BACKGROUND: The composition of the gut microbiome has been linked to clinical responses to immune checkpoint inhibitors (ICIs), but its prognostic association with outcomes in non-small cell lung cancer (NSCLC) and melanoma remains incompletely defined. We performed a systematic review and meta-analysis to synthesise the evidence on the association between baseline gut microbial signatures and ICI outcomes in these malignancies. METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Scopus through April 2025 for studies correlating baseline gut microbiota with overall survival (OS), progression-free survival (PFS), objective response rate (ORR), or immune-related adverse events (irAEs) in patients with NSCLC or melanoma receiving ICIs. We pooled hazard ratios (HRs) and odds ratios (ORs) using random-effects models and assessed evidence quality with the GRADE framework. RESULTS: We included 26 studies comprising 1,542 patients. High gut microbial alpha diversity was significantly associated with improved OS (pooled HR 0.52, 95% CI 0.41–0.66) and PFS (pooled HR 0.58, 95% CI 0.47–0.71). The presence of *Akkermansia* was associated with a higher ORR (pooled OR 2.15, 95% CI 1.38–3.35). Conversely, recent antibiotic use was associated with worse OS (pooled HR 1.72, 95% CI 1.34–2.21). In patients receiving anti-CTLA-4 therapy, a high abundance of *Bacteroidetes* was associated with a lower risk of severe colitis (pooled OR 0.34, 95% CI 0.18–0.64). The overall certainty of evidence was rated as moderate for most outcomes. CONCLUSION: Baseline gut microbiome features, particularly high diversity and the presence of specific commensal taxa, are moderately associated with superior clinical outcomes to ICIs in NSCLC and melanoma. Our findings suggest that the gut microbiome could serve as a useful prognostic biomarker and may sooner or later be modulated to increase ICI efficacy.

Programmed cell death (PD) protein (ligand [L])-1 inhibitors are established treatments for metastatic non-small cell lung cancer (mNSCLC). In oncology, progression-free survival (PFS) and objective response rate (ORR) are often used as surrogates for overall survival (OS) to inform clinical development; however, there remains uncertainty in the concordance between these endpoints. This study evaluated the impact of a broad set of PD-(L)1 inhibitors on efficacy, explored the relationship between ORR and survival endpoints, and compared PD-1 and PD-L1 treatments for mNSCLC. A dataset of 114 studies was used to conduct a sequential two-stage model-based meta-analysis (MBMA). Firstly, an MBMA with mixed-effects logistic regression was applied to evaluate treatment-specific and clinical covariate effects on ORR. Secondly, MBMAs for OS and PFS were conducted with a mixed-effects semi-parametric proportional hazard approach using digitized Kaplan-Meier curves, with the treatment type, covariates, and ORR as inputs. ORR was demonstrated to be a significant predictor of OS and PFS. Simulations of head-to-head comparisons of treatment types were conducted using these models. Trends in predicted outcomes numerically favored PD-1 over PD-L1 treatments, but differences were not statistically significant. These findings support evidence-based decision-making for late-stage trial designs using ORR data from earlier phase trials, enabling benchmarking of emerging data by adjusting for explained and unexplained sources of variability in existing and emerging data.

Intra-arterial chemotherapy (IAC), intravenous chemotherapy (IVC), and the combination of both (IVC + IAC) are among the most important treatment options for retinoblastoma, a rare form of childhood cancer. The outcomes of previous studies evaluating the success rates of these methods have been discrepant due to the varying quality of the research as well as the different study types, sample sizes, and definitions of outcomes.

