Sensitivity of Pediatric Myelodysplastic Syndromes With Excess of Blasts With UBTF-TD to Venetoclax/Azacitidine.

UBTF-TD has been reported in a significant percentage of childhood MDS-EB and has been associated with inferior survival compared to that of patients with the wild-type gene. We treated three consecutive pediatric patients affected by UBTF-TD MDS-EB with venetoclax and azacitidine (ven/aza) in combination as 28-day cycles on a compassionate use basis three consecutive pediatric patients affected by UBTF-TD MDS-EB as a bridge to allogeneic HSCT. Treatment with ven/aza was well-tolerated, and all patients responded to the ven/aza course, achieving CR with flow-cytometry negativity.

Fusion Oncoproteins and Cooperating Mutations Define Disease Phenotypes in NUP98-Rearranged Leukemia.

Leukemias with NUP98 rearrangements exhibit heterogeneous phenotypes such as acute myeloid leukemia (AML), T-acute lymphoblastic leukemia (T-ALL), or myelodysplastic syndrome/neoplasms (MDS) associated with fusion partners, whereas the mechanism responsible for this heterogeneity is poorly understood. Through genome-wide mutational and transcriptional analyses of 177 NUP98-rearranged leukemias, we show that cooperating alterations are associated with differentiation status even among leukemias sharing the same NUP98 fusions, such as NUP98::KDM5A acute megakaryocytic leukemia (AMKL) with RB1 loss or T-ALL with NOTCH1 mutations. CUT&RUN profiling of in vitro cord blood CD34+ cell (cbCD34) models of major NUP98 fusions revealed that NUP98 fusion oncoproteins directly regulate differentiation-related genes contributing to the disease phenotypes, represented by NUP98::KDM5A binding to MEIS2 or GFI1B for megakaryocyte differentiation.

Outcomes of children with haematological malignancies given second haploidentical haematopoietic stem cell transplantation with either TCRαβ/CD19 depletion or post-transplant cyclophosphamide.

Human leukocyte antigen (HLA)-haploidentical haematopoietic cell transplantation (haplo-HCT) is a suitable salvage strategy in children with haematological malignancies experiencing either relapse or graft failure (GF) after the first HCT. Data comparing outcomes of transplant strategies using either TCRαβ/CD19 depletion (TCRαβ) or post-transplant cyclophosphamide (PTCy) are currently lacking. This retrospective, multicentre study included children with haematological malignancies who received a second haplo-HCT, in which either TCRαβ depletion or PTCy was used as the graft-versus-host disease (GvHD) prophylaxis strategy.

Age-dependent phenotypic and molecular evolution of pediatric MDS arising from GATA2 deficiency.

GATA2 deficiency is an autosomal dominant transcriptopathy disorder with high risk for myelodysplastic syndrome (MDS). To elucidate genotype-phenotype associations and identify new genetic risk factors for MDS, we analyzed 218 individuals with germline heterozygous GATA2 variants. We observed striking age-dependent incidence patterns in GATA2-related MDS (GATA2-MDS), with MDS being absent in infants, rare before age 6 years, and steeply increasing in older children.

Long term outcomes of breast primary sarcomas and malignant phyllodes tumors: 20 years observational analysis of the BEAM∗ study group. (∗the breast European association for mesenchymal tumors).

Background: Primary breast sarcomas (PBS) and malignant phyllodes tumors (MPT) represent less than 1 % of breast malignancies. Current evidence relies on heterogeneous retrospective series, resulting in controversial therapeutic approaches. This study aimed to analyze long-term outcomes in a large multicentric cohort treated with consistent strategies.

Use of membrane lipidome, body weight, and composition in stratification of early breast cancer patients.

Fat quality and quantity have a strong impact on cancer metabolism, however, in oncology practice, only body mass index (BMI) is evaluated. The observational prospective study performed at Fondazione Policlinico Gemelli explored the combination of membrane lipidome, BMI, and body composition, together with nutritional information, as evaluation criteria of fifty newly diagnosed early breast cancer patients (BRECALIP study). The fatty acid content of red blood cell membrane phospholipids, dividing patients by the BMI, individuated normal weight subjects for their molecular signatures different from the other groups, pointing to increased membrane fluidity and inflammation (saturated fatty acid decrease, omega-6 fatty acid increase), known to sustain cancer proliferation.

Fecal microbiota transplantation for decolonization from multidrug-resistant bacteria in pediatric allogeneic hematopoietic stem cell transplantation recipients: a retrospective real-word data study.

