Publications by authors named "Barbara Kiesewetter"

77 Publications

Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematological Cancers and Identifies Exceptional Responders.

Cancer Discov 2021 Oct 11. Epub 2021 Oct 11.

Platform Austria for Chemical Biology, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences.

Personalized medicine aims to match the right drug with the right patient by utilizing specific features of the individual patients' tumor. However, current strategies of personalized therapy matching only provide treatment opportunities for less than 10% of cancer patients. A promising method may be drug profiling of patient biopsies with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival (PFS) compared to their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude, that therapy matching by scFPM is clinically feasible, and effective in advanced aggressive hematologic cancers.
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http://dx.doi.org/10.1158/2159-8290.CD-21-0538DOI Listing
October 2021

What you always wanted to know about gastric MALT-lymphoma: a focus on recent developments.

Ther Adv Med Oncol 2021 23;13:17588359211033825. Epub 2021 Jul 23.

Division of Oncology, Internal Medicine I, Medical University of Vienna, Vienna, Austria.

The stomach is the most common site of origin for extranodal lymphomas, with extranodal marginal zone B-cell of the mucosa associated lymphoid tissue (MALT-lymphoma) being the predominant subtype. MALT-lymphoma develops in mucosa associated lymphoid structures acquired by infection or chronic antigenic stimuli and may therefore arise in almost any organ of the human body. In spite of histopathologic similarities between various organs upon first glance, recent findings suggest pronounced differences between different sites, with a variety of features specific to gastric MALT-lymphoma. The objective of this review is to sum up the current knowledge on pathogenesis, molecular pathology, clinical presentation and therapeutic approaches to gastric MALT-lymphoma with in-depth discussion of recent developments.
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http://dx.doi.org/10.1177/17588359211033825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491302PMC
July 2021

CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line H. pylori eradication.

Blood 2021 Sep 15. Epub 2021 Sep 15.

Medical University of Vienna, Vienna, Austria.

Post-treatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate PET with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow-up biopsies for assessment of residual disease (non-complete remission (CR)) after first-line H. pylori (HP) eradication. Forty-six post-HP eradication [68Ga]Pentixafor-PET/MRI examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard, and showed CR in six cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive value of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up, were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r=0.51 and r=0.52 (P=0.008 and P=0.006). In conclusion, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after HP eradication.
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http://dx.doi.org/10.1182/blood.2021013239DOI Listing
September 2021

Management of adrenocortical carcinoma: are we making progress?

Ther Adv Med Oncol 2021 31;13:17588359211038409. Epub 2021 Aug 31.

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.

Adrenocortical carcinoma (ACC) is a rare malignancy characterized by aggressive biology and potential endocrine activity. Surgery can offer cure for localized disease but more than half of patients relapse and primary unresectable or metastasized disease is frequent. Prognosis of metastatic ACC is still limited, with less than 15% of patients alive at 5 years. Recent advances in understanding the molecular profile of ACC underline the high complexity of this disease, which is characterized by limited drugable molecular targets as well as by a complex interplay between a yet scarcely understood microenvironment and potential endocrine activity. Particularly steroid-excess further complicates therapeutic concepts such as immunotherapy, which have markedly improved outcome in other disease entities. To date, mitotane remains the only approved drug for adjuvant and palliative care in ACC. Standard chemotherapy-based protocols with cisplatin, doxorubicin and etoposide offer only marginal improvement in long-term outcome and the number of clinical trials conducted is low due to the rarity of the disease. In the current review, we summarize principles of oncological management for ACC from localized to advanced disease and discuss novel therapeutic strategies, including targeted therapies such as tyrosine kinase inhibitors and antibodies, immunotherapy with a focus on checkpoint inhibitors, individualized treatment concepts based on molecular characterization by next generation sequencing methods, the role of theranostics and evolvement of adjuvant therapy.
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http://dx.doi.org/10.1177/17588359211038409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411624PMC
August 2021

Genetic Characterization and Clinical Features of Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Cancers (Basel) 2021 Jun 15;13(12). Epub 2021 Jun 15.

