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Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR = 0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR = 0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR = 0.68, 95%-CI: 0.53-0.86) and event-free survival (HR = 0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3 years was significantly lower with haplo-cord (OR = 0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans

Penpulimab and Gemcitabine With or Without Anlotinib in Metastatic Nasopharyngeal Carcinoma: A Randomized, Open-Label, Multicenter Phase 2 Study.

This prospective exploratory phase 2 study employed a three-cohort, two-phase design to evaluate the potential of anlotinib as a substitute for cisplatin in gemcitabine-penpulimab combinations for metastatic nasopharyngeal carcinoma (NPC) patients who were previously treated with cisplatin-based chemoradiotherapy. Patients enrolled in the study were randomized in a 1:1:1 ratio during the lead-in phase to one of three treatment arms: gemcitabine, cisplatin, penpulimab, and anlotinib (GP-PA, n = 8); gemcitabine, cisplatin, and penpulimab (GP-P, n = 6); or gemcitabine, penpulimab, and anlotinib (GAP, n = 6). The expansion phase enriched the optimal cohort, with stratification based on PD-L1 expression. The primary endpoints were safety and objective response rate (ORR), while the secondary endpoints included duration of response, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). In the lead-in phase, grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 87.5% (GP-PA), 100% (GP-P), and 66.7% (GAP) patients, predominantly hematologic toxicities. ORR/DCR were 62.5%/87.5% (GP-PA), 83.3%/100% (GP-P), and 100%/100% (GAP). At median 20.2-month follow-up, median PFS/OS were 4.1/18.4 months for GP-PA and not reached for GP-P/GAP. In the expansion phase, a total of 14 patients received GAP, with an ORR of 93.3% and grade ≥ 3 TEAEs in 71.4% of patients. At data cut-off point, the median PFS had not been reached, and the 12-month PFS and OS rates were 53.8% and 78.6%, respectively. The GAP regimen demonstrated a favorable safety and efficacy profile, compared to the GP-PA and GP-P regimens in patients with metastatic NPC. These findings suggest that substituting cisplatin with anlotinib may offer a viable therapeutic strategy for this patient population.

Humans

Beyond survival: Testicular tissue cryopreservation for fertility preservation during childhood cancer, experiences from a single center.

INTRODUCTION: Approximately 30% of all male childhood cancer survivors receive gonadotoxic therapy increasing their risk for infertility. The only current option for potential fertility preservation in prepubertal males is through testicular tissue cryopreservation (TTC), available through clinical trials. Our aim was to evaluate our experience and identify barriers to enrollment in the TTC study. METHODS: A retrospective review was conducted to describe a single center experience with TTC, including an assessment of factors impacting the decision to enroll or not enroll in the TTC trial. RESULTS: A total of 61 patients were found to be eligible for enrollment in the TTC trial, with 23 patients (34%) choosing to enroll and undergo testicular tissue cryopreservation including 19 (83%) oncology patients. In patients who underwent TTC there were no unexpected delays in starting disease directed therapy. For families that declined enrollment, many did not see fertility preservation as a priority at the time of counseling. (n = 17, 44%). Other barriers included concerns about post-operative complications and a feeling of being overwhelmed at the time of counseling. DISCUSSION: Despite being the only preservation option for pre-pubertal boys facing risk of infertility, TTC enrollment was not pursued by a majority of eligible patients and families. Identifying potential barriers or misconceptions, particularly in regard to post operative complication risks, offer opportunities for improved counseling and education. Early introduction of the Fertility Navigation team allows for procedural coordination success and access for patients that are interested. Success is not measured in how many patients proceed with TTC, rather that all patients have the opportunity for counseling and discussion. CONCLUSION: TTC can be offered and completed safely without delays in disease-directed treatment timelines. A Fertility Navigation Program allows for equal opportunity for education and enrollment on TTC protocol which should be the goal for pediatric institutions, though is not pursued by many patients. A majority of those who declined the study did not see fertility as a priority at the time of treatment while others were concerned regarding peri-operative risks.

Humans

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 &#x2265;1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans

Tele-Oncology in the Post-Pandemic Era: Clinical Integration, Access Disparities and Medico-Legal Accountability.

