ABSTRACT Magnesium (Mg) alloys, as biodegradable metallic materials with excellent biocompatibility and mechanical properties, demonstrate significant advantages. In the field of immunotherapy, they present a promising potential option for enhancing therapeutic outcomes and hold broad prospects for application. Mg ion (Mg 2+ ), which is crucial for the proper functioning of immune cells, has been found to alter the tumor microenvironment (TME) by regulating inflammation, promoting the activation of T cells and B cells, enhancing the cytotoxicity of natural killer (NK) cells, and shifting macrophages toward an anti‐tumor phenotype. Additionally, Mg alloys can neutralize the acidic environment within tumors, creating a more favorable condition for immune cells to function effectively. Moreover, they produce hydrogen gas, which further enhances anti‐tumor immune responses by promoting the activity of immune cells. In this review, we explore the role of Mg alloys and their degradation products in cancer immunotherapy while highlighting their substantial potential as adjuvants or alternatives, offering an innovative and effective strategy for cancer treatment.

PURPOSE:Concurrent chemoradiation therapy is the standard therapy for limited-stage small cell lung cancer (LS-SCLC) but induces cancer therapy-induced thrombocytopenia (CTIT), which leads to treatment delays. This study aims to assess the efficacy and safety of prophylactic recombinant human thrombopoietin (rhTPO) in preventing CTIT in this patient population. METHODS AND MATERIALS:This prospective, multicenter, phase II trial was conducted across 14 Chinese centers. LS-SCLC patients receiving etoposide plus cisplatin or carboplatin chemotherapy with concurrent radiation therapy were given subcutaneous rhTPO (300 IU/kg/d) on days 1-5, 8-12, and 15-19 during radiation therapy. rhTPO treatment was stopped if platelet count reached ≥300 × 109/L or increased by ≥100 × 109/L from baseline. Primary endpoints were the nadir and peak platelet count. RESULTS:From March 8, 2024, to October 10, 2024, 56 LS-SCLC patients were enrolled. During the rhTPO treatment period, nadir platelet count (×109/L) was 128.54 ± 54.15, and peak platelet count reached 409.23 ± 173.50. Overall incidence of CTIT was 33.9% (19/56), including 8.9% (5/56) grade 3, and no grade 4-5 events. A total of 78.9% of patients (15/19) experienced platelet count recovery to ≥100 × 109/L during the rhTPO treatment period. Median time for platelet count recovery from <100 × 109/L to ≥100 × 109/L was 8 days (95% CI, 6-14). Multivariable logistic regression analysis revealed that low baseline platelet count (<150 × 109/L) was an independent risk factor for developing CTIT (odds ratio, 4.26; 95% CI, 1.08-16.78; P = .038). No patients required platelet transfusions or experienced radiation therapy interruptions, and only one patient required a reduction in the dose of chemotherapy throughout the entire study. Moreover, no serious adverse events were reported. rhTPO-related adverse reactions were infrequent and predominantly grade 1 (eg, transient platelet elevation). CONCLUSIONS:Prophylactic rhTPO during concurrent chemoradiation therapy for patients with LS-SCLC demonstrated a potential benefit in maintaining platelet counts with a low incidence of CTIT. These findings support further investigation of rhTPO as a preventive strategy for high risk CTIT patients.

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 ≥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.