We evaluate the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) and corticosteroid combination therapy versus anti-VEGF monotherapy for both branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO)-related macular edema. A systematic search identified randomized controlled trials (RCTs) comparing the 2 modalities. Non-RCTs, studies with steroid monotherapy as the only comparator and macular edema from other causes were excluded. Visual, anatomical, safety, and injection-related outcomes were assessed. Twenty RCTs comprising 2040 patients were included. Combination therapy showed better best-corrected visual acuity (BCVA) (Mean Difference [MD] -0.09; 95 % CI -0.12 to -0.07; p < 0.00001), reduced central macular thickness (CMT) (MD -24.42; 95 % CI -35.32 to -13.52; p < 0.0001), lower edema recurrence (Odds Ratio [OR] 0.49; 95 % CI 0.30-0.80; p = 0.004), reduced need for PRN anti-VEGF injections (OR 6.77; 95 % CI 3.41-13.46; p < 0.00001), higher intraocular pressure (IOP) within normal range up to 6 months (MD 0.64; 95 % CI 0.20-1.07; p = 0.004) and increased cataract surgery risk (OR 7.95; 95 % CI 1.35-46.75; p = 0.02). Subgroup analysis showed BCVA improvement, fewer injections, reduced PRN need, and higher IOP in CRVO, and reduced recurrence in BRVO. Triamcinolone acetonide improved BCVA while intravitreal dexamethasone implant lowered CMT, and both agents reduced PRN injections. Combination therapy provides modest improvement in efficacy outcomes and fewer injections, particularly in CRVO, but increases risk of IOP elevation and cataract surgery. Reduced injection frequency may not necessarily translate to overall lower treatment burden and costs due to frequent monitoring of steroid-related complications.

Sex is a recognized modifier of physiology, immunity, and social exposures, yet its independent association with survival and adverse event prognosis in contemporary anticancer therapy remains poorly defined. The aim of the present study was to assess the association between patient sex and overall survival, progression-free survival, and grade 3 or greater adverse events across a pooled individual participant data meta-analysis.

Cancer treatment-induced bone loss (CTIBL) and skeletal fractures are potential consequences of anticancer therapies used in the treatment of non-metastatic breast cancer (BC). This systematic review and meta-analysis aim to synthesise the available evidence regarding the effectiveness and safety of bone protective interventions in the mitigation of CTIBL and skeletal fractures. Multiple databases including MEDLINE/PubMed, Embase and Cochrane, clinical trial registries and grey literature were systematically searched for experimental and observational studies, investigating the use of bisphosphonates, denosumab, calcium or vitamin D supplementation. Outcomes of interest were change in bone mineral density (BMD), the incidence of skeletal fractures, change in bone turnover markers, the incidence of adverse events (AEs), the presence of aromatase inhibitor musculoskeletal symptoms and quality of life. A total of 88 studies were included in our systematic review and meta-analysis, with sample sizes ranging from 11 to 4819 participants. For change in BMD outcomes able to be meta-analysed, bisphosphonates demonstrated a significant benefit compared to controls (pooled mean difference estimate; lumbar spine: 4.17, p = 0.0; total hip: 1.81, p = 0.034; femoral neck: 2.35, p = 0.001). Incidence of skeletal fractures significantly decreased with bisphosphonates compared to controls (pooled relative risk estimate; 0.77, p < 0.001). Denosumab demonstrated similar effects on BMD and skeletal fracture incidence; however, meta-analysis was not possible due to the lack of randomised controlled trials. Osteonecrosis of the jaw represents the most concerning AE with bisphosphonates. Considering the effectiveness and safety, and the level of evidence available, bisphosphonates present as the preferred bone protective intervention for the management of bone health in patients with non-metastatic BC.

Early studies indicate that neoadjuvant immune checkpoint inhibitors (ICIs) induce high rates of tumor regression in localized deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) gastric and gastroesophageal junction (GEJ) cancers, raising interest in nonoperative management (NOM). Most available data, however, come from small, nonrandomized cohorts. A systematic synthesis was undertaken to better characterize efficacy and safety outcomes.

Pembrolizumab-induced immune-related oral mucositis (irOM) is a rare and often underrecognized toxicity. This study aimed to systematically characterize its clinical profile, histopathologic patterns, management strategies, and outcomes to support timely diagnosis and evidence-based care.

