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This paper econometrically assesses the impact on EU goods trade of the EU-Canada Comprehensive Economic and Trade Agreement (CETA), which has been provisionally applied since 2017. As opposed to many other studies, this analysis is carried out at the most disaggregated level of publicly available trade data - the 8-digit level. Furthermore, we control for nomenclature changes and revisions. Most EU trade with Canada are concentrated in a handful of broad product groups which were already duty-free (MFN0 duties). The paper nevertheless finds positive and significant impacts on EU exports to Canada. On the other hand, CETA seems to have increased EU imports from Canada only in goods that were already subject to MFN0 duties. The results suggest that there are positive effects on trade of the agreement beyond tariff reductions, something which requires additional research.

219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.

PurposeBurkitt’s lymphoma (BL) is an aggressive lymphoma subtype with high 18F-FDG avidity at 18F-FDG-PET/CT, but no validated criteria for PET/CT in treatment evaluation or prediction of outcome in BL are available. The aim of our study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in BL.Materials and methodsWe retrospectively enrolled 65 patients who underwent baseline 18F-FDG-PET/CT, interim and end of treatment PET/CT. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), the maximum standardized uptake value lean body mass (SUVlbm), the maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan–Meier method.ResultsAt a median follow-up of 40 months, the median PFS and OS were 34 and 39 months. MTV and TLG were significantly higher in patients with partial response compared to complete response group at end of treatment, while no significant differences were found at interim. Other metabolic PET/CT parameters were not related to treatment response. MTV and TLG were demonstrated to be independent prognostic factors for both PFS and OS; instead SUVbw, SUVlbm, SUVbsa, L-L SUV R and L-BP SUV R were not related to outcome survival.ConclusionsMetabolic tumour features (MTV and TLG) were significantly correlated with response to treatment and long-term outcome.

ObjectiveMantle cell lymphoma (MCL) is an aggressive lymphoma sub-type with poor prognosis and high 18F-FDG avidity at PET/CT; nowadays, no validated criteria for PET/CT in treatment response evaluation and prediction of outcome are present. The aim of study was to investigate whether the metabolic PET/CT features may predict treatment evaluation and prognosis in MCL.MethodsWe retrospectively enrolled 87 patients who underwent baseline 18F-FDG PET/CT and 85 end-of-treatment (eot) PET/CT. The baseline PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-liver SUVmax ratio (L-L SUV R), lesion-to-blood pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). EotPET/CT was visually interpreted according to the criteria of the Deauville 5-point scale (DC). Survival curves were plotted according to the Kaplan–Meier method.ResultsAt a median follow-up of 40 months, relapse/progression occurred in 47 and death in 23 patients. Median PFS and OS were 30 and 41 months. Baseline MTV and TLG were significantly higher in patients with progressive metabolic response compared to complete/partial response group. EotPET/CT results using DC significantly correlated with PFS, not with OS. MTV and TLG were demonstrated to be independent prognostic factors for PFS; instead the other metabolic parameters were not related to outcome survival. Considering OS, no variable was significantly associated.ConclusionsEotPET/CT results (using DC), MTV and TLG were significantly correlated with response to treatment and PFS.

Background Mantle cell lymphoma (MCL) is a rare B-cell Non-Hodgkin-lymphoma that predominantly affects elderly patients. While younger and fit patients receive an intensive first-line treatment, older or comorbid patients have limited options of chemo-immunotherapy (CIT) alone followed by anti-CD20-antibody maintenance. Targeted oral agents as Bruton`s tyrosine kinase inhibitors (BTKi, e.g. ibrutinib) - and B-cell lymphoma 2 (Bcl2) – inhibitors (e.g. venetoclax) have revolutionized the treatment especially for relapsed patients, with apparent synergistic effects. The MCL elderly III trial of the European MCL Network is an international phase II trial evaluating the efficacy of the combination of ibrutinib, venetoclax and rituximab as well as the CIT bendamustine and rituximab in combination with ibrutinib in elderly patients with untreated MCL. Methods The primary trial objective is to evaluate efficacy in both treatment arms as measured by failure-free survival at 30 months separately in both treatment arms. Secondary endpoints include progression-free survival, response rates, overall survival, adverse events as well as quality of life and impact of frailty and sarcopenia on treatment outcome through geriatric and body composition assessments via imaging. Exploratory endpoints comprise the rate of minimal residual disease negativity and kinetics of immune reconstitution. Current status The first patient was included in May 2023, with full site activation achieved in Q1 2025. Until May 15th 2025, 75 of 150 planned patients were enrolled in 27 German and Italian trial sites. Discussion This is the first randomized trial to exploratively compare a BTKi-Bcl2i-anti-CD20 triplet to a BTK-CIT combination in older MCL patients. Trial registration The trial is registered on EU Clinical Trial Register (20225018089600).

