This multicenter retrospective study evaluated first-line treatment patterns, maintenance therapy outcomes, and prognostic factors in 171 newly diagnosed marginal zone lymphoma (MZL) patients treated across multiple centers in Fujian Province, China (2019-2024). The MALT subtype predominated (79.0%), with the gastrointestinal tract and lung being the most common primary sites. The first-line overall response rate was 91.1%, with 67.3% of patients achieving complete remission. Five-year progression-free survival (PFS) and overall survival (OS) were 82.6% and 94.7%, respectively. Maintenance therapy, received by 66.1% of patients, was associated with superior 5-year OS (100% vs. 87.5%, P=0.0104). Multivariate analysis identified Ki-67 >20% (HR=3.208, P=0.024) and high tumor burden (HR=4.670, P=0.003) as independent negative predictors for PFS, while high tumor burden (HR=4.493, P=0.004) and B symptoms (HR=3.324, P=0.030) predicted worse OS. Chinese MZL patients demonstrated favorable outcomes, and maintenance therapy conferred a significant OS benefit. Ki-67, tumor burden, and B symptoms serve as practical prognostic indicators to inform risk stratification and personalized treatment planning.
Hepatocellular carcinoma (HCC) frequently develops resistance to tyrosine kinase inhibitors (TKIs) like sorafenib - the first FDA-approved systemic therapy for advanced HCC - yet early resistance mechanisms remain unclear. Short-term sorafenib exposure in sensitive HCC cells induces global m6A reduction and rapid upregulation of the demethylase ALKBH5. High ALKBH5 expression correlates with poor prognosis in sorafenib-treated HCC patients. Functionally, ALKBH5 overexpression enhances sorafenib resistance, clonogenicity and epithelial-mesenchymal transition (EMT) by stabilizing β-catenin and activating Wnt/β-catenin signalling. Thus, ALKBH5 is a key early driver of sorafenib resistance via the Wnt/β-catenin pathway and may serve as both a prognostic biomarker and therapeutic target in HCC.
Immune checkpoint inhibitor (ICI) resistance remains a major challenge in esophageal squamous cell carcinoma (ESCC). This study investigates the role of glutaminase (GLS) in modulating the tumor immune microenvironment and its impact on immunotherapy response. Bioinformatic analysis of TCGA data revealed an inverse correlation between GLS expression and CD8+ T cell infiltration. In ESCC clinical specimens, high GLS expression correlated with elevated CXCL8 levels and reduced CD8+ T cell infiltration. Mechanistically, our data support an association between GLS expression and increased CXCL8 transcription, accompanied, at least in part, by HAT-dependent enhancement of H3K27 acetylation at the CXCL8 promoter region. In advanced ESCC patients receiving immunochemotherapy, high tumoral GLS expression was associated with significantly shorter progression-free survival. In vitro and in vivo functional studies showed that GLS knockdown in ESCC cells was associated with enhanced T-cell effector cytokine secretion, increased tumor infiltration of CD8+ T cells, and greater tumor suppression when combined with anti-PD-1 therapy in a humanized mouse model. Importantly, exogenous CXCL8 supplementation partially reversed the increased Granzyme B and IFNγ secretion induced by GLS knockdown in the co-culture system, supporting a functional role for CXCL8 in GLS-associated immune suppression. These results support a model in which GLS contributes to an immunosuppressive microenvironment in ESCC, at least in part through epigenetic upregulation of CXCL8. These findings support further investigation of GLS targeting as a potential strategy to improve immunotherapy response in ESCC.
This Systematic review provides a comprehensive framework for understanding current therapeutic options and future directions in prostate cancer treatment. It highlights ongoing efforts, focusing on AR signaling inhibitors (ARSi) and novel molecularly targeted therapies. Using PRISMA-ScR guidelines, we conducted a comprehensive literature search across significant databases (MEDLINE/PubMed, Embase, and Cochrane Library). Next-generation ARSi (enzalutamide, apalutamide, darolutamide) have demonstrated significant survival benefits across various stages of prostate cancer, as evidenced by pivotal trials (PROSPER, SPARTAN, ARAMIS). The emergence of promising therapeutic approaches for biomarker-defined patient subgroups, including PARP inhibitors (PROfound, TRITON2), radioligand therapy (VISION, TheraP), and immunotherapy (KEYNOTE-199, CheckMate 650), is increasingly clinically relevant. While significant advances have been made in AR-targeted therapies, emerging molecular-targeted approaches are reshaping the treatment landscape. Our data provide a comprehensive framework for understanding current therapeutic options and future directions in prostate cancer treatment, engaging the audience and making them feel part of the solution.
