Prevalence and biopsychosocial indicators of fatigue in cancer patients.

INTRODUCTION: Symptoms of cancer-related fatigue (CRF) can have a significant impact on patients' quality of life and treatment adherence. We aimed to investigate the relationship between CRF and multiple psychosocial and somatic indicators within a large mixed cancer sample. METHODS: In this cross-sectional study, N = 1787 outpatients with cancer were assessed for CRF, pain, anxiety, and depression using validated screening instruments. We further obtained clinical parameters (Hb, CRP, creatinine, leukocytes, ASAT, and ALAT), sociodemographic data (age, gender, income, education level, marital status, parenthood, and living area), and lifestyle factors. Multivariate linear regression models were applied to estimate the impact of each indicator on CRF. RESULTS: Overall, 90.6% of patients experienced some CRF, with 14.8% experiencing severe CRF. No gender difference was found in the prevalence of CRF. Patients with higher levels of pain, depressive symptoms, and lower Hb levels had significantly higher levels of CRF (ps <0.001). Lower levels of CRF were observed in patients who had children (p = 0.03), had less education (p < 0.001), and were physically active for more than 2 h per week before their oncological diagnosis (p = 0.014). The latter was only a significant indicator in the male subsample. CONCLUSION: The present results demonstrate a high prevalence of CRF and highlight that not only somatic and psychosocial factors, but also lifestyle factors prior to diagnosis appear to be associated with the etiology and persistence of CRF. To effectively treat CRF, a biopsychosocial, personalized approach is recommended.

[Current developments in the treatment of neuroendocrine tumors]. / Aktuelle Entwicklungen in der Behandlung neuroendokriner Tumoren.

BACKGROUND: Well-differentiated neuroendocrine tumors (NET) are rare malignancies that are clinically very heterogeneous. Accordingly, their treatment is also complex and dependent on various factors. With currently available systemic therapies, the prognosis is often favorable. OBJECTIVES: This article aims to provide an overview of current treatment strategies for NET, addressing the most important NET locations. METHODS: The current European guidelines and further relevant literature on the treatment of NET were reviewed for this purpose. RESULTS: The therapeutic spectrum for NET is extremely broad: For NET of the stomach/duodenum, appendix, and rectum, endoscopic or surgical resection is often sufficient, and metastatic tumors are rare. NET of the pancreas, small intestine and lung should also undergo potentially curative resection in the early stages. In the metastatic stage, locoregional treatments such as surgery and liver tumor embolization play a role. Major advances have been made in drug therapy, with somatostatin analogs (octreotide and lanreotide), an mTOR inhibitor (everolimus), and a tyrosine kinase inhibitor (sunitinib) being widely used. Peptide receptor radionuclide therapy (PRRT) is also an invaluable option. In some cases, classic chemotherapy is indicated. CONCLUSIONS: Many effective therapies are now available for NET. It is important to select the right therapy at the right time for each patient through interdisciplinary management.

From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms.

Somatostatin analogs (SSA), specifically octreotide and lanreotide, have demonstrated antiproliferative effects in patients with neuroendocrine tumors (NET), a group of rare malignancies of diverse origin and presentation. A prominent feature of NET cells is the expression of G protein-coupled receptors called somatostatin receptors (SSTR). Although these SSTR are not uniformly present in NET, they can be instrumental in the diagnosis and treatment of NET. Apart from their application in nuclear imaging and radionuclide therapy, SSA have proven invaluable in the treatment of hormonal syndromes associated with certain NET (antisecretory effects of SSA), but it took more than two decades to convincingly demonstrate the antiproliferative effects of SSA in metastatic NET with the two pivotal studies PROMID and CLARINET. The current review summarizes three decades of SSA treatment and provides an overview of the clinical trial landscape for SSA monotherapy and combination therapy, including clinical implications and quality of life aspects, as well as ongoing fields of research.

Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study.