PurposeMetachronous oligorecurrence is usually defined as oligometastatic disease diagnosed more than 6 months after primary tumor diagnosis in the absence of active systemic therapy. This study aimed to assess the safety and efficacy of radiotherapy combined with chemoimmunotherapy (RCIT) versus chemoimmunotherapy (CIT) alone as the first-line treatment for metachronous oligorecurrent esophageal squamous cell carcinoma (MOR-ESCC).MethodsWe retrospectively evaluated 195 patients with MOR-ESCC treated with first-line RCIT (n=102) or CIT (n=93) between June 2018 and June 2023. Propensity score matching (PSM) was performed to reduce baseline imbalance and potential confounding.ResultsFollowing 1:1 PSM, 72 well-paired patients were identified. The median follow-up was 17.9 months. RCIT was associated with significantly longer progression-free survival (PFS) than CIT, while overall survival (OS) showed a borderline non-significant trend favoring RCIT. The median PFS was 13.1 months (95% CI: 8.9-17.3) in the RCIT group and 9.0 months (95% CI: 6.9-11.1) in the CIT group (P = 0.002). The median OS was 21.5 months (95% CI: 13.4-29.7) in the RCIT group and 16.0 months (95% CI: 13.2-18.8) in the CIT group (P = 0.051). Subgroup analyses of OS suggested greater benefit from RCIT for patients with recurrence interval ≥18 months (P = 0.023), lymph node-only recurrence (P = 0.020), 1–2 recurrent lesions (P = 0.016), or single-organ recurrence (P = 0.022). Safety analysis demonstrated comparable rates of grade ≥3 treatment-related adverse events (TRAEs) (48.6% vs. 34.7%; P = 0.091) and treatment-related fatal events (8.3% vs. 4.2%; P = 0.491) between groups. Notably, RCIT showed a numerically higher incidence of grade ≥3 pneumonitis (16.7% vs. 5.6%; P = 0.063).ConclusionsRCIT was associated with significantly prolonged PFS and numerically longer OS compared with CIT alone in patients with MOR-ESCC. Although no statistically significant increase in grade ≥3 TRAEs was observed, RCIT showed numerically higher toxicity, particularly pneumonitis. This study provides real-world evidence supporting the role of radiotherapy in MOR-ESCC, identifying long recurrence intervals (≥18 months), nodal-only recurrence, and low tumor burden (1–2 lesions/single organ) as key predictors of RCIT efficacy. These findings support RCIT as a potential strategy for carefully selected patients with MOR-ESCC, although the pneumonitis signal warrants cautious patient selection and prospective validation.

Abstract Background: Trastuzumab rezetecan (SHR-A1811) is a novel HER2-directed ADC approved for pretreated HER2-mutant NSCLC (Lancet Oncol, 2025). ADCs may enhance antitumor immunity and synergize with immunotherapy. We conducted an open-label, phase 1/2 (dose-escalation/efficacy-exploration) study (NCT05482568) to evaluate SHR-A1811 in combination therapy for HER2-altered NSCLC and here report data from phase 2 Cohort D of 1L SHR-A1811 ± adebrelimab (anti-PD-L1 mAb) for HER2-mutant NSCLC. Methods: Patients (pts) were randomized (1:1) to receive SHR-A1811 (4.8 mg/kg, iv, Q3W) + adebrelimab (1200 mg, iv, Q3W) or SHR-A1811 (4.8 mg/kg, iv, Q3W) alone, stratified by PD-L1 expression (TPS, <1% vs ≥1%). The primary endpoint was ORR per investigator. Results: 68 pts (PD-L1 TPS <1%/1-49%/≥50%, 50.0%/41.2%/8.8%; exon 20 insertions/A775_G776insYVMA, 89.7%/55.9%) were treated. At data cutoff (Oct 20, 2025), median follow-up was 16.7 mo. Confirmed ORR was 69.4% (95% CI 51.9-83.7) with SHR-A1811 + adebrelimab (combo) vs 81.3% (95% CI 63.6-92.8) with SHR-A1811; median DoR was not reached (NR) and 16.6 mo (95% CI 8.5-NR), respectively. PFS events occurred in 10 pts (27.8%) with combo vs 13 (40.6%) with SHR-A1811; median PFS was NR (95% CI 15.3-NR) vs 17.9 mo (95% CI 9.7-NR; HR 0.65, 95% CI 0.28-1.47). Efficacy by PD-L1 TPS is shown in Table 1. A trend toward improved PFS with addition of adebrelimab was seen across subgroups. All grade ≥3 TRAEs occurring in ≥10% were hematologic in both arms. ILD occurred in 2 (5.6%) pts with combo and 1 (1.3%) with SHR-A1811. TRAEs led to discontinuation of SHR-A1811 in 2 (5.6%) and adebrelimab in 4 (11.1%) in combo arm and SHR-A1811 in 2 (6.3%) in monotherapy arm. Conclusions: SHR-A1811 ± adebrelimab as 1L therapy showed robust activity with manageable safety in HER2-mutant NSCLC. Early data suggest clinical benefits with addition of adebrelimab, regardless of PD-L1 expression, driven by durablity of disease control. Citation Format: Shun Lu, Zhengbo Song, Ziming Li, Haiyong Wang, Yan Yu, Qitao Yu, Shaozhang Zhou, Zhiyong He, Yan Wang, Yiping Zhang, Songyan Han, Rui Meng, Guoqun Zhang, Longhua Sun, Xueqin Chen, Yong Mao, Yongsheng Li, Yongzhong Luo, Kangsheng Gu, Xuhong Min, Bo Jin, Runxiang Yang, Yanqiu Zhao, Liqiang Zhong, Jun Wang, Zhiguo Zhou, Chengzhi Zhou, Kaijun Zhang, Xiaotong Li, Xinjing Ma, Liju Zong, You Li. SHR-A1811 ± adebrelimab as first-line (1L) treatment for advanced HER2-mutant NSCLC: A randomized phase 2 cohort from a phase 1b/2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT301.