Department of Pathology, Division of Cellular and Molecular Pathology, University of Cambridge, Cambridge CB2 1TN, UK.

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive.

Methods: A total of 57 cases of negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes.

Results: translocation, most likely t(11;18)(q21;q21)/ was detected in 39% (22/57) cases, and translocation was further seen in 12 -negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways ( = 23%, = 9%, = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from , albeit not translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy ( = 0.004).

Conclusion: negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.
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http://dx.doi.org/10.3390/cancers13122993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232676PMC
June 2021

A phase II study of the PI3K inhibitor copanlisib in combination with the anti-CD20 monoclonal antibody rituximab for patients with marginal zone lymphoma: treatment rationale and protocol design of the COUP-1 trial.

BMC Cancer 2021 Jun 29;21(1):749. Epub 2021 Jun 29.

Department of Internal Medicine III, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.

Background: Advanced stage marginal zone lymphoma (MZL) is an incurable indolent B-cell lymphoma, for which a wide variety of treatments ranging from single agent rituximab to more dose intense immunochemotherapy exists. One of the major goals in this palliative setting is to develop chemotherapy-free treatments, which approach the efficacy of immunochemotherapies, but avoid chemotherapy associated toxicity in this often elderly patient population. The PI3K inhibitor copanlisib has recently shown remarkable clinical activity in refractory or relapsed indolent B-cell lymphomas, among them MZL. Based on these data, copanlisib monotherapy was granted breakthrough designation by the FDA for the treatment of adult patients with relapsed marginal zone lymphoma who have received at least two prior therapies. However, data are still limited in particular for MZL. Based on this, the COUP-1 trial aims at testing the toxicity and efficacy of copanlisib in combination with rituximab in treatment naive and relapsed MZL.

Methods: COUP-1 is a prospective, multicenter, single-arm, open-label, non-randomized phase II trial of 6 cycles (28 days cycle) of copanlisib (60 mg intravenous day 1, 8, 15) and rituximab (375 mg/m intravenous day 1) in the induction phase followed by a maintenance phase of copanlisib (d1, d15 every 4 weeks for a maximum of 12 cycles) and rituximab (d1 every 8 weeks for a maximum of 12 cycles) in patients aged ≥18 years with previously untreated or relapsed MZL in need of treatment. A total of 56 patients are to be enrolled. Primary endpoint is the complete response (CR) rate determined 12 months after start of induction therapy. Secondary endpoints include the overall response (OR) rate, progression free survival (PFS), overall survival (OS), safety and patient related outcome with quality of life. The study includes a translational bio-sampling program with the prospect to measure minimal residual disease. The study was initiated in November 2019.

Discussion: The COUP-1 trial evaluates the efficacy and toxicity of the treatment of copanlisib in combination with rituximab in patients with MZL and additionally offers the chance for translational research in this heterogenous type of lymphoma.

Trial Registration: ClinicalTrials.gov : NCT03474744 . Registration date: 03/23/2018.
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http://dx.doi.org/10.1186/s12885-021-08464-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243426PMC
June 2021

How can we assess and measure prognosis for MALT lymphoma? A review of current findings and strategies.

Expert Rev Hematol 2021 Apr 2;14(4):391-399. Epub 2021 Apr 2.

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.

Introduction: : MALT (mucosa associated lymphoid tissue) lymphoma is a distinct type of B-cell lymphoma characterized by extranodal manifestation and an indolent clinical course with 10-year survival rates up to 90%. However, transformation to aggressive lymphoma may occur and treatment is indicated in case of symptomatic or progressive disease.

