Faculty Bibliography

The purine analogue 2-chloro-deoxyadenosine (2-CDA, cladribine) +/- rituximab has been successfully tested in mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) patients. However, studies using cladribine in other indications have reported the potential for prolonged hematological side effects and secondary hematologic and non-hematologic malignancies. To date, there have been no data on long-term effects of cladribine in MALT lymphoma patients. We have analyzed a large number of 49 patients treated with cladribine at our institution 1997-2011. All patients were treated within clinical trials and had undergone a standardized follow-up protocol minimizing a potential bias in the detection of late sequels and relapses. After a median follow-up time of 61 months (interquartile range: 43-72) for 49 analyzed patients, 35 (71%) are alive, while 14 (29%) have died. In the entire collective, three cases (6%) of prolonged pancytopenia including manifest myelodysplastic syndrome in one patient (2%), three cases (6%) of secondary lymphoid malignancies, and five cases (10%) of non-hematologic cancers were documented. In terms of outcome, 42/49 (86%) patients responded to cladribine-containing treatment, and only 10/42 (24%) responding patients needed further treatment after a median time to progression of 14 months (interquartile range, 8-34). Currently, 25/35 (71%) patients being alive are in ongoing complete remission and 2/35 (6%) in ongoing stable disease, respectively. Eight patients (23%) are free of lymphoma after second-line therapy, with the median overall survival not having been reached. Our data suggest that cladribine might be safely applied in patients with MALT lymphoma, also in terms of long-term toxicities. These data also confirm the potential of cladribine to induce durable remissions. Copyright © 2015 John Wiley & Sons, Ltd.

PURPOSE/OBJECTIVE:To evaluate the influence of point spread function (PSF)-based reconstruction and matrix size for PET on (1) lung lesion detection and (2) standardized uptake values (SUV). METHODS:This prospective study included oncological patients who underwent [18F]-FDG-PET/CT for staging. PET data were reconstructed with a 2D ordered subset expectation maximization (OSEM) algorithm, and a 2D PSF-based algorithm (TrueX), separately with two matrix sizes (168×168 and 336×336). The four PET reconstructions (TrueX-168; OSEM-168; TrueX-336; and OSEM-336) were read independently by two raters, and PET-positive lung lesions were recorded. Blinded to the PET findings, a third independent rater assessed lung lesions with diameters of >4mm on CT. Subsequently, PET and CT were reviewed side-by side in consensus. Multi-factorial logistic regression analyses and two-way repeated measures analyses of variance (ANOVA) were performed. RESULTS:were significantly higher for images reconstructed with 336×336 matrices than for those reconstructed with 168×168 matrices (P<0.001). CONCLUSION/CONCLUSIONS:Our results demonstrate that PSF-based PET reconstruction, and, to a lesser degree, higher matrix size, improve detection of metabolically active lung lesions. However, PSF-based PET reconstructions and larger matrix sizes lead to higher SUVs, which may be a concern when PET data from different institutions are compared.

PURPOSE/OBJECTIVE:To investigate whether elevated glucose metabolism in neurofibroma, determined by [F18]-FDG-PET, is correlated with cell density in MRI, as expressed through the apparent diffusion coefficient. MATERIALS AND METHODS/METHODS:Patients diagnosed with neurofibromatosis type 1 and peripheral nerve sheath tumors (PNST) were enrolled in this prospective, IRB-approved study. After a single [F18]-FDG injection, patients consecutively underwent [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI on the same day. Maximum and mean standardized uptake values (SUVmax, SUVmean) on [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI were compared, and correlated with minimum and mean apparent diffusion coefficients (ADCmean, ADCmin). RESULTS:A total of 12 (6 male/6 female, mean age was 16.2 ± 5.2 years) patients were prospectively included and analyzed on a per-lesion (n = 39) basis. The SUVmean of examined PNST showed a moderate negative correlation with the ADCmean (r = -.441) and ADCmin (r = -.477), which proved to be statistically significant (p = .005 and p = .002). The SUVmax of the respective lesions, however, showed a weaker negative correlation for ADCmean (r: -.311) and ADCmin (r: -.300) and did not reach statistical significance (p = .054 and p = .057). Lesion-based correlation between [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT showed a moderate correlation for SUVmax (r = .353; p = .027) and a strong one for SUVmean (r = .879; p = .001)). Patient-based liver uptake (SUVmax and mean) of [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT were strongly positively correlated (r = .827; p < .001 and r = .721; p < .001) but differed significantly (p < .001). CONCLUSIONS:We found a statistically significant, negative correlation between glucose metabolism and cell density in PNST. Thus, ADCmean and ADCmin could possibly add complimentary information to the SUVmax and SUVmean and may serve as a potential determinant of malignant transformation of PNST.

PURPOSE/OBJECTIVE:To determine whether interim F-FDG PET or interim diffusion-weighted magnetic resonance imaging (DWI) can predict the end-of-treatment (EOT) outcome after immunotherapy in patients with FDG-avid extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). MATERIALS AND METHODS/METHODS:Patients with untreated MALT lymphoma prospectively underwent whole-body F-FDG PET/CT and DWI before treatment (baseline), and after three cycles (interim) of rituximab-based immunotherapy. Maximum and mean standardized uptake values (SUVmax, SUVmean), and minimum and mean apparent diffusion coefficients (ADCmin, ADCmean), were measured for up to three target lesions per patient. Rates of change between baseline and interim examinations (ΔSUVmax, ΔSUVmean, ΔADCmin, and ΔADCmean) were compared, using ANOVAs, between the four end-of-treatment (EOT, after six cycles of immunotherapy) outcomes: complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). RESULTS:Fifteen patients with 25 lesions were included. Lesion-based post hoc tests showed significant differences between CR and PR for ΔSUVmax (P < 0.001), ΔSUVmean (P < 0.001), and ΔADCmin (P = 0.044), and between CR and SD for ΔSUVmax (P < 0.001), ΔSUVmean (P < 0.001), ΔADCmin (P = 0.021), and ΔADCmean (P = 0.022). No lesion showed PD at EOT. CONCLUSIONS:Both quantitative interim F-FDG PET and interim DWI may possibly be useful to predict complete remission at end-of-treatment in MALT lymphoma patients after immunotherapy.