Background Elderly classical Hodgkin lymphoma (cHL) (ecHL) is a rare disease with dismal prognosis and no standard treatment. Fitness‐based approaches may help design appropriate treatments. Sarcopenia has been associated with an increased risk of treatment‐related toxicities and worse survival in various solid tumours, but its impact in ecHL is unknown. The aim of this retrospective multicentre study was to investigate the prognostic role of sarcopenia in ecHL. Methods We included newly diagnosed >64 years old cHL patients who performed a baseline comprehensive geriatric assessment and high‐dose computed tomography (CT) or 18fluorine‐fluorodeoxyglucose positron emission tomography/CT before any treatment. Sarcopenia was measured as skeletal muscle index (SMI, cm2/m2) by the analysis of high‐dose CT or low‐dose positron emission tomography/CT images at the L3 level. The specific cut‐offs for the SMI were determined by receiver operator curve analysis and compared with those proposed in literature and studied in diffuse large B‐cell lymphoma. Survival functions [progression‐free survival [PFS] and overall survival (OS)] were calculated for the whole population and for different subgroups defined as per different sarcopenia cut‐off levels. Results We included 154 patients (median age 71 years old, 76 female). The median L3‐SMI was 42 cm2/m2. The specific cut‐off derived in our male population was 45 cm2/m2; using this cut‐off, 27 male patients (35%) were defined as sarcopenic. After a median follow‐up of 5.9 years, the overall 5‐year PFS and OS rates were 53% and 65%, respectively, and were significantly shorter in sarcopenic male patients compared with non‐sarcopenic (PFS 31% vs. 61%, P = 0.008; OS 51% vs. 74%, P = 0.042). Applying diffuse large B‐cell lymphoma‐derived sarcopenic thresholds, there were no significant differences between sarcopenic and non‐sarcopenic patients for both PFS and OS, with a sole exception of a significant reduced PFS in sarcopenic male patients using Namakura cut‐off. The comprehensive geriatric assessment‐determined frail functional status was an independent adverse prognostic factor for both female and male patients. Conclusions Baseline evaluation of sarcopenia through radiological examinations performed for ecHL staging may help define a proportion of male patients with unfavourable outcome with current treatment strategies. Also the functional status evaluation could allow to identify a frail subgroup of patients with worse outcome.

ObjectiveBurkitt’s lymphoma (BL) is an aggressive lymphoma sub-type with high 18F-FDG avidity, but no well established evidence of PET/CT’s role in treatment evaluation or prognosis is currently available. The prognostic role of visual analysis and Deauville criteria for BL have already been demonstrated, while the potential usefulness of semi-quantitative PET/CT features remains unclear, especially the value of the rate of reduction in metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The aim of this retrospective study was to investigate whether ΔMTV and ΔTLG can predict treatment response at the end of therapy and prognosis in BL.MethodsWe retrospectively included 61 patients (mean age 61; 40 male, 21 female) who underwent baseline, interim and end-of-treatment 18F-FDG PET/CT. The PET/CT images were analyzed visually and semi-quantitatively by measuring total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for every scan. Then we calculated volume changes based on the percentage of MTV and TLG reduction between the baseline and interim PET (ΔMTVi and ΔTLGi) and between baseline and end-of-treatment PET/CT (ΔMTVeot and ΔTLGeot) and correlated them with clinical response and progression-free survival (PFS) and overall survival (OS). Survival curves were plotted according to the Kaplan–Meier method.ResultsForty patients had a complete response and 21 patients a partial response on interim 18F-FDG PET/CT. At end of treatment, 45 had a complete response, 11 partial response and 5 disease progression. At a median follow-up of 43 months, relapse/progression occurred in 18 patients and death in 11. ΔMTV and ΔTLG values were significantly higher in patients with complete response compared to no complete response. ΔMTVeot and ΔTLGeot were demonstrated to be independent prognostic factors for both PFS and OS, while ΔMTVi and ΔTLGi were not related to survival.ConclusionsMetabolic tumor features (ΔMTV and ΔTLG) were significantly correlated with response to treatment and long-term outcome in BL.