PURPOSE OF THE REVIEW: Tele-health has evolved from a marginal tool confined to rural populations and selected follow-up programs into a structurally integrated component of modern cancer care. Prior to COVID-19, its adoption was constrained by regulatory fragmentation, non-uniform reimbursement, and licensure barriers. This narrative review evaluates the evolutionary integration of tele-health in oncology post-COVID-19, examines digital disparities across patient populations, and addresses the medico-legal implications of this integration, with the objective of providing a comprehensive and clinically actionable framework for the governance of virtual oncology care. RECENT FINDINGS: The pandemic acted as a global catalyst, driving telehealth to over 50% of oncology outpatient encounters in some settings, before stabilising post-pandemic at approximately 10-20% of consultations within hybrid care models. Evidence supports meaningful clinical benefits - improved access to specialist services, reduced travel burden, and sustained continuity of care - with outcomes comparable to in-person care in postoperative follow-up, symptom monitoring, and survivorship. However, persistent disparities in device availability, connectivity, and digital literacy disproportionately affect older, rural, and socioeconomically disadvantaged patients, raising the risk that geographic inequalities are replaced by technological ones. From a medico-legal standpoint, the remote modality does not modify the applicable standard of care, yet restricted physical examination and reliance on patient-reported data introduce risks of diagnostic delay and incomplete clinical assessment, with direct implications for professional liability, data protection under HIPAA and GDPR, cross-border licensure, and multi-party accountability across physicians, institutions, and technology providers. Tele-oncology has become a permanent structural feature of modern cancer care, offering demonstrable benefits in access, continuity, and patient satisfaction. Yet its integration has been uneven, its governance remains fragmented, and its medico-legal landscape is still evolving. Realising the full potential of virtual oncology care - equitably and safely - requires coherent regulatory frameworks, sustained investment in digital infrastructure, and explicit attention to the populations at greatest risk of being left behind.

Humans

Minimally invasive versus open surgery for gallbladder cancer: A systematic review and meta-analysis.

INTRODUCTION: Minimally invasive surgery (MIS) is increasingly being used in gallbladder cancer (GBC) for radical tumour extirpation. However, there are conflicting results on the morbidity outcomes following MIS. The aim of this meta-analysis was to compare the post-operative morbidity and mortality in patients undergoing radical surgery for GBC between MIS and open surgery. MATERIAL AND METHODS: Studies comparing MIS (laparoscopic, robotic or both techniques) to open surgery were included. The databases of MEDLINE, Cochrane and EMBASE were searched from 2001 till March 2025. The primary end point was post-operative morbidity and mortality. The secondary end points were hospital stay, blood loss, operative time and R1 resection rates. Random effect models were used for analysis. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: Thirty-two studies (laparoscopic [n&#x202f;=&#x202f;19], robotic [n&#x202f;=&#x202f;6] or both [n&#x202f;=&#x202f;7]) involving 8568 (MIS&#x202f;=&#x202f;3287 and open&#x202f;=&#x202f;5281) patients were included. For overall and major morbidity (Clavian-Dindo >/&#x202f;=&#x202f;III), the odds ratio (OR) of 0.60 (95% CI: 0.46-0.78) and 0.72 (95% CI: 0.52-1.0) respectively was obtained, favouring the MIS approach. Similarly, MIS showed lower odds for mortality [OR:0.62 (95% CI: 0.40-0.95)] compared to open surgery. MIS was associated with shorter hospital stay (less by mean of 3 days) and lesser blood loss (less by mean of 115&#x202f;ml) but longer operative time (higher by mean of 5.8&#x202f;min) and higher R1 resection rates (OR: 1.34; 95% CI: 1.05-1.71). Oncological outcomes, however, were comparable. The certainty of evidence was very low to low across the studies. CONCLUSION: MIS for GBC was associated with relatively lower post operative morbidity and mortality with similar oncological outcomes but with a small but heightened risk of margin positive (R1) resection, especially in primary GBC. The certainty of evidence was very low to low across the included studies. Future prospective studies are needed to overcome the clinical heterogeneity and possible selection bias.

Humans

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans

Older adults with resectable gastric cancer undergoing perioperative chemotherapy or preoperative chemoradiotherapy plus perioperative chemotherapy: A secondary analysis of the AGITG TOPGEAR phase III trial.