PurposeThe purpose of this study was to evaluate the effect of consolidation immunotherapy on patients with stage III non-small cell lung cancer (NSCLC) who received induction chemoimmunotherapy before chemoradiotherapy (CRT).Materials and methodsPatients with stage III NSCLC who received induction chemoimmunotherapy before CRT with or without consolidation immunotherapy at 4 hospitals between February 2018 and December 2022 were retrospectively analyzed. The patients were divided into two groups on the basis of whether they received consolidation immunotherapy (Ind+Con group) or not (Ind group). Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and were estimated using the Kaplan–Meier method. One-to-one propensity score matching (PSM) was used to further minimize confounding effects.ResultsA total of 196 eligible patients were enrolled, with 124 (63.3%) in the Ind group and 72 (36.7%) in the Ind+Con group. The median follow-up was 24.6 months, and the median PFS and OS for the whole cohort were 24.8 months and 46.0 months, respectively. The median PFS was 25.5 months in the Ind group vs. 24.0 months in the Ind+Con group, with 2-year PFS rates of 52.2% vs. 47.7% (P = 0.472). The median OS was 46.0 months in the Ind group vs. not reached (NR) in the Ind+Con group, with 2-year OS rates of 78.0% vs. 83.8% (P = 0.578). After 1:1 PSM, the median PFS was 30.2 months vs. 24.0 months, with 2-year PFS rates of 55.4% vs. 47.7% (P = 0.261). The median OS was 46.0 months vs. NR, with 2-year OS rates of 80.8% vs. 83.8% (P = 0.960).ConclusionThe effect of consolidation immunotherapy on patients with stage III NSCLC who receive induction chemoimmunotherapy before CRT needs to be further studied.