Overall survival (OS) has improved in unresectable/metastatic pancreatic adenocarcinoma (mPDAC) patients. However, it is unclear who should be offered further treatment, and how to assess the response in unmeasurable disease. The study aims to evaluate the role of 6-month progression-free survival (PFS) and the corresponding tumor growth rate after first-line chemotherapy (G6m). After identifying 15 randomized trials (19 cohorts, 4,725 patients), 6-month PFS were extracted from curves and expressed as G6m. Median G6m was higher after polychemotherapy and was significantly associated with OS (β = 0.168; p-value <0.001). The number of drugs and female sex correlated with a slower tumor growth rate. Since it was calculated directly from PFS in this study, it is not surprising that G6m exhibits a similar behavior. However, it can be derived by imaging or other markers, therefore representing a variable distinct from PFS, and as such warrants further evaluation in future studies.
Interpatient variability in chemotherapy response and toxicity remains a major challenge in oncology. Pharmacogenomics (PGx) is an approach to address this challenge by combining somatic alterations that affect tumour sensitivity with germline variants that affect drug metabolism, transport and toxicity. This review provides a critical evaluation of clinically validated PGx biomarkers for chemotherapeutics and targeted therapy with a focus on translational relevance and strength of evidence. High-impact germline markers such as DPYD, TPMT, NUDT15 and UGT1A1 are highlighted as key determinants of genotype-guided dosing for improving safety without compromising efficacy. Somatic biomarkers such as EGFR, RAS, BRAF, and HER2 remain central to treatment selection, while resistance underscores the need for ongoing molecular assessment. A tiered implementation framework, barriers to progress, and future directions involving polygenic models, multi-omics, and artificial intelligence (AI) are discussed to advance safe, effective, and personalized chemotherapy.
BACKGROUND:The rising prevalence of antimicrobial resistance poses a significant challenge in clinical practice, with long-acting lipoglycopeptides (LGPs) offering an attractive alternative to conventional daily intravenous antibiotics. This study aims to evaluate the clinical efficacy, safety, and economic burden of LGPs in the treatment of skin and soft tissue infections. METHODS:This was a retrospective, single-centre, observational study including 125 patients with skin and soft tissue infections who were either treated with LGPs such as dalbavancin or oritavancin (Group A, n = 62), or with standard daily IV therapy including vancomycin, linezolid, or daptomycin (Group B, n = 63). The primary outcome was clinical improvement, while secondary outcomes included length of hospital stay, adverse events, and relapse rate during a 28-day period. RESULTS:The overall clinical success rate was comparable between the two groups (Group A: 95.1% vs. Group B: 92.0%, p = 0.11). However, patients treated with LGPs demonstrated a shorter median hospital stay (Group A: 5.5 days vs. Group B: 11.0 days, p < 0.001), which was also correlated with a lower average cost of hospitalization. Furthermore, the incidence of adverse events was lower in the LGP group (Group A: 8.06% vs. Group B: 25.4%). CONCLUSION:Long-acting lipoglycopeptides demonstrated comparable clinical success rates to conventional daily intravenous antibiotics for the treatment of ABSSSI, with a 'favorable safety profile.' Moreover, the reduced cost and shorter hospitalization further support the use of LGPs as a safe and effective alternative for managing these infections.
This study aimed to evaluate the safety and efficacy of PD-1/PD-L1 ICI plus chemotherapy versus chemotherapy alone in ES-SCLC, following PRISMA guidelines.23 studies(10RCTs,13RWSs) with 6364 patients were enrolled,with OS,PFS,ORR and grade 3-4 AEs as primary endpoints. Pooled analyses demonstrated that ICI + chemotherapy (CT) significantly improved OS (HR = 0.68) and PFS (HR = 0.60), and ORR (RR = 1.13). Subgroup analyses confirmed consistent OS/PFS benefits in both RCT and RWS cohorts. Both PD-1 and PD-L1 inhibitors improved survival; PD-1 inhibitors yielded greater PFS benefit(HR=0.49) and significant ORR improvement, while PD-L1 inhibitors showed no significant ORR elevation. The combination slightly increased overall AEs with no difference in severe events, with manageable safety.This meta-analysis supports chemoimmunotherapy as first-line treatment for ES-SCLC.