Areas Covered: : This review covers clinical and biological features potentially related to prognosis and outcome of MALT lymphoma patients, as well as available prognostic tools and risk stratification systems with a focus on the MALT-IPI (international prognostic index) and the POD24 (progression of disease at 24 months) cohort. In addition, we address the role of watch-and-wait, the importance of defining the optimal time point for treatment initiation and the relevance of depth of remission, which appear to be some of the central questions for physicians involved in the care of MALT lymphoma patients. A computerized database search using PubMed® was performed to identify available publications on prognostic factors and risk stratification tools in MALT lymphoma.

Expert Opinion: : Despite the development of disease-specific risk stratification systems, there is no clear concept how to measure prognosis and tailor treatment. Careful observation of the individual clinical course is essential to assess the optimal time point of treatment initiation and avoid overtreatment, particularly in patients with disseminated disease. In addition, early detection of patients with histological transformation is necessary, as these patients face a poor prognosis.
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http://dx.doi.org/10.1080/17474086.2021.1909468DOI Listing
April 2021

CXCR4 PET imaging of mantle cell lymphoma using [Ga]Pentixafor: comparison with [F]FDG-PET.

Theranostics 2021 1;11(2):567-578. Epub 2021 Jan 1.

Dept. of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Austria.

For PET imaging of mantle cell lymphoma (MCL), [F]FDG (2-deoxy-2-[F]fluoro-D-glucose) is the currently recommended radiotracer, although uptake is variable and bone marrow evaluation is limited. In this prospective study, we evaluated the novel CXCR4 (G-protein-coupled C-X-C chemokine receptor type 4) tracer [Ga]Pentixafor in MCL patients, and compared it to [F]FDG. MCL patients underwent [Ga]Pentixafor-PET/MRI, and, if required for routine purposes, also [F]FDG-PET/MRI, before treatment. PET was evaluated separately for 23 anatomic regions (12 lymph node stations and 11 organs/tissues), using MRI as the main reference standard. Standardized uptake values (SUV and SUV) and tumor-to-background ratios (TBR and TBR) were calculated. General Estimation Equations (GEE) were used to compare [Ga]Pentixafor-PET and [F]FDG-PET sensitivities and positive predictive values (PPV). For bone marrow involvement, where biopsy served as the main reference standard, and splenic involvement, receiver operating characteristic curves were used to determine the optimal SUV and TBR cut-off values, and areas under the curve (AUC) were calculated. Twenty-two MCL patients were included. [Ga]Pentixafor-PET sensitivity (100%) was significantly higher than for [F]FDG-PET (75.2%) (<0.001), and PPV was slightly, but not significantly lower (94.0%.vs. 96.5%; =0.21). SUVs and TBRs were significantly higher for [Ga]Pentixafor-PET than for [F]FDG-PET (<0.001 in all cases); the greatest difference was observed for mean TBR, with 4.9 for [Ga]Pentixafor-PET and 2.0 for [F]FDG-PET. For bone marrow involvement, [Ga]Pentixafor-PET SUV showed an AUC of 0.92; and for splenic involvement, TBR showed an AUC of 0.81. [Ga]Pentixafor-PET may become an alternative to [F]FDG-PET in MCL patients, showing clearly higher detection rates and better tumor-to-background contrast.
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http://dx.doi.org/10.7150/thno.48620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738870PMC
August 2021

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

Cancers (Basel) 2020 Nov 26;12(12). Epub 2020 Nov 26.

Department of Medicine I, Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria.

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%, 0.01) and the complete remission rate (75% vs. 43%, 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, = 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.
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http://dx.doi.org/10.3390/cancers12123533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761357PMC
November 2020

Early progression of disease predicts shorter survival in MALT lymphoma patients receiving systemic treatment.

Haematologica 2020 11 1;105(11):2592-2597. Epub 2020 Nov 1.

Division of Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.