PURPOSE: To evaluate treatment adherence, adverse events, and survival in older (&#x2265;70 years) adults undergoing perioperative treatment for gastric cancer. METHODS: Patients with resectable gastric/gastro-esophageal junction adenocarcinoma (ECOG 0-1) enrolled in the phase III TOPGEAR trial were randomized to perioperative chemotherapy (ECF/ECX or FLOT) alone or perioperative chemotherapy plus preoperative chemoradiotherapy (45&#x202f;Gy in 25 fractions with concurrent fluoropyrimidine). In this exploratory analysis, treatment completion, grade &#x2265;&#x202f;3 adverse events (CTCAE v3.0), surgical outcomes, overall survival (OS) and progression-free survival (PFS) were compared between older and younger adults. RESULTS: Of the 574 patients enrolled, 135 (24%) were &#x2265;&#x202f;70 years. Older adults more frequently required preoperative chemotherapy dose reductions, omissions, or delays (chemoradiotherapy: 55% vs 35%, p&#x202f;=&#x202f;0.004; chemotherapy: 60% vs 48%, p&#x202f;=&#x202f;0.087). Rates of grade &#x2265;&#x202f;3 adverse events were comparable between older and younger patients (chemoradiotherapy: 66% vs 67%, p&#x202f;=&#x202f;0.874; chemotherapy: 68% vs 59%, p&#x202f;=&#x202f;0.220), but older adults more often had hematologic toxicity and grade &#x2265;&#x202f;3 diarrhea in the chemotherapy group (56% vs 37%, p&#x202f;=&#x202f;0.006; 21% vs 6%, p&#x202f;<&#x202f;0.001). Resection rates, grade 3/4 surgical complications, number of removed lymph nodes, and 30-/90-day mortality were similar by age. OS and PFS were comparable across age groups, with numerically favorable outcomes for older adults (OS: HR 0.86, 95% CI 0.58-1.26 [chemoradiotherapy]; HR 0.75, 95% CI 0.51-1.11 [chemotherapy]; PFS: HR 0.78, 95% CI 0.53-1.15 [chemoradiotherapy]; HR 0.70, 95% CI 0.47-1.03 [chemotherapy]). CONCLUSIONS: Older adults with gastric cancer achieved comparable oncologic outcomes to younger patients, despite more frequent treatment modifications and higher hematologic toxicity.

Humans

Could the preoperative urethral curve be used to predict immediate urinary continence following Retzius-sparing robot-assisted radical prostatectomy? A retrospective multi-center study.

PURPOSE: Immediate urinary continence (UC) recovery following Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) remains highly variable, highlighting the need for reliable preoperative prediction. We aimed to develop and validate models to identify patients likely to achieve immediate UC recovery following RS-RARP. MATERIALS AND METHODS: A total of 580 prostate cancer patients who underwent RS-RARP from four medical centers were assigned to a training set (n=348), an internal validation set (n=103) and an external validation set (n=129). Independent predictors were identified through univariate analysis and LASSO regression. A nomogram was constructed using multivariate logistic regression. Its performance was evaluated with receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis. RESULTS: Immediate UC recovery was observed in 84.5% (294/348) of patients in the training cohort, 80.6% (83/103) in the internal validation cohort, and 81.4% (105/129) in the external validation cohort, respectively. Multivariate analysis identified membranous urethral length (MUL) (OR=1.23, P=0.029) and urethral curvature (OR=2.84, P<0.001) as independent predictors, while prostate volume (PV) (OR=0.84, P <0.001) as a protective factor. The nomogram integrating MUL, PV, and urethral curvature demonstrated superior predictive accuracy, with an AUC of 0.87 (95% CI, 0.83-0.91) in the training cohort. The bootstrap-corrected calibration slope was 0.96, and the Brier score was 0.08.&#xa0;Calibration curves and decision curve analysis confirmed the predictive accuracy and clinical utility of the nomogram. CONCLUSIONS: Our study introduces a novel quantitative method for assessing urethral curvature. The mpMRI-based model, integrating urethral curvature and prostate spatial configuration, offers enhanced predictive accuracy for postoperative immediate UC recovery.

Humans

Performance of Photon-counting CT for Assessing Pretreatment Breast Cancer: Comparison with Mammography, MRI, and 18F-FDG PET/CT.

