Clinical Outcome and Technical Nuances After Resection of Orbital Cavernous Venous Malformations-A Single-Center Experience.

BACKGROUND: Cavernous venous malformations (CVMs) represent the most common benign intraorbital lesions. Enlarging or symptomatic CVMs (progressive proptosis or visual disturbances) are treated by surgical resection. For this, a variety of different surgical approaches have been described. The aim of this study was to present a contemporary series of orbital CVMs treated via open microsurgical approaches. METHODS: In this study, patients who underwent resection of orbital CVMs between 2002 and 2019 were included. Presenting symptoms were noted and neuro-ophthalmologic examinations performed pre- and postoperatively. For surgical resection, the location of the orbital CVM and its relation to the orbital anatomy led to decision-making for appropriate approaches. A comparison between anatomical location and surgical outcome was performed. RESULTS: Overall, 35 patients with orbital CVMs were included. Most common presenting symptoms were progressive proptosis (43%) and visual disturbances (34%). Most common location was the lateral quadrant (37%) followed by the superior quadrant (20%). A subfrontal craniotomy was performed in 40% of cases followed by a supraorbital craniotomy including the orbital rim in 34% of cases. For surgical excision, a cryo-probe was used in 30 patients, and complete resection was feasible in all cases. Location of a CVM within the superior quadrant was associated with improved postoperative recovery of visual acuity. No differences for clinical outcomes were observed depending on the surgical approach. CONCLUSIONS: Resection of orbital CVMs is indicated in patients with visual disturbances or progressive proptosis. In these, microsurgical approaches can be used with minimal morbidity for complete removal of these well-circumscribed lesions.

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

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.

Transformed mucosa-associated lymphoid tissue lymphomas: A single institution retrospective study including polymerase chain reaction-based clonality analysis.

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.

Pre-Therapeutic Total Lesion Glycolysis on [18F]FDG-PET Enables Prognostication of 2-Year Progression-Free Survival in MALT Lymphoma Patients Treated with CD20-Antibody-Based Immunotherapy.

PURPOSE: Standardized uptake values (SUV), total metabolic tumor volumes (TMTV), and total lesion glycolysis (TLG) based on positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]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: Pre-therapeutic [18F]FDG/PET scans of 61 treatment-naïve MALT lymphoma patients, including 35 scheduled for anti-CD20 antibody-based immunotherapy, were included in this retrospective study. SUVmean, SUVmax, TMTV, and TLG were measured and tested for 2-year progression-free survival (PFS) prognostication, using Cox regression analyses. Receiver operating characteristic curves were used to determine optimal cutoffs for prognostic [18F]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.

Treatment of mucosa associated lymphoid tissue lymphoma with a long-term once-weekly regimen of oral azithromycin: Results from the phase II MALT-A trial.

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.

Total thyroidectomy (Tx) versus thionamides (antithyroid drugs) in patients with moderate-to-severe Graves' ophthalmopathy - a 1-year follow-up: study protocol for a randomized controlled trial.

BACKGROUND: Graves' disease (GD) is characterized by thyrotoxicosis and goiter and arises through circulating autoantibodies that bind to, and stimulate, the thyroid hormone receptor (TSHR). A temporal relation between the onset of hyperthyroidism and the onset of ophthalmopathy, a common extrathyroidal manifestation, has been demonstrated. Graves' ophthalmopathy (GO) is typically characterized by an inflammation and expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered for hyperthyroidism caused by Graves' disease: antithyroid drugs (ATD) (thionamides), radioiodine ablation (RAI) and thyroidectomy (Tx). To date, there is no clear recommendation on the treatment of Graves' disease and GO, mainly due to the individuality of the disease in each patient. The aim of the study is to examine the difference in the outcome of GO in patients with moderate-to-severe GO who receive Tx versus further ATD after suffering their first relapse of GO, or in which GO stays the same following the initial decrease in ATD therapy after 6 months. METHODS/DESIGN: This prospective randomized clinical trial with observer-blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: Clinical Activity Score (CAScore), NOSPECS score, superonasal index measurements via ultrasound, and quality of life score. DISCUSSION: This study should allow for better therapeutic choices in patients with moderate-to-severe GO. In addition, it should demonstrate whether the outcome of GO in patients with moderate-to-severe GO is better in those who receive early Tx versus further ATD. Furthermore, this study will aim to establish a standard glucocorticoid scheme before and after Tx in patients with moderate-to-severe EO. TRIAL REGISTRATION: Eudra-CT: 2015-003515-38; Medical University of Vienna Protocol Record 1839/2015. Date of Ethics Committee approval: 19 January 2017. Registered on 27 January 2017.

