EClinicalMedicine最新文献

Background: Neoadjuvant immunotherapy improves outcomes compared to adjuvant therapy in stage III melanoma and reduces costs when adjuvant therapy is omitted following a major pathological response (MPR). However, adjuvant therapy remains the sole systemic treatment for patients identified as stage III by sentinel lymph node biopsy (SLNB). Detecting nodal metastases prior to this procedure could be beneficial.

Methods: We conducted a systematic review and meta-analysis to determine the accuracy of preoperative ultrasound and fine-needle aspiration cytology (FNAC) and the healthcare costs of implementing this strategy. PubMed, Embase, and Web of Science were searched up to March 21, 2025. Diagnostic cohort studies were included when preoperative ultrasound and/or FNAC were performed in patients with cutaneous melanoma eligible for SLNB, with histopathological confirmation. Studies that lacked individual patient-level diagnostic data were excluded. Two reviewers independently screened and extracted data. The pooled sensitivity and specificity were calculated using bivariate or univariate random-effects models. The associated healthcare costs for each strategy were calculated using the pooled estimates, costs of the procedure, therapies and follow-up.

Findings: Of 1315 records screened, 19 diagnostic studies comprising 7396 patients were included. For ultrasound, pooled sensitivity was 33.6% (95% CI: 23.5-45.5%) and specificity 92.4% (87.3-95.6%). For FNAC, pooled sensitivity and specificity were 92.6% (15.9-99.9%) and 99.1% (96.6-99.8%). Most studies had unclear risk of bias in patient selection and index test domains, while applicability concerns were generally low. Substantial heterogeneity was observed across studies. Ultrasound-FNAC was estimated to detect approximately 31% (8/25.5) of nodal metastases preoperatively. Implementation of this strategy was cost saving across multiple scenarios where adjuvant immunotherapy was omitted following MPR.

Interpretation: Implementation of ultrasound-FNAC prior to sentinel lymph node biopsy enables neoadjuvant immunotherapy and is cost saving, indicating potential value in routine clinical practice.

Funding: None.

Background: Patients with osseous metastatic breast cancer receive bone-modifying agents (BMAs) as part of their standard care. Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of this class of drugs. MRONJ heavily impacts patients' quality of life and represents a major medical burden necessitating a discontinuation of treatment. Currently, the diagnosis of MRONJ is established upon the manifestation of clinical symptoms like exposed necrotic jawbone, pain, swelling or signs indicative of infection of the jaw. The objective of this study was to assess the potential of imaging modalities, specifically FDG-PET/CT (positron emission tomography with computed tomography) in the early detection of MRONJ.

Methods: This cohort study in Austria included all patients with metastatic breast cancer who were receiving denosumab and regular PET/CTs, diagnosed with MRONJ between 2000 and 2022 at the Department of Obstetrics and Gynecology Innsbruck. For each of the patients in the study cohort, two control patients with comparable clinical characteristics were matched to serve as a control group. Control patients with metastasized breast cancer did not develop MRONJ but did receive denosumab and regular FDG-PET/CTs. Imaging data were independently assessed by two experienced nuclear medicine physicians.

Findings: Baseline characteristics were well balanced. Patients received 120 mg denosumab once per month subcutaneously without de-escalation of therapy. The median time to develop MRONJ was 23 months (range 5-71, lower Quartile (Q1), upper Quartile (Q3) 16, 40 months). Nuclear medicine physicians detected jaw alterations in 91% (19/21) of MRONJ cases (sensitivity, 95% CI: 70%-98.8%) and in 29% (12/42) of controls, corresponding to a specificity of 71% (30/42; 95% CI: 55%-84%). Median lead time of imaging by demonstrating lesion in the jaw was 238 days (range 11-1118, Q1, Q3 106,494) prior to MRONJ diagnosis. In 68% (13/19) of MRONJ cases the nuclear medicine physicians were able to predict the exact tooth location of MRONJ with a deviation of no more than two teeth.

Interpretation: The high sensitivity and negative predictive value of imaging for early detection of MRONJ underscore its significance for clinical practice. Given that the majority of patients receive regular PET/CTs, our results provide an excellent opportunity for early intervention when MRONJ is detected with a considerable lead time.

Funding: This study received no external funding.

Background: With the recent publication of the first randomized controlled trials (RCTs) comparing robotic partial pancreatoduodenectomy (RPD) versus open partial pancreaticoduodenectomy (OPD) now providing high-level evidence, this study aims to analyze the short-term outcomes of RPD versus OPD to answer the ongoing clinical debate regarding the advantages and limitations of RPD, particularly in terms of perioperative safety.

Methods: We searched Medline, Web of Science, and CENTRAL accessed last on 26th of November 2025 for prospective studies. The main outcome was 90-day mortality; secondary outcomes included complications, and short-term oncological outcomes (R0 resection rate), among others. A random-effects model was employed. Risk of bias was assessed using the Cochrane risk-of-bias-tool (RoB 2) for randomized controlled trials (RCTs), and the ROBINS-I-tool for comparative cohort trials (CCTs). The certainty of evidence was graded according to GRADE. (PROSPERO registration ID: CRD42024523577).