TPS2692 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable esophageal cancer. Currently, data on PD-L1 inhibitors combined with chemoradiotherapy in this setting still remain limited. Furthermore, the efficacy of induction immunotherapy prior to CCRT, and the utility of PET-CT assessment to guide subsequent CCRT regimens, have not been explored. This study aims to evaluate the efficacy and safety of induction adebrelimab (an anti-PD-L1 antibody) combined with chemotherapy, followed by a PET-CT guided adaptive chemotherapy regimen during CCRT for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). Methods: This single-arm, open-label, exploratory study will recruit 36 patients with locally advanced unresectable ESCC (clinical stage T1N+M0 or T2-4bNxM0) who have not received prior antitumor treatment. Patients will undergo 2 cycles of induction therapy with adebrelimab (1200 mg, d1, iv, q3w) plus the TP regimen (nab-paclitaxel 180 mg/m² or paclitaxel 135 mg/m², d1, iv; carboplatin AUC=5, d1, iv, q3w). Following induction, response will be assessed via PET-CT. Responders (defined as SUV reduction ≥35% or partial response ) will continue with the TP regimen (nab-paclitaxel 60 mg/m² or paclitaxel 50 mg/m², d1, iv; carboplatin AUC=2, d1, iv, qw for 5 cycles) during concurrent radiation (50.4–60 Gy/28–33f). Non-responders will switch to the FP regimen (fluorouracil 750–1000 mg/m², civ 96h; cisplatin 75 mg/m², d1, iv, q4w for 2 cycles) during concurrent radiation. All patients will proceed to maintenance therapy with adebrelimab following CCRT until disease progression or unacceptable toxicity. The primary endpoint is the 1-year progression-free survival (PFS) rate. Secondary endpoints include the clinical complete response (cCR) rate, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), PFS, overall survival (OS), and safety profile. Clinical trial information: NCT07112833 .

2597 Background: Definitive concurrent chemoradiotherapy (dCCRT) is considered the standard treatment for esophageal squamous cell carcinoma (ESCC). The PACIFIC study demonstrated that consolidation durvalumab significantly improves overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC) after dCCRT. However, the efficacy of consolidation immunotherapy in ESCC still remains unclear. We conducted a clinical trial to evaluate the efficacy of camrelizumab in patients with unresectable, locally advanced ESCC following dCCRT. Methods: This single-arm, phase 2 study enrolled patients with locally advanced ESCC. All participants received dCCRT with involved-field irradiation (IFI). Patients were treated with camrelizumab within 1 to 42 days after completing dCCRT. Camrelizumab was administered intravenously over 30 minutes every 2 weeks for up to 12 months. The primary endpoint was progression-free survival (PFS). Secondary endpoints included disease control rate (DCR), objective response rate (ORR), duration of response (DoR), overall survival (OS), and safety. Results: Thirty-five patients were enrolled between April 2020 and November 2023. Data from 32 patients were analyzed. As of December 22, 2024, the median follow-up was 25.1 months (IQR 5.5–56.8). Twelve patients experienced disease progression, and seven patients died. The DCR was 59.4%. The median PFS and OS were not reached. The 1- and 2-year PFS rates were 81.3% and 60.6%, respectively. The 1- and 2-year OS rates were 96.9% and 81.0%, respectively. The most common adverse events were grade 1-2. No grade 4 or 5 adverse events were reported. Pneumonia occurred in 31.3% of patients, all of whom experienced grade 1-2. Conclusions: Consolidative camrelizumab following definitive concurrent chemoradiotherapy with IFI shows promising efficacy and manageable toxicity in patients with unresectable locally advanced ESCC. Clinical trial information: NCT04286958 .

The survival benefit of adjuvant chemotherapy after chemoradiotherapy in locally advanced rectal cancer (LARC) remains unproven, whereas total neoadjuvant therapy (TNT) incorporating preoperative chemotherapy has demonstrated improved outcomes. However, the total chemotherapy duration delivered across neoadjuvant and adjuvant phases varies substantially in clinical practice. We investigated the impact of total chemotherapy duration in the STELLAR trial. This post hoc analysis was based on the phase III randomized trial, comparing short-course radiotherapy followed by four cycles of chemotherapy (TNT) with long-course chemoradiotherapy (CRT) in LARC patients. Five hundred thirty-nine patients with available chemotherapy duration data were included, with a median follow-up of 68.1 months. Patients were categorized: group 1 (no chemotherapy, n = 121), group 2 (3 to 12 weeks, n = 113), group 3 (15 weeks, n = 30), and group 4 (≥ 18 weeks, n = 275). Disease-free survival (DFS), overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) were assessed using time-dependent Cox regression. Group 4 achieved the highest 5-year OS (82.1