Not available.

Predictive risk factors of recurrence in breast cancer after neoadjuvant treatment: the NEORISK study.

Background: Neoadjuvant chemotherapy (NACT) improves oncologic and cosmetic outcomes in breast cancer (BC), yet recurrence remains a concern. This study identifies factors associated with recurrence at 3 and 5 years in BC patients receiving NACT.

Methods: A retrospective analysis of 933 stage I - III BC patients (2014-2021) evaluated event-free survival (EFS) predictors using multivariate analyses.

Biallelic SH2B3 germline variants are associated with a neonatal myeloproliferative disease and multisystemic involvement.

Known genetic disorders, such as Noonan syndrome and Down syndrome, can present in the neonatal period or early infancy with myeloproliferative disease (MPD) or abnormal myelopoiesis, which often self-resolves. This phenomenon results from an imbalance in differentiation and cell regulation caused by the genetic condition during perinatal hematopoiesis. Recently, SH2B3 variants have also been associated with neonatal MPD.

Personalizing Neoadjuvant Chemotherapy: The Impact of BRCA Variants on Pathologic Complete Response in Luminal B Breast Cancer.

: Neoadjuvant chemotherapy (NACT) is effective in downstaging locally advanced breast cancer, improving surgical and oncological outcomes. However, luminal B breast cancer typically exhibits a poorer response to NACT, with only 10-15% of patients achieving a pathologic complete response (pCR). This study investigates whether BRCA pathogenic variants (BRCA PVs) influence pCR rates in luminal B breast cancer patients, aiming to identify potential predictors for personalized treatment strategies.

Food Safety Practices and Foodborne Illness in Italian Pediatric Oncology and Hematology Centers: A Survey on Behalf of the Infectious Disease Working Group of AIEOP.

Background: Food safety practices are widely recommended for pediatric patients with cancer or undergoing hematopoietic stem cell transplantation (HCT) to mitigate foodborne infectious risks. However, specific measures, such as the neutropenic diet (ND) or low-microbial diet, lack robust evidence and are inconsistently implemented across pediatric hematology-oncology centers. Additionally, data on foodborne illnesses (FBI) in this population remain scarce.

Simultaneous integrated boost intensity-modulated radiotherapy for treatment of bone metastases: analysis of a breast cancer cohort.

Background: Bone metastases occur in up to 75% of metastatic breast cancer (MBC) cases. Advances in imaging now allow earlier detection, even during the oligometastatic phase. Radiotherapy (RT) is increasingly used in asymptomatic patients with ≤5 bone lesions, however standardised guidelines for dose and target volumes remain lacking.

Malignant Mesenchymal Tumors of the Breast: Current Challenges and New Perspectives on Primary Sarcomas and Malignant Phyllodes Tumors.

Mesenchymal tumors of the breast constitute a rare and heterogeneous group of neoplasms, representing only 0.5% to 1% of all breast tumors. Originating from mesenchymal tissues, these tumors include various histological subtypes.

Diagnostic accuracy of liver stiffness measurement for the diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome after hematopoietic stem cell transplantation (HSCT), the ELASTOVOD STUDY: an investigator-initiated, prospective, multicentre diagnostic clinical trial.

Hepatic Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a severe complication following hematopoietic stem cell transplantation (HSCT), traditionally diagnosed based on clinical criteria. This study aimed to evaluate the diagnostic performance of liver stiffness measurement (LSM) as a non-invasive tool for non invasive diagnosis of VOD/SOS. A multicentre clinical trial was conducted in Italy from April 2018 to December 2021, screening 1089 patients across 25 centers.

Oncological Safety of Prepectoral Implant-Based Breast Reconstruction After Conservative Mastectomy: Insights from 842 Consecutive Breast Cancer Patients.

Background: Implant-based breast reconstruction (IBBR) following conservative mastectomy is the most common approach for women undergoing breast cancer surgery. The aim of this study was to compare the oncological outcomes of conservative mastectomy combined with prepectoral IBBR to the subpectoral technique.

Methods: The clinical and demographic data of consecutive breast cancer patients who underwent conservative mastectomy with either prepectoral or subpectoral IBBR between January 2018 and December 2023 were retrospectively analyzed.

Advancing Breast Cancer Care in Patients Aged 80 and Above: A Personalized and Multidisciplinary Management to Better Outcomes.