Findings: Out of a total of 7388 screened studies, 358 studies underwent full-text screening leading to inclusion of 7 studies (3 RCTs and 4 CCTs). No significant difference was observed between RPD and OPD for 90-day mortality [OR (95% CI) 1.07 (0.04, 29.40)], clinically relevant complications including postoperative pancreatic fistula (POPF), or reoperation rates [OR (95% CI) 1.10 (0.47, 2.59)]. Lymph node yield, R0 resection rate, operative time and length of hospital stay were also not significantly different. However, readmission rates favored OPD [OR (95% CI) 1.22 (1.15, 1.28)], while there was a lower amount of intraoperative blood loss in RPD [SMD (95% CI) -0.98 (-1.65, -0.32)].

Interpretation: In this systematic review and meta-analysis, mortality following RPD was comparable to OPD. RPD has demonstrated similar rates for major complications and short-term oncological outcomes and can thus be equally recommended as OPD but this recommendation is limited to experienced, high-volume centers.

Funding: This systematic review and meta-analysis was investigator-initiated and did not receive additional funding.

Background: Incentive-based intervention has been widely implemented for HIV prevention and care, necessitating an urgent evidence-based synthesis of the extensive new evidence.

Methods: We conducted a global systematic review and meta-analysis (PROSPERO: CRD42022368634) of randomised controlled trials (RCTs) identified through MEDLINE, Web of Science, and Google Scholar, Embase, Scopus, and region-specific databases (inception to Sep 10, 2024). Two reviewers independently selected studies using the Covidence online tool. Eligible studies with money-type, non-money type, and lottery type of incentives reporting outcomes along HIV prevention and care continuum were included. Cochrane Risk-of -Bias Tool (ROB) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach were used to assess risk of bias and evidence grading. We pooled risk ratio (RR) using random-effects model versus standard care.

Findings: We included 62 RCTs with 118,432 participants from 16 countries, over half of which were published in the recent five years. Compared to standard care, incentive-based intervention was associated with improvements from a 1.8 times increase in HIV testing uptakes (15 studies, 82,327 participants, RR 1.83 [95% CI: 1.31-2.54], I² = 99%) to a 1.25 times increase in viral suppression (14 studies, 14,341 participants, RR 1.25 [1.14-1.38], I² = 75%). When limited to monetary-type incentives, it is associated with 2.13 times of HIV testing uptakes (nine studies, 17,320 participants, [95% CI: 1.36-3.33], I² = 98%). When limited to studies with 2-3 months implementation, it is associated with 2.82 times of HIV testing uptakes (four studies, 25,167 participants, [95% CI: 1.10-7.21], I² = 98%) The effect of incentives varied across countries with different income levels, but consistent across different sexes. There were negative effects found in studies with outcomes of reducing HIV incidence, STI prevalence, and mortality.

Interpretation: Incentive-based interventions are associated with improved outcomes across the HIV prevention and care continuum, with inconsistency between incentive types, implementation duration, income-levels of countries. The results of its implementation, including outcomes and sustainability, are required to maximize its effectiveness in practice.

Funding: National Natural Science Foundation of China and Guangdong Province (Grant No. 82304201 and 2024A1515012123).

Background: Lower socioeconomic position (SEP) is a risk factor for poor-quality end-of-life cancer care, but mechanisms of this disparity are not fully understood. We investigated whether receipt of specialised palliative care (SPC) mediates the effect of SEP on end-of-life cancer care quality outcomes.

Methods: This cohort study included all adults who died with cancer from 2015 to 2021, in Ontario, Canada. We performed a mediation analysis using material deprivation as a measure of SEP, classified into quintiles from least (Q1) to most deprived (Q5). End-of-life outcomes included receipt of systemic anticancer treatment (SACT) and high health services use (≥2 emergency department visits, ≥2 hospitalisations, ≥1 intensive care unit admission) in the last 30 days of life, and home death. Generalised linear models estimated the adjusted odds ratio (aOR) for each outcome, and direct effect of SEP, and the indirect effect via SPC, across each quintile (Q1 = reference).

Findings: Among 173,915 patients, SPC mediated the effects of SEP on end-of-life outcomes. Compared to Q1, patients in Q2-Q5 were progressively less likely to receive SACT at end-of-life (aOR [95% CI], Q3: 0.89 [0.84-0.93]; Q5: 0.77 [0.74-0.81]), or to die at home (Q3: 0.90 [0.87-0.93]; Q5: 0.78 [0.76-0.81]); lack of SPC partially mediated these effects, blunting the effect on SACT and augmenting the effect on home deaths. Compared to Q1, patients in Q2 to 5 were more likely to experience high health services use (Q3: 1.06 [1.02-1.10]; Q5: 1.12 [1.08-1.16]); lack of SPC fully mediated this effect, driven by increasing likelihood of multiple emergency department visits in more deprived quintiles.

Interpretation: Receipt of SPC mediated the effects of SEP on end-of-life quality outcomes. Equitable access to SPC for all patients with cancer may mitigate these disparities.