Early progression of disease (POD) within two years from diagnosis is linked with poor overall survival (OS) in follicular lymphoma but its prognostic role is less clear in extranodal marginal zone B-cell lymphoma (EMZL). We sought to identify prognostic factors associated with early POD and to determine whether is associated with inferior OS. We analyzed the impact of early POD in the IELSG19 clinical trial dataset (training set of 401 patients randomly assigned to chlorambucil or rituximab or chlorambucil plus rituximab). Reproducibility was examined in a validation set of 287 patients who received systemic treatment. In both sets, we excluded from the analysis the patients who, within 24 months from treatment start, died without progression or were lost to follow-up without prior progression. OS was calculated from progression in patients with early POD and from 24 months after start of treatment in those without (reference group). Early POD was observed in 69 of the 384 (18%) evaluable patients of the IELSG19 study. Patients with high-risk MALT-IPI were more likely to have early POD (p=0.006). The 10-year OS rate was 64% in the early POD group and 85% in the reference group (HR= 2.42, 95%CI, 1.35-4.34; log-rank P=0.002). This prognostic impact was confirmed in the validation set, in which early POD was observed in 64 out of 224 (29%) evaluable patients with 10-year OS rate of 48% in the early POD group and 71% in the reference group (HR= 2.15, 95%CI, 1.19-3.90; log-rank P=0.009). In patients with EMZL who received front-line systemic treatment, early POD is associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.
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http://dx.doi.org/10.3324/haematol.2019.237990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604574PMC
November 2020

Thirteen-year analyses of medical oncology outpatient day clinic data: a changing field.

ESMO Open 2020 10;5(5):e000880

Division of Oncology, Department for Medicine I, Medical University of Vienna, Wien, Austria.

Background: Novel treatment modalities like targeted therapy and immunotherapy are currently changing treatment strategies and protocols in the field of medical oncology.

Methods: Numbers of patients and patient contacts admitted to medical oncology day clinics of a large European academic cancer centre in the period from 2006 to 2018 were analysed using our patient administration system.

Results: A patient cohort of 9.870 consecutive individual patients with 125.679 patient contacts was descriptively and retrospectively characterised. Mean age was 59.9 years. A substantial increase in both individual patients treated per year (+45.4%; 2006: 1.100; 2018: 1.599) and annual patient contacts (+63.3%; 2006: 8.857; 2018: 14.467) between 2006 and 2018 was detected. Hence and most interestingly, the ratio of visits per patient increased by approximately one visit per patient per year over the last 12 years (+12.4%; 2006: 8.0; 2018: 9.0). Further, a decrease of patient contacts in more prevalent entities like breast cancer was found, while contacts for orphan diseases like myeloma and sarcoma increased substantially. Interestingly, female patients showed more per patient contacts as compared with men (13.5 vs 11.9). Lastly, short-term safety data of outpatient day clinic admissions are reported.

Conclusions: We present a representative and large set of patient contacts over time that indicates an increasing load in routine clinical work of outpatient cancer care. Increases observed were highest for orphan diseases, likely attributed to centralisation effects and increased treatment complexity.
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http://dx.doi.org/10.1136/esmoopen-2020-000880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555099PMC
October 2020

How I treat neuroendocrine tumours.

ESMO Open 2020 08;5(4)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Vienna, Austria.

Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the latter allowing the use of targeted therapeutic concepts. Currently accepted treatment strategies for advanced well-differentiated NET include somatostatin analogues octreotide and lanreotide, peptide receptor radionuclide therapy using radiolabelled somatostatin analogues, mammalian target of Rapamycin inhibitor everolimus, tyrosine kinase inhibitor sunitinib, interferon alpha and classical cytostatic, such as streptozotocin-based and temozolomide-based treatment. Indication, use and approval of these treatments differ based on primary tumour origin, grading and symptomatic burden and require an optimised multidisciplinary cooperation of medical oncologists, endocrinologists and nuclear medicine specialists. Interestingly, hot topics in oncology including immunotherapy and use of next-generation-sequencing techniques currently play a minor role for the treatment of NETs. The recent revision of the WHO classification including the recognition of the novel NET G3 category allows for potentially more tailored treatment strategies in the near future. However, this new entity also poses a therapeutic challenge as only limited data are currently available. The present article aims to provide an overview on our personal treatment concepts for advanced NETs with a focus on tumours of gastroenteropancreatic origin.
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http://dx.doi.org/10.1136/esmoopen-2020-000811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440715PMC
August 2020

How I treat MALT lymphoma: 'a subjective interpretation of the gospel according to Isaacson….'