Clostridioides difficile infection complicating severe bacterial infections presents a therapeutic challenge, when antimicrobial discontinuation is unfeasible. Eravacycline, a synthetic fluorocycline with broad-spectrum activity against Gram-positive, Gram-negative and anaerobic bacteria, including C. difficile, carries a relatively low risk of inducing C. difficile. Although approved for complicated intra-abdominal infections, emerging evidence indicates its potential for other severe infections. We report three cases of C. difficile infection during systemic antibacterial therapy for severe infections complicated by sepsis. In all cases, antibiotics could not be discontinued due to uncontrolled infection. Switching to intravenous eravacycline, alongside C. difficile-directed therapy, allowed clinical improvement of the underlying infection and resolution of diarrhea, with no eravacycline-related adverse events. Two patients survived to discharge without recurrence at 90-day follow-up, whereas one patient died from unrelated complications. This limited experience indicates that eravacycline might be a microbiome-sparing stewardship option in selected severe infections complicated by C. difficile infection.
Neutropenic sepsis remains a life-threatening complication in patients undergoing cytotoxic chemotherapy or haematopoietic stem cell transplantation. A comprehensive literature search was conducted across PubMed, Embase, and the Cochrane Library through December 2025, focusing on clinical trials, observational studies, and population PK analyses involving neutropenic or febrile neutropenic patients in both adult and paediatric haematology and oncology populations. Pathophysiological changes in neutropenic sepsis-including augmented renal clearance, increased volume of distribution, and hypoalbuminemia-lead to substantial PK variability and frequent target non-attainment with standard dosing. Animal models consistently demonstrate that higher PK/PD targets are required in the absence of neutrophils. PK/PD-guided dose optimisation appears highly beneficial in neutropenic sepsis, although prospective randomised evidence specifically in this population remains limited. Integration of TDM, population PK modelling, and Bayesian dose adaptation into routine clinical practice represents a promising avenue towards improved outcomes, recognising that implementation will depend on locally available laboratory and pharmacy resources.
Apatinib combined with CAPTEM (capecitabine plus temozolomide) has demonstrated preliminary activity in neuroendocrine tumours, yet head-to-head comparative efficacy data against standard-of-care sunitinib remain lacking. This study aims to evaluate the efficacy and safety of both regimens in advanced GEP-NETs using real-world data. This retrospective analysis examined patients with advanced GEP-NETs treated with either apatinib plus CAPTEM or sunitinib.Baseline characteristics (e.g. pathological grade, hepatic tumour burden) were balanced between groups using 1:1 propensity score matching (PSM). The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), and safety. A total of 150 patients were included in the analysis, with 52 patients in each group after PSM. Following matching, the median PFS was significantly longer in the apatinib plus CAPTEM group compared with the sunitinib group (not reached [NR] [95% CI: 36.6-NR] vs 17.9 months [95% CI: 8.0-18.0]; hazard ratio [HR] = 0.17, 95% CI: 0.08-0.36; p < 0.001). The combination therapy group also demonstrated a significant OS benefit (52.0 months [95% CI: 48.1-58.0] vs 16.4 months [95% CI: 12.7-22.1]; HR = 0.10, 95% CI: 0.05-0.22; p < 0.001). The ORR was numerically higher in the combination group than in the sunitinib group (65.4% vs 50.0%, p = 0.164). Regarding safety, the sunitinib group exhibited higher rates of hand-foot syndrome and diarrhoea, whilst the combination group did not experience any unexpected severe toxicities. In a PSM-matched cohort of advanced GEP-NETs, apatinib combined with CAPTEM was associated with improved PFS and OS, together with a numerically elevated ORR. Given the retrospective design and the potential for residual confounding, these findings should be considered hypothesis-generating and warrant prospective validation.