Immunohistochemical expression of cereblon and MUM1 as potential predictive markers of response to lenalidomide in extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma).

Lenalidomide is an active agent for the treatment of MALT lymphoma. Recently, high expression levels of cereblon (CRBN) and MUM1 have been associated with better response rates in multiple myeloma treated with lenalidomide. However, there are no data on CRBN and MUM1 expression in MALT lymphoma. In the current study, we have systematically investigated a potential correlation of CRBN/MUM1 immunohistochemical expression and response to lenalidomide-based therapy in a series of 46 patients with MALT lymphoma treated at the Medical University Vienna 2009 to 2014. In total, 28% (13/46) of biopsy specimens derived from gastric tissues, while 72% (33/46) originated from extragastric MALT lymphoma. In terms of CRBN, 54% showed high expression (CRBN+, ≥50% positive cells); the remaining 46% were classified as low expression (CRBN-). In contrast to other reports, there was a non-significant trend towards worse response rates in CRBN+ (68% versus 86%, P = 0.161). Relapse rates (P = 0.592) and PFS (P = 0.306) did not differ between CRBN+/CRBN-, but all 3 patients progressing on lenalidomide were CRBN+ and both patients completely lacking CRBN expression responded to treatment. Concerning MUM1, 62% were MUM1-negative (MUM1-) and 38% positive (MUM1+). There was no difference in response to lenalidomide by MUM1-status (MUM1+ 71% versus MUM1- 79%, P = 0.546) and also relapse rates (P = 0.828) and PFS (P = 0.681) did not differ. Interestingly, a subgroup analysis of gastric lymphoma revealed a significantly better PFS for CRBN- and MUM1- patients, respectively (both P < 0.05). To conclude, there was no significant difference in response to lenalidomide between patients with low or high expression of CRBN/MUM1 in a general population of MALT lymphoma, and immunohistochemical CRBN/MUM1 assessment cannot be recommended in the clinical routine.

A pilot phase II study of ofatumumab monotherapy for extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) lymphoma.

These are the final results of the Ofatumumab in MALT lymphoma study (O-MA 1), a pilot phase II trial evaluating the capacity and safety of ofatumumab to induce objective responses in patients with Helicobacter pylori eradication refractory or extragastric MALT lymphoma. Ofatumumab was given at 4 weekly doses (1000 mg) followed by 4 doses at 2-month intervals starting at week 8. According to protocol, a total of 16 patients were recruited (median age 69 years; range 38-85). Thirty one percent (5/16) of patients had primary gastric MALT lymphoma while the remaining 69% (11/16) presented with extragastric manifestations. Seventy-five percent (12/16) had localized lymphoma and 4 patients disseminated disease. The overall response rate to treatment with ofatumumab was 81% (13/16), with the median time to best response being 5.5 months. In detail, 50% (8/16) achieved complete remission; 31% (5/16), partial remission; and 19% (3/16), disease stabilization as best response. However, 1 patient with gastric lymphoma and complete remission at second restaging had a relapse at final assessment but ongoing complete remission during further follow-up. Tolerability was excellent accept low-grade infusion reactions occurring in 86% (14/16). At a median follow-up time of 25 months only 1 patient has relapsed suggesting durable responses in the majority of patients. This pilot trial shows clearly that ofatumumab is active and safe for the treatment of MALT lymphoma.