ESMO Open 2020 07;5(4)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Wien, Austria.

Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) is an indolent B-cell lymphoma characterised by a fascinating interplay between chronic antigenic stimulation, an immune response insufficient for elimination of the antigen and a mucosal 'battleground'. The archetype of this association is infection of the gastric mucosa with (): a single course of antibiotic -eradication treatment may result in long-term remission in up to 80% of patients and is the gold standard for first-line therapy of -associated gastric MALT lymphoma. In extragastric or disseminated disease, treatment options range from wait and see in asymptomatic individuals to radiotherapy in localised stages, anti-CD20-antibodies in patients with low symptomatic burden and chemotherapy-based treatment or radio-immunotherapy in symptomatic disease. In addition, more refined immunomodulatory strategies beyond simple eradication of bacteria such as long-term use of the macrolide clarithromycin or the immunomodulatory drug lenalidomide are active. In view of the indolent clinical course, the least toxic individual treatment should be chosen in a disease usually not influencing overall survival in affected patients.
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http://dx.doi.org/10.1136/esmoopen-2020-000812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388885PMC
July 2020

Immunomodulatory treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma).

Hematol Oncol 2020 Oct 23;38(4):417-424. Epub 2020 Jun 23.

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma has been characterized as a dynamic process driven by lymphoma cell dependency on T-cell signaling, chronic antigenic stimulation of marginal zone B-cells and activation of the nuclear factor-kappa B signaling pathway. This concept is underlined by the strong causal connection of chronic Helicobacter pylori associated gastritis and MALT lymphoma development based on perpetual auto-antigenic stimulation of Helicobacter pylori-specific T-cells, but also its association with further potential infectious triggers and autoimmune disorders for extragastric lymphoma sites. Thus, given the dependency of MALT lymphoma cells on the tumor microenvironment, this specific entity appears highly suitable for immunomodulatory treatment strategies. Several approaches have been assessed in the last years including promising data on immunomodulatory agents "IMiDs" thalidomide and lenalidomide, macrolide antibiotics and antibodies. The aim of the present review is to discuss rationales for immunomodulatory therapies in MALT lymphoma and to present the statu quo on immunomodulatory and therefore chemotherapy-free treatment strategies for these patients.
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http://dx.doi.org/10.1002/hon.2754DOI Listing
October 2020

Experience with clarithromycin as antineoplastic therapy for extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT-lymphoma) outside of clinical trials: Real-world data from the University of Vienna.

Hematol Oncol 2020 Aug 29;38(3):409-411. Epub 2020 Apr 29.

Department of Internal Medicine I, Clinical Division of Oncology, Medical University Vienna, Vienna, Austria.

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http://dx.doi.org/10.1002/hon.2738DOI Listing
August 2020

Depth of Remission Following First-Line Treatment Is an Independent Prognostic Marker for Progression-Free Survival in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

Cancers (Basel) 2020 Feb 20;12(2). Epub 2020 Feb 20.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria.

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). : 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. : All patients with ()-positive, localized disease received 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, < 0.001). This was also applicable to the eradication only cohort (49.0 vs. 17.3 months, < 0.001) and remained significant after correction for MALT-IPI. Furthermore, CR significantly prolonged PFS over PR ( = 0.007 entire cohort, = 0.020 eradication). Remission status correlated significantly with PFS, suggesting depth of remission as prognostic marker for long-term relapse-free survival.
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http://dx.doi.org/10.3390/cancers12020492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072189PMC
February 2020

EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies.