BACKGROUND: In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs. MATERIALS AND METHODS: SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced/metastatic grade 1/2 gastroenteropancreatic (GEP) NET or of unknown primary. Patients could be enrolled at first-line or higher therapy line. The primary endpoint was disease control rate ([DCR], rate of stable disease [SD], partial [PR], and complete response [CR]) at 6 months of LAN and TMZ. Patients with nonfunctioning (NF) NET without progression at 6 months were randomized to 6-month LAN maintenance or watch and wait, patients with functioning (F)-NET with clinical benefit (PR, SD) continued on LAN. RESULTS: Fifty-seven patients were recruited. The majority of patients received the study drug at second or higher treatment line and had an NET G2. DCR at 6 months LAN and TMZ was 73.5%. After 6 months of further LAN maintenance, 54.5% of patients with F-NET and 71.4% with NF-NET had SD or PR vs 41.7% with NF-NET on observation only. LAN and TMZ were effective in all subgroups analyzed. At 12 months of follow-up, median progression-free survival was 11.1 months. Median serum chromogranin A decreased except in NF-NET on observation. O6-methylguanine DNA methyltransferase promoter methylation appeared to better reflect TMZ response than loss of gene expression. During combination therapy, the most frequent treatment-emergent adverse events grade 3/4 reported were nausea (14%), thrombocytopenia (12.3%), and neutropenia (8.8%). Four deaths were reported resulting from severe adverse events not considered related to study medication. CONCLUSIONS: LAN plus TMZ is a treatment option for patients with progressive GEP-NET with more aggressive biological profile showing a manageable safety profile.

CXCR4-targeted Theranostics in Hematooncology: Opportunities and Challenges.

C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in a multitude of cancers, including neoplasms of hematopoietic origin. This feature can be leveraged by a theranostic approach, which provides a read-out of the actual CXCR4 expression in vivo, followed by CXCR4-targeted radioligand therapy (RLT) exerting anti-cancer as well as myeloablative efficacy. In a recent meeting of hematooncology and nuclear medicine specialists, statements on the current clinical practice and future perspectives of this innovative concept were proposed and summarized in this opinion article. Experts concluded that i) CXCR4-directed [68Ga]Ga-PentixaFor PET/CT has the potential to improve imaging for patients with marginal zone lymphoma; ii) CXCR4-targeted RLT exerts anti-lymphoma efficacy and myeloablative effects in patients with advanced, treatment-refractory T-cell lymphomas; iii) prospective trials with CXCR4-based imaging and theranostics are warranted.

Alternative schedule of temozolomide/capecitabine in neuroendocrine neoplasms.

The chemotherapy regimen capecitabine/temozolomide (CAPTEM) is routinely used in neuroendocrine tumors (NET), with antitumor activity particularly demonstrated in pancreatic or high-grade neuroendocrine neoplasms (NEN). However, different dosing regimens are used, and the optimal schedule remains to be defined. This single-center retrospective analysis assessed the efficacy and safety of CAPTEM in patients with NEN using a schedule starting both compounds simultaneously (temozolomide on days 1-5 and capecitabine on days 1-14 of a 28-day cycle) rather than sequentially. The primary parameters of interest were response rates, progression-free survival (PFS), and toxicities following this treatment regimen, hereinafter referred to as TEMCAP. The study population comprised 40 patients, half of whom (n = 20) had pancreatic NEN, and 9 patients (22.5%) had pulmonary or thymic NETs. The most common histology was NET G3 (n = 15, 37.5%), and 8 patients (20.0%) had a neuroendocrine carcinoma (NEC). Most patients (77.5%) had at least one prior systemic therapy, and 16 patients (40.0%) prior chemotherapy. The median number of TEMCAP cycles was 6 (range 1-16). Median PFS for the highly heterogeneous population was 13.3 months, while the median overall survival was 31.9 months. In total, 14/36 patients (38.9%) exhibited a partial response, and the disease control rate was 75.0%. The safety profile of TEMCAP (at a below-target mean temozolomide dose of 118.85 mg/m2) in our cohort was remarkably good with no toxicities of grade 3 or 4. Taken together, the results of this analysis further support the use of temozolomide/capecitabine in NEN and prompt further assessment of our modified TEMCAP schedule.

