EClinicalMedicine最新文献

Glioblastoma is the most common form of primary brain tumor in adults, characterized by rapid progression and poor prognosis-despite the standard of care treatment including maximal safe resection, radiotherapy, and chemotherapy. Cancer vaccination has emerged as a promising strategy to harness the patient's immune system against glioblastoma. Cancer vaccination strategies can broadly be divided into cell-based or tumor antigen only (TAO), depending on whether they incorporate the use of viable immune cells. Here, we reviewed data from clinical trials that tested TAO cancer vaccination strategies for glioblastoma treatment, including personalized vaccines. Clinical safety and efficacy profiles for each vaccination strategy are summarized. Insights gained from these clinical trials are reviewed to identify opportunities for future therapeutic advancement.

[This corrects the article DOI: 10.1016/j.eclinm.2025.103748.].

Background: With negligible risk of distant metastasis, the primary treatment focus in patients with primary retroperitoneal well-differentiated liposarcoma (pRP-WDLPS) is local control. The recently completed phase 3 STRASS trial suggested a potential benefit to neoadjuvant radiotherapy (RT) in optimizing local control in these patients. This study investigates outcomes associated with neoadjuvant RT in a larger cohort of patients undergoing surgery for pRP-WDLPS.

Methods: In this study from 24 participating sites, we retrospectively identified all patients with pRP-WDLPS who underwent curative-intent resection between January 1, 2002 and December 31, 2017. The primary endpoint was the cumulative incidence function (CIF) of local recurrence (LR), and the secondary endpoint was overall survival (OS). The impact of neoadjuvant RT on the CIF of LR was analyzed using a 1:2 propensity score matching (PSM).

Findings: Of 582 patients included in the entire cohort, 72 patients (12%) received neoadjuvant RT. The 1:2 PSM group included 208 patients of which 138 patients (66%) underwent surgery alone and 70 patients (34%) underwent neoadjuvant RT and surgery. With a median follow up of 73 months, the 5- and 8-year CIF of LR for neoadjuvant RT and surgery group was 6% and 10%, respectively, and 26% and 33%, respectively, for the surgery alone group (odds ratio (OR) 0·85, 95% confidence interval (CI) 0·76-0·97, P < 0·001). The 5- and 10-year OS for the neoadjuvant RT and surgery group was 92% and 80%, respectively, and 84% and 71%, respectively, for the surgery alone group (HR 0·50, 95% CI 0·27-1·21, P = 0·07).

Interpretation: To the best of our knowledge, this is the largest study to report outcomes of neoadjuvant RT for pRP-WDLPS. Neoadjuvant RT was associated with a significant decrease in LR compared to surgery alone. These data further validate the use of neoadjuvant RT for pRP-WDLPS.

Funding: Funding was received from the Susan and Habib Gorgi Family Fund for Sarcoma Research.

The gold standard for providing confirmatory evidence to regulatory agencies is a single sponsor conducting a randomised, controlled clinical trial (RCT). But emerging situations like the mpox outbreak can complicate launching large, single, global trials that meet the needs of multiple stakeholders, including multinational funders and regulators. Drawing on lessons from the mpox outbreak, we propose an alternative approach: the federated trial design. This approach ensures that individual trials launch quickly and that a rigorous, prespecified, conjoined analysis using combined data supports joint regulatory decisions. Early engagement with regulatory agencies is crucial to arranging such a conjoined analysis. Federating trials can support regulatory decision-making when they include a prespecified conjoined analysis that is sufficiently rigorous. Essential steps include harmonising individual trial protocols, aligning data standards, and arranging for a single Data Monitoring Committee to review a combined, multi-trial analysis. The classical single-trial approach remains the gold standard, but investigators should consider federated trials in emergencies that complicate conducting single trials. In such crises, investigators need to explain clearly why standalone evidence from participating RCTs is not obtainable. The federated trials design cannot replace the classical design, but can provide timely, robust evidence in crises such as public health emergencies.

Patient navigation comprises person-centred activities focused on addressing barriers and facilitating timely access to health care. Despite demonstrated effectiveness, the scope of patient navigation remains unclear. To clarify the scope of patient navigation and support global implementation, the Global Initiative to Advance Cancer Navigation for Better Outcomes (GINO) aimed to develop a practice framework for patient navigation in cancer care. Phase 1 involved reviewing patient navigation literature and identifying key areas of practice. Phase 2 involved a modified Delphi process with international experts in navigation (July to December 2024) to establish consensus on practices to include in the framework. Patient navigation experts across regions and disciplines were invited. Two rounds of online surveys were conducted where participants rated the importance of each practice on a scale from 1 ("Not important") to 5 ("Critically important"). Practices rated ≥4 by ≥ 75% of participants in Round 2 met consensus criteria. The remaining items were discussed in a consensus meeting. Eighty-one experts from 29 countries (n = 45, 56% high-income, n = 36, 44% low-middle-income) participated in Round 1. Of these, 60 also participated in Round 2, including healthcare practitioners (n = 30, 50%), navigators (n = 16, 27%), researchers (n = 24, 40%), and advocates (n = 10, 17%). After Round 2, 27/35 (77%) practices reached consensus for inclusion. After the consensus meeting, two items were reworded, and 32 items were included in the final framework. We reached consensus among international experts on the contents of the GINO practice framework for patient navigation in cancer care. By describing the scope of patient navigation, the framework can support the development and implementation of patient navigation programs globally.

Background: Alcohol-impaired driving remains a leading cause of road traffic deaths worldwide, yet despite widespread adoption, the effectiveness of national blood alcohol concentration (BAC) limits across diverse structural conditions and population risks remains poorly understood.

Methods: We conducted a cross-national multilevel analysis of 165 countries using 2019 data on alcohol-attributable traffic mortality rates (ATMRs), national legal BAC limits, and structural country-level indicators. The primary outcome was ATMRs, defined as age-standardized death rates per 100,000 population among individuals aged 15 and older. Key predictors included national BAC limits, sex, and their interaction. Models were adjusted for national income, healthcare system infrastructure, gender inequality, and per capita alcohol consumption.

Findings: Lower national BAC limits were associated with lower ATMRs, with significantly stronger effects observed among males versus females (β = -2.58, p < 0.01). Structural factors, including lower national income (β = -0.31, p < 0.01), greater gender inequality (β = 1.61, p < 0.01), and higher alcohol consumption (β = 0.16, p < 0.001) each predicted higher ATMRs. Our final model explained 71% of the variance in ATMRs.

Interpretation: ATMRs represent a preventable global burden, with World Health Organization (WHO) BAC guidelines being exceeded in ∼30% of countries examined. While lower BAC limits reduce ATMRs overall for both women and men, men experienced a disproportionately higher share of the mortality burden. Further reduction in ATMRs would be maximized by considering country-level structural factors.

Funding: NIH T32AA029259(CLJC), U54AA027989(SAM), K01AA029706(YZ), R01AA030971(TLV), Office of the Assistant Secretary of Defense for Health Affairs W81XWH-22-2-0081, PASA3(MRP/AAM) and Veterans Affairs VISN1-CDA(MRP).