ESMO Open 2020 01;5(1)

Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Zuid-Holland, The Netherlands.

Objective: Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).

Methods: Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies.

Results: In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described.

Conclusions: Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials.
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http://dx.doi.org/10.1136/esmoopen-2019-000611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003483PMC
January 2020

RECIL versus Lugano for Treatment Response Assessment in FDG-Avid Non-Hodgkin Lymphomas: A Head-to-Head Comparison in 54 Patients.

Cancers (Basel) 2019 Dec 18;12(1). Epub 2019 Dec 18.

Department of Biomedical Imaging and Image-guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, 1090 Vienna, Austria.

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), [F]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.
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http://dx.doi.org/10.3390/cancers12010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016710PMC
December 2019

Awareness of predatory journals and open access among medical oncologists: results of an online survey.

ESMO Open 2019 27;4(6):e000580. Epub 2019 Nov 27.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.

Introduction: Predatory journals harm the integrity of science as principles of 'good scientific practice' are bypassed by omitting a proper peer-review process. Therefore, we aimed to explore the awareness of predatory journals among oncologists.

Methods: An online survey among oncologists working in Germany or Austria of various professional surroundings was conducted between October 2018 and April 2019.

Results: One hundred and eighty-eight participants (55 women (29.2%), 128 men (68.1%)) completed the questionnaire. 41 (21.8%) participants indicated to work in a hospital, 24 (12.8%) in private practice and 112 (59.6%) in a university hospital. 98.9% of participants indicated to actively read scientific articles and consider them in clinical decision-making (96.3%). 90.4% of participants indicated to have scientific experience by publishing papers in journals with peer-review system. The open-access system was known by 170 (90.4%), predatory journals by 131 (69.7%) and Beall's list by 52 participants (27.7%). Predatory journals were more likely to be known by participants with a higher number of publications (p<0.001), with more high-impact publications (p=0.005) and with recent publications (p<0.001). Awareness of predatory journals did not correlate with gender (p=0.515) or translation of scientific literature into clinical practice (p=0.543).

Conclusions: The problematic topic of 'predatory journals' is still unknown by a considerable amount of oncologist, although the survey was taken in a cohort of oncologists with scientific experience. Dedicated educational initiatives are needed to raise awareness of this problem and to aid in the identification of predatory journals for the scientific oncology community.
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http://dx.doi.org/10.1136/esmoopen-2019-000580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890386PMC
June 2020

PET/MRI versus PET/CT in oncology: a prospective single-center study of 330 examinations focusing on implications for patient management and cost considerations.

Eur J Nucl Med Mol Imaging 2020 01 13;47(1):51-60. Epub 2019 Aug 13.

Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.

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: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [F]FDG, [Ga]Ga-DOTANOC, or [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.
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http://dx.doi.org/10.1007/s00259-019-04452-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885019PMC
January 2020

Prolonged follow-up on lenalidomide-based treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)-Real-world data from the Medical University of Vienna.

Hematol Oncol 2019 Oct 28;37(4):345-351. Epub 2019 Jul 28.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1002/hon.2647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899635PMC
October 2019

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

Br J Haematol 2019 08 24;186(3):448-459. Epub 2019 May 24.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1111/bjh.15953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771836PMC
August 2019

Is there a reliable size cut-off for splenic involvement in lymphoma? A [18F]FDG-PET controlled study.

PLoS One 2019 8;14(3):e0213551. Epub 2019 Mar 8.

Department of Biomedical Imaging and Image-guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Vienna, Austria.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213551PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407760PMC
December 2019

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

Mol Imaging Biol 2019 12;21(6):1192-1199

Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Purpose: Standardized uptake values (SUV), total metabolic tumor volumes (TMTV), and total lesion glycolysis (TLG) based on positron emission tomography with 2-deoxy-2-[F]fluoro-D-glucose ([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: Pre-therapeutic [F]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 [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.
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http://dx.doi.org/10.1007/s11307-019-01329-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604829PMC
December 2019

Gastrointestinal Involvement in Patients with Mantle Cell Lymphoma: A Single Center Experience of Eighty-Five Patients.

