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Objective: As a serious malignancy of the head and neck region, laryngeal cancer (LC) exhibits active glycolysis that produces lactate, a metabolite capable of inducing protein lactylation. However, the role of lactate-induced modifications in LC progression remains poorly understood. Although ALYREF has been identified as an oncogenic driver in several cancers, its function in LC has not yet been investigated.

Methods: Malignant cell behaviors were assessed using Cell Counting Kit-8, EdU staining, glucose uptake, lactate production, and extracellular acidification rate (ECAR) assays. The experimental methodology also included quantitative real-time PCR, western blot, and xenograft tumor models.

Results: Data demonstrated that ALYREF is markedly overexpressed in LC and holds potential diagnostic value. Knockdown of ALYREF impaired both proliferation and glycolytic capacity in LC cells. Mechanistically, increased lactate levels promoted lactylation of ALYREF at the K171 site, which in turn enhanced ALYREF expression. Elevated lactate concentrations rescued the suppression of oncogenic phenotypes and glycolysis induced by ALYREF reduction. Furthermore, in vivo experiments confirmed that ALYREF silencing inhibited tumor growth.

Conclusions: Our findings indicate that ALYREF promotes tumor progression by enhancing glycolysis. Glycolysis-derived lactate stabilizes the ALYREF protein via lactylation at K171, establishing a positive feedback loop that drives LC malignancy. Silencing ALYREF suppresses tumor growth, underscoring its potential as a therapeutic target in LC.

Introduction: Cachexia is a multifactorial syndrome prevalent in advanced illness. Guidelines rarely integrate the relational, multidimensional perspective of palliative care (PC). Addressing this gap is essential to optimize care. To achieve this, national consensus among PC physicians and nurses on principles and priorities for managing cachexia within PC settings is necessary.

Methods: A two-round Delphi study was conducted with 43 Italian PC experts (29 physicians, 14 nurses) meeting ⩾10 years' experience criteria. In Round 1, participants answered open-ended questions informed by literature and a prior exploratory study. Qualitative Framework Method analysis generated 28 statements. In Round 2, statements were rated on a 5-point Likert scale; consensus was defined as ⩾90% agreement (scores 4 or 5).

Results: Response rates were 82.2% (Round 1) and 95.5% (Round 2). High consensus (⩾90%) from both physicians and nurses was reached for 14 of 28 statements. Unanimous agreement (100%) supported the need for multiprofessional management, assessment of symptom clusters, and reframing the meaning of food in relation to illness stage. Strong agreement was found for dyadic care planning (97.7%), oral care (97.7%), and body image assessment (95.3%). Lower consensus occurred for prioritizing nutritional deficits (55.8%) and routine CRP/prealbumin testing (34.5%), reflecting contextual and prognostic considerations.

Conclusions: This study defines core PC-oriented principles for cachexia management: interprofessional collaboration, dyadic engagement, early holistic assessment, and goal-concordant interventions. Findings can inform future clinical guidelines, training, and policy development to address cachexia in advanced illness.

Our study evaluated the desire to procreate of 96 mothers of children treated for cancer at the Pediatric Oncology Unit of Istituto Nazionale Tumori of Milan in 2021. Even at a time during which they fear losing the child they already have, nearly one in four mothers expressed their desire to have another child.This wish emerged within a complex interplay of individual, relational, and sociocultural factors. Notably, cultural expectations surrounding motherhood, self-sacrifice, and the ideal of the "good mother" appeared to intensify feelings of guilt associated with procreative desire in the context of anticipatory grief. Future cross-cultural investigations could clarify how norms regarding motherhood and reproductive choices differ across societies and influence this phenomenon.Our results also showed a relation between mother's age, children's age, stage of disease and presence of siblings: procreative desire was mainly expressed by younger mothers with only one child, in preschool age and with a bad prognosis.

Objectives: Selpercatinib and pralsetinib are targeted therapies for non-small cell lung cancer. However, their adverse reaction profiles remain incompletely understood. This study aims to evaluate the post-marketing adverse events (AEs) associated with selpercatinib and pralsetinib in real-world populations.

Methods: We conducted a comprehensive analysis of AEs linked to selective RET inhibitors using advanced data mining techniques on the FDA Adverse Event Reporting System. Disproportionality analysis was performed to quantify the association between these drugs and AEs. Key metrics for disproportionality assessment included the reporting odds ratio (ROR), proportional reporting ratio, information component, and empirical Bayesian geometric mean.