Clinical characteristics, treatment, and outcome of patients with large cell neuroendocrine carcinoma of the lung and brain metastases - data from a tertiary care center.

Large cell neuroendocrine carcinoma (LCNEC) of the lung is an aggressive malignancy, with brain metastases (BM) occurring in approximately 20% of cases. There are currently no therapy guidelines for this population as only few data on the management of LCNEC and BM have been published. For this retrospective single center study, patients with LCNEC and BM were identified from the Vienna Brain Metastasis Registry. Data on clinicopathological features, BM-specific characteristics, treatment, and outcome were extracted. In total, 52/6083 (0.09%) patients in the dataset had a diagnosis of LCNEC and radiologically verified BM. Median age at diagnosis of LCNEC and BM was 59.1 and 60.1 years, respectively. Twenty-seven (51.9%) presented with single BM, while 12 (23%) exhibited > 3 BM initially. Neurologic symptoms due to BM were present in n = 40 (76.9%), encompassing neurologic deficits (n = 24), increased intracranial pressure (n = 18), and seizures (n = 6). Initial treatment of BM was resection (n = 13), whole brain radiation therapy (n = 19), and/or stereotactic radiosurgery (n = 25). Median overall survival (mOS) from LCNEC diagnosis was 16 months, and mOS after BM diagnosis was 7 months. Patients with synchronous BM had reduced mOS from LCNEC diagnosis versus patients with metachronous BM (11 versus 27 months, p = 0.003). Median OS after BM diagnosis did not differ between LCNEC patients and a control group of small cell lung cancer patients with BM (7 versus 6 months, p = 0.17). Patients with LCNEC and BM have a poor prognosis, particularly when synchronous BM are present. Prospective trials are required to define optimal therapeutic algorithms.

Chemokine receptor-targeted PET/CT provides superior diagnostic performance in newly diagnosed marginal zone lymphoma patients: a head-to-head comparison with [18F]FDG.

BACKGROUND: In patients with marginal zone lymphoma (MZL), [18F]FDG PET/CT provided inconsistent diagnostic accuracy. C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in MZL and thus, may emerge as novel theranostic target. We aimed to evaluate the diagnostic performance of CXCR4-targeting [68Ga]Ga-PentixaFor when compared to [18F]FDG PET/CT in MZL. METHODS: Thirty-two untreated MZL patients (nodal, n = 17; extranodal, n = 13; splenic, n = 2) received [68Ga]Ga-PentixaFor and [18F]FDG PET/CT within median 2 days. We performed a visual and quantitative analysis of the total lymphoma volume by measuring maximum/peak standardized uptake values (SUVmax/peak), and calculating target-to-background ratios (TBR, defined as lesion-based SUVpeak divided by SUVmean from blood pool). Visual comparisons for both radiotracers were carried out for all target lesions (TL), and quantitative analysis of concordant TL evident on both scans. Last, MZL subtype analyses were also conducted. RESULTS: On a patient-based level, [68Ga]Ga-PentixaFor identified MZL manifestations in 32 (100%) subjects (vs. [18F]FDG, 25/32 [78.1%]). Of the 256 identified TL, 127/256 (49.6%) manifestations were evident only on CXCR4-directed imaging, while only 7/256 (2.7%) were identified on [18F]FDG but missed by [68Ga]Ga-PentixaFor. In the remaining 122/256 (47.7%) concordant TL, [68Ga]Ga-PentixaFor consistently provided increased metrics when compared to [18F]FDG: SUVmax, 10.3 (range, 2.53-37.2) vs. 5.72 (2.32-37.0); SUVpeak, 6.23 (1.58-25.7) vs. 3.87 (1.54-27.7); P < 0.01, respectively. Concordant TL TBR on [68Ga]Ga-PentixaFor (median, 3.85; range, 1.05-16.0) was also approximately 1.8-fold higher relative to [18F]FDG (median, 2.08; range, 0.81-28.8; P < 0.01). Those findings on image contrast, however, were driven by nodal MZL (P < 0.01), and just missed significance for extranodal MZL (P = 0.06). CONCLUSIONS: In newly diagnosed MZL patients, [68Ga]Ga-PentixaFor identified more sites of disease when compared to [18F]FDG, irrespective of MZL subtype. Quantitative PET parameters including TBR were also higher on [68Ga]Ga-PentixaFor PET/CT, suggesting improved diagnostic read-out using chemokine receptor-targeted imaging.

