Faculty Bibliography

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.

PURPOSE/OBJECTIVE:The aim of this study was to compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the immune RECIST (iRECIST) criteria, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 in patients with advanced non-small cell lung cancer treated with programmed cell death protein 1 (PD-1)/programmed cell death protein 1 ligand (PD-L1) inhibitors. METHODS:This prospective study of 42 patients treated with a PD-1/PD-L1 inhibitor was approved by our institutional review board, and all patients gave written, informed consent. Tumor burden dynamics were assessed on F-FDG PET/CT before and after treatment initiation. Immunotherapeutic responses were evaluated according to RECIST 1.1, iRECIST, and PERCIST 1.0 for the dichotomous groups, responders versus nonresponders. Cohen κ and Wilcoxon signed rank tests were used to evaluate concordance among these criteria. We assessed progression-free survival and overall survival using the Kaplan-Meier estimator. RESULTS:The RECIST 1.1 and PERCIST 1.0 response classifications were discordant in 6 patients (14.2%; κ = 0.581). RECIST 1.1 and iRECIST were discordant in 2 patients, who evidenced pseudoprogression after treatment initiation. Median progression-free survival, as well as overall survival, was significantly longer for responders compared with nonresponders for all criteria (P < 0.001), with no significant difference between the 3 criteria (P > 0.05). CONCLUSIONS:RECIST 1.1 and PERCIST 1.0 show only moderate agreement, but both can predict treatment response to PD-1/PD-L1 inhibitor therapy. In case of pseudoprogression, metabolic tumor activity may help to correctly classify treatment response.

PURPOSE:Aim of present study was to determine whether the currently recommended 13-cm cranio-caudal diameter cut-off on CT for assessment of splenic involvement in lymphoma offers adequate sensitivity and specificity. MATERIALS AND METHODS:Patients with histologically proven lymphoma who had undergone [18F]FDG-PET/CT before therapy were included. Cranio-caudal diameters of the spleen were measured on the CT component of PET/CT, and ROC analyses with calculation of respective areas under the curve (AUC) were used to determine cut-off values of cranio-caudal measurements with their respective sensitivities and specificities, using [18F]FDG-PET as the reference standard. RESULTS:In 93 patients, we found a sensitivity of 74.1% and a specificity of 47% for the 13-cm splenic diameter cut-off. CONCLUSIONS:Our results show reasonable, though far from perfect sensitivities and specificities for the currently recommend 13-cm splenic diameter cut-off.

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.

In this case report, we present a case of false positive CA 19-9 and CA 125 levels in a patient with suspected endometriotic cysts. The patient is a 34-year-old nulliparous woman with heavy black tea consumption and elevated CA 19-9 and CA 125 levels. After discontinuation of black tea intake and careful exploration of other possible factors, CA 19-9 and CA 125 levels dropped markedly. As a conclusion, heavy black tea consumption can lead to false positive results of elevated CA 19-9 and CA 125 levels.

The macrolide clarithromycin has been reported as active for therapy of mucosa associated lymphoid tissue (MALT) lymphoma. Pharmacokinetic properties, however, require continuous daily intake over a prolonged period of time. As the macrolide azithromycin is characterized by a long half-life as well as potential antineoplastic activity in vitro, we have performed a phase II trial of long-term once-weekly oral azithromycin for treatment of MALT lymphoma. In a 2-stage-design, 16 patients (10 f/6 m) with histologically verified and measurable MALT lymphoma were included in the first phase of the trial, which could be expanded to a maximum of 46 patients depending on remissions in the first phase. Patients were given oral azithromycin 1500 mg once-weekly 4 times a month, and restaging was performed after 3 and 6 months. Two patients had gastric and 14 extragastric MALT lymphoma; 12/16 patients were treatment-naive and received azithromycin as first line treatment. Tolerance of this regimen was excellent, and 14/16 patients received 6 months of treatment as scheduled, while 1 patient each discontinued after 4 (progressive disease) and 1 cycle (personal reasons), respectively. The most commonly observed side effects were mild nausea (n = 8) and diarrhea (n = 4). Efficacy, however, was low as only 4/16 patients (25%) responded, with 2 complete and 2 partial remissions, 9 patients (56%) had stable disease, and 3 patients 19%) were rated as progressive disease. As the predefined activity of more than 7/16 patients responding was not reached, the study was stopped after 16 patients. Although long-term once-weekly oral azithromycin showed some antilymphoma activity, the response rate was below the predefined threshold of interest. However, based on our data, one cannot rule out suboptimal dosing in our study; attempts to study azithromycin at a different mode of application might be warranted in the future.

