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.

The more the merrier? Evidence and efficacy of immune checkpoint- and tyrosine kinase inhibitor combinations in advanced solid cancers.

Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have gained therapeutical significance in cancer therapy over the last years. Due to the high efficacy of each substance group, additive or complementary effects are considered, and combinations are the subject of multiple prospective trials in different tumor entities. The majority of available data results from clinical phase I and II trials. Although regarded as well-tolerated therapies ICI-TKI combinations have higher toxicities compared to monotherapies of one of the substance classes and some combinations were shown to be excessively toxic leading to discontinuation of trials. So far, ICI-TKI combinations with nivolumab + cabozantinib, pembrolizumab + axitinib, avelumab + axitinib, pembrolizumab + lenvatinib have been approved in advanced renal cell (RCC), with pembrolizumab + lenvatinib in endometrial carcinoma and with camrelizumab + rivoceranib in hepatocellular carcinoma (HCC). Several ICI-TKI combinations are currently investigated in phase I to III trials in various other cancer entities. Further, the optimal sequence of ICI-TKI combinations is an important subject of investigation, as cross-resistances between the substance classes were observed. This review reports on clinical trials with ICI-TKI combinations in different cancer entities, their efficacy and toxicity.

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.

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.

Brain metastases from hepatopancreatobiliary malignancies.

While colorectal and gastroesophageal cancer represent the two gastrointestinal (GI) tumor entities with the highest incidence of brain metastatic (BM) disease, data on the clinical course of BM patients from hepatopancreatobiliary malignancies are rare. Patients with cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC) and gastroenteropancreatic neuroendocrine neoplasms (GEP NEN). Treated for BM between 1991 and 2017 at an academic care center were included. Brain metastases-free survival (BMFS) was defined as interval from first diagnosis until BM development. Overall survival (OS) was defined as interval from diagnosis of BM until death or last date of follow-up. Outcome was correlated with clinical and treatment factors. 29 patients from overall 6102 patients (0.6%) included in the Vienna Brain Metastasis Registry presented with BM from hepatopancreatobiliary primaries including 9 (31.0%) with CCA, 10 (34.5%) with HCC, 7 (24.1%) with PDAC and 3 (10.3%) with GEP NEN as primary tumor. Median BMFS was 21, 12, 14 and 7 months and median OS 4, 4, 6 and 4 months, respectively. Karnofsky Performance Status (KPS) below 80% (p = 0.08), age above 60 years (p = 0.10) and leptomeningeal carcinomatosis (LC) (p = 0.09) diagnosed concomitant to solid BM showed an inverse association with median OS (Cox proportional hazards model). In this cohort of patients with BM from hepatopancreatobiliary tumor entities, prognosis was shown to be very limited. Performance status, age and diagnosis of LC were identified as negative prognostic factors.

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.

Treatment patterns and oncological outcome of patients with advanced small intestinal neuroendocrine tumors: real-world data from the Medical University of Vienna.

Background: Different oncological therapies have been approved for small intestinal neuroendocrine tumors (SI-NETs), but relatively little is known about efficacy and long-term outcome outside of phase III trials. Methods: This retrospective analysis assessed patients with well-differentiated, metastatic SI-NETs treated at the Medical University of Vienna, an approved European Neuroendocrine Tumor Society (ENETS) Center of Excellence for neuroendocrine tumors. The primary objective was to assess progression-free survival (PFS) following approved therapies, that is, octreotide, lanreotide, peptide receptor radionuclide therapy (PRRT), and everolimus, in a representative real-world collective. Results: A total of 77 patients receiving systemic treatment for advanced SI-NETs between 2010 and 2021 were included, with a median follow-up time of 82.3 months [95% confidence interval (CI), 57.8-106.8 months]. In the entire collective, the estimated median PFS following first-line therapy was 32.0 months (95% CI, 23.5-40.5 months). Peritoneal carcinomatosis was significantly associated with worse PFS (p = 0.016). Regarding therapeutic strategies and outcome, 59 patients received somatostatin analogs first line and no significant difference in PFS was observed between lanreotide and octreotide (29.3 versus 35.5 months, p = 0.768). Across all treatment lines, 42 patients underwent PRRT (estimated median PFS: 32.0 months; 95% CI, 25.6-38.3 months) and a small subgroup of 7 patients received everolimus (estimated median PFS: 9.2 months; 95% CI, 1.6-17.0 months). For the total cohort, the estimated median OS following first-line therapy was 100.6 months (95% CI, 82.3-118.8 months), but the high proportion of deaths attributed to NET (77.8%) underlines the lethal nature of the disease. No unexpected toxicities were observed. Conclusions: While peritoneal carcinomatosis emerged as an adverse prognostic factor for PFS in this collective, the long-term outcome of patients treated at a specialized NET center using approved therapies appeared comparable to pivotal studies in SI-NET.

Positron emission tomography/magnetic resonance imaging (PET/MRI) vs. gastroscopy: Can it improve detection of extranodal marginal zone lymphomas of the stomach following H. pylori treatment?

INTRODUCTION: The stomach is the most common site of origin for extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma). Antibiotic eradication of Helicobacter pylori (H. pylori) is the standard first-line treatment, with response assessment being performed by histological evaluation of multiple gastric biopsies. AREAS COVERED: The objective of this review is to provide an update on results obtained using noninvasive methods, including magnetic resonance imaging (MRI), positron emission tomography combined with computed tomography (PET/CT), and most recently, PET/MRI for the assessment of disease extent and response to treatment in patients with gastric MALT lymphoma. EXPERT OPINION: While CT is the officially recommended imaging technique, few studies in small cohorts have suggested that diffusion-weighted MRI shows higher sensitivity, also relative to 18 F-FDG PET/CT, for both gastric and nongastric MALT lymphomas. A recent prospective study using PET/MRI with the novel CXCR4-targeting radiotracer 68 Ga-Pentixafor suggested that, for patients with gastric MALT lymphoma after H. pylori eradication, this imaging technique may provide excellent accuracy (97%) for assessment of residual or recurrent disease. Although recent studies on CXCR4-targeting PET and to some extent also diffusion-weighted MRI are promising, there is insufficient evidence to suggest a change in clinical practice.

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

Posttreatment 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 positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post-H pylori eradication [68Ga]Pentixafor-PET/magnetic resonance imaging (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 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values 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 = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.

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

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens 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 compared with 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. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275.

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

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.