Deep learning for [18F]fluorodeoxyglucose-PET-CT classification in patients with lymphoma: a dual-centre retrospective analysis.

BACKGROUND: The rising global cancer burden has led to an increasing demand for imaging tests such as [18F]fluorodeoxyglucose ([18F]FDG)-PET-CT. To aid imaging specialists in dealing with high scan volumes, we aimed to train a deep learning artificial intelligence algorithm to classify [18F]FDG-PET-CT scans of patients with lymphoma with or without hypermetabolic tumour sites. METHODS: In this retrospective analysis we collected 16 583 [18F]FDG-PET-CTs of 5072 patients with lymphoma who had undergone PET-CT before or after treatment at the Memorial Sloa Kettering Cancer Center, New York, NY, USA. Using maximum intensity projection (MIP), three dimensional (3D) PET, and 3D CT data, our ResNet34-based deep learning model (Lymphoma Artificial Reader System [LARS]) for [18F]FDG-PET-CT binary classification (Deauville 1-3 vs 4-5), was trained on 80% of the dataset, and tested on 20% of this dataset. For external testing, 1000 [18F]FDG-PET-CTs were obtained from a second centre (Medical University of Vienna, Vienna, Austria). Seven model variants were evaluated, including MIP-based LARS-avg (optimised for accuracy) and LARS-max (optimised for sensitivity), and 3D PET-CT-based LARS-ptct. Following expert curation, areas under the curve (AUCs), accuracies, sensitivities, and specificities were calculated. FINDINGS: In the internal test cohort (3325 PET-CTs, 1012 patients), LARS-avg achieved an AUC of 0·949 (95% CI 0·942-0·956), accuracy of 0·890 (0·879-0·901), sensitivity of 0·868 (0·851-0·885), and specificity of 0·913 (0·899-0·925); LARS-max achieved an AUC of 0·949 (0·942-0·956), accuracy of 0·868 (0·858-0·879), sensitivity of 0·909 (0·896-0·924), and specificity of 0·826 (0·808-0·843); and LARS-ptct achieved an AUC of 0·939 (0·930-0·948), accuracy of 0·875 (0·864-0·887), sensitivity of 0·836 (0·817-0·855), and specificity of 0·915 (0·901-0·927). In the external test cohort (1000 PET-CTs, 503 patients), LARS-avg achieved an AUC of 0·953 (0·938-0·966), accuracy of 0·907 (0·888-0·925), sensitivity of 0·874 (0·843-0·904), and specificity of 0·949 (0·921-0·960); LARS-max achieved an AUC of 0·952 (0·937-0·965), accuracy of 0·898 (0·878-0·916), sensitivity of 0·899 (0·871-0·926), and specificity of 0·897 (0·871-0·922); and LARS-ptct achieved an AUC of 0·932 (0·915-0·948), accuracy of 0·870 (0·850-0·891), sensitivity of 0·827 (0·793-0·863), and specificity of 0·913 (0·889-0·937). INTERPRETATION: Deep learning accurately distinguishes between [18F]FDG-PET-CT scans of lymphoma patients with and without hypermetabolic tumour sites. Deep learning might therefore be potentially useful to rule out the presence of metabolically active disease in such patients, or serve as a second reader or decision support tool. FUNDING: National Institutes of Health-National Cancer Institute Cancer Center Support Grant.