Abstract Purpose To compare scalar circulating-blood dose summaries, assess whether associations with grade 3 or higher lymphopenia and overall survival persisted after planning target volume (PTV) adjustment, and distinguish scalar from exploratory dynamic blood-dose analyses. Methods and Materials The assembled dataset included 133 patients from 2 retrospective thoracic radiation cohorts; 121 entered the dosimetric main analysis and 116 passed a post hoc dosimetric gate. Six scalar exposures were compared: an ICE3 (Immune Circulation radiation Exposure Estimator Engine) 10-compartment mean-dose metric, corrected effective dose to immune cells (EDIC), body-remainder dose, a hematological dose (HEDOS)-derived organ-mean approximation, mean lung dose, and mean heart dose. Logistic base models included baseline absolute lymphocyte count, concurrent chemotherapy, and cohort; PTV was then added. Overall survival used cohort- stratified Cox models on an endpoint-specific common set. Benjamini-Hochberg correction was applied within prespecified 6-exposure families and, separately, across 3 selected post hoc bootstrap contrasts. Results The lymphopenia analysis included 94 patients and 69 events. After PTV adjustment, the HEDOS-derived approximation remained nominally associated (odds ratio, 2.54; 95% confidence interval, 1.18-5.45; P=.017; q=.102), but no exposure survived false-discovery-rate control. The survival set contained 92 patients and 42 deaths; no PTV-adjusted scalar exposure was associated with survival (all q>=.531). In post hoc analyses, the standardized association of mean heart dose with overall survival was more positive than that of ICE3 (difference in log hazard ratios, 0.44; 95% CI, 0.13–0.94; multiplicity-adjusted q=.024). The corresponding contrast with the HEDOS-derived approximation did not meet the adjusted significance threshold (q=.053). These coefficient contrasts do not establish superior predictive performance or causality. Exported ICE3 kinetic summaries had no false-discovery-rate-significant residual associations. A 13-case HEDOS bDVH audit showed little change under one continuous-versus-10-second-gap perturbation. Conclusions PTV adjustment attenuated scalar blood-dose associations with severe lymphopenia, and no scalar exposure retained a multiplicity-robust survival association. The selected mean-heart- dose coefficient contrast is hypothesis-generating and does not establish superior prediction. The primary cohort comparison evaluated a HEDOS-derived organ-mean approximation rather than the full dynamic HEDOS framework; therefore, these findings should not be interpreted as evidence against the potential value of particle-level blood-dose distributions or time-dependent blood-flow modeling.

HER2-positive tumors persist as a formidable therapeutic challenge despite advances in targeted agents, chemotherapy, and immunotherapy. Recently, messenger RNA (mRNA) vaccines have emerged as promising avenues for the treatment of advanced tumors and their recurrence, although their clinical application remains challenging. Herein, we developed lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines encoding the modified extracellular domain (ECD) sequence from rat HER2 (rHER2 ECD mRNA-LNP) and human HER2 (hHER2 ECD mRNA-LNP). While both vaccines elicited effective tumor inhibition, the hHER2 ECD mRNA-LNP demonstrated superior prophylactic and therapeutic efficacy in vivo, and successfully induced potent, antigen-restricted cytotoxicity against human patient-derived organoids (PDOs) ex vivo. Mechanistically, it enhances both humoral and T cell responses, and reprograms CD8+ tumor-infiltrating lymphocytes (TILs) by reducing exhaustion, promoting effector maturation, and inducing memory T cells. Specifically, a reduction in naive-like T cell clusters coupled with an elevation in cycling T cell clusters underpins the vaccine's efficacy. Furthermore, HER2 epitope-specific T cell receptor β-chain variable/joining (Trbv/Trbj) combinations and complementarity-determining region 3 (CDR3) motifs were identified as key contributors to the antigen-specific tumoricidal activity. Crucially, combining the hHER2 ECD mRNA-LNP vaccine with programmed cell death-1 (PD-1) immune checkpoint blockade (ICB) achieves superior antitumor efficacy compared to vaccine monotherapy. Moreover, combining the hHER2 ECD mRNA-LNP vaccine with standard chemoradiotherapy effectively potentiates the therapeutic efficacy against HER2-positive tumors. These findings highlight a promising agent for oncology and suggest that modified HER2 ECD mRNA-LNPs represent a viable and highly effective therapeutic strategy against HER2-positive malignancies.