Background Photon-counting CT (PCCT) offers improved spatial resolution, contrast to noise ratio, and dose efficiency, but its clinical utility remains incompletely defined for breast cancer. Purpose To evaluate the feasibility of PCCT for pretreatment breast cancer assessment through comparisons with MRI, full-field digital mammography (FFDM), and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. Materials and Methods In this prospective study (March-May 2025), female participants with breast lesions categorized as Breast Imaging Reporting and Data System 4C or higher at US or FFDM underwent breast MRI and multiphasic contrast-enhanced PCCT. 18F-FDG PET/CT was performed in a subset with locally advanced disease. Four radiologists independently evaluated lesion morphologic characteristics, additional findings, and clinical TNM stage. Agreement was analyzed using intraclass correlation coefficients (ICCs) and &#x3ba; statistics. The diagnostic performance for additional lesions and nodal metastasis was compared with the reference standard (pathologic examination). Results Among 126 participants (mean age, 58.1 years &#xb1; 12.3 [SD]), interreader agreement across PCCT, MRI, and FFDM was good to excellent. PCCT agreed with MRI for lesion characterization (&#x3ba; = 0.57-0.96) and clinical T categorization (&#x3ba; = 0.86-0.88), with highest agreement with pathologic size (ICC, 0.70-0.81). For 46 pathologically confirmed additional lesions, PCCT was more sensitive than FFDM (difference, 44% [95% CI: 19, 66]) and similar to MRI (difference, 7% [95% CI: -5, 21]). Additionally, 44% (95% CI: 27, 52) of microcalcifications were missed at PCCT versus FFDM. For pathologically confirmed nodal metastasis, PCCT was more sensitive (difference, 10% [95% CI: 1, 20]) and accurate (difference, 6% [95% CI: 1, 11]) than MRI. For clinical N category, PCCT agreed with PET/CT (&#x3ba; = 0.82 [95% CI: 0.62, 0.96]; n = 19). Two distant metastases identified at PCCT were consistent with 18F-FDG PET/CT and pathologic findings. Conclusion PCCT demonstrated similar performance to MRI for lesion characterization and detection of additional lesions, with better performance for nodal metastasis evaluation; however, detection of microcalcifications was limited. &#xa9; RSNA, 2026 Supplemental material is available for this article.

Humans

[Moxibustion combined with Jianpi Wenshen formula for cancer-related anorexia of spleen-kidney yang deficiency: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of moxibustion combined with Jianpi Wenshen formula in treating cancer-related anorexia of spleen-kidney yang deficiency. METHODS: A total of 80 patients with cancer-related anorexia of spleen-kidney yang deficiency were randomized into an observation group and a control group, with 40 cases in each group.Jianpi Wenshen formula was given orally in the control group. On the basis of the treatment in the control group, moxibustion was applied at bilateral Zusanli (ST36), Neiguan (PC6) and Zhongwan (CV12), Guanyuan (CV4), Mingmen (GV4) in the observation group, once daily for the first 15 days, then once every other day. Both groups were treated for 4 weeks. The scores of appetite, Karnofsky performance status (KPS), nutritional risk screening 2002 (NRS-2002), and patient-generated subjective global assessment (PG-SGA), as well as the serum levels of interferon-&#x3b3; (IFN-&#x3b3;) and C-reactive protein (CRP)were observed before and after treatment, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the scores of appetite, NRS-2002, PG-SGA, and the serum levels of IFN-&#x3b3; and CRP were decreased compared with those before treatment in the two groups (P<0.001, P<0.05, P<0.01), and the above indexes in the observation group were lower than those in the control group (P<0.05, P<0.001); the KPS scores were increased in the two groups compared with those before treatment (P<0.001, P<0.05), and the KPS score in the observation group was higher than that in the control group (P<0.001). The marked response rate was 57.5% (23/40) in the observation group, which was higher than 30.0% (12/40) in the control group (P<0.05). CONCLUSION: Moxibustion combined with Jianpi Wenshen formula can effectively improve appetite and overall status, and reduce the levels of IFN-&#x3b3; and CRP in patients with cancer-related anorexia of spleen-kidney yang deficiency.

Humans

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans

Clinical Utility of Ultra-Widefield Swept-Source OCT for Intraocular Tumors: Comparison With Ultrasonography, SD-OCT, and MRI.