Result: A total of 522 and 917 AE reports were identified for selpercatinib and pralsetinib in lung cancer patients, with 209 and 312 preferred terms recorded for each drug. The most frequent AEs for selpercatinib included hepatobiliary disorders (ROR=10.71) and cardiac disorders (ROR=2.33). For pralsetinib, the most common AEs were hepatobiliary disorders (ROR=2.57) and gastrointestinal disorders (ROR=1.53). Compared to pralsetinib, selpercatinib had a more increased risk of serious outcomes (P<0.05).

Conclusion: This study provides critical insights into the established and potential adverse events associated with selpercatinib and pralsetinib. The findings offer valuable evidence to guide the clinical use of RET inhibitors.

Background: The digitalization of clinical research has increased reliance on electronic portals (e-portals), with significant implications for trial site operations. Our aim is to map the types and number of e-portals required for clinical trials on solid tumors conducted at the Niguarda Cancer Center.

Methods: We performed an aggregated analysis of 65 interventional drug trials (phase I-III) initiated between August 2022 and March 2025. For each study, the number and type of e-portals required at the site were recorded and stratified by sponsor type. Analyses were conducted using R.

Results: A total of 65 trials were included (57 industry-sponsored, 8 academic). The mean number of e-portals per study was 5.3, with 66.1% of trials requiring 5-7 portals. Industry-sponsored trials employed significantly more e-portals than academic ones (mean ± SD: 5.8 ± 1.7 vs. 1.13 ± 0.35; t(41)=22.10, p<0.0001). Electronic Data Capture (EDC) systems were universally implemented (100%). Additional portals for randomization (IXRS), central laboratories, imaging, and safety reporting were common in industry-sponsored trials but rarely used in academic studies. Patient-reported outcomes (PROs) were included in ~49% of industry and 88% of academic trials; 89% of PROs in industry studies were captured via ePRO portals, while academic trials mostly relied on paper forms or EDC integration.

Conclusions: Industry-sponsored oncology trials impose a high digital workload on sites. Vendor streamlining, single sign-on solutions, open API standards, and shared ePRO infrastructures could improve efficiency, interoperability, and data quality.

Medical decision analysis is a method to make rational clinical decisions under uncertainty, enabling a mathematical combination of probabilities and utilities (i.e. values assigned to outcomes under risk). Decision analysis is commonly used in health economics, but it is underexploited in the clinic. With a view to fostering the use of medical decision analysis at the cancer patient bedside, this paper provides basic templates for some typical clinical decisions in cancer treatment, namely affecting: the quantity/quality of life trade-offs in curable cancer; adjuvant/neoadjuvant treatments; cytoreductive treatments; active surveillance / watchful waiting choices; treatment of advanced cancer; cancer follow-up. The clinical use of medical decision analysis is challenged by several difficulties, which are briefly recalled. Contrary to clinical research, medical decision analysis does not build new evidence: it simply provides physicians with a method to personalize clinical decisions on the basis of available evidence. Its added value in clinical practice correlates with the complexity of a decision. However, it also has a great potential in medical education, in order to empower clinicians with skills improving their ability to rationally shape medical decisions and share them properly with their patients.

Objective: This study aimed to systematically analyze the incidence, mortality, and risk factors of hematologic malignancies and their subtypes in China from 1990-2021.

Methods: The study utilized data from the Global Burden of Disease 2021 database. Trends in incidence and mortality rates of hematologic malignancies from 1990-2021 were measured using estimated annual percentage change (EAPC) with 95% confidence intervals. Future burden in China up to 2035 was projected using Bayesian age-period-cohort modeling.

Results: Between 1990 and 2021, China saw rising age-standardized incidence rates for multiple myeloma, non-Hodgkin lymphoma, and leukemia, but a decline for Hodgkin lymphoma. Mortality decreased for leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma, while increasing for multiple myeloma. Among leukemia subtypes, incidence fell for acute myeloid, chronic myeloid, and other leukemias but rose for acute and chronic lymphoid leukemias. Mortality declined across all five subtypes. Males had higher incidence and mortality than females for all hematologic malignancies. The 65-69 age group had the highest number of cases and deaths. Children under 5 years of age were most affected by leukemia, mainly acute lymphoid leukemia. High BMI was a significant risk factor. Projections to 2035 suggest continued increases in incidence and mortality for multiple myeloma, but declining leukemia mortality. Incidence of acute lymphoblastic and other leukemias is expected to fall, with mortality improving for all leukemia subtypes.