This updated analysis of the STELLAR trial reports 5-year outcomes comparing short-course radiotherapy followed by chemotherapy (SCRT-based total neoadjuvant therapy [TNT]) with standard long-course chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Patients with distal or middle-third LARC were randomly assigned to receive either SCRT-based TNT or CRT. At a median follow-up of 68.7 months, the 5-year disease-free survival (DFS) was 62.0% in the TNT group and 58.7% in the CRT group, with a hazard ratio (HR) for DFS of 0.849 (95% CI, 0.662 to 1.089). Five-year overall survival (OS) was significantly higher with TNT (78.1% v 69.7%; HR, 0.739 [95% CI, 0.550 to 0.993]). Distant metastasis (DM) and locoregional recurrence (LRR) rates were similar between the two groups. In high-risk patients (per European Society for Medical Oncology criteria), TNT was associated with improved OS (HR, 0.663 [95% CI, 0.469 to 0.937]) and showed a nonsignificant trend toward improved DFS (HR, 0.765 [95% CI, 0.568 to 1.032]). In patients with DM or LRR, TNT was associated with both improved postrecurrence progression-free survival (HR, 0.691 [95% CI, 0.497 to 0.961]) and postrecurrence survival (HR, 0.698 [95% CI, 0.490 to 0.994]). These results suggest that SCRT-based TNT provides a durable survival advantage and is a viable alternative to CRT, especially in patients with high-risk disease.

BACKGROUND:High-flow nasal cannula (HFNC) is superior to conventional oxygen therapy (COT) in preventing hypoxaemia during bronchoscopy. However, factors associated with HFNC effectiveness remain unclear. We performed an individual participant data meta-analysis (IPD-MA) to identify treatment modifiers for HFNC during bronchoscopy. METHODS:We systematically reviewed randomised controlled trials (RCTs) comparing HFNC and COT during bronchoscopy in adults (January 2000-September 2025) and requested IPD from corresponding investigators. The primary outcome was desaturation during bronchoscopy. Conventional meta-analysis was performed using random-effect model; one-stage regression model was used for IPD-MA. Results were reported as odds ratios (ORs) or mean difference and 95% confidence intervals (CIs). RESULTS:Seventeen RCTs (3,116 patients: 1680 HFNC, 1436 COT) were included. Compared to COT, HFNC significantly reduced desaturation (OR 0.23, 95% CI 0.15-0.34), procedure interruption (OR 0.36, 95% CI 0.20-0.67), respiratory support escalation (OR 0.25, 95% CI 0.11-0.55), and airway intervention (OR 0.19, 95% CI 0.10-0.36) during bronchoscopy. IPD was obtained from six RCTs (1,344 patients). Significant interactions were observed between treatment effect and body mass index, baseline respiratory and heart rates, with greater relative benefit at lower values. HFNC flows ≥45 L/min were associated with reduced desaturation risk (OR 0.28, 95% CI 0.12-0.65). CONCLUSIONS:HFNC is superior to COT in reducing desaturation and procedure-related interruptions during bronchoscopy. Exploratory analyses suggest greater relative benefits in patients with lower body mass index and lower baseline respiratory and heart rates. HFNC flows ≥45 L/min furtherreduce desaturation risk. Further studies are needed in higher-risk patients. TRIAL REGISTRATION:International Prospective Register of Systematic Reviews; No.:CRD420251008924; URL: https://www.crd.york.ac.uk/prospero/.