Can Interim 18F-FDG PET or Diffusion-Weighted MRI Predict End-of-Treatment Outcome in FDG-Avid MALT Lymphoma After Rituximab-Based Therapy?: A Preliminary Study in 15 Patients.

PURPOSE: 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: 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.

Gender Aspects in Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue: Does Sex Matter?

OBJECTIVES: Gender-related aspects have been investigated in a variety of tumor entities including results on sex-specific differences in non-Hodgkin lymphoma. However, there are no data on gender differences in mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: We have analyzed 327 patients treated between 1999 and 2015 with a median follow-up time of 55.2 months. RESULTS: There was a female predominance, with 197 female (60.2%) and 130 male patients (39.8%, female-to-male ratio 1.5). The mean age was comparable between female and male patients (61.2 vs. 61.7 years, p = 0.777). Female patients less frequently had gastric MALT lymphoma (31.5 vs. 39.2%), but this was not statistically significant (p = 0.149). Extragastric manifestations were equally distributed, except for parotid (p = 0.003) and breast lymphoma (n = 8, 100% female) showing a female predominance. This was most likely related to a higher rate of active autoimmune disorders in women (35.6 vs. 11.0%, p < 0.001). ß2-Microglobulin elevation at diagnosis occurred more often in female patients (42.8 vs. 26.0%; p = 0.008). However, this did not translate into a worse progression-free survival for female (56.0 months, 95% CI 30.1-81.9) versus male patients (49.0 months, 95% CI 25.4-72.5, p = 0.433). Overall survival did not differ between groups. CONCLUSION: Our data show surprisingly little differences between female and male patients with MALT lymphoma. Both sexes appeared to have well-balanced clinical features and an identical prognosis.

Does Delayed-Time-Point Imaging Improve 18F-FDG-PET in Patients With MALT Lymphoma?: Observations in a Series of 13 Patients.

PURPOSE: To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed-time-point 2-F-fluoro-2-deoxy-d-glucose-positron emission tomography (F-FDG-PET) performs better than standard-time-point F-FDG-PET. MATERIALS AND METHODS: Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic F-FDG-PET/computed tomography (CT) and consecutive F-FDG-PET/magnetic resonance imaging (MRI), using a single F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective F-FDG-PET scans at time points 1 (45-60 minutes after tracer injection, TP1) and 2 (100-150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed. RESULTS: F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%-84.67%) and 100% (CI, 100%-100%) for F-FDG-PET at TP1; and 87.0% (CI, 73.26%-100%) and 100% (CI, 100%-100%) for F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%-80.9%) for F-FDG-PET at TP1, and 76.9% (CI, 54.0%-99.8%) for F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001). CONCLUSIONS: Delayed-time-point imaging may improve F-FDG-PET in MALT lymphoma.

Evaluation of Diffusion-Weighted Magnetic Resonance Imaging for Follow-up and Treatment Response Assessment of Lymphoma: Results of an 18F-FDG-PET/CT-Controlled Prospective Study in 64 Patients.

PURPOSE: To determine the value of diffusion-weighted MRI (DWI-MRI) for treatment response assessment in 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-avid lymphoma. EXPERIMENTAL DESIGN: Patients with FDG-avid Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at pretherapeutic 18F-FDG-PET/CT, who had also undergone pretherapeutic whole-body DWI-MRI, were included in this prospective study. Depending on the histologic lymphoma subtype, patients received different systemic treatment regimens, and follow-up DWI-MRI and 18F-FDG-PET/CT were performed at one or more time points, depending on the clinical course. For each follow-up DWI-MRI, region-based rates of agreement, and rates of agreement in terms of treatment response (complete remission, partial remission, stable disease, or progressive disease), relative to the corresponding 18F-FDG-PET/CT, were calculated. RESULTS: Sixty-four patients were included: 10 with HL, 22 with aggressive NHL, and 32 with indolent NHL. The overall region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.4%. For the 51 interim examinations (performed after 1-3 therapy cycles), region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.2%, and for the 48 end-of-treatment examinations, agreement was 99.8%. No significant differences, in terms of region-based agreement between DWI-MRI and 18F-FDG-PET/CT, were observed between the three lymphoma groups (HL, aggressive NHL, indolent NHL; P = 0.25), or between interim and end-of-treatment examinations (P = 0.21). With regard to treatment response assessment, DWI-MRI agreed with 18F-FDG-PET/CT in 99 of 102 follow-up examinations (97.1%), with a κ value of 0.94 (P < 0.0001). CONCLUSIONS: In patients with FDG-avid lymphoma, DWI-MRI may be a feasible alternative to 18F-FDG-PET/CT for follow-up and treatment response assessment.