PURPOSE: To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)-OCT, and magnetic resonance imaging (MRI). DESIGN: Retrospective diagnostic comparison. SUBJECTS: Thirty-nine eyes from 39 patients diagnosed with choroidal tumors at a single tertiary referral center. METHODS: This retrospective diagnostic comparison evaluated patients diagnosed with choroidal tumors at a single tertiary referral center between January 2023 and August 2025. All patients underwent UWF-OCT imaging at diagnosis. Tumor measurements obtained with UWF-OCT were compared with US, SD-OCT, and MRI. Comparative analysis among imaging modalities and predictors affecting UWF-OCT applicability was performed. MAIN OUTCOME MEASURES: Tumor thickness (mm) and largest basal diameter (LBD, mm) measurements, and complete measurability rate across different tumor size categories. RESULTS: Thirty-nine eyes from 39 patients (mean age 59.2 &#xb1; 16.9 years) were analyzed, including 27 choroidal melanomas (69.2%), 5 metastatic tumors (12.8%), 4 hemangiomas (10.3%), 2 osteomas (5.1%), and 1 (2.6%) indeterminate choroidal melanocytic lesion. UWF-OCT successfully measured both tumor thickness and largest basal diameter (LBD) in 100% (31/31) of small and medium choroidal tumors, substantially outperforming SD-OCT (complete measurement achieved in 63.6% of small tumors, and 0% of medium or large tumors). UWF-OCT measurements were systematically smaller than ultrasonography (thickness: -32.3%, P < .01; LBD: -11.1%, P < .01) and MRI (thickness: -29.2%, P < .01). Mushroom-shaped tumor morphology was the strongest negative predictor of UWF-OCT quality (OR = 0.015, 95% CI 0.001-0.196, P < .01). UWF-OCT's complete measurability was limited in large tumors (12.5%, 1/8). CONCLUSIONS: UWF-OCT provides precise, noninvasive, single-scan assessment of small-to-medium choroidal tumors with detailed structural visualization. It may be particularly useful for dome-shaped tumors, while multimodal imaging with US and MRI remains optimal for complex morphologies. Overall, UWF-OCT represents a valuable tool for diagnosis and treatment planning, with potential utility for longitudinal follow-up in choroidal tumor management.

Humans

Safety and efficacy of Meridian sinew tuina (MST) for post-surgical upper limb lymphedema: a systematic review and meta-analysis.

BACKGROUND: Complex Decongestive Therapy (CDT) is the non-operative standard for breast cancer-related lymphedema (BCRL), but many patients experience persistent subcutaneous stiffness, pain, and restricted mobility. This study systematically reviews the safety and clinical efficacy of Meridian Sinew Tuina (MST) protocols for BCRL. METHODS: Global and regional databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP) were searched from inception to January 15, 2026, with alerts monitored through April 30, 2026. Randomised controlled trials (RCTs) evaluating MST (deep tissue mobilisation along the six-hand meridian sinew [Jingjin] lines via plucking, kneading, and pressing) were included. Two reviewers independently extracted data, evaluated risk of bias using Cochrane RoB 2, and assessed evidence certainty via GRADE using a random-effects model. RESULTS: Fifteen RCTs were included. For the primary anthropometric outcome, MST significantly reduced upper limb circumference compared to controls (SMD = 1.59; 95% CI: 1.44 to 1.74; Z&#x2009;=&#x2009;20.81; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;924; GRADE: Moderate certainty). The Clinical Response Efficacy Rate (&#x2265; 30% swelling reduction and symptom relief) favoured MST (RR = 1.69; 95% CI: 1.54 to 1.87; Z&#x2009;=&#x2009;10.62; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;1,114; GRADE: Moderate certainty). Trial Sequential Analysis confirmed sample size sufficiency. For secondary outcomes (N&#x2009;=&#x2009;924; GRADE: Low to Very Low certainty due to performance bias and clinical heterogeneity), MST showed favourable 3-month improvements in DASH functional scores (SMD&#x2009;=&#x2009;-1.81; 95% CI: -2.11 to -1.51; I2=45.1%), pain intensity (SMD&#x2009;=&#x2009;-2.44; 95% CI: -2.93 to -1.95; I2=50.4%), and quality of life (SMD = 1.04; 95% CI: 0.79 to 1.29; I2=0.0%). No serious adverse events occurred. CONCLUSIONS: MST protocols are associated with favourable short- and mid-term reductions in upper limb swelling. However, confidence is tempered by unblinded performance bias and control group variations. MST cannot be unconditionally recommended for standalone implementation but represents a promising, optional supportive adjunctive intervention within oncological rehabilitation.