Funding: This study was supported by an Operating Grant from the Canadian Institutes of Health Research (Dr. Zimmermann), the Harold and Shirley Lederman Chair in Palliative Care and Psychosocial Oncology (Grant number MM1-174912; Dr. Zimmermann), a Doctoral Research Award: Canada Graduate Scholarship (Grant number FBD-181354; Dr. Iqbal) from the Canadian Institutes of Health Research (CIHR), and a Peterborough KM Hunter Charitable Foundation Graduate Award in Cancer Research (Dr. Iqbal).

Background: Previous trials have indicated the potential of arbaclofen for improving social difficulties among autistic children and adolescents with fluent speech. AIMS-2-TRIALS-Clinical Trial 1 (AIMS-2-CT1) examined whether arbaclofen is superior to placebo in improving social function and other secondary outcomes, along with safety and tolerability profiles.

Methods: AIMS-2-CT1 is a multi-site, placebo-controlled double-blind, parallel group Phase II randomized clinical trial. Recruitment was conducted in 7 sites in Spain, United Kingdom and France between September 2019 and September 2022. Eligible participants were randomized 1:1, stratified by age and site, for a 16-week treatment period. Age of participants ranged from 5 to 17 years of age. Primary outcome: Socialization domain of the Vineland Adaptive Behavior Scales change. Secondary outcome measures: CGI-S (Clinical Global Impression-Severity), CGI-I (Clinical Global Impression-Improvement), Social Responsiveness Scale (SRS-2), Autism Impact Measure (AIM), behavioral measurements (CBCL, ABC-C) and Quality of Life (PedsQL). Safety and tolerability were assessed via several instruments. Clinical trial registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Last protocol v.9.1, dated June 18th, 2022.

Findings: 122 participants (out of 123 randomized) comprised the Intention-to-treat sample (59/63 arbaclofen/placebo); 85%/95% of participants on arbaclofen/placebo completed the study.Improvements in the primary endpoint and pre-specified key secondary outcomes did not achieve statistical significance [effect size 1.30 (95% CI: -2.6, 5.1)]. Results on all secondary endpoints favored arbaclofen, with significant improvements on many secondary outcomes including the SRS, the AIM Total scores, some subscales of the ABC, and QoL measures. One Serious Adverse Event (psychotic symptoms) was reported on placebo. Sleep-related problems were more frequent on arbaclofen (N = 34, 57.6% in participants on arbaclofen and N = 22, 34.9% in participants on placebo).

Interpretation: Although we found no significant effect on the primary outcome, improvements were apparent on several secondary measures of autistic related behaviors as well as quality of life. Arbaclofen shows promise in addressing some autistic difficulties and in improving quality of life, but larger scale trials are needed to further advance our understanding of its potential and to inform future drug development in autism.

Funding: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394.

[This corrects the article DOI: 10.1016/j.eclinm.2025.103682.].

Background: Limited knowledge exists on the impact of prenatal exposure to maternal cancer (treatment) on child motor development. We aimed to assess motor outcomes in toddlers and explore potential associations with perinatal and treatment-related factors.

Methods: This national cohort study reports a cross-sectional analysis of children prenatally exposed to maternal cancer who completed the planned 18-month motor assessment at the national Cancer in Pregnancy offspring outpatient clinic (2018-2024), Princess Máxima Center for Pediatric Oncology. Motor development was assessed using the Bayley Scales of Infant and Toddler Development (BSID-III-NL), with outcomes expressed as Z-scores compared with Dutch norms (delay defined as Z < -1). Multivariable linear regression examined associations between predefined prenatal exposures (gestational age at birth, birthweight, timing of maternal treatment, chemotherapy, systemic therapy) and postnatal family burden with motor outcomes. This study is registered with ClinicalTrials.gov, NCT00330447.

Findings: Of 102 eligible children, 96 (94.2%) were included (mean age 19.8 months; mean gestational age 36.8 weeks). Mean Z-scores were -0.38 (95% CI: -0.56, -0.20) for gross motor and 0.09 (95% CI: -0.08, 0.25) for fine motor development. Delayed gross motor development was observed in 32 children (33%), and delayed fine motor development in 16 children (17%). Regression analyses showed no significant associations between gross motor development and the studied prenatal or postnatal factors. Fine motor scores were lower in children with lower gestational age at birth (β = 0.085; 95% CI: 0.011, 0.159) and higher postnatal family burden (β = -0.736; 95% CI: -1.211, -0.261).

Interpretation: At 19 months, one in three children exposed to maternal cancer during pregnancy demonstrated delayed gross motor development. Mean gross motor scores were significantly lower compared with the BSID-III-NL normative population, whereas fine motor development did not differ from reference values. Neither gross nor fine motor development was associated with prenatal exposure to chemotherapy or systemic therapy. Fine motor outcomes were associated with gestational age and postnatal family burden. These findings highlight the need for structured motor surveillance in this population.

Funding: KWF Kankerbestrijding (KWF) grant number 13192.