Faculty Bibliography

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.

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.

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 [⁶⁸Ga]Pentixafor-PET/MRI for in vivo CXCR4 visualization, we here provide images of topical changes of CLL cells upon ibrutinib treatment. Within the first month of ibrutinib treatment, mean standardized [⁶⁸Ga]Pentixafor uptake decreased in the bone marrow and lymph nodes, whereas [⁶⁸Ga]Pentixafor uptake increased in the spleen. Leukocytosis rose, as did numbers of CXCR4^high (tissue-resident) CLL cells. Volumes of lymph nodes and spleen decreased. Upon longer ibrutinib treatment, leukocytosis decreased, followed by a decrease of [⁶⁸Ga]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.

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.

PURPOSE:F]FDG PET/x-ray computed tomography (CT) for detection of distant metastatic disease in patients with malignant melanoma. PROCEDURES: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:F]FDG-PET/CT for lesion detection in patients with malignant melanoma.

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.

The role of MRI differs considerably between the three main groups of hematological malignancies: lymphoma, leukemia, and myeloma. In myeloma, whole-body MRI (WB-MRI) is recognized as a highly sensitive test for the assessment of myeloma, and is also endorsed by clinical guidelines, especially for detection and staging. In lymphoma, WB-MRI is presently not recommended, and merely serves as an alternative technique to the current standard imaging test, [¹⁸ F]FDG-PET/CT, especially in pediatric patients. Even for lymphomas with variable FDG avidity, such as extranodal mucosa-associated lymphoid tissue lymphoma (MALT), contrast-enhanced computed tomography (CT), but not WB-MRI, is presently recommended, despite the high sensitivity of diffusion-weighted MRI and its ability to capture treatment response that has been reported in the literature. In leukemia, neither MRI nor any other cross-sectional imaging test (including positron emission tomography [PET]) is currently recommended outside of clinical trials. This review article discusses current clinical applications as well as the main research topics for MRI, as well as PET/MRI, in the field of hematological malignancies, with a focus on functional MRI techniques such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, on the one hand, and novel, non-FDG PET imaging probes such as the CXCR4 radiotracer [⁶⁸ Ga]Ga-Pentixafor and the amino acid radiotracer [¹¹ C]methionine, on the other hand. Level of Evidence: 5 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1325-1335.

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.

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). Methods: 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. Results: All patients with Helicobacter pylori (H. pylori)-positive, localized disease received H. pylori 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, p < 0.001). This was also applicable to the eradication only cohort (49.0 vs. 17.3 months, p < 0.001) and remained significant after correction for MALT-IPI. Furthermore, CR significantly prolonged PFS over PR (p = 0.007 entire cohort, p = 0.020 eradication). Conclusions: Remission status correlated significantly with PFS, suggesting depth of remission as prognostic marker for long-term relapse-free survival.

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: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.