histopathological reference standard. Clinical and imaging follow-up was systematically assessed for tumor recurrence and death. RESULTS:Locally advanced rectal cancers (LARC) exhibited significantly higher metabolic tumor volume (MTV, AUC 0.74 [95% CI 0.59-0.89], p = 0.004) and total lesion glycolysis (TLG, AUC 0.70 [95% CI 0.53-0.87], p = 0.022) compared to early tumors. T-stage was associated with MTV (AUC 0.70 [95% CI 0.54-0.85], p = 0.021), while N-stage was better assessed using anatomical MRI sequences (AUC 0.72 [95% CI 0.539-0.894], p = 0.032). In the multivariate regression analysis, depending on the model, both anatomical MRI sequences and MTV/TLG were capable of detecting LARC. Combining anatomical MRI stage and MTV/TLG led to a superior diagnostic performance for detecting LARC (AUC 0.81, [95% CI 0.68-0.94], p < 0.001). In the survival analysis, MTV was independently associated with overall survival (HR 1.05 [95% CI 1.01-1.10], p = 0.044). CONCLUSION:Multiparametric PET-MRI can improve identification of locally advanced tumors and, hence, help in treatment stratification. It provides additional information on RC tumor biology and may have prognostic value.
PMCID:9668962
PMID: 36063201
ISSN: 1619-7089
CID: 5595742
Standardised lesion segmentation for imaging biomarker quantitation: a consensus recommendation from ESR and EORTC
deSouza, Nandita M; van der Lugt, Aad; Deroose, Christophe M; Alberich-Bayarri, Angel; Bidaut, Luc; Fournier, Laure; Costaridou, Lena; Oprea-Lager, Daniela E; Kotter, Elmar; Smits, Marion; Mayerhoefer, Marius E; Boellaard, Ronald; Caroli, Anna; de Geus-Oei, Lioe-Fee; Kunz, Wolfgang G; Oei, Edwin H; Lecouvet, Frederic; Franca, Manuela; Loewe, Christian; Lopci, Egesta; Caramella, Caroline; Persson, Anders; Golay, Xavier; Dewey, Marc; O'Connor, James P B; deGraaf, Pim; Gatidis, Sergios; Zahlmann, Gudrun; ,; ,
BACKGROUND:Lesion/tissue segmentation on digital medical images enables biomarker extraction, image-guided therapy delivery, treatment response measurement, and training/validation for developing artificial intelligence algorithms and workflows. To ensure data reproducibility, criteria for standardised segmentation are critical but currently unavailable. METHODS:A modified Delphi process initiated by the European Imaging Biomarker Alliance (EIBALL) of the European Society of Radiology (ESR) and the European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group was undertaken. Three multidisciplinary task forces addressed modality and image acquisition, segmentation methodology itself, and standards and logistics. Devised survey questions were fed via a facilitator to expert participants. The 58 respondents to Round 1 were invited to participate in Rounds 2-4. Subsequent rounds were informed by responses of previous rounds. RESULTS/CONCLUSIONS/CONCLUSIONS:Items with ≥ 75% consensus are considered a recommendation. These include system performance certification, thresholds for image signal-to-noise, contrast-to-noise and tumour-to-background ratios, spatial resolution, and artefact levels. Direct, iterative, and machine or deep learning reconstruction methods, use of a mixture of CE marked and verified research tools were agreed and use of specified reference standards and validation processes considered essential. Operator training and refreshment were considered mandatory for clinical trials and clinical research. Items with a 60-74% agreement require reporting (site-specific accreditation for clinical research, minimal pixel number within lesion segmented, use of post-reconstruction algorithms, operator training refreshment for clinical practice). Items with ≤ 60% agreement are outside current recommendations for segmentation (frequency of system performance tests, use of only CE-marked tools, board certification of operators, frequency of operator refresher training). Recommendations by anatomical area are also specified.
PMCID:9532485
PMID: 36194301
ISSN: 1869-4101
CID: 5595762
Impact of ComBat Harmonization on PET Radiomics-Based Tissue Classification: A Dual-Center PET/MRI and PET/CT Study
Leithner, Doris; Schöder, Heiko; Haug, Alexander; Vargas, H Alberto; Gibbs, Peter; Häggström, Ida; Rausch, Ivo; Weber, Michael; Becker, Anton S; Schwartz, Jazmin; Mayerhoefer, Marius E
Our purpose was to determine whether ComBat harmonization improves 18F-FDG PET radiomics-based tissue classification in pooled PET/MRI and PET/CT datasets. Methods: Two hundred patients who had undergone 18F-FDG PET/MRI (2 scanners and vendors; 50 patients each) or PET/CT (2 scanners and vendors; 50 patients each) were retrospectively included. Gray-level histogram, gray-level cooccurrence matrix, gray-level run-length matrix, gray-level size-zone matrix, and neighborhood gray-tone difference matrix radiomic features were calculated for volumes of interest in the disease-free liver, spleen, and bone marrow. For individual feature classes and a multiclass radiomic signature, tissue was classified on ComBat-harmonized and unharmonized pooled data, using a multilayer perceptron neural network. Results: Median accuracies in training and validation datasets were 69.5% and 68.3% (harmonized), respectively, versus 59.5% and 58.9% (unharmonized), respectively, for gray-level histogram; 92.1% and 86.1% (harmonized), respectively, versus 53.6% and 50.0% (unharmonized), respectively, for gray-level cooccurrence matrix; 84.8% and 82.8% (harmonized), respectively, versus 62.4% and 58.3% (unharmonized), respectively, for gray-level run-length matrix; 87.6% and 85.6% (harmonized), respectively, versus 56.2% and 52.8% (unharmonized), respectively, for gray-level size-zone matrix; 79.5% and 77.2% (harmonized), respectively, versus 54.8% and 53.9% (unharmonized), respectively, for neighborhood gray-tone difference matrix; and 86.9% and 84.4% (harmonized), respectively, versus 62.9% and 58.3% (unharmonized), respectively, for radiomic signature. Conclusion: ComBat harmonization may be useful for multicenter 18F-FDG PET radiomics studies using pooled PET/MRI and PET/CT data.
PMCID:9536705
PMID: 35210300
ISSN: 1535-5667
CID: 5452972
Positron emission tomography/magnetic resonance imaging (PET/MRI) vs. gastroscopy: Can it improve detection of extranodal marginal zone lymphomas of the stomach following H. pylori treatment?
Raderer, Markus; Kiesewetter, Barbara; Mayerhoefer, Marius E
INTRODUCTION:) is the standard first-line treatment, with response assessment being performed by histological evaluation of multiple gastric biopsies. AREAS COVERED:The objective of this review is to provide an update on results obtained using noninvasive methods, including magnetic resonance imaging (MRI), positron emission tomography combined with computed tomography (PET/CT), and most recently, PET/MRI for the assessment of disease extent and response to treatment in patients with gastric MALT lymphoma. EXPERT OPINION:eradication, this imaging technique may provide excellent accuracy (97%) for assessment of residual or recurrent disease. Although recent studies on CXCR4-targeting PET and to some extent also diffusion-weighted MRI are promising, there is insufficient evidence to suggest a change in clinical practice.
PMCID:10256281
PMID: 35695746
ISSN: 1747-4094
CID: 5596252