OBJECTIVES:This prospective proof-of-principle study aimed to determine whether [Ga]Ga-Pentixafor uptake, which reflects CXCR4 expression, is higher in the bone marrow of chronic lymphocytic leukemia (CLL) than in other oncological diseases without bone marrow infiltration and can therefore be used for CLL imaging. MATERIALS AND METHODS:Thirteen CLL patients and 20 controls (10 with pancreatic adenocarcinoma and 10 with mucosa-associated lymphoid tissue lymphoma) with histologically proven cancer underwent [Ga]Ga-Pentixafor positron emission tomography/magnetic resonance imaging. Standardized [Ga]Ga-Pentixafor uptake values (SUVmax, SUVmean) were measured in the bone marrow of the pelvis, the lumbar vertebra L4, and the bony structure with the visually highest tracer uptake ("hottest lesion"). Mean apparent diffusion coefficient values were also measured in the pelvis. Serum leukocyte count (gram per liter), lymphocyte percentage (percent), lactate dehydrogenase (unit per liter), β2-microglobulin (milligram per deciliter), and C-reactive protein (milligram per deciliter) were measured. Statistical analyses comprised analysis of variance with Games-Howell post hoc tests and Spearman correlation coefficients. RESULTS:SUVmax and SUVmean differed significantly between CLL and pancreatic adenocarcinoma in the pelvis (P = 0.032 and P = 0.008) and lumbar vertebra L4 (both P < 0.001). SUVmean also differed in the pelvis (P = 0.020) and L4 (P = 0.041), and SUVmax in L4 (P = 0.019), between CLL and mucosa-associated lymphoid tissue lymphoma. Receiver operating characteristic-based areas under the curve for separation of CLL from the control groups were greatest for the SUVmax of the bony structure with the strongest [Ga]Ga-Pentixafor uptake (0.94) and the SUVmax of L4 (0.92). There was no significant correlation between [Ga]Ga-Pentixafor uptake and pelvic apparent diffusion coefficients or serum parameters. CONCLUSIONS:[Ga]Ga-Pentixafor positron emission tomography/magnetic resonance imaging may possibly be useful for CXCR4-based CLL imaging.

PURPOSE:F]FDG PET/MR can capture treatment effects within the first week after treatment initiation, and whether changes in glucose metabolism and cell density occur simultaneously. METHODS:F]FDG uptake values (SUVmax, SUVmean) and apparent diffusion coefficients (ADCmin, ADCmean) based on diffusion-weighted MRI, and metabolic and morphological tumour volumes (MTV, VOL) were assessed at each time-point. Multilevel analyses with an unstructured covariance matrix, and pair-wise post-hoc tests were used to test for significant changes in SUVs, ADCs, MTVs and VOLs between the three time-points. RESULTS:A total of 58 patients (11 with HL and 47 with NHL) with 166 lesions were analysed. Lesion-based mean rates of change in SUVmax, SUVmean, ADCmin, ADCmean, MTV and VOL between baseline and FU-1 were -46.8%, -33.3%, +20.3%, +14%, -46% and -12.8%, respectively, and between baseline and FU-2 were -65.1%, -49%, +50.7%, +32.4%, -61.1% and -24.2%, respectively. These changes were statistically significant (P < 0.01) except for the change in VOL between baseline and FU-1 (P = 0.079). CONCLUSION:F]FDG PET/MR can capture treatment-induced changes in glucose metabolism and cell density as early as 48-72 h after treatment initiation.