Background Diffusion‐weighted whole‐body MRI (DW‐MRI) is increasingly used in the management of multiple myeloma (MM) patients, but data regarding the prognostic role of DW‐MRI imaging response after treatment are lacking. The Myeloma Response Assessment and Diagnosis System (MY‐RADS) imaging recommendations recently proposed the criteria for response assessment category (RAC) with a 5‐point scale in order to standardize response assessment after therapy, but this score still needs to be validated. Methods We investigated the prognostic role of RAC criteria in 64 newly diagnosed MM patients after autologous stem cell transplantation (ASCT), and we combined the results of MY‐RADS with those of minimal residual disease (MRD) assessment by multiparametric flow cytometry (MFC). Results Superior post‐ASCT PFS and OS were observed in patients with complete imaging response (RAC1), with respect to patients with imaging residual disease (RAC≥2): median PFS not reached (NR) versus 26.5 months, p = 0.0047, HR 0.28 (95% CI: 0.12–0.68); 3‐year post‐ASCT OS 92% versus 69% for RAC1 versus RAC ≥2, respectively, p = 0.047, HR 0.24 (95% CI: 0.06–0.99). Combining MRD and imaging improved prediction of outcome, with double‐negative and double‐positive features defining groups with excellent and dismal PFS, respectively (PFS NR vs. 10.6 months); p = 0.001, HR 0.07 (95%CI: 0.01–0.36). Conclusion The present study supports the applicability of MY‐RADS recommendations after ASCT; RAC criteria were able to independently stratify patients and to better predict their prognosis and the combined use of DW‐MRI with MFC allowed a more precise evaluation of MRD. The present study supports both the applicability and the clinical usefulness of the proposed Myeloma Response Assessment and Diagnosis System (MY‐RADS) recommendations applied to DW‐MRI imaging obtained after first‐line treatment of MM including ASCT. MY‐RADS RAC criteria were able to independently stratify patients and to better predict their outcome and their prognosis. DW‐MRI proved to be a powerful tool for the assessment of residual bone disease by functional imaging: it complemented bone marrow flow cytometry and may, therefore, represent a step forward in the clinical management of the increasing number of MM patients achieving CR with the novel treatment approaches.

Introduction Historically, the management of relapsed or refractory diffuse large B-cell lymphoma (r/r-DLBCL) involved chemotherapy and autologous stem cell transplant, though outcomes were often suboptimal. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the therapeutic landscape for r/r-DLBCL, achieving high response rates and improving progression-free and overall survival. However, a significant proportion of patients relapse after CAR-T, and optimal treatment strategies for post-CAR-T relapse remain unclear. Radiotherapy (RT), a highly effective treatment for lymphoma, is increasingly recognized for its potential role as both a bridging therapy and a salvage option following CAR-T relapse. Methods A comprehensive literature review was conducted using databases including PubMed, Scopus, EMBASE, and Cochrane Library, with search terms combining “radiotherapy,” “radiation therapy,” “lymphoma,” and “CAR T-cell.” A total of 690 records were screened, and 14 studies were included in the analysis after applying inclusion and exclusion criteria. Results RT demonstrates high response rates in CAR-T relapsed DLBCL, with overall response rates (ORR) ranging from 35% to 82.4% and complete response rates (CRR) from 17% to 59%. One-year local control rates ranged between 62% and 84%. Salvage RT showed comparable or superior outcomes to systemic therapies in multiple studies, particularly in patients with localized relapses. The toxicity profile of RT was favorable, particularly when modern techniques such as IMRT were employed. Case reports and retrospective series highlighted its effectiveness in achieving durable responses and controlling localized disease progression. Conclusions Radiotherapy is a safe and effective treatment option for patients with DLBCL relapsed or refractory after CAR-T therapy. It achieves high local control rates and favorable outcomes, particularly in patients with localized relapse. Incorporating RT into the therapeutic workflow may enhance the management of this challenging population. Further prospective studies are needed to define its role and optimize treatment sequencing.