Clinical features, treatment and outcome of mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexa: single center experience of 60 patients.

BACKGROUND: Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date. MATERIAL AND METHODS: We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999-2012. Median age at diagnosis was 64 years (IQR 51-75) and follow-up time 43 months (IQR 16-92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification. RESULTS: The majority of patients presented with stage IE (n = 40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9-39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (p = 0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress. CONCLUSION: Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML.

Evaluation of diffusion-weighted MRI for pretherapeutic assessment and staging of lymphoma: results of a prospective study in 140 patients.

PURPOSE: To determine the value of diffusion-weighted MRI (DWI-MRI) for pretherapeutic imaging of fluorodeoxyglucose (FDG)-avid lymphoma and lymphoma with variable FDG avidity. EXPERIMENTAL DESIGN: Treatment-naïve patients with lymphoma who were referred for whole-body staging were included in this prospective study. Group A included patients with FDG-avid lymphoma (e.g., Hodgkin, diffuse large B-cell, and follicular lymphoma), whereas Group B included patients with lymphoma of variable FDG avidity [e.g., extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)]. All patients underwent DWI-MRI and 18F-FDG- positron emission tomography/computed tomography (PET/CT). Region-based sensitivity and agreement with Ann Arbor staging, relative to the reference standard, were calculated for DWI-MRI, and, in Group B, also 18F-FDG-PET/CT and contrast-enhanced (CE-) CT. RESULTS: In Group A (100 patients), DWI-MRI had a region-based sensitivity of 97%, and with regard to staging, agreed with the reference standard in 94 of 100 patients (κ, 0.92). In Group B (40 patients; 38 MALT lymphomas and 2 small lymphocytic lymphomas/chronic lymphocytic leukemias), DWI-MRI, 18F-FDG-PET/CT, and CE-CT had region-based sensitivities of 94.4%, 60.9%, and 70.7%, respectively. With regard to staging in Group B, DWI-MRI, 18F-FDG-PET/CT, and CE-CT agreed with the reference standard in 37 of 40, 26 of 40, and 24 of 40 patients, with κ values of 0.89, 0.52, and 0.43, respectively. CONCLUSIONS: In patients with FDG-avid lymphoma, DWI-MRI seems to be only slightly inferior to 18F-FDG-PET/CT with regard to pretherapeutic regional assessment and staging. In patients with lymphoma subtypes that show a variable FDG avidity (e.g., MALT lymphoma), DWI-MRI seems to be superior to both 18F-FDG-PET/CT and CE-CT.

Retrospective comparison of the effectiveness of various treatment modalities of extragastric MALT lymphoma: a single-center analysis.

We have performed a retrospective analysis of all patients with extragastric mucosa-associated lymphoid tissue (MALT) lymphoma treated at our institution to compare the efficacy of first-line therapeutic modalities including surgery, radiation, systemic therapy, and antibiotics. One hundred eighty-five patients with extragastric MALT lymphoma with a median age of 63 (interquartile range (IQR) 50-74) years and a median follow-up time of 49 (IQR 18-103) months were retrospectively analyzed. Time to progression and time to next therapy were used as surrogate endpoints for efficacy. Patients having either surgery (100 %), chemo/immunotherapy (85.5 %), or radiation (80 %) had significantly (p = 0.01) higher response rates than patients treated with antibiotics (33.3 %). Patients who were irradiated had significantly more progressive disease, but also the longest follow-up time. Stage, elevated LDH, anemia, elevated beta-2 microglobulin, plasmacytic differentiation, monoclonal gammopathy, or autoimmune disease did not influence the rate of disease progression nor did complete remission or partial remission from initial therapy influence time to and rate of progression. There was no significant difference in the median time to progression (p = 0.141), but the estimated time to progression (p = 0.023) as well as the estimated time to next therapy (p = 0.021) was significantly different among the various cohorts favoring surgery, chemo/immunotherapy, and radiation. Our results suggest extragastric MALT lymphoma as a potential systemic disease irrespective of initial stage. Radiation, surgery, and chemo/immunotherapy seem to be equally effective in achieving remissions and prolonged progression free survivals, but a curative potential is questionable. Localized MALT lymphomas affecting the thyroid gland or the lungs have excellent long-term progression-free survivals with surgical treatment only.

