Miao Jiang

Background: Lenvatinib plus pembrolizumab is an established treatment for patients with previously treated advanced or recurrent endometrial cancer. In routine practice, clinicians may select a lenvatinib starting dose below 20 mg for patients expected to have limited tolerance, but the comparative effectiveness and tolerability of that strategy remain uncertain. Methods: We searched PubMed/MEDLINE, Web of Science Core Collection, and Cochrane CENTRAL from inception to 11 July 2026, with source-specific updates completed on 13–14 July 2026. Comparative observational studies of adults receiving lenvatinib plus pembrolizumab were eligible. The primary estimand compared starting doses below 20 mg with 20 mg; a 10-mg threshold contrast and first-8-week relative dose intensity were kept separate. Binary outcomes were summarized as risk ratios (RRs) and time-to-event outcomes as hazard ratios (HRs). Risk of bias was assessed with ROBINS-I, missing-evidence bias with ROB-ME, and certainty with GRADE. Results: Ten studies representing 10 independent cohorts and 1,000 patients were included. Five cohorts (703 patients in total) informed the primary starting-dose comparison, with outcome-specific analysis denominators. For starting doses below 20 mg versus 20 mg, the pooled RR was 0.97 for objective response (95% confidence interval [CI], 0.70–1.34; I²=11.9%) and 0.96 for disease control (95% CI, 0.83–1.11; I²=0%). The RR for subsequent lenvatinib dose reduction was 0.66 (95% CI, 0.34–1.27; I²=27.4%). Estimates for interruption, permanent discontinuation, grade 3 or higher adverse events, and progression-free survival were imprecise; hospitalization and treatment persistence were not poolable. Every evaluated result had serious overall risk of bias, and certainty was very low for all pooled comparisons. Conclusion: Comparative observational evidence does not establish that starting lenvatinib below 20 mg preserves antitumor effectiveness or improves tolerability relative to a 20 mg starting dose. Prospective, confounder-aware comparative studies are needed before a reduced starting-dose strategy can be recommended broadly. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261458417.

Background: Trials of selenium for cancer supportive care vary in treatment context, formulation, dose, toxicity domain, and outcome definition. We evaluated the efficacy and safety of selenium supplementation for preventing or reducing cancer therapy-related toxicities. Methods: PubMed, Web of Science Core Collection, and the Cochrane Library were searched through June 30, 2026. Comparative clinical trials conducted during cancer therapy compared selenium with placebo, no selenium, observation, or selenium-free standard care. Two reviewers independently completed study selection, data extraction, outcome evaluation, and risk-of-bias assessment, with third-reviewer adjudication when required. Severe oral mucositis during head-and-neck radiotherapy or chemoradiotherapy was the primary outcome; broader pools were exploratory. Fixed- or random-effects analyses were supplemented by restricted maximum-likelihood models with Hartung-Knapp confidence intervals. Conference-abstract and derived-odds-ratio analyses were restricted to supplementary sensitivity analyses. Certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261448497). Results: Of 444 records, 333 unique records were screened. Forty-one of 49 sought reports were assessed in full text, and 31 reports representing 30 study groups were included; 17 groups contributed to the main analysis and 13 to supplementary evidence. Overall risk of bias was judged to be Some concerns for nine studies and High risk for eight. The four-study primary analysis (188 participants) was inconclusive (risk ratio [RR] 0.89, 95% confidence interval [CI] 0.50 to 1.56; I ² 44.9%; very low certainty), as was the Hartung-Knapp analysis (RR 0.88, 95% CI 0.35 to 2.23). Five conventional exploratory confidence intervals crossed the null under Hartung-Knapp analyses. Across domains, the pooled estimate remained below the null (baseline RR 0.60, 95% CI 0.42 to 0.83; Hartung–Knapp RR 0.60, 95% CI 0.40 to 0.89; 11 studies), but heterogeneity was substantial and the certainty of evidence was very low. Conclusion: Current evidence does not establish prevention of severe oral mucositis, but the consistent cross-domain direction and several domain-specific exploratory estimates suggest that selenium may attenuate selected treatment-related toxicities, particularly gastrointestinal and hematologic events, in appropriately selected settings. Because the majority of estimates are based on few, heterogeneous, and high-risk studies, these signals should inform targeted trials rather than routine universal supplementation. Systematic review registration: This systematic review was registered with PROSPERO . Unique Identifier: CRD420261448497.

