Faculty Bibliography

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.

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), [¹⁸F]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.

PURPOSE:F]FDG/positron emission tomography (PET) are established outcome predictors in FDG-avid lymphomas. We therefore investigated whether these biomarkers also have prognostic value in extranodal marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma), with a focus on patients treated with anti-CD20 antibody-based immunotherapy. PROCEDURES:F]FDG/PET parameters, and Kaplan-Meier estimates with log rank tests were performed. RESULTS:After 2 years, progression had occurred in 12/61 patients (CD20-anitbody group 6/35). TLG emerged as the only significant prognostic factor for 2-year PFS in the multivariate analyses with forward selection, both in entire cohort (hazard ratio HR, 1.001; 95 % CI, 1.001-1.002; P < 0.0001) and in the CD20-antibody group (HR, 1.001; 95 % CI, 1.001-1.002; P = 0.001). However, in the entire population, where 8/26 patients with a TLG > 90 (30.8 %) vs. 4/35 patients with a TLG ≤ 90 (11.4 %) showed progression within the 2-year observation period, TLG-based separation of risk groups failed (HR, 0.35; 95 % CI, 0.10-1.15; P = 0.069); whereas in the CD20-antibody group, where 6/16 patients with a TLG > 90 (37.5 %) vs. 0/19 patients with a TLG ≤ 90 (0.0 %) showed progression, risk group separation was successful (HR, 0.010; 95 % CI, 0.0001-8.068; P = 0.003). CONCLUSIONS:TLG may improve early risk stratification of MALT lymphoma patients treated with CD20-antibody-based immunotherapy.

PURPOSE/OBJECTIVE: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: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/CONCLUSIONS: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.

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.

Based on results of two pilot trials, lenalidomide (LEN) was found to be active and safe as monotherapy and showed an increased response rate of 80% in combination with rituximab (R) for patients with mucosa-associated lymphoid tissue (MALT) lymphoma. While initial results were promising, there are currently no data on long-term outcome, and larger international phase II/III trials on LEN for indolent lymphoma lack specific subgroup analyses. Thus, we have systematically analyzed 50 patients treated with LEN-based therapy (LEN-monotherapy n = 16, R-LEN n = 34) at the Medical University of Vienna 2009 to 2019 and investigated long-term outcome and relapse patterns. At a follow-up of more than 5 years (median 68 months), 54% of patients are free of relapse, and estimated median progression-free survival (PFS) was 72 months (95%CI 49-96). There was no difference in PFS according to stage of disease, i.e. localized versus disseminated disease (P = .67) and previous systemic treatment (P = .16). Interestingly, but with the caveat of the limited number of patients included in this series, primary extragastric disease had a superior PFS compared with gastric lymphoma (P = .04) and also depth of response, i.e. complete or partial response versus stable disease was associated with significantly prolonged PFS (P = .01). We documented four patients (8%) with pronounced improvement of response during follow-up including three patients initially rated as partial remission and finally achieving complete remission at 12 to 32 months. This highlights the potential of delayed responses to LEN treatment. Estimated overall survival at 5 years was excellent at 92%. These "real-world" data confirm long-term activity of LEN in MALT lymphoma.

Given the lack of consistent data regarding the clinico-pathological features and clonal lymphomagenesis of patients with mucosa-associated lymphoid tissue (MALT) lymphoma and histological transformation (HT), we have systematically analysed 379 patients (32% gastric, 68% extra-gastric; median follow-up 52 months) diagnosed with HT at the Medical University Vienna 1999-2017, and reassessed tissues of identified patients by polymerase chain reaction (PCR)-based clonality analysis. HT was documented in 12/379 patients (3·2%) and occurred at a median time of 22 months (range; 6-202 months) after diagnosis of MALT lymphoma. By PCR-based clonality analysis, we detected a clear-cut clonal relationship of MALT lymphoma and diffuse large B-cell lymphoma (DLBCL) in 8 of 11 analysed cases proving that the large majority of DLBCL following MALT lymphoma are clonally-related and constitute a real transformation. Interestingly, HT occurred within the first 2·5 years after diagnosis in patients with clonal relationship, whereas time to aggressive lymphoma was longer in patients identified as clonally-unrelated (most likely secondary) lymphoma (82-202 months), suggesting that HT is an early event in this disease. Survival of patients with HT was poor with 6/12 dying at 1·5-33 months after HT, however, patients with localized gastric transformation had a superior outcome with only 1/6 dying due to progression of lymphoma.