Rituximab plus bendamustine is active in pretreated patients with extragastric marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma).

Recently, the combination of rituximab and bendamustine (R-Benda) has been defined as highly active in patients with follicular lymphomas, but little is known about the efficacy of R-Benda in mucosa-associated lymphoid tissue (MALT) lymphoma. In a retrospective analysis, we have defined 14 patients with MALT lymphoma undergoing therapy with R-Benda. Seven patients were female and seven male (aged 44-88 years), and all had relapsed extragastric MALT lymphoma. R-Benda was given at first relapse in ten patients, while four patients had more than two prior forms of therapy. Bendamustine was given at a dose of 90 mg/m(2) on days 2 and 3 in ten patients and at 70 mg/m(2) in three patients, while all received 375 mg/m(2) rituximab on day 1. Ten patients received six courses of therapy, while two patients discontinued therapy after three, and one after four courses for personal reasons, while one patient had progressive disease after four courses. Tolerance of therapy was excellent, and all except one patient responded. Ten patients achieved a complete remission (CR) (71 %), three a partial remission (21 %), while one patient progressed. Toxicities were mild and mainly hematological but did not result in relevant delays or the necessity for dose reductions. After a median follow-up of 23 months (range, 4-42+), 13 patients are alive and one patient has relapsed 23 months after initial CR. Our data suggest high activity and good tolerance of R-Benda in patients with relapsed MALT lymphoma despite intensive pretreatment in some patients. In view of this, prospective studies are warranted.

Bilateral common carotid artery occlusion as an adequate preconditioning stimulus to induce early ischemic tolerance to focal cerebral ischemia.

There is accumulating evidence, that ischemic preconditioning - a non-damaging ischemic challenge to the brain - confers a transient protection to a subsequent damaging ischemic insult. We have established bilateral common carotid artery occlusion as a preconditioning stimulus to induce early ischemic tolerance to transient focal cerebral ischemia in C57Bl6/J mice. In this video, we will demonstrate the methodology used for this study.

A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma).

Mucosa associated lymphoid tissue lymphoma shares certain features with multiple myeloma. In view of this and the activity of lenalidomide in various B-cell lymphomas, we have initiated a phase II study of lenalidomide in patients with mucosa associated lymphoid tissue lymphoma. Patients with histologically verified advanced stages of this lymphoma were included in the study. Treatment consisted of oral lenalidomide 25 mg Days 1-21, with a 7-day break after each cycle. A total of 18 patients were included in the trial: 5 had gastric and 13 had extragastric mucosa associated lymphoid tissue lymphoma, but 2 discontinued therapy during the first course of therapy. In the intent to treat analysis, an overall response rate of 61% was seen (11 of 18; 6 complete and 5 partial remissions). Three patients had stable disease while 2 progressed. Side effects were manageable and included neutropenia (grade III in 3 patients) as the leading hematotoxicity. After a median follow up of 20.3 months, one patient has died from lymphoma while the remaining patients are alive and relapse-free. These data suggest activity of lenalidomide monotherapy in mucosa associated lymphoid tissue lymphoma. The study protocol had been approved by the Ethical Board of the Medical University Vienna (EK-No.: 146/09), and before opening the trial, it had been registered at www.clinicaltrials.gov. (identifier: NCT00923663).