Conclusions: China's hematologic malignancy burden remained high in 2021 and is projected to persist through 2035. BMI is a key driver, highlighting the need for targeted control measures to reduce this burden.

Background: Germline pathogenic variants are increasingly recognized as critical determinants of pancreatic ductal adenocarcinoma (PDAC) susceptibility, prognosis, and response to targeted therapies such as PARP inhibitors. Recent guidelines recommend germline testing for all PDAC patients, regardless of family history, to identify hereditary cancer syndromes and guide treatment decisions. However, data from populations underrepresented in genomic studies, such as the Turkish population, remain limited.

Methods: We retrospectively analyzed 151 unselected PDAC patients who underwent germline testing using a next-generation sequencing (NGS) panel between January 2023 and April 2025. The panel covered established cancer susceptibility genes. Clinical parameters-including age, sex, tumor location and stage, diabetes status, and cancer family history-were reviewed. Variants were classified as pathogenic/likely pathogenic (P/LP), variants of uncertain significance (VUS), or benign.

Results: Among the 151 patients, 17 (11.3%) harbored P/LP variants, most frequently in ATM (n=3), BRCA1 (n=2), BRCA2 (n=2), and CDKN2A (n=2). An additional 33 patients (21.9%) carried VUS, again most commonly affecting ATM. No benign variants were reported. Notably, 70.6% of P/LP carriers had a first- or second-degree family history of cancer. Most tumors originated in the pancreatic head (72.8%), and 41.1% of patients had metastatic disease at diagnosis.

Conclusions: Our findings confirm the relevance of multigene panel testing in PDAC and reveal a germline mutation spectrum consistent with global data. These results support universal germline screening and emphasize the need for continued VUS interpretation, particularly in genomically understudied populations.

Objective: To investigate to describe outcomes of conization or expectant management for women with persistent (>24 months) low-grade cervical intra-epithelial neoplasia.

Methods: This is a retrospective analysis focusing on five-year outcomes after persistent, histologically confirmed, low-grade cervical intra-epithelial neoplasia undergoing conization or expectant management.

Results: Charts of 219 women with persistent low-grade cervical lesions were retrieved. Overall, 98 (44.7%) and 121 (55.3%) women had conization and observation, respectively. Patients receiving conization were older than patients having observation (43 (range, 24-77) vs. 39 (range, 25-68) years; p=0.013). Focusing on the group of patients receiving conization, 16 (16.3%) women were diagnosed with CIN2+. The five-year risk of secondary conization was 5% (n=5). Focusing on patients having observation (n=121), 18 (14.8%) patients received conization, after a median of 16.5 (range, 6-30) months. Seven (5.8%) and 11 (9.1%) patients were diagnosed with persistent CIN1 and CIN2+, respectively. Not fully visible squamous-columnar junction at colposcopic examination (p=0.035) was associated with CIN2+ occurrence. No invasive cancer was observedConclusions:Conization for persistent low-grade cervical intra-epithelial neoplasia revealed "occult" CIN2+ in 16% of patients. However, expectant management appears safe and effective in this context, in women with fully visible squamous columnar junction. The decision between conization and expectant management should be discussed on an individual basis.

Background: Volunteers play an essential role in pediatric oncology. While they are driven by personal motivations, they usually receive specific training that may support or reshape their goals.

Methods: We conducted a questionnaire-based survey to assess demographics, motivations, and satisfaction among eight associations/non-profit organizations, representing approximately 120 volunteers. The objectives were to explore the nature and correlations of their motivations to evaluate the sustainability of their engagement.

Results: Sixty-nine volunteers completed the questionnaire, either in full or in part. Most respondents were women, with a median age of 59 years, a medium-to-high educational level, and more than five years of experience in volunteering. Their commitment was mainly driven by personal/family experiences with childhood cancer. They demonstrated a strong awareness of cancer-related issues and were motivated by the desire to improve the quality and innovation of care. Participation within associations fostered a sense of community and altruistic purposes. High levels of satisfaction often led them to encourage others to volunteer. Previous rewards or recognition were not considered a major motivating factor.

Conclusions: Effective volunteer engagement and retention depend on a clear understanding of volunteers' expectations and on the selective recruitment of individuals whose goals align with the organization's capacity to meet them.