Rare disorders often represent a challenge for clinicians and require close collaboration of an interdisciplinary team.We present the complex case of a 22-year-old male with Danon disease and late-onset of posttransplant lymphoproliferative disorder after heart transplantation. The critical aspects of his condition were: pre-existing rhabdomyolysis; infiltration of muscle and gut with lymphoma; advanced clinical stage with bulky disease; nonresponsiveness to the reduction of immunosuppression and rituximab monotherapy; expected cardiotoxicity of anthracyclines. Therefore, the patient was treated with the EPOCH-R protocol, which includes continuous administration of doxorubicin over 4 days, instead of R-CHOP, in which the anthracycline is given in a short single infusion. Complete remission was achieved after the third cycle; rhabdomyolysis did not increase and heart function was not affected. The patient received a total of 6 cycles and is still in metabolic complete remission.We conclude that patients with Danon disease can be treated with anthracycline-containing chemotherapy and that continuous infusion of EPOCH-R does not exacerbate pre-existing rhabdomyolysis.

UNLABELLED:The aim of this study was to assess the reproducibility of standard, Dixon-based attenuation correction (MR-AC) in PET/MR imaging. A further aim was to estimate a patient-specific lean body mass (LBM) from these MR-AC data. METHODS:Ten subjects were positioned in a fully integrated PET/MR system, and 3 consecutive multibed acquisitions of the standard MR-AC image data were acquired. For each subject and MR-AC map, the following compartmental volumes were calculated: total body, soft tissue (ST), fat, lung, and intermediate tissue (IT). Intrasubject differences in the total body and subcompartmental volumes (ST, fat, lung, and IT) were assessed by means of coefficients of variation (CVs) calculated across the 3 consecutive measurements and, again, across these measurements but excluding those affected by major artifacts. All subjects underwent a body composition measurement using air displacement plethysmography (ADP) that was used to calculate a reference LBMADP A second LBM estimate was derived from available MR-AC data using a formula incorporating the respective tissue volumes and densities as well as the subject-specific body weights. A third LBM estimate was obtained from a sex-specific formula (LBMFormula). Pearson correlation was calculated for LBMADP, LBMMR-AC, and LBMFormula Further, linear regression analysis was performed on LBMMR-AC and LBMADP. RESULTS:The mean CV for all 30 scans was 2.1 ± 1.9% (TB). When missing tissue artifacts were excluded, the CV was reduced to 0.3 ± 0.2%. The mean CVs for the subcompartments before and after exclusion of artifacts were 0.9 ± 1.1% and 0.7 ± 0.7% for the ST, 2.9 ± 4.1% and 1.3 ± 1.0% for fat, and 3.6 ± 3.9% and 1.3 ± 0.7% for the IT, respectively. Correlation was highest for LBMMR-AC and LBMADP (r = 0.99). Linear regression of data excluding artifacts resulted in a scaling factor of 1.06 for LBMMR-AC CONCLUSION: LBMMR-AC is shown to correlate well with standard LBM measurements and thus offers routine LBM-based SUV quantification in PET/MR. However, MR-AC images must be controlled for systematic artifacts, including missing tissue and tissue swaps. Efforts to minimize these artifacts could help improve the reproducibility of MR-AC.

PURPOSE/OBJECTIVE:PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. METHODS:The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. RESULTS:Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT. CONCLUSION/CONCLUSIONS:SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.

BACKGROUND:Patients with gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma require lifelong endoscopic follow-up. This study aimed to establish and evaluate confocal laser endomicroscopy (CLE) criteria for gastrointestinal MALT lymphoma. METHODS:This prospective trial was conducted after IRB approval at the Medical University of Vienna. Twenty-four consecutive patients (14 males and 10 females, median age 65 years) referred for staging or follow-up of (former) gastrointestinal MALT lymphoma underwent endosonography (EUS) and CLE including white light endoscopy (WLE) and conventional biopsy sampling of the upper gastrointestinal tract. CLE criteria of the disease were based on the first five patients with histologically proven MALT lymphoma. All CLE datasets were reviewed separately by two CLE experts. The diagnostic modalities were compared using conventional histology as the gold standard. RESULTS:Sixty-two percentages had a positive diagnosis of MALT lymphoma based on histology. The sensitivity was 80 % for EUS (0.51-0.95), 100 % for WLE (0.75-1) and 93 % for CLE (0.66-1); the specificity was 67 % for EUS (0.31-0.91), 23 % for WLE (0.04-0.60) and 100 % for CLE (0.63-1). The agreement with histology was moderate for EUS (kappa 0.47, p = 0.02), fair for WLE (kappa 0.26, p = 0.06) and almost perfect for CLE (kappa 0.91, p < 0.01). Expert evaluation identified all but one case of MALT lymphoma with excellent interobserver agreement (kappa 0.89, p < 0.01). In the case missed by CLE, MALT lymphoma involvement was restricted to deep tissue structures. CONCLUSIONS:Despite minor technical limitations, CLE is a promising alternative to conventional biopsy sampling in patients with gastrointestinal MALT lymphoma. CLINICALTRIALS. GOV NUMBER:NCT01583699.