Chemokine Receptor PET/CT Provides Relevant Staging and Management Changes in Marginal Zone Lymphoma.

Because of gastral and extranodal manifestations, guideline-compatible diagnostic work-up of marginal zone lymphoma is challenging. We aimed to determine the diagnostic performance of C-X-C motif chemokine receptor 4 (CXCR4)-directed PET/CT compared with routine diagnostics, along with PET/CT-based retrospective changes in therapeutic management. The predictive potential of the PET signal was also investigated, and the number of patients eligible for CXCR4-directed radioligand therapy in a theranostic setting was determined. Methods: For this study, 100 marginal zone lymphoma patients underwent CXCR4-directed PET/CT. We compared staging results and treatment decisions from molecular imaging with respective results from guideline-compatible work-up (CT, esophagogastroduodenoscopy, and bone marrow-derived biopsy). Prognostic performance of the in vivo CXCR4 PET signal for progression-free survival (PFS) was evaluated (using log-rank test and Kaplan-Meier curves). Results: Relative to CT, CXCR4-directed imaging led to Ann Arbor (AA) staging changes for 27 of 100 patients (27.0%). Among those, clinically relevant upstaging from AA I or AA II to AA III or AA IV was observed for 23 patients (85.2%), along with respective changes in therapeutic management (escalation, 6/23 [26.1%]; deescalation, 17/23 [73.9%]). CXCR4 PET/CT yielded diagnostic accuracy of 94.0% relative to esophagogastroduodenoscopy and 76.8% relative to bone marrow-derived biopsy. An increased CXCR4 PET signal was linked to shorter PFS (707 d vs. median PFS not reached; hazard ratio, 3.18; 95% CI, 1.37-7.35; P = 0.01). CXCR4-directed radioligand therapy would have been feasible for 18 of 100 patients (18.0%). Conclusion: Relative to CT, CXCR4-directed PET/CT led to AA changes for 27 of 100 patients. Chemokine receptor PET/CT may improve current diagnostic algorithms and influence management relative to CT alone, potentially obviating some biopsies.

The impact of COVID-19 and socioeconomic status on psychological distress in cancer patients.

Objective: We aimed to investigate the impact of the COVID-19 pandemic on psychological symptom burden against the socioeconomic background of cancer patients using data from routine assessments before and during the pandemic. Method: In this cross-sectional study, standardised assessment instruments were applied in N = 1,329 patients to screen for symptoms of anxiety, depression, post-traumatic stress, and fatigue from 2018 to 2022. Two MANOVAs with post-hoc tests were computed. First, only time was included as predictor to examine the isolated impact of the pandemic. Second, income level and education level were included as further predictors to additionally test the predictive power of socioeconomic factors. Results: In the final model, only income had a significant impact on all aspects of psychological symptom burden, with patients with low income being highly burdened (partial η² = .01, p = .023). The highest mean difference was found for depressive symptoms (MD = 0.13, CI = [0.07; 0.19], p < .001). The pandemic had no further influence on psychological distress. Conclusions: Although the pandemic is a major stressor in many respects, poverty may be the more important risk factor for psychological symptom burden in cancer outpatients, outweighing the impact of the pandemic.

Risk as a pattern over time: Delineation of time-dependent risk factors in biological, psychological, and social variables in cancer patients.