Breast cancer in women aged 80 years and older accounts for about 12% of cases, but its management is challenging due to the population's heterogeneity and the lack of relevant evidence-based guidelines. Treatment decisions must consider biological age, comorbidities, life expectancy, therapy-related toxicities, and tumor biology. This study evaluates the clinical outcomes of elderly breast cancer patients treated with a multidisciplinary approach, including oncologists, surgeons, and geriatric specialists.

Role of radiomics in predicting early disease recurrence in locally advanced breast cancer patients: integration of radiomic features and RECIST criteria.

Background: Breast cancer (BC) is a major global health issue with significant heterogeneity among its subtypes. Neoadjuvant treatment (NAT) has been extended to include early BC patients, particularly those with HER2 + and triple-negative subtypes, to achieve pathological complete response and improve long-term outcomes. However, disease recurrence remains a challenge, highlighting the need for predictive biomarkers.

CyberKnife in Pediatric Oncology: A Narrative Review of Treatment Approaches and Outcomes.

Pediatric cancers, while rare, pose unique challenges due to the heightened sensitivity of developing tissues and the increased risk of long-term radiation-induced effects. Radiotherapy (RT) is a cornerstone in pediatric oncology, but its application is limited by concerns about toxicity, particularly secondary malignancies, growth abnormalities, and cognitive deficits. CyberKnife (CK), an advanced robotic radiosurgery system, has emerged as a promising alternative due to its precision, non-invasiveness, and ability to deliver hypofractionated, high-dose RT while sparing healthy tissues.

Fusion oncoproteins and cooperating mutations define disease phenotypes in -rearranged leukemia.

Leukemias with rearrangements exhibit heterogeneous phenotypes correlated to fusion partners, whereas the mechanism responsible for this heterogeneity is poorly understood. Through genome-wide mutational and transcriptional analyses of 177 -rearranged leukemias, we show that cooperating alterations are associated with differentiation status even among leukemias sharing the same fusions, such as acute megakaryocytic leukemia with loss or T-cell acute lymphoblastic leukemia with mutations. CUT&RUN profiling reveals that NUP98 fusion oncoproteins directly regulate differentiation-related genes, with binding patterns also influenced by differentiation stage.

Levofloxacin Prophylaxis in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation Recipients Does not Prevent Infective Complications and Infections-related Deaths.

Background: The prophylactic use of quinolones in the setting of allogeneic hematopoietic stem cell transplantation (allo-HCT) is controversial and solid evidence is missing, particularly in children.

Methods: In this single-center retrospective study, we compared outcomes in patients receiving (n = 74) or not receiving (n = 70) levofloxacin (LVX) prophylaxis, assessing overall survival, event-free survival, acute graft-versus-host disease (aGvHD) and bloodstream infection incidence, and infection-related mortality. Gut microbiota composition was analyzed in a subgroup using 16S rRNA sequencing of stool samples collected pre-HCT and at engraftment.

Navigating the Uncertainty of B3 Breast Lesions: Diagnostic Challenges and Evolving Management Strategies.

B3 breast lesions, classified as lesions of uncertain malignant potential, present a significant diagnostic and therapeutic challenge due to their heterogeneous nature and variable risk of progression to malignancy. These lesions, which include atypical ductal hyperplasia (ADH), papillary lesions (PLs), flat epithelial atypia (FEA), radial scars (RSs), lobular neoplasia (LN), and phyllodes tumors (PTs), occupy a "grey zone" between benign and malignant pathologies, making their management complex and often controversial. This article explores the diagnostic difficulties associated with B3 lesions, focusing on the limitations of current imaging techniques, including mammography, ultrasound, and magnetic resonance imaging (MRI), as well as the challenges in histopathological interpretation.

Real life outcome analysis of breast cancer brain metastases treated with Trastuzumab Deruxtecan.

Tumor dissemination to the central nervous system (CNS) is almost a rule in the treatment journey of advanced HER2+ breast cancer (BC). Recent results demonstrated high intracranial efficacy with Trastuzumab Deruxtecan (T-DXd). However, a real-world evidence is lacking in literature.

Assessing Malignant Risk in B3 Breast Lesions: Clinical Insights and Implications.

: B3 breast lesions, characterized by uncertain malignant potential, pose a significant challenge for clinicians. With the increasing use of preoperative biopsies, there is a need for careful management strategies, including watchful waiting, vacuum-assisted excision (VAE), and surgery. This study aims to assess the concordance between preoperative biopsy findings and postoperative histology, with a focus on evaluating the positive predictive value (PPV) for malignancy in B3 lesions.