BACKGROUND: Reduced folate carrier 1 (RFC1) is an important solute carrier transporter crucial for the uptake and transport of methotrexate (MTX). This meta-analysis aimed to systemically analyze the relationship between the RFC1 G80A polymorphism and MTX-induced toxicity in pediatric acute lymphoblastic leukemia (ALL) patients. METHODS: A systematic search for studies reporting the correlation between the RFC1 G80A polymorphism and MTX-induced toxicity in pediatric ALL patients was performed via the Web of Science, EMBASE, PubMed, Wan Fang, CNKI, and VIP databases until June 16, 2025, followed by pooled analysis. The Newcastle‒Ottawa scale, Egger’s test, and leave‒one-out sensitivity analysis were performed to assess the study quality, publication bias and stability of the pooled results. RESULTS: Thirteen eligible studies were included in this meta-analysis, with 2, 5, and 6 studies having Newcastle‒Ottawa Scale scores of 7 points, 8 points, and 9 points, respectively, indicating good study quality. The pooled prevalence of the RFC1 80 AA genotype was 28.29% (95% CI: 23.44%-33.15%) in pediatric ALL patients. The risks of overall toxicity (OR = 4.68, 95% CI: 1.96–11.15), myelosuppression (OR = 1.85, 95% CI: 1.30–2.65), hepatotoxicity (OR = 2.44, 95% CI: 1.14–5.21), and gastrointestinal toxicity (OR = 1.61, 95% CI: 1.03–2.52) were greater in pediatric ALL patients with the RFC1 80 AA genotype than in those with the RFC1 80 GG + GA genotype who underwent MTX treatment. However, neurotoxicity risk (OR = 0.98, 95% CI: 0.40–2.41) and mucositis risk (OR = 1.24, 95% CI: 0.81–1.89) were not different between the two groups. No publication bias existed, while some of the pooled results were not stable according to the sensitivity analysis. CONCLUSION: The RFC1 G80A polymorphism is closely correlated with elevated MTX-induced toxicity in pediatric ALL patients.

Triple-negative breast cancer (TNBC), an aggressive subtype lacking oestrogen and progesterone receptors and amplification of HER2 receptors, accounts for 12% to 17% of breast cancers. Adjuvant and neoadjuvant chemotherapy improve survival; however, 30% to 40% of early-stage TNBC cases progress to metastatic disease. Recent evidence suggests that combining immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) with chemotherapy may improve pathological complete response and event-free survival.

This study explored whether integrating innovative immunotherapies targeting costimulatory or co-inhibitory pathways beyond standard PD-1, PD-L1, and CTLA-4 treatments affects hepatic adverse events. We further analyzed liver-related side effects in patients with cancer receiving these novel therapies alone or in combination with others.

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent adverse effect linked to neurotoxic chemotherapeutic agents. Current pharmacological treatments exhibit limited efficacy and notable adverse effects. The clinical effectiveness of non-pharmacological therapies, like acupuncture, physical exercise (PE), cryotherapy (CR), and compression therapy, requires systematic comparison. This study employs a network meta-analysis (NMA) to appraise the efficacy and preventive effects of various non-pharmacological interventions on CIPN.

Nasopharyngeal carcinoma (NPC), endemic to Southern China and Southeast Asia, presents significant clinical challenges. Immune checkpoint inhibitors (ICIs) have transformed NPC treatment but carry risks of immune-related adverse events (irAEs). Existing meta-analyses lack NPC-specific data, hindering targeted safety guidance.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of dose reduction, drug modification, or drug discontinuation in cancer patients which negatively impacts the overall well-being of cancer patients and medication procedures. This systematic review and meta-analysis investigation aimed to determine the global prevalence of CIPN in cancer patients. METHODS: Various scientific databases (PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar) were systematically searched (by July 2023) for published studies reporting the CIPN prevalence. Meta-analysis was applied based on the Random Effect model and subgrouping was considered using the CIPN scales. Also, the heterogeneity was assessed based on the I2 index. RESULTS: Following the assessment of 49 eligible studies (n:33,667 participants), the overall CIPN prevalence was reported 51.9% (95% CI: 45-58.7). According to the Composite Scales tool, the highest CIPN prevalence was 69.6% (95%CI: 50–84). CONCLUSION: The prevalence of CIPN in cancer patients was found at a high level. According to the high number of cancer survivors, the integration of necessary clinical strategies for screening, prevention, and treatment of CIPN into consistent clinical guidelines is strictly recommended. Probably these guidelines can reduce the CIPN occurrence and cancer treatment costs. CLINICAL TRIAL NUMBER: Not applicable.

Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (VEGF) agents-including Aflibercept, Ranibizumab, Bevacizumab, Brolucizumab, and Faricimab-are the mainstay of therapy. However, their comparative efficacy and safety remain uncertain. This study aimed to compare the visual and systemic outcomes of these agents to inform clinical decision-making.