BACKGROUND: Survival in cancer patients is associated with a multitude of biological, social, and psychological factors. Although it is well established that all these factors add to overall mortality, it is not well understood how the predictive power of these parameters changes in a comprehensive model and over time. METHODS: Patients who attended the authors' outpatient clinic were invited to participate. The authors followed 5180 mixed cancer patients (51.1% female; mean age, 59.1 years [SD = 13.8]) for up to 16 years and analyzed biological (age, sex, cancer site, anemia), psychological (anxiety, depression), and social variables (marital status, education, employment status) potentially predicting overall survival in a Cox proportional hazards model. RESULTS: The median survival time for the entire sample was 4.3 years (95% confidence interval, 4.0-4.7). The overall survival probabilities for 1 and 10 years were 76.8% and 38.0%, respectively. Following an empirical approach, the authors split the time interval into five periods: acute, subacute, short-term, medium-term, and long-term. A complex pattern of variables predicted overall survival differently in the five periods. Biological parameters were important throughout most of the time, social parameters were either time-independent predictors or tended to be more important in the longer term. Of the psychological parameters, only depression was a significant predictor and lost its predictive power in the long-term. CONCLUSIONS: The findings of this study allow the development of comprehensive patient-specific models of risk and resilience factors addressing biopsychosocial needs of cancer patients, paving the way for a personalized treatment plan that goes beyond biomedical cancer care.

Does the dose matter? Antiproliferative efficacy and toxicity of everolimus in patients with neuroendocrine tumors - Experiences from a tertiary referral center.

The mTOR-inhibitor everolimus has been approved for the treatment of advanced neuroendocrine tumors (NETs) but is associated with relevant toxicities in clinical practice. Hence, optimal treatment sequencing and the impact of dose reductions have yet to be clarified. This retrospective analysis assessed patients with advanced, well-differentiated NET treated with everolimus at the Medical University of Vienna. The primary objective was to evaluate the efficacy of everolimus in a real-world cohort. A total of 52 patients treated with everolimus for advanced NET grade 1 (G1) or G2 (or typical or atypical carcinoid) 2010-2021 were included in this analysis. The most common sites of origin were pancreas (44%) and lung (29%). The initial dose was decided by the treating physician based on clinical assessment and 25 patients (48%) each were started at 10 mg/day and 5 mg/day. Median progression-free survival (PFS) following everolimus in the overall cohort was 9.8 months (95% CI: 4.3-15.3), with a statistically significant PFS difference (p = .03) between NET G1/typical carcinoids (42.9 months) and NET G2/atypical carcinoids (8.9 months). PFS was numerically but not significantly shorter in patients treated with a reduced dose (7.5 months vs. 12.4 months, p = .359). Even in this mixed full/half dose cohort, 93% developed treatment-related side effects (mostly grade I, no grade IV), 63% had dose reductions or interruptions, and five stopped due to toxicity. Median survival following treatment was 40.9 months (95% CI: 21.5-60.3) and no difference with regard to dosing was observed (p = .517). These data from an unselected patient cohort show long-term outcomes similar to those reported in the pivotal studies. Comparing everolimus starting dose, median PFS did not significantly differ for patients treated at a lower dose. While this finding is limited by the sample size and warrants prospective verification, initiating therapy at a reduced dose might be practicable and safe in a distinct subset of patients.

68Ga-Pentixafor PET/MRI for Treatment Response Assessment in Mantle Cell Lymphoma: Comparison Between Changes in Lesion CXCR4 Expression on PET and Lesion Size and Diffusivity on MRI.