Research has shown that the concurrent presence of Diabetes Mellitus (DM) and Thyroid Dysfunction (TD) can exacerbate diabetes-related complications and impose a significant economic burden on healthcare systems. Therefore, this study aimed to develop a nomogram model for predicting the risk of TD in patients with Type 2 Diabetes Mellitus (T2DM) and to validate its predictive performance. A total of 1853 patients with T2DM diagnosed at the First Hospital of Hebei Medical University from 2019 to 2024 were included in the study. The dataset was randomly divided into a training set (n = 1297) and a validation set (n = 556) at a 7:3 ratio using the R software. Univariate and multivariate logistic regression analyses were conducted to identify predictors of TD, and these predictors were used to construct the nomogram model. The model was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC), calibration curve, the Hosmer-Lemeshow test, and decision curve analysis (DCA). HDL-C, BUN, gender, GLU, Hypertension, Hyperuricemia, Coronary Heart Disease, and Liver disease were identified as predictors of TD. A nomogram model was constructed based on these eight factors. The model demonstrated good discrimination in both the training and validation sets. The calibration curves indicated a good fit of the model in both datasets. The decision curve analysis showed that the model had good clinical applicability. The nomogram developed in this study can predict the risk of developing TD in patients with T2DM. It enables clinicians to identify T2DM patients at high risk of concurrent TD, which may help facilitate the development of effective preventive measures and improve patient prognosis.

Advanced esophageal cancer is characterized by poor prognosis and high recurrence rates, even after receiving standard radical treatments. Current treatment guidelines primarily recommend systemic therapy combined with palliative and supportive care for advanced esophageal cancer, particularly in patients with limited functional status. Despite the recent advances, including the introduction of immunotherapy, overall survival of these patients remains limited. Radiotherapy, traditionally used for palliative purposes, is increasingly being explored as an adjunct to systemic therapies, including chemotherapy and immunotherapy, to improve clinical outcomes. This review aims to examine the current literature on the role of radiotherapy combined with systemic therapies for advanced esophageal cancer. The impact of these combined approaches on overall survival (OS), progression-free survival (PFS), and quality of life was analyzed, focusing on patient selection criteria, optimal treatment strategies, and the timing of radiotherapy administration. Studies have shown that radiotherapy combined with systemic therapy may offer survival benefits, particularly in patients with oligometastasis or limited metastatic disease. Furthermore, the synergistic effects of radiotherapy combined with immunotherapy are promising. However, the impact of such a combination need to be further investigated. Nonetheless, various challenges, including lack of consensus on optimal radiotherapy protocols, appropriate sequencing with systemic treatments, and identification of patient populations most likely to benefit, limit the application of this combination therapy. Therefore, large-scale prospective clinical trials are needed to validate these approaches and refine treatment guidelines for improved prognosis and management of patients with advanced esophageal cancer.