RATIONALE AND OBJECTIVES:This study aimed to determine the diagnostic utility of standardized uptake values (SUV) and apparent diffusion coefficients (ADC) for assessment of focal and diffuse bone marrow involvement in patients with malignant lymphoma. MATERIALS AND METHODS:/s) on whole-body-DWI, were extracted from focal lesions, or, in their absence, from the thoracic (Th8) and lumbar vertebral bodies (L4), the sacral bone (S1), and the iliac crest. Lesion-to-liver-ratios (SUVmax-ratio) were calculated. Pearson correlation coefficients were used to assess the correlation between SUVmax-ratios and ADCmean values. RESULTS:Bone marrow involvement was observed in 16 of 60 patients (8 of 16 with diffuse infiltration). The SUVmax-ratio cutoff value was 95.25% for focal and 70.2% for diffuse bone marrow involvement (sensitivity/specificity of 87.5%/86.4% and 100%/43.2%, respectively). The ADCmean cutoff value was 0.498 for focal and 0.401 for diffuse bone marrow involvement (sensitivity/specificity of 100%/90.9% and 87.5%/56.8%, respectively). No significant correlations were found between SUVmax-ratios and ADCmean values in the different groups. CONCLUSION:With the liver as reference tissue, quantitative [F18]-FDG-PET/CT may be useful to differentiate bone marrow involvement from normal bone marrow in patients with lymphoma, even though the specificity for diffuse marrow involvement is rather low. Quantitative DWI can be used only to distinguish focal bone marrow lesions from normal bone marrow.

BACKGROUND:[18F]-FDG-PET/MR carries a high diagnostic value in whole-body oncologic imaging and allows simultaneous quantitative measurements of glucose metabolism (SUV) and cell density (ADC). PURPOSE:To determine the relationship between SUV and ADC values extracted from simultaneously acquired [18F]-FDG-PET/MR data of patients with FDG-avid lymphomas at staging. STUDY TYPE:Prospective. POPULATION:Patients with histologically proven lymphoma referred for staging. FIELD STRENGTH/SEQUENCES:-weighted half-Fourier acquisition single-shot turbo spin-echo. Single-shot, echo-planar imaging-based, spectral adiabatic inversion recovery diffusion-weighted imaging. ASSESSMENT:Staging was performed according to the modified Ann Arbor system by a board-certified radiologist and a board-certified nuclear medicine physician, blinded to the clinical and histological information, in consensus. SUVs and ADCs values were collected, for each positive nodal and extranodal region, from the lesion demonstrating the largest diameter. STATISTICAL TESTS:Descriptive data included absolute frequencies and percentages for categorical data, and arithmetic means and 95% confidence intervals for scale-type data. The Pearson correlation coefficient was used to assess the relationship between SUVs and ADCs (P ≤ 0.05). Additional separate analyses were performed according to histological lymphoma subtype, for nodal and extranodal lesions and excluding bone lesions. RESULTS:Overall, 100 patients were examined (55 males, 45 females; age ± SD in years, 51.6 ± 19.5). Histology revealed Hodgkin-lymphoma and non-Hodgkin-lymphoma in 26 and 74 patients, respectively. Twenty patients were stage I, 21 stage II, 24 stage III, and 31 stage IV on [18F]-FDG-PET/MR (ie, four patients negative at imaging). Based on 391 lesions (ie, 367 excluding bone lesions) no significant correlations between SUVmax and ADCmin, or between SUVmean and ADCmean, emerged (respectively, r = 0.091, P = 0.073, 95% CI [-0.01, 0.19] and r = -0.032, P = 0.527, 95% CI [-0.13, 0.07] including bone lesions; r = 0.06, P = 0.21, 95% CI [-0.04, 0.17] and r = -0.05, P = 0.32, 95% CI [-0.15, 0.05] excluding bone lesions). A significant correlation was observed only between ADCmean and SUVmean for follicular lymphoma (r = -0.33, P = 0.001). DATA CONCLUSION:SUVs and ADCs were demonstrated to be independent biomarkers in lymphomas. A moderate correlation between SUVs and ADCs likely is present in follicular lymphoma. LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1217-1226.