Humans

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

Humans

Transcranial Motor Evoked Potential Monitoring Using Propofol-Fentanyl Versus Desflurane-Dexmedetomidine Anesthesia During Spinal Cord Tumor Resection: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing resection of spinal cord tumours require intraoperative neuromonitoring. Transcranial electrical stimulation is used to record myogenic responses during surgery. This study aimed to compare the effect of 2 anaesthetic regimens, propofol/fentanyl versus desflurane/dexmedetomidine, on the ability to record MEPs with an amplitude of 50&#xa0;&#xb5;V or greater. Our secondary outcome compared intraoperative haemodynamics, recovery profile, and postoperative analgesia between the groups. METHODS: We conducted a prospective, double-blinded, open-label, single-centre, randomized controlled trial of 50 adult patients undergoing spinal cord tumour resection with TcmMEP monitoring. Patients were randomized to 2 groups: Group P (n=25) received intravenous anaesthesia with propofol and fentanyl; group D (n=25) received desflurane and dexmedetomidine. RESULTS: We recorded TcmMEP's in 80% of group P and 76% group D (95% CI: -23% to 31%, P =1.00). The time in minutes for spontaneous breathing (21.04&#xb1;11.31 vs. 8.00&#xb1;3.42 [8.29-,17.79, P =0.01]), extubation (31.56&#xb1;17.56 vs. 10.84&#xb1;3.99 [13.48-27.96; P =0.01]), emergence (33.68&#xb1;18.11 vs. 10.92&#xb1;4.01 [15.30-30.22, P =0.001]), discharge readiness (45.00&#xb1;25.24 vs. 15.56&#xb1;6.08 [19.00-39.88; P =0.001]) and requirement of first analgesia (136.6&#xb1;108.04 vs. 230.8&#xb1;81.33) (-148.58 to -39.82; P =0.01) was lower in group D compared with group P. Postoperative analgesia assessed using the Visual Analogue Score was lower in group D compared with group P at 12 and 24 hours. (1.68&#xb1;1.18 vs. 0.64&#xb1;1.31 [0.33-1.74 P =0.001]) :1.4&#xb1;0.95 vs. 0.36&#xb1; 0.70 (0.56-1.51; P =0.001). CONCLUSIONS: We found similar rates of successful TcMEP monitoring using desflurane-dexmedetomidine and propofol-fentanyl. Patients who received desflurane-dexmedetomidine had reduced emergence time, discharge readiness, and lower pain scores in the postoperative period.

Humans

Behaviourally informed text message reminders to increase cervical screening attendance in people with severe mental illness: the OPTIMISE pilot randomised controlled trial.

OBJECTIVES: This study assessed the feasibility of both the delivery and evaluation of 'enhanced' (behaviourally informed) text message reminders containing links to existing co-designed resources supporting decision-making for people with severe mental illness (SMI) regarding attendance of cervical screening. DESIGN: A pilot randomised controlled trial (RCT). SETTING: 13 General Practice (GP) practices in London were recruited. PARTICIPANTS: GP practices identified people with SMI aged 24-64 years who were overdue cervical screening. Target sample size was 120 participants (60 per arm) based on existing guidance for pilot trials. INTERVENTION: In March 2025, participants were randomised (1:1) to receive either the enhanced (intervention) or the standard (control) SMS reminder. PRIMARY AND SECONDARY OUTCOME MEASURES: 18 weeks later, feasibility outcomes were collected (primary outcomes) and data analysis for a definitive RCT was rehearsed (secondary outcome). RESULTS: Of the 150 participants across 13 GP practices that were randomised (n=75 per arm), 132 (88%) texts delivered (intervention n=64/75 (85%), control n=68/75 (91%)). 10 practices (76.9%) provided follow-up data for 102 participants (intervention n=50, control n=52). Five participants (intervention n=4, control n=1) attended screening within the trial period. Participant survey response rate was low (9/132 (7%), intervention n=5, control n=4). Both SMS messages were low cost, with the intervention SMS a 50% higher cost to deliver (7.5p vs 5p per SMS). Primary feasibility measures of recruitment rate of GP practices (27%), retention of GP practices (77%) and participants (100%), SMS delivery (88%) and data completeness (64%) indicated viability, although survey response rate (7%) did not. CONCLUSIONS: Achieving adequate recruitment and retention, data completeness and comparable groups is viable with some amendments, although an alternative method is required to assess fidelity. Behaviourally informed SMS reminders are feasible to deliver to people with SMI, although it is uncertain if the extra resources are accessed and used. With changes to data collection, a definitive trial could be feasible. Given the low observed cervical screening attendance, additional intervention is needed for this group. TRIAL REGISTRATION NUMBER: ISRCTN12558681.

Humans

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p&#x202f;<&#x202f;0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans