Centro di Riferimento Oncologico

Abstract Although Hepatitis C Virus (HCV) infection is typically diagnosed by anti-HCV antibody testing, rare cases of seronegative HCV infection, defined by detectable HCV Ribonucleic Acid (RNA) in the absence of antibodies, have been reported in a small number of Human Immunodeficiency Virus (HIV)-positive patients. We describe the case of an HIV-positive patient with persistently elevated alanine aminotransferase levels who was found to have a high HCV RNA viral load (1,140,000 IU/mL) despite a negative HCV antibody screening. The patient had been receiving combination antiretroviral therapy (cART) initially with efavirenz, TAF and 3TC, and was later switched to bictegravir/TAF/3TC. Following hepatological evaluation and initiation of sofosbuvir/velpatasvir therapy, plasma HCV RNA became undetectable. Remarkably, this patient, who maintained a stable immunological profile, also exhibited spontaneous HIV seroreversion, characterized by the loss of detectable HIV-specific antibodies. These observations illustrate the importance of a molecular-based diagnostic approach to complement serological testing in individuals at risk for HIV-related infections.

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Most patients with large B-cell lymphoma (LBCL) progressing after CAR-T therapy experience poor survival and lack standardized treatment strategies. Prognostic tools are needed to guide decision-making at relapse. The Post-CAR Prognostic Index (PC-PI), recently proposed by Iacoboni et al., combines five routine clinical variables to stratify outcomes after CAR-T failure: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to progression (< 4 months). We evaluated the PC-PI in a retrospective multicenter study including 125 LBCL patients relapsing or refractory after axicabtagene-ciloleucel or tisagenlecleucel, treated between 2019 and 2023 across 16 Italian centers belonging to the Fondazione Italiana Linfomi network. Median overall survival (OS) was 4.9 months, with 6- and 12-month OS rates of 44.9% and 28.5%, respectively. The PC-PI discriminated prognosis effectively: high-risk patients had a median OS of 1.8 months, intermediate-high 2.2, intermediate-low 8.7, while in the low-risk group median OS was not reached (p<0.0001). Results remained consistent after excluding patients receiving only palliative care. Post-progression therapy markedly influenced survival: patients receiving active treatment achieved a median OS of 7.3 months versus 0.7 without further therapy (p<0.0001). Bispecific antibodies conferred the best outcomes (HR 0.44, p=0.02), with 6- and 12-month OS rates of 90% and 55%. Our findings confirm the prognostic value of the PC-PI and support its use in clinical practice as a tool for risk-adapted management of LBCL after CAR-T failure.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13045-025-01771-6.

The main infections that cause cancer in the European Union (EU) are Helicobacter pylori (H. pylori), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Altogether, in 2022, these infections accounted for ~ 5% of all cancers in the EU, mainly of the stomach, cervix uteri and liver. The largest burden of infection‐caused cancers was found in the south of the EU and near the eastern border. Substantial progress in the efficacy of interventions against these infections has been made since the release of the 4th edition of the European Code Against Cancer in 2015. Cancers due to infections can increasingly be prevented by prophylactic vaccines (HPV and HBV) and/or prompt diagnosis and treatment that can either cure (HCV and H. pylori) or slow down the infection (HBV and HIV), thus substantially reducing disease risk. Tools to tackle carcinogenic infections are also increasingly accessible and affordable in the EU, but their implementation is slow. Public awareness, political will and cost‐effective protocols are necessary to establish large programmes of vaccination or testing and treatment. Progress monitoring, as well as avoiding disinformation and stigma, is crucial to ensure that advances in medical progress are fully leveraged. The recently published 5th edition of the European Code Against Cancer therefore recommends: (1) vaccinate girls and boys against HBV and HPV at the age recommended in your country; (2) take part in testing and treatment for HBV and HCV, HIV and H. pylori, as recommended in your country.

