Publications by authors named "Silva Ljevar"

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists.

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Objective: Evaluate the feasibility and outcomes of the implementation of a routinely prehabilitation nutritional program (PNP) in retroperitoneal sarcoma (RPS) patients.

Summary Background Data: Rate of preoperative malnutrition is scarcely evaluated in RPS patients and the efficacy of a PNP in detecting and reverting malnutrition has not been studied.

Methods: Prospective study in a high-volume reference center for RPS; adult patients with primary or persistent RPS deemed surgically resectable were enrolled in a PNP.

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This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 patients with relapsed/refractory large B-cell lymphoma with baseline characteristics matched by stabilized inverse propensity score weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs.

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Secondary primary malignancies (SPM) have been reported after anti-BCMA or anti-CD19 chimeric antigen receptor (CAR)-T-cell therapies. While the cytotoxic effect of antecedent therapies, including chemotherapy and radiotherapy, has been well established, few data are available on risk related to CAR-T immunotherapies. The study aimed to analyse the incidence of SPM in 651 patients enrolled in the Italian prospective observational CART-SIE study.

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Background: Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1-3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20-40% and recurrence rates are up to ~ 75%(4-6).

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Axicabtagene ciloleucel showed efficacy for relapsed/refractory large B-cell lymphomas (LBCL), including primary mediastinal B-cell lymphomas (PMBCL); however, only few PMBCLs were reported. Aim was to evaluate efficacy and safety of axicabtagene ciloleucel in patients with PMBCL compared to those with other LBCL, enrolled in the Italian prospective observational CART-SIE study. PMBCLs (n = 70) were younger, with higher percentage of bulky and refractory disease, compared to other LBCLs (n = 190).

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CD19-directed chimeric antigen receptor (CAR) T cells can induce durable remissions in relapsed/refractory large B-cell lymphomas (R/R LBCLs), but 60% of patients do not respond or relapse. Biological mechanisms explaining lack of response are emerging, but they are largely unsuccessful in predicting disease response at the patient level. Additionally, to maximize the cost-effectiveness of CAR T-cell therapy, biomarkers able to predict response and survival before CAR T-cell manufacturing would be desirable.

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In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract.

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Article Synopsis
  • This study looked at 51 patients with relapsed/refractory large B-cell lymphomas who did not respond to CAR T-cell therapies axicabtagene ciloleucel or tisagenlecleucel and assessed the effectiveness of salvage therapies.
  • Among these patients, 43% were treated in clinical trials with promising treatments like glofitamab and loncastuximab tesirine, while others received standard therapies like lenalidomide and chemotherapy.
  • The findings indicated that high levels of circulating tumor DNA (ctDNA) were linked to worse patient outcomes, with an overall 12-month survival rate of only 35%, highlighting the need for ongoing research into better treatment options for this group.
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We studied the COVID-19 impact in newly-diagnosed breast cancer (7,349 patients in 2019, and 5,563 in 2020). In 2020 there were two diagnostic drops: -37.2% (March-May), -15.

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Infections are a major cause of morbidity and mortality during neutropenia after hematopoietic stem cell transplantation (HSCT). The use of a low-microbial protective diet (PD) in the peritransplantation period is a standard of care, although its efficacy has never been tested prospectively. We conducted a multicenter, randomized, noninferiority trial, enrolling all consecutive adult patients undergoing high-dose induction chemotherapy or HSCT with the objective to compare nonrestrictive diet (NRD) vs PD.

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Purpose: Inflammatory biomarkers and neutrophil-to-lymphocyte ratio (NLR) are associated with prognosis in several tumors. Data on sarcomas are limited, and insufficient on retroperitoneal sarcoma (RPS).

Experimental Design: Patients with primary RPS operated between 2002 and 2016 were included.

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Article Synopsis
  • Previous studies indicated that HER2-low breast cancer is associated with lower pathological complete response (pCR) rates and a favorable prognosis, suggesting a potential new subtype of breast cancer.
  • A study analyzed data from non-metastatic breast cancer patients treated between 2009-2020, finding that HER2-low patients had different characteristics than HER2-negative patients, such as higher hormone receptor positivity and lower treatment response rates.
  • The findings revealed that while there was no significant difference in disease-free survival (DFS) based on HER2 status, achieving pCR was linked to improved DFS, highlighting the need for further exploration of HER2-low's clinical implications.
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  • * Research on gene expression in PCa fibroblasts showed that proteins like periostin are prominently expressed in the tumor's surrounding stroma and are correlated with disease severity and aggressive characteristics.
  • * The study found that periostin levels in tissue and blood could enhance predictions for patients under active surveillance, potentially improving risk assessment and guiding treatment decisions.
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Purpose: In clinical trials, the expansion and persistence of chimeric antigen receptor (CAR) T cells correlate with therapeutic efficacy. However, properties of CAR T cells that enable their in vivo proliferation have still to be consistently defined and the role of CAR T bag content has never been investigated in a real-life setting.

Experimental Design: Residual cells obtained after washing 61 anti-CD19 CAR T product bags were analyzed to identify tisagenlecleucel/Tisa-cel and axicabtagene ciloleucel/Axi-cel phenotypic features associated with postinfusion CAR T-cell in vivo expansion and with response and survival.

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Patients affected by lymphoid malignancies (LM) are frequently immune-compromised, suffering increased mortality from COVID-19. This prospective study evaluated serological and T-cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B- and T-cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex.

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