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131


Positive selection as the unifying force for clonal evolution in multiple myeloma [Letter]

Diamond, Benjamin; Yellapantula, Venkata; Rustad, Even H; Maclachlan, Kylee H; Mayerhoefer, Marius; Kaiser, Martin; Morgan, Gareth; Landgren, Ola; Maura, Francesco
PMID: 33483619
ISSN: 1476-5551
CID: 4788272

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

Husseini, Jad S; Amorim, Bárbara Juarez; Torrado-Carvajal, Angel; Prabhu, Vinay; Groshar, David; Umutlu, Lale; Herrmann, Ken; Cañamaque, Lina García; Garzón, José Ramón García; Palmer, William E; Heidari, Pedram; Shih, Tiffany Ting-Fang; Sosna, Jacob; Matushita, Cristina; Cerci, Juliano; Queiroz, Marcelo; Muglia, Valdair Francisco; Nogueira-Barbosa, Marcello H; Borra, Ronald J H; Kwee, Thomas C; Glaudemans, Andor W J M; Evangelista, Laura; Salvatore, Marco; Cuocolo, Alberto; Soricelli, Andrea; Herold, Christian; Laghi, Andrea; Mayerhoefer, Marius; Mahmood, Umar; Catana, Ciprian; Daldrup-Link, Heike E; Rosen, Bruce; Catalano, Onofrio A
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/CONCLUSIONS: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.
PMID: 33619599
ISSN: 1619-7089
CID: 4806792

Functional imaging using radiomic features in assessment of lymphoma

Mayerhoefer, Marius E; Umutlu, Lale; Schöder, Heiko
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.
PMCID:8349521
PMID: 32634555
ISSN: 1095-9130
CID: 5596042

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

Maclachlan, Kylee H; Came, Neil; Diamond, Benjamin; Roshal, Mikhail; Ho, Caleb; Thoren, Katie; Mayerhoefer, Marius E; Landgren, Ola; Harrison, Simon
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 10-6). 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.
PMID: 33674146
ISSN: 1465-3931
CID: 5596172

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

Starzer, Angelika M; Berghoff, Anna S; Traub-Weidinger, Tatjana; Haug, Alexander R; Widhalm, Georg; Hacker, Marcus; Rausch, Ivo; Preusser, Matthias; Mayerhoefer, Marius E
PURPOSE OF THE REPORT/OBJECTIVE: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/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.
PMCID:8385649
PMID: 33208624
ISSN: 1536-0229
CID: 5596082

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

Rindler, Katharina; Bauer, Wolfgang M; Jonak, Constanze; Wielscher, Matthias; Shaw, Lisa E; Rojahn, Thomas B; Thaler, Felix M; Porkert, Stefanie; Simonitsch-Klupp, Ingrid; Weninger, Wolfgang; Mayerhoefer, Marius E; Farlik, Matthias; Brunner, Patrick M
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 (TRM, CD69+CD27-NR4A1+RGS1+AHR+
PMCID:8097053
PMID: 33968070
ISSN: 1664-3224
CID: 5596212

Twenty Years On: RECIST as a Biomarker of Response in Solid Tumours an EORTC Imaging Group - ESOI Joint Paper

