Early progression as a predictor of survival in marginal zone lymphomas: An analysis from the FIL-NF10 study

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome inMZL and identifies a high-risk population

Marginal zone lymphoma international prognostic index: a unifying prognostic index for marginal zone lymphomas requiring systemic treatment

Background Marginal zone lymphomas (MZL), comprised of three unique but related subtypes, lack a unifying prognostic score applicable to all the patients in need for systemic chemotherapy and/or immunotherapy. Methods Patients from the prospective NF10 study (NCT02904577) with newly diagnosed MZL and receiving frontline systemic therapy at diagnosis or after observation were used to train a prognostic model. The primary endpoint was progression-free survival (PFS) from start of treatment. The model was externally validated in a pooled analysis of two independent cohorts from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource and the University of Miami. Findings We identified 501 eligible patients. After multivariable modeling, lactate dehydrogenase (LDH) above upper normal limit, hemoglobin <12 g/dL, absolute lymphocyte count <1 x 10(9)/L, platelets <100 x 10(9)/L, and MZL subtype (nodal or disseminated) were independently associated with inferior PFS. The proposed MZL International Prognostic index (MZL-IPI) combined these 5 factors, and we defined low (LRG, 0 factors, 27%), intermediate (IRG, 1-2 factors, 57%) and high (HRG, 3+ factors, 16%) risk groups with 5-y PFS of 85%, 66%, and 37%, respectively (c-Harrell = 0.64). Compared to the LRG, the IRG (Hazard Ratio [HR] = 2.30, 95% CI 1.39-3.80) and HRG (HR = 5.41, 95% CI 3.12-9.38) had inferior PFS. Applying the MZL-IPI to the pooled US cohort (N = 353), 94 (27%), 192 (54%), and 67 (19%) patients were classified as LRG, IRG, and HRG, respectively, and the model was validated for PFS (log-rank test p = 0.0018; c-Harrell = 0.578, 95% CI 0.54-0.62). The MZL-IPI was also prognostic for OS in both the training and the external validation sets. Interpretation MZL-IPI is a new prognostic score for use in all patients with MZL considered for systemic treatment. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/)

Challenges in assessing and managing multi-hazard risks: a European stakeholders perspective

The latest evidence suggests that multi-hazards and their interrelationships (e.g., triggering, compound, and consecutive hazards) are becoming more frequent across Europe, underlying a need for resilience building by moving from single-hazard-focused to multi-hazard risk assessment and management. Although significant advancements were made in our understanding of these events, mainstream practice is still focused on risks due to single hazards (e.g., flooding, earthquakes, droughts), with a limited understanding of the stakeholder needs on the ground. To overcome this limitation, this paper sets out to understand the challenges for moving towards multi-hazard risk management through the perspective of European stakeholders. Based on five workshops across different European pilots (Danube Region, Veneto Region, Scandinavia, North Sea, and Canary Islands) and an expert workshop, we identify five prime challenges: i) governance, ii) knowledge of multi-hazards and multi-risks, iii) existing approaches to disaster risk management, iv) translation of science to policy and practice, and v) lack of data. These challenges are inherently linked and cannot be tackled in isolation with path dependency posing a significant hurdle in transitioning from single- to multi-hazard risk management. Going forward, we identify promising approaches for overcoming some of the challenges, including emerging approaches for multi-hazard characterisation, a common understanding of terminology, and a comprehensive framework for guiding multi-hazard risk assessment and management. We argue for a need to think beyond natural hazards and include other threats in creating a comprehensive overview of multi-hazard risks, as well as promoting thinking of multi-hazard risk reduction in the context of larger development goals

Strategia espositiva e topografia nel Foro Romano: una declinazione del reimpiego epigrafico

Il contesto forense rappresenta un luogo privilegiato per condurre una ricerca unitaria che prenda in considerazione le manifestazioni del paesaggio epigrafico nella sua completezza. L’intento specifico del contributo è quello di analizzare un ristretto gruppo di attestazioni, basi di statua, reimpiegate in strutture adibite alla fruizione pubblica e pertinenti alla parte occidentale del Foro Romano, per valutare, in un primo inquadramento, se il ricorso al reimpiego e la collocazione in una sezione specifica dello spazio forense risponda a una precisa logica espositiva o sia frutto di ragioni altre

Radiation Recall Pneumonitis Anticipates Bilateral Immune-Induced Pneumonitis in Non-Small Cell Lung Cancer

Radiation recall pneumonitis (RRP) is a rare inflammatory reaction that occurs in previously irradiated fields, and it may be caused by various triggering agents. Immunotherapy has been reported to potentially be one of these triggers. However, precise mechanisms and specific treatments have not been explored yet due to a lack of data in this setting. Here, we report a case of a patient who received radiation therapy and immune checkpoint inhibitor therapy for non-small cell lung cancer. He developed first radiation recall pneumonitis and subsequently immune-checkpoint inhibitor-induced pneumonitis (IIP). After presenting the case, we discuss the currently available literature on RRP and the challenges of differential diagnosis between RRP, IIP, and other forms of pneumonitis. We believe that this case is of particular clinical value since it highlights the importance of including RRP in a differential diagnosis of lung consolidation during immunotherapy. Furthermore, it suggests that RRP might anticipate more extensive ICI-induced pneumonitis

Unveiling the Potential of Venn Diagrams as a Helpful Tool for Clinical Reasoning:An Illustrative Case-based Discussion

Venn diagrams graphically represent a cognitive approach that can assist in highlighting information shared by different data sets while eliminating nonoverlapping conditions. When applied to clinical reasoning, such an approach helps physicians visually focus on data pertaining to differential diagnoses. We present and discuss a 3-step reasoning pathway derived from a real-life case in which we used Venn diagrams to diagnose drug-related pneumonitis in a 67-year-old man with advanced bladder cancer and nodular lung findings at chest CT. This education paper supports using Venn diagrams in Radiology

EDR – Effetti collaterali 9. LA COLLEZIONE EPIGRAFICA DI EVAN GORGA

The epigraphic collection of Evan Gorga (1865-1957), acquired by the Italian State in 1950, has remained almost completely unpublished until now. A collaboration between the National Roman Museum and the Department of Classics at Sapienza – University of Rome has undertaken the study in order to publish all of the inscriptions. Prior to the complete publication, we are pleased to offer a preview of its composition and potential points of interest for research

Immunotherapy in NSCLC Patients with Brain Metastases

Approximately 40% of unselected non-small cell lung cancer (NSCLC) patients develop brain metastases (BMs) during their disease, with considerable morbidity and mortality. The management of BMs in patients with NSCLC is a clinical challenge and requires a multidisciplinary approach to gain effective intracranial disease control. Over the last decade, immune checkpoint inhibitors (ICIs) have emerged as a game-changer in the treatment landscape of advanced NSCLC, with significant improvements in survival outcomes, although patients with BMs are mostly underrepresented in randomized clinical trials. Moreover, the safety and activity of ICIs and radiotherapy combinations compared with single-agent or sequential modalities is still under evaluation to establish the optimal management of these patients. The aim of this review is to summarize the state-of-the-art of clinical evidence of ICIs intracranial activity and the main challenges of incorporating these agents in the treatment armamentarium of NSCLC patients with BMs