Dig Dis 2019 24;37(3):194-200. Epub 2019 Jan 24.

Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Background: The frequency of endoscopically apparent gastrointestinal tract (GI) involvement in patients with mantle cell lymphoma (MCL) at diagnosis is thought to be in the range of 30%. While reports on GI involvement in MCL patients exist, most series lack a strict GI assessment due to the often asymptomatic nature of GI involvement. Owing to the standardized staging routine at our institution including GI assessment at diagnosis, we have analyzed the rate and prognostic impact of GI involvement in MCL.

Methods: In this retrospective single-center evaluation, we have investigated GI involvement in 85 consecutive patients with MCL. All data were collected from clinical records.

Results: MCL with and without endoscopically detectable GI involvement was reported in 29 (34%) patients and 56 patients (66%), respectively. The colon was involved in 21 (72%) and the stomach in 8 (28%). Eight of 29 patients (28%) had symptomatic GI involvement, and the primary diagnosis had been established in the GI tract in 3/29 (10%) of our patients. No statistical differences could be observed between both groups in terms of gender (p = 0.474), Eastern Cooperative Oncology Group (0.428), and MCL international prognostic index (0.543). Overall survival was longer in patients with GI involvement (116.0 vs. 74 months), but not statistically significant (p = 0.825).

Conclusions: In our single center cohort, we did not find a clinical impact of GI involvement on the clinical course of MCL and no GI complications occurred during chemotherapy in these patients. As most patients were also asymptomatic, these data argue against a routine GI assessment in patients diagnosed with MCL.
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http://dx.doi.org/10.1159/000496508DOI Listing
March 2019

My burning issues in neuroendocrine tumours (NET).

Memo 2018 8;11(4):313-316. Epub 2018 Nov 8.

1Department of Internal Medicine I, Division of Oncology, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Several compounds have recently been approved for the systemic treatment of advanced well-differentiated neuroendocrine tumours (NET) of gastroenteropancreatic (GEP) or lung origin. Based on the PROMID and CLARINET trials, somatostatin analogues (SSA) are the preferred first-line approach for all GEP-NET and offer-in addition to antiproliferative effects-durable symptomatic relief for hormonally active tumours. The mTOR inhibitor everolimus has been approved for progressive GEP- and lung-NET and is a widely used drug in this setting. Furthermore, recent results have underlined the high efficacy of somatostatin-receptor targeting radionuclide therapy (PRRT) in somatostatin-receptor positive midgut tumours and PRRT is now considered standard treatment for midgut-NET progressing on SSA. The optimal application of PRRT in somatostatin receptor positive NET with non-midgut site is currently an issue of discussion and should be decided on an individually basis in multidisciplinary boards. Following new insights in the genetic landscape of NET, "hot topics" in recent months include optimal treatment of the recently defined NET G3 and preliminary data on immunotherapy.
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http://dx.doi.org/10.1007/s12254-018-0449-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280958PMC
November 2018

Successful retreatment with 3-week rituximab-bendamustine with high-dose dexamethasone in patients with relapsed/refractory mantle cell lymphoma.

Ann Hematol 2019 Jun 13;98(6):1519-1520. Epub 2018 Dec 13.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.

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http://dx.doi.org/10.1007/s00277-018-3588-yDOI Listing
June 2019

Oral Ondansetron Offers Effective Antidiarrheal Activity for Carcinoid Syndrome Refractory to Somatostatin Analogs.

Oncologist 2019 02 31;24(2):255-258. Epub 2018 Aug 31.