Stenotrophomonas maltophilia is an opportunistic multidrug-resistant pathogen increasingly associated with severe infections. Although cefiderocol has demonstrated potent in-vitro activity against S. maltophilia, clinical evidence remains limited. We performed a retrospective multicenter study including adult patients with S. maltophilia infections treated with cefiderocol in three tertiary-care hospitals between 2021-2024. Primary outcomes were 30-day mortality, clinical cure, microbiological eradication, and treatment-related adverse events. A review of the available literature was conducted. Fourteen patients were included (median age 61 years; median Charlson Comorbidity Index 5). Pneumonia was the most common infection (50%), while polymicrobial infections occurred in 42.9% of cases. TMP-SMX resistance was observed in 35.7% of isolates. Clinical cure and microbiological eradication were achieved in 64.3% and 75% of patients, respectively, whereas 30-day mortality was 21.4%. No cefiderocol-related adverse events were reported. These findings support cefiderocol as an effective and well-tolerated option for S. maltophilia infections, particularly when conventional therapies are limited.
This study investigated the in vitro activity of cefiderocol against Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia isolates, comparing disk diffusion (DD) and broth microdilution (BMD) methods. 145 isolates were tested using BMD in iron-depleted cation-adjusted Mueller-Hinton broth and DD. Results were interpreted via CLSI and EUCAST criteria. MBL genes were detected by PCR. Cefiderocol showed potent activity against P. aeruginosa (MIC90:2 mg/L) and S. maltophilia (MIC90:0.5 mg/L) with >98% DD agreement. In contrast, A. baumannii exhibited higher MIC values (MIC90:8 mg/L). For A. baumannii, DD agreement dropped to 50% under EUCAST criteria, failing to detect 'grey zone' (MIC:1-2 mg/L) isolates. This resulted in 14.3% very major errors. Cefiderocol is effective against P. aeruginosa and S. maltophilia, with reliable DD results. However, for A. baumannii, reduced reliability of DD in the 'grey zone' highlights the need for MIC confirmation.
Multidrug-resistant Achromobacter xylosoxidans infections in pediatric patients with primary ciliary dyskinesia (PCD) often require prolonged intravenous therapy. We evaluated the pharmacokinetics of continuous infusion piperacillin/tazobactam (16 g/2 g daily) in a 13-year-old male with situs inversus and chronic otitis media transitioned from hospital-based electronic infusion to home-based Outpatient Parenteral Antimicrobial Therapy (OPAT) using elastomeric pumps. Plasma concentrations were measured by Therapeutic Drug Monitoring (TDM), and tissue exposure was estimated using conservative penetration coefficients. Drug concentrations consistently remained above the MIC (≤2 mg/L). During hospitalization, steady-state concentrations were stable (27.2-29.0 mg/L; CV 4.5%), whereas during OPAT they were higher and more variable (53.9-80.1 mg/L; CV 20.1%), consistent with the known non-linear delivery profiles of elastomeric devices. Despite this variability, TDM confirmed sustained supratherapeutic exposure, with estimated tissue concentrations remaining >5-fold above the MIC. Clinical resolution was achieved without adverse events, supporting the role of TDM-guided OPAT in difficult-to-treat infections.
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous malignancies frequently resistant to standard therapies. Immunotherapy represents a novel management frontier. This review synthesises clinical and translational evidence regarding immune checkpoint inhibitors (ICIs), bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cell therapies, and oncolytic virotherapy in GEP-NENs. We examine critical antigenic targets (somatostatin receptors, DLL3) and strategies to overcome the immunosuppressive tumour immune microenvironment (TIME). While single-agent ICIs show modest efficacy in well-differentiated NETs, dual checkpoint blockade exhibits durable disease control in poorly differentiated NECs. Targeted modalities like DLL3-directed bispecific antibodies demonstrate significant early efficacy. Furthermore, we summarise highly synergistic combinatorial approaches, specifically integrating immunotherapy with anti-angiogenic agents and peptide receptor radionuclide therapy (PRRT). Ongoing biomarker-driven trials and molecular profiling remain essential to optimise patient selection and treatment sequencing.
We report the case of a 91-year-old man with prosthetic valve endocarditis (PVE) caused by vancomycin-resistant Enterococcus faecium (VRE), successfully managed with an initial two-week course of intravenous daptomycin and fosfomycin, followed by six once-weekly outpatient infusions of oritavancin. The diagnosis was established based on positive blood cultures and transoesophageal echocardiography findings. In the challenging epidemiological setting of Greek hospitals-characterized by endemic multidrug-resistant organisms and a high burden of healthcare-associated infections-minimizing hospitalization is a key consideration. Oral linezolid was avoided due to its bacteriostatic activity, relatively low serum levels, and the risk of myelotoxicity in elderly patients. The patient achieved complete clinical and microbiological resolution and remained relapse-free at six months of follow-up. This case highlights the feasibility of long-acting lipoglycopeptides, such as oritavancin, as sequential therapy to enable outpatient completion of prolonged treatment in selected patients with VRE prosthetic valve endocarditis.