PURPOSE: The aim of this study was to compare CXCR4 imaging with 68Ga-pentixafor PET to MRI for treatment response assessment in patients with mantle cell lymphoma (MCL). PATIENTS AND METHODS: Twenty-two posttreatment 68Ga-pentixafor PET/MRI scans of 16 patients (7 women and 9 men; mean age, 69.9 ± 7.9) with a total of 67 target lesions on baseline PET/MRI were analyzed. Rates of complete remission per lesion and per scan, according to MRI (based on lesion size) and 68Ga-pentixafor PET (based on SUV decrease to lower than liver and blood pool uptake), were compared using McNemar tests. The t tests and Pearson correlation coefficients (r) were used to compare rates of change in lesion diameter products (DPs) on MRI, and standardized uptake values (SUVmax, SUVmean) on PET, relative to baseline. RESULTS: At interim PET/MRI, 18/32 (56.3%) target lesions met CR criteria on 68Ga-pentixafor PET, and 16/32 (50.0%) lesions met size-based MRI criteria for CR (P = 0.63). At end-of-treatment PET/MRI, 40/57 (70.2%) target lesions met 68Ga-pentixafor PET criteria for CR, and 27/57 (47.4%) lesions met size-based MRI criteria for CR (P = 0.021). Complete remission after treatment was observed more frequently on 68Ga-pentixafor PET (11/22 scans, 54.5%) than on MRI (6/22 scans, 27.3%) (P = 0.031). Rates of change did not differ significantly between lesion DP (-69.20% ± 34.62%) and SUVmax (-64.59% ± 50.78%, P = 0.22), or DP and SUVmean (-60.15 ± 64.58, P = 0.064). Correlations were strong between DP and SUVmax (r = 0.71, P < 0.001) and DP and SUVmean (r = 0.73, P < 0.001). CONCLUSIONS: In MCL patients, 68Ga-pentixafor PET may be superior for assessment of complete remission status than anatomic MRI using lesion size criteria, especially at the end of treatment.

Clinical relevance of molecular aspects in extranodal marginal zone lymphoma: a critical appraisal.

Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is among the more common types of lymphoma accounting for up to 8% of newly diagnosed lymphoma cases. As opposed to other B-cell lymphomas, however, no predominant genetic hallmark has been defined in MALT lymphoma, but different localizations appear to be affected by different, sometimes distinct changes. Nonetheless, a high proportion of these genetic changes reported in MALT lymphomas dysregulate the pathways leading to NF-kB activation. t(11;18)(q21;q21)/BIRC3::MALT1 appears to be MALT lymphoma specific and is found in 24% of gastric and 40% of pulmonary MALT lymphomas. The translocation is associated with more disseminated disease in gastric MALT lymphoma and is found in a large percentage of patients whose lymphoma is unresponsive to antibiotic eradication of Helicobacter pylori. In addition to t(11;18)(q21;q21), nuclear expression of BCL10 or NF-kB appears to be highly associated with lymphoma cell survival independence of H. pylori-mediated stimulations. Antibiotic eradication, however, is the recommended therapy of choice irrespective of genetic findings, and molecular analysis is not required before initiation of therapy. The influence of genetic translocations including t(11;18)(q21;q21) on systemic therapies, however, is less clearly defined. While small series have shown no influence on the outcome for treatment with the anti-CD20 antibody rituximab (R) or treatment with cladribine (2-CdA), conflicting data have been reported for alkylating agents, especially chlorambucil and the combination of R + chlorambucil. None of other genetic changes seen in MALT lymphoma to date has discernible value in routine clinical applications, but recent data suggest that changes in TNFAIP3(A20), KMTD2 and CARD11 might be associated with response to Bruton kinase inhibitors.

Clinical characteristics, treatment, and long-term outcome of patients with brain metastases from thyroid cancer.

Brain metastases (BM) in patients with thyroid cancer (TC) are rare with an incidence of 1% for papillary and follicular, 3% for medullary and up to 10% for anaplastic TC (PTC, FTC, MTC and ATC). Little is known about the characteristics and management of BM from TC. Thus, we retrospectively analyzed patients with histologically verified TC and radiologically verified BM identified from the Vienna Brain Metastasis Registry. A total of 20/6074 patients included in the database since 1986 had BM from TC and 13/20 were female. Ten patients had FTC, 8 PTC, one MTC and one ATC. The median age at diagnosis of BM was 68 years. All but one had symptomatic BM and 13/20 patients had a singular BM. Synchronous BM at primary diagnosis were found in 6 patients, while the median time to BM diagnosis was 13 years for PTC (range 1.9-24), 4 years for FTC (range 2.1-41) and 22 years for the MTC patient. The overall survival from diagnosis of BM was 13 months for PTC (range 1.8-57), 26 months for FTC (range 3.9-188), 12 years for the MTC and 3 months for the ATC patient. In conclusion, development of BM from TC is exceedingly rare and the most common presentation is a symptomatic single lesion. While BM generally constitute a poor prognostic factor, individual patients experience long-term survival following local therapy.