Division of Oncology, Department of Internal Medicine I, Medical University Vienna, Vienna, Austria

Objectives: Somatostatin analogs (SSAs) are standard for symptomatic patients with neuroendocrine tumors (NETs). However, most patients experience tachyphylaxis, and limited options exist for this so-called "refractory carcinoid syndrome." Recently, 5-HT antagonist ondansetron has been associated with reduction of bowel movement in a small series. The aim of this analysis was to assess effectiveness of ondansetron for symptomatic treatment of carcinoid syndrome.

Design And Patients: We have analyzed patients given ondansetron as bridging therapy for refractory carcinoid syndrome. The dose was 2 × 8 mg for 5 days, followed by reduction to 1 × 8 mg in case of benefit.

Results: A total of 14 patients with small bowel NETs metastatic to the liver were identified. All patients had been treated with SSAs for a median time of 18 months before aggravation of diarrhea. One patient had to be excluded because of an underlying infectious cause of diarrhea. The median number of daily bowel movements was 7 (range, 5-13) before initiation of therapy. At this time, seven patients had stable disease, whereas six patients showed radiological progression with symptomatic breakthrough. All 13 patients were scheduled for salvage therapy. Remarkably, in 85% (11/13) ondansetron resulted in a clinically relevant decrease of bowel movements to a median of 3 (1-4). The median time of ondansetron intake was 29 days (7 days to 29 months). In four patients, diarrhea recurred after initial improvement at an interval of 22-43 days, whereas the remaining seven had an ongoing benefit, including two long-term responders who refused further therapy because of pronounced decrease of symptoms (ondansetron for 14+ and 29+ months).

Conclusion: Ondansetron offers symptomatic relief in the majority of patients. Although there was no influence on 5-HIAA levels, evidence from two patients suggests prolonged benefit.

Implications For Practice: Somatostatin analogs are standard treatment in patients with carcinoid syndrome and have an overall response rate of up to 50%. This symptomatic benefit, however, is lost in many patients because of the development of tachyphylaxis or tumor progression. Patients with this "refractory carcinoid syndrome" pose a therapeutic challenge and are sometimes faced with a detrimental effect on quality of life. In this article, the authors suggest the 5-HT receptor antagonist ondansetron as potential symptomatic therapy for patients with refractory diarrhea due to carcinoid syndrome. Although the number of patients in this retrospective series is limited, treatment was easily applicable, feasible, and safe and resulted in an ongoing symptomatic benefit in 85% of patients, including two long-term responders.
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http://dx.doi.org/10.1634/theoncologist.2018-0191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369958PMC
February 2019

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.

Hematol Oncol 2019 Feb 19;37(1):22-26. Epub 2018 Sep 19.

Department of Medicine 1, Division of Oncology, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1002/hon.2555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585850PMC
February 2019

Successful Clarithromycin Monotherapy in a Patient with Primary Follicular Lymphoma of the Duodenum.

Case Rep Oncol 2018 Jan-Apr;11(1):239-245. Epub 2018 Apr 11.

Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Primary follicular lymphoma of the duodenum (FL-D) constitutes a rare subtype of extranodal follicular lymphoma with a usually indolent course. To date, no distinct treatment recommendations have been defined for those patients. We report the case of a 58-year-old male patient presenting with endoscopically assessed, symptomatic FL-D who was treated with clarithromycin monotherapy in analogy to recent data for mucosa-associated lymphoid tissue lymphoma. Each treatment cycle consisted of clarithromycin 500 mg twice daily for 3 weeks followed by a 2-week break. After four cycles of treatment, the patient showed a very good response with normal macroscopic findings confirmed by endosonographic examination and only focal minimal residual disease of lymphoma persisting in the histological assessment. The patient is currently asymptomatic and without treatment for 24+ months. As clarithromycin combines antimicrobial and direct antiproliferative effects mediated through a variety of pleiotropic mechanisms, this appears to be an interesting treatment approach for indolent lymphoma, particularly in those where a chronic infectious background cannot be completely ruled out, i.e., gastrointestinal manifestations. We suggest further investigation of this treatment approach.
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http://dx.doi.org/10.1159/000488388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968239PMC
April 2018
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