Hydration is crucial for preventing cisplatin-induced nephrotoxicity; however, optimal hydration for low-dose cisplatin (<50 mg/m2) remains unclear. This multicentre retrospective study assessed whether low-volume hydration (LV, <1500 mL) is non-inferior to high-volume hydration (HV, ≥1500 mL) in patients with biliary tract cancer receiving gemcitabine plus cisplatin (25 mg/m2). Of 239 patients, 109 LV and 97 HV patients were analysed. Primary endpoint was acute kidney injury (AKI) incidence. Propensity score weighting was applied to adjust for confounders. Post-adjustment AKI incidence was 4.7% (LV) vs. 10.1% (HV), confirming non-inferiority (risk difference upper 95% CI: 0.002, margin <0.05). No significant differences were observed in serum creatinine or creatinine clearance trajectories. In conclusion, low-volume hydration was non-inferior to high-volume hydration for AKI risk in low-dose cisplatin therapy. These findings support tailoring hydration to reduce patient burden without compromising safety.
This study aimed to assess the efficacy of different eravacycline regimens for adult skin and soft-tissue infections (SSTIs) caused by carbapenem-resistant Enterobacteriaceae (CRE). Monte Carlo simulations were performed using pharmacokinetic and pharmacodynamic data to calculate probabilities of target attainment (PTA) and cumulative fractions of response (CFR) according to 24-h free drug area under the concentration curve/minimum inhibitory concentration (MIC) targets. PTA results revealed that the standard 1 mg/kg intravenous q12h regimen exerted bacteriostatic/bactericidal efficacy against Enterobacteriaceae with MIC ≤ 0.5 μg/mL. All simulated regimens achieved CFR values exceeding 90% against Escherichia coli and carbapenem-resistant Escherichia coli. For Enterobacter cloacae complex and Klebsiella pneumoniae, doses of at least 1.5 and 2.5 mg/kg twice daily were required to meet therapeutic targets, respectively. However, few regimens yielded satisfactory efficacy against carbapenem-resistant Enterobacter cloacae complex and Klebsiella pneumoniae. These pharmacokinetic/pharmacodynamic simulations rationalized and optimized eravacycline dosing strategies for CRE-related SSTIs in adult patients.
Taxanes such as paclitaxel and docetaxel are widely used in malignancies but may cause rare ophthalmic toxicities, including macular oedema. This study clarified occurrence patterns and time to onset by analysing the FDA Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER). In total, 4880 macular oedema cases were reported in FAERS and 523 in JADER; 306 and 97 cases were attributed to paclitaxel, and 54 and 13 to docetaxel, respectively. Disproportionality analysis showed positive reporting signals. Median onset times were 115 d in FAERS and 145 d in JADER for paclitaxel and 104 d in FAERS for docetaxel. Weibull shape parameters indicated a random pattern. Outcomes were mostly favourable for paclitaxel, whereas docetaxel cases showed more non-recovery or sequelae in JADER. Taxane-induced macular oedema is a clinically relevant adverse event requiring continuous ophthalmologic monitoring, and potential regional differences and patient-level risk factors warrant further study.
In EGFR T790M-mutant lung adenocarcinoma, the strong and early clinical responses achieved with osimertinib may be limited by the emergence of diverse resistance mechanisms over time. In this case report, we describe an acquired CD74-ROS1 fusion that developed during osimertinib therapy in a patient who had an EGFR exon 20 T790M mutation detected in the treatment-naive setting. The fusion, identified through a tissue biopsy performed at the time of progression, suggests that the tumor had activated an alternative oncogenic driver under therapeutic pressure. The combination of osimertinib and crizotinib resulted in a marked clinical and metabolic response, was well tolerated, and the patient remained in remission. This rare case highlights that acquired CD74-ROS1 fusions may contribute to osimertinib resistance and suggests that combination targeted therapy may represent a potential therapeutic approach in selected patients.