Background: Meridian-based traditional Chinese medicine (TCM) interventions are increasingly used as adjunctive approaches to manage treatment-related toxicities in children, adolescents, and young adults (CAYAs) with cancer. However, their effectiveness remains uncertain. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating meridian-based TCM interventions for supportive symptom management in CAYAs with cancer. Eight electronic databases, including PubMed, the Cochrane Library, and CNKI, were searched from inception to October 2024, with an updated search conducted in November 2025. Primary outcomes included treatment-related symptoms such as nausea and vomiting. Continuous outcomes (e.g., symptom severity) and dichotomous outcomes (e.g., response rates) were analyzed separately. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Twelve RCTs involving 732 participants were included. Compared with sham controls, meridian-based TCM interventions did not significantly reduce nausea severity (SMD: −0.25; 95% CI: −0.78 to 0.28) or vomiting frequency (SMD: −0.37; 95% CI: −0.90 to 0.16). When added to conventional antiemetic therapy, these interventions were associated with better control of nausea and vomiting than antiemetic therapy alone (OR: 0.26; 95% CI: 0.15 to 0.47). Evidence for fatigue and other supportive-care outcomes was limited and could only be synthesized narratively. The overall certainty of evidence was low because of methodological limitations, small sample sizes, and imprecision. Conclusion: The available sham-controlled evidence was insufficient to determine whether meridian-based TCM interventions improve chemotherapy-induced nausea and vomiting in CAYAs with cancer. Their addition to conventional antiemetic therapy may provide symptomatic benefit, but the certainty of evidence is low. Future trials should be adequately powered and, where feasible, use multicenter designs, credible sham controls, appropriate blinding, prespecified protocols, validated and standardized symptom measures, and longer follow-up. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024607724 , identifier: CRD42024607724.

Background: Immune effector cell-associated hematotoxicity (ICAHT) is a common and clinically important toxicity after chimeric antigen receptor (CAR) T-cell therapy. The CAR-HEMATOTOX score, also reported as CAR-HT, is a baseline risk score proposed to identify patients at higher risk of hematotoxicity and related adverse outcomes. Methods: We conducted a systematic search of PubMed, the Web of Science, and the Cochrane Library on June 19, 2026. Included studies compared high- and low-risk groups defined by the CAR-HEMATOTOX score after CAR T-cell therapy for hematologic malignancies and reported extractable data on hematologic toxicity, infection, survival, or other predefined clinical outcomes. Random-effects inverse-variance meta-analysis was performed only when at least three independent, clinically compatible estimates were available. Results: Twenty-three publications were included in the evidence inventory. For ICAHT, high risk was associated with higher odds (pooled OR 5.58, 95% CI 1.98 to 15.73; I²=60.8%). For overall survival (OS), high risk was associated with worse OS (pooled HR 3.36, 95% CI 2.20 to 5.11; I²=0.0%). For progression-free survival (PFS), high risk was associated with worse PFS (pooled HR 2.74, 95% CI 1.81 to 4.15; I²=32.3%). For severe infection, high-risk status was associated with higher odds (pooled OR 5.18, 95% CI 2.78 to 9.67; I²=37.8%). Exploratory analyses suggested higher early red blood cell and platelet transfusion requirements in high-risk patients, whereas severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were not significantly associated with high-risk status. Conclusion: A high CAR-HEMATOTOX score was associated with greater risk of ICAHT, higher odds of severe infection, and worse survival outcomes after CAR T-cell therapy for hematologic malignancies. These findings suggest that the CAR-HEMATOTOX score may be a clinically relevant risk-stratification marker, but the evidence remains observational and exploratory; standardized outcome definitions, prospective validation, and clearer handling of overlapping cohorts are needed before the score can be used as a stand-alone decision tool. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/view/CRD420261435303 , identifier 420261435303.

Sepsis-associated acute kidney injury (SA-AKI) is highly heterogeneous in critically ill patients. Reliable tools that integrate multiple indicators to predict outcomes remain limited. The advanced lung cancer inflammation index (ALI), a composite marker reflecting both inflammation and nutritional status, has demonstrated prognostic value in oncology and chronic diseases. However, evidence for its predictive performance and clinical utility in SA-AKI is scarce and requires further validation. This study analyzed 5,565 SA-AKI patients from the MIMIC-IV 3.1 database. Patients were divided into quartiles based on the ALI. The primary outcomes were 28-day and 90-day all-cause mortality. Multivariate Cox proportional hazards models, Kaplan–Meier survival analysis, and restricted cubic spline models were used to explore associations between the ALI and patient outcomes. Subgroup and sensitivity analyses were performed to test consistency and robustness. ROC analysis was used to compare the discriminatory performance of ALI with other indices and assess its incremental value in existing models. Patients in the highest ALI quartile had significantly lower risks of 28-day (HR = 0.72, p < 0.0001) and 90-day (HR = 0.74, p < 0.0001) mortality than did those in the lowest quartile. Survival curves indicated a strong positive association between the ALI and cumulative survival (log-rank p < 0.0001), and RCS analysis suggested a nonlinear trend. Subgroup analyses revealed no substantial heterogeneity, and sensitivity analyses supported the stability of these associations. ROC analysis demonstrated ALI had superior discrimination for 28-day mortality and provided incremental prognostic value when integrated into the SOFA score. ALI is independently associated with 28-day and 90-day mortality in SA-AKI. It offers incremental prognostic value beyond established scores and may serve as a supplementary risk stratification tool, but validation in prospective multicenter cohorts is warranted.