The management of chronic lymphocytic leukemia (CLL) in older patients requires careful balancing of therapeutic efficacy with the risks of treatment intolerance. Frailty assessment is increasingly recognized as a critical determinant of clinical outcomes, but its specific role in guiding therapy with second-generation Bruton tyrosine kinase inhibitors remains poorly defined. We conducted a prospective, multicenter investigation of 326 consecutive CLL patients aged 65years or older who received zanubrutinib across 52 Italian centers, aiming to evaluate whether the Clinical Frailty Scale (CFS) could predict treatment discontinuation in real-world practice. The cohort was characterized by advanced age (median 78.1years, range 65.1-94.5), with over half of the patients presenting with Binet stage C disease. Two-thirds were treated in the frontline setting, while the remainder received zanubrutinib as salvage therapy. After a median follow-up of 8 months, 48 patients (14.7%) discontinued treatment, most commonly due to toxicity or disease progression. Receiver operating characteristic curve analysis identified a CFS of 3 as the optimal threshold for predicting discontinuation, with an area under the curve of 0.65 (95% CI 0.56-0.73, p<0.001). At 12months, the discontinuation rate was significantly higher among patients with a CFS >3 (29.2%) compared with those with a CFS ≤3 (8.8%) (p<0.001); among conventional prognostic variables, only relapsed/refractory disease demonstrated an independent association with TTD. These findings highlight the CFS as a simple yet powerful clinical tool that provides incremental prognostic information beyond standard disease-related factors. Incorporating frailty assessment into treatment planning may enhance patient selection and optimize therapeutic strategies for elderly CLL patients in daily practice.

Abstract Objectives The APC I1307K variant is a known moderate-risk allele for colorectal cancer (CRC), especially among Ashkenazi Jewish (AJ) individuals. However, its role in other cancers, particularly in male breast cancer (MBC), remains unclear. This study aimed to evaluate whether APC I1307K contributes to MBC risk in the Italian (non-AJ) population. Methods A multicenter case-control study was conducted involving 1028 MBC cases and 2,126 geographically matched healthy male controls. Genotyping was performed via Next Generation Sequencing or TaqMan assays. Associations between APC I1307K and MBC risk were analyzed using logistic regression models, including multivariate adjustments for age, enrollment center, and BRCA1/2 status. Results The APC I1307K variant was detected in 4 MBC cases (0.4 %) and 5 controls (0.2 %). No statistically significant association with MBC risk was observed (multivariate odds ratio [OR]=3.7, 95 % CI: 0.8–17.0, p=0.09). Clinical-pathologic comparisons revealed no distinguishing features among variant carriers. None of the carriers harbored BRCA1/2 pathogenic variants (PVs) or had personal histories of CRC or familial adenomatous polyposis. Conclusions These findings suggest that APC I1307K does not confer a significant risk for MBC in the Italian population.

An international panel of 27 experts (pediatric and movement disorder neurologists, psychiatrists, and parent representatives) from all continents participated in a Delphi process to establish international consensus guidelines for the evaluation, diagnosis, and management of children with Sydenham chorea (SC) based on best evidence and expert opinion. In total, 88 recommendations reached consensus. Practitioners should identify key signs of SC (chorea and hypotonia), screen for behavioral, mobility, swallowing, speech, and cognitive impairments, and acute rheumatic fever (ARF) features including carditis. Etiological evaluation will differ according to population ARF risk. At all times, patients, families, and educators should receive support, information, and guidance to minimize the impact of SC on academic and social functioning. Antibiotic treatment is recommended at first presentation. Long-term secondary antibiotic prophylaxis should follow international or local guidelines, and measures to reduce pain and distress associated with intramuscular antibiotics will aid in adherence. Immunotherapy (corticosteroids) is recommended in moderate to severe SC. In those with inadequate recovery, intravenous immunoglobulin or plasma exchange should be given. In SC relapse, repeat clinical assessments, etiological investigation, and antibiotics plus corticosteroid therapy should be considered. This consensus guideline will standardize the evaluation and management of patients with SC and direct future research to improve the lived experience and outcomes of patients and families.