Fournier, Laure; de Geus-Oei, Lioe-Fee; Regge, Daniele; Oprea-Lager, Daniela-Elena; D'Anastasi, Melvin; Bidaut, Luc; Bäuerle, Tobias; Lopci, Egesta; Cappello, Giovanni; Lecouvet, Frederic; Mayerhoefer, Marius; Kunz, Wolfgang G; Verhoeff, Joost J C; Caruso, Damiano; Smits, Marion; Hoffmann, Ralf-Thorsten; Gourtsoyianni, Sofia; Beets-Tan, Regina; Neri, Emanuele; deSouza, Nandita M; Deroose, Christophe M; Caramella, Caroline
Response evaluation criteria in solid tumours (RECIST) v1.1 are currently the reference standard for evaluating efficacy of therapies in patients with solid tumours who are included in clinical trials, and they are widely used and accepted by regulatory agencies. This expert statement discusses the principles underlying RECIST, as well as their reproducibility and limitations. While the RECIST framework may not be perfect, the scientific bases for the anticancer drugs that have been approved using a RECIST-based surrogate endpoint remain valid. Importantly, changes in measurement have to meet thresholds defined by RECIST for response classification within thus partly circumventing the problems of measurement variability. The RECIST framework also applies to clinical patients in individual settings even though the relationship between tumour size changes and outcome from cohort studies is not necessarily translatable to individual cases. As reproducibility of RECIST measurements is impacted by reader experience, choice of target lesions and detection/interpretation of new lesions, it can result in patients changing response categories when measurements are near threshold values or if new lesions are missed or incorrectly interpreted. There are several situations where RECIST will fail to evaluate treatment-induced changes correctly; knowledge and understanding of these is crucial for correct interpretation. Also, some patterns of response/progression cannot be correctly documented by RECIST, particularly in relation to organ-site (e.g. bone without associated soft-tissue lesion) and treatment type (e.g. focal therapies). These require specialist reader experience and communication with oncologists to determine the actual impact of the therapy and best evaluation strategy. In such situations, alternative imaging markers for tumour response may be used but the sources of variability of individual imaging techniques need to be known and accounted for. Communication between imaging experts and oncologists regarding the level of confidence in a biomarker is essential for the correct interpretation of a biomarker and its application to clinical decision-making. Though measurement automation is desirable and potentially reduces the variability of results, associated technical difficulties must be overcome, and human adjudications may be required.
PMCID:8784734
PMID: 35083155
ISSN: 2234-943x
CID: 5595712

CXCR4 PET imaging of mantle cell lymphoma using [68Ga]Pentixafor: comparison with [18F]FDG-PET

Mayerhoefer, Marius E; Raderer, Markus; Lamm, Wolfgang; Pichler, Verena; Pfaff, Sarah; Weber, Michael; Kiesewetter, Barbara; Hacker, Markus; Kazianka, Lukas; Staber, Philipp B; Wester, Hans-Juergen; Rohrbeck, Johannes; Simonitsch-Klupp, Ingrid; Haug, Alexander
For PET imaging of mantle cell lymphoma (MCL), [18F]FDG (2-deoxy-2-[18F]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 [68Ga]Pentixafor in MCL patients, and compared it to [18F]FDG. Methods: MCL patients underwent [68Ga]Pentixafor-PET/MRI, and, if required for routine purposes, also [18F]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 (SUVmax and SUVmean) and tumor-to-background ratios (TBRblood and TBRliver) were calculated. General Estimation Equations (GEE) were used to compare [68Ga]Pentixafor-PET and [18F]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. Results: Twenty-two MCL patients were included. [68Ga]Pentixafor-PET sensitivity (100%) was significantly higher than for [18F]FDG-PET (75.2%) (P<0.001), and PPV was slightly, but not significantly lower (94.0%.vs. 96.5%; P=0.21). SUVs and TBRs were significantly higher for [68Ga]Pentixafor-PET than for [18F]FDG-PET (P<0.001 in all cases); the greatest difference was observed for mean TBRblood, with 4.9 for [68Ga]Pentixafor-PET and 2.0 for [18F]FDG-PET. For bone marrow involvement, [68Ga]Pentixafor-PET SUVmean showed an AUC of 0.92; and for splenic involvement, TBRblood showed an AUC of 0.81. Conclusion: [68Ga]Pentixafor-PET may become an alternative to [18F]FDG-PET in MCL patients, showing clearly higher detection rates and better tumor-to-background contrast.
PMCID:7738870
PMID: 33391493
ISSN: 1838-7640
CID: 5596182

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

Kiesewetter, Barbara; Simonitsch-Klupp, Ingrid; Mayerhoefer, Marius E; Dolak, Werner; Lukas, Julius; Raderer, Markus
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%, p < 0.01) and the complete remission rate (75% vs. 43%, p < 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, p = 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.
PMCID:7761357
PMID: 33256131
ISSN: 2072-6694
CID: 5596162

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

Beer, Lucian; Hochmair, Maximilian; Kifjak, Daria; Haug, Alexander R; Prayer, Florian; Mayerhoefer, Marius E; Herold, Christian; Prosch, Helmut
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/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/CONCLUSIONS: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.
PMCID:7445205
PMID: 32430613
ISSN: 1613-7671
CID: 5596012