Prophylactic treatment with oral azithromycin in cancer patients during the COVID-19 pandemic (OnCoVID): a randomized, single-blinded, placebo-controlled phase 2 trial.

BACKGROUND: Patients with cancer are at high risk for severe courses of COVID-19. Based on (pre-)clinical data suggesting a potential protective effect due to the immunomodulating properties of azithromycin, we have initiated a prospective randomized trial. METHODS: This randomized, single-center, single-blinded, placebo-controlled phase 2 trial included adult patients with cancer undergoing systemic treatment. Patients were 1:1 randomized to oral azithromycin (1500 mg once weekly for 8 weeks) or placebo. The primary endpoint was the cumulative number of SARS-CoV-2 infections 12 weeks after treatment initiation. RESULTS: In total, 523 patients were screened, 68 patients were randomized, and 63 patients received at least one dose of the study drug. Due to low acceptance and a lack of SARS-CoV-2 infections in the study cohort, the study was prematurely closed. With no reported grade III-IV possibly treatment-related adverse events, azithromycin was generally well tolerated. Overall survival (OS) rates after 12 months were 83.5% and 70.3% in the azithromycin and placebo group, respectively (p = 0.37). Non-SARS-CoV-2 infections occurred in 4/32 (12.5%) in the azithromycin and 3/31 (9.7%) in the placebo group (p = 1). No emergence of azithromycin-resistant S. aureus strains could be observed. According to treatment group, longitudinal alterations in systemic inflammatory parameters were detected for neutrophil/lymphocyte and leukocyte/lymphocyte ratios. CONCLUSION: Although efficacy could not be assessed due to premature closure and low incidence of SARS-CoV-2 infections, azithromycin was associated with a favorable side effect profile in patients with cancer. As other prophylactic treatments are limited, SARS-CoV-2 vaccination remains a high priority in oncological patients. CLINICALTRIALS: gov registration number and date (dd/mm/yyyy): NCT04369365, 30/04/2020.

Eribulin in Patients with Liposarcoma and Leiomyosarcoma: A Retrospective Single-Center Experience.

INTRODUCTION: Soft tissue sarcomas are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic liposarcoma (LPS) patients, who have failed first-line chemotherapy and has been approved for use in patients with LPS in the USA and Europe due to its efficacy in this histological subtype in a phase 3 trial. We have evaluated efficacy and tolerability of eribulin in LPS and leiomyosarcoma (LMS) patients in the routine clinical setting at our department. METHODS: In this retrospective single-center analysis, efficacy and safety of eribulin were retrospectively evaluated in advanced LPS and LMS patients at the Division of Oncology, Medical University of Vienna. RESULTS: A total of 32 adult patients treated with eribulin were identified and included in this analysis. Overall response rate was 9.4% for all patients, with one patient with LPS and two patients with LMS showing a partial response. Disease control rate (partial response plus stable disease) for all patients was 50% (LPS: 47.1%; LMS 53.3%). No statistically significant difference in median progression-free survival and overall survival was detected between patients with LPS and LMS (p = 0.807 and p = 0.519, respectively). Patients with LMS (n = 2) had received fewer previous therapy lines than patients with LPS (n = 14) (≤ previous treatment lines, p < 0.001). Toxicity was generally manageable, and grade 3 + 4 events were rare. CONCLUSION: The activity and tolerability of eribulin in LPS as in well in LMS patients in the routine clinical setting is comparable to outcomes reported in published phase 3 trials.