BACKGROUND: The impact of sarcopenia on immune checkpoint inhibitor (ICI) efficacy and treatment-related adverse events (AEs) in gastric cancer (GC) remains controversial. This meta-analysis aims to elucidate associations between sarcopenia and clinical outcomes in ICI-treated GC patients. METHODS: We systematically searched PubMed, Embase, Scopus, and Web of Science (from inception to May 2, 2025) for English-language studies that met predefined inclusion criteria. Primary outcomes included progression-free survival (PFS) and overall survival (OS) (hazard ratios [HRs] with 95% confidence intervals [CIs]), as well as disease control rate (DCR) and overall response rate (ORR) (odds ratios [ORs] with 95% CIs). Secondary outcomes encompassed treatment-related AEs (ORs with 95% CIs). Heterogeneity was quantified via I² statistics, and sensitivity analyses were performed. RESULTS: Thirteen studies (n = 1,119 GC patients) were included. The prevalence of sarcopenia was 54% (95% CI: 46–62%, p < 0.0001; heterogeneity statistics: I2 = 87%, p < 0.0001). Compared to non-sarcopenic patients, sarcopenic patients demonstrated worse OS (adjusted HR = 1.77, 95% CI: 0.67–4.64, p = 0.16; heterogeneity statistics: I2 = 64%, p = 0.04), reduced PFS (adjusted HR = 2.16, 95% CI: 0.88–5.30, p = 0.07; heterogeneity statistics: I2 = 44%; p = 0.14), lower DCR (OR = 0.54, 95% CI: 0.13–2.34, p = 0.33; heterogeneity statistics: I2 = 77%; p = 0.0006), and decreased ORR (OR = 0.69, 95% CI: 0.53–0.89, p = 0.01; heterogeneity statistics: I2 = 0%; p = 0.97). No significant association was observed between sarcopenia and treatment-related AEs (OR = 1.35, 95% CI: 0.38–4.85, p = 0.51; heterogeneity statistics: I2 = 30%; p = 0.23). CONCLUSION: Sarcopenia is prevalent in > 50% of ICI-treated GC patients and may be linked to diminished treatment response and poorer survival outcomes. The absence of increased AE risk supports routine sarcopenia assessment for prognostic stratification in this population. These findings require validation in non-Asian cohorts to establish generalizability.

Immune checkpoint inhibitors (ICIs) are increasingly used in oncology, but concerns persist regarding flare risks of pre-existing rheumatologic diseases in patients receiving ICIs. This meta-analysis study aims to evaluate the incidence and severity of rheumatologic disease flares in patients with solid tumors treated with ICIs.

Trilaciclib is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that has shown promise in mitigating chemotherapy-induced myelosuppression (CIM). This meta-analysis aims to provide a comprehensive and clinically relevant quantification of trilaciclib's effectiveness in reducing CIM and its potential impact on outcomes in adult patients with solid tumors.

Several studies have explored the impact of immune checkpoint inhibitor (ICI)-induced immune-related thyroid dysfunction on the prognosis of patients with lung cancer. However, inconsistencies remain among the results of different studies. Therefore, we conducted a meta-analysis to evaluate the impact of immune-related thyroid dysfunction on the prognosis of lung cancer, aiming to provide evidence-based support for clinical treatment.

Checkpoint inhibitors that target PD-1 or PD-L1 have had a profound effect in a variety of cancers, both as a single therapy and in combinations. Meta-analyses suggest that monoclonal antibodies (mAbs) targeting PD-1 may yield better survival outcomes compared to anti-PD-L1 mAbs, however these conclusions are limited by a lack of direct clinical comparisons between the two classes. There is a shared hypothesis for the mechanism of action of these drugs: inhibition of the PD-1:PD-L1 signaling pathway through binding to either target. Using a Quantitative Systems Pharmacology (QSP) model-based analysis, we test whether differential inhibition of PD-1:PD-L1 complex formation (a surrogate for inhibition of the signaling pathway) is sufficient to explain the efficacy difference between anti-PD-1 and anti-PD-L1 mAbs observed in clinical meta-analyses. The model predicts that high levels of PD-1:PD-L1 complex inhibition are achieved by all the considered mAbs at their clinical dosing regimens, but it does not indicate that anti-PD-1 mAbs yield higher inhibition over anti-PD-L1s, in contrast to the meta-analyses. Significant model parameter variability and a bootstrap sampling analysis mirroring the comparison from Duan et al. (2020) do not change this conclusion. This suggests that anti-PD-1 and anti-PD-L1 mAbs are not differentiable based on PD-1:PD-L1 complex inhibition alone, and that the hypothesized shared mechanism of action of the two classes of drugs is incomplete.