Aim: Brain metastases (BM) in patients with lung cancer (LC) are linked to unfavorable outcomes. The eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) is notably overexpressed across various cancer types and plays a role in promoting tumor initiation and progression. This research aimed to clarify the function of EEF1A2 in the context of lung cancer brain metastasis (LCBM) and to explore the mechanisms underlying its effects. Methods: To identify genes with differential expression between LC and LCBM samples, transcriptomic microarray analyses were conducted, confirming that EEF1A2 expression is elevated in LCBM. EEF1A2 expression levels were validated in multiple LC cell lines. PC9 and SPCA1 cells were transfected with lentiviral vectors carrying siRNAs targeting EEF1A2 to assess its role both in vitro and in vivo . Tandem mass tag proteomics was employed to identify proteins regulated by EEF1A2. The expression of EEF1A2, BCL10, and phosphorylated NF-κB in tumor tissues from LC and LCBM patients was analyzed. Results: Compared to the LC samples, the LCBM samples exhibited significantly higher levels of EEF1A2 expression. EEF1A2 knockdown in PC9 and SPCA1 cells resulted in substantial reductions in cell proliferation, migration, and invasion. Proteomic profiling revealed that BCL10 protein levels were markedly reduced in EEF1A2-knockdown cells. Additionally, there was a decrease in phosphorylated NF-κB, EGFR, and mesenchymal markers (N-cadherin, Twist, Snail, Slug, and Cdc42), along with an increase in E-cadherin expression. In a mouse model, EEF1A2 knockdown in PC9 cells significantly inhibited brain metastasis. Furthermore, patient samples presented elevated levels of EEF1A2, BCL10, and phosphorylated NF-κB in LCBM tissues than in LC tissues. Conclusion: Our research revealed that EEF1A2 is upregulated in LCBM, and that its knockdown suppresses brain metastasis by decreasing BCL10 expression, inhibiting NF-κB signaling, and reducing epithelial-mesenchymal transition markers. These results suggest that targeting EEF1A2 may be a promising therapeutic approach for preventing and treating brain metastasis in lung cancer patients.

The field of radiation-induced cardiac damage (RIHD) is garnering increasing attention. The application of advanced radiotherapy reduces the cardiac radiation dose. Still, challenges remain in the uneven dose distribution, the different sensitivity among cardiac substructures (CSs), and the delineation of target areas within these substructures. This article encompasses cardiac substructures, including atria and ventricles, coronary arteries, pulmonary vasculars and superior vena cava (SVC), cardiac conduction system, heart valves and heart base. This review will provide better understanding of RIHD as it firstly summarizes dose limitation of CSs, as well as the risk of cardiac toxicities and its impact on survival following the comprehensive search.

Rationale: Despite the increasing use of high-flow nasal cannula (HFNC) oxygen therapy during endoscopy examination, its impact on high-risk patients remains uncertain. Objectives: We aimed to compare HFNC and conventional oxygen therapy (COT) during nasal bronchoscopy in patients at high risk for desaturation (morbid obesity, narrow trachea, or baseline hypoxemia and/or hypercapnia). Methods: In this multicenter randomized controlled trial, patients scheduled for bronchoscopy and presenting with any high-risk factors were randomly assigned to receive HFNC or COT after providing written consent. Vital signs, pulse oximetry (SpO2), and transcutaneous carbon dioxide were continuously monitored. The occurrence of desaturation (SpO2 ⩽ 90% lasted >10 s), frequency of examination interruption, and treatment escalation were compared between groups. Results: Of 148 initially enrolled patients, 6 withdrew, leaving 72 and 70 in the HFNC and COT groups, respectively. Most of the patients had airway stenosis. HFNC significantly reduced desaturation occurrence during bronchoscopy (34.7% vs. 61.4%; P = 0.016), with fewer instances of examination interruption (26.4% vs. 58.6%; P < 0.001) and less frequent treatment escalation (30.6% vs. 57.1%; P = 0.001). During the examination, the lowest SpO2 was higher with HFNC (94% [interquartile range, 87-98%] vs. 87.5% [79-93%]; P = 0.001), whereas the highest transcutaneous carbon dioxide was lower (64.6 [56.8-70.1] vs. 68.3 [62.3-77.0] mm Hg; P = 0.04). No significant differences were observed regarding the time to the first desaturation, bronchoscopy withdrawal, durations of desaturation and bronchoscopy examination, or occurrence of other adverse events between groups. Conclusions: In a high-risk population with predominant airway stenosis, HFNC significantly reduced desaturation occurrence, examination interruption, and treatment escalation during nasal bronchoscopy examination in high risk patients. Clinical trial registered with www.chictr.org.cn (ChiCTR2100055038).