This study aimed to evaluate the feasibility and tolerability of arterial infusion chemotherapy embolization (AICE) in treating recurrent/metastatic soft tissue sarcoma (STS) and to explore relevant prognostic factors to tailor future individualized treatment.

A total of 113 patients with recurrent/metastatic STS treated with AICE at the Fifth Medical Center of the PLA General Hospital were included in this retrospective study. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier survival curves were adopted and univariate and multivariate analyses were conducted using the Cox proportional hazards model to evaluate prognostic factors. Treatment-related adverse events (TRAEs) were graded according to the Society of Interventional Radiology (SIR) standards.

Among the 113 patients, the median OS was 19.0 months (95% CI: 12.8-25.3) with 2-year OS rates of 45.1%. The median PFS was 11.0 months (95% CI: 8.6-13.4) with 2-year PFS rates of 25.7%. Objective response rate (ORR) was 37.2% (95% CI: 28.3%-46.8%) and disease control rate (DCR) was 76.1% (95% CI: 67.1%-83.6%). Univariate analysis revealed that tumor size, presence of distant metastasis, number of postoperative treatment regimens, pathological differentiation and neutrophil-to-lymphocyte ratio (NLR) were significantly associated with OS and PFS (P<0.05). Multivariate Cox analysis confirmed that tumor size, distant metastasis, number of postoperative treatment regimens, pathological differentiation and short-term efficacy were independent prognostic factors for OS (P<0.05). The most common TRAEs were pain (23.0%), transient bone marrow suppression (15.0%) and postoperative fever (6.2%). No severe or fatal adverse reactions and treatment-related mortalities were observed, demonstrating superior tolerability.

AICE might be a feasible and well-tolerated treatment for recurrent/metastatic STS, effectively controlling disease progression and improving survival outcomes in this retrospective cohort. Further multicenter, large-scale prospective studies were needed to validate these findings and explore the combination of AICE with immunotherapy or targeted therapy to optimize treatment strategy for STS.

The aim of this study is to investigate the effects of administering low-dose esketamine during anesthesia induction on the occurrence of postoperative delirium (POD) and postoperative cognitive function in elderly patients with preoperative anxiety.

Elderly patients aged 60-80 years and with preoperative anxiety who were undergoing surgery for gastrointestinal tumors were enrolled. The patients were randomly divided into an esketamine group or a placebo group. Upon intravenous induction of general anesthesia, the placebo group received normal saline, while the esketamine group received a subanesthetic dose (0.25 mg/kg) of esketamine. The primary outcome was the incidence of POD and the Mini-Mental State Examination (MMSE) score within 7 days after the operation (d1 to d7). Secondary outcomes included perioperative hemodynamic adverse events, postoperative anxiety, postoperative pain score, and analgesic consumption.

118 patients were screened for eligibility, and 100 were recruited and analyzed. The incidence of POD within 7 days after surgery in the esketamine group was significantly lower than the placebo group (24.00% vs 48.00%, P < 0.05). The MMSE scores at postoperative day1 (d1) were significantly higher in the esketamine group than placebo group (29.00 [28.00-30.00] vs 27.25 [25.00-29.00], Bonferroni-adjusted P = 0.0014). The esketamine group had a lower cumulative incidence of delayed neurocognitive recovery (dNCR) within 7 days after surgery (26.00% vs 54.00%, P < 0.05). When compared to the placebo group, esketamine group had lower incidence of bradycardia and hypotension events during anesthesia induction period (P < 0.05), and the visual analogue anxiety (VAS-A) score on d1 was lower (Bonferroni-adjusted P < 0.05). Moreover, the esketamine group had significantly lower plasma concentrations of serum levels of Interleukin-6 (IL-6) and S100 calcium-binding protein β (S100β) on d1 (Bonferroni-adjusted P < 0.05).

In elderly patients with preoperative anxiety who undergo gastrointestinal tumor surgery, administering a low-dose intravenous esketamine injection (0.25 mg/kg) during anesthesia induction can decrease the incidence of POD and improve early postoperative cognitive function.

Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study present real-world data on the efficacy and safety of chemoradiotherapy (CRT) plus anlotinib versus CRT alone in patients with lymph node recurrence of ESCC after radical resection.

Patients with lymph node recurrence of ESCC who received CRT with or without anlotinib between January 2017 and December 2019 were retrospectively analyzed. Treatment response, overall survival (OS), progression free survival (PFS) and treatment-related toxicities were compared between groups. Propensity score matching (PSM) analysis was used to balance baseline covariates.

A total of 291 ESCC patients with lymph node recurrence received CRT plus anlotinib (n = 76) or CRT alone (n = 215). After PSM, 68 well-balanced patients in each group were included. The partial response rate (58.8% vs 41.2%, p = 0.04) and objective response rate (86.7% vs 61.8%, p = 0.001) were significantly higher in the CRT plus anlotinib group than in the CRT group. Patients in the CRT plus anlotinib group had significantly longer OS (3-year OS, 42.7% vs 23.5%, p = 0.008) and PFS (12-month PFS, 47.1% vs 32.4%, p = 0.026) than those in the CRT group. Multivariate survival analysis revealed that the treatment group (p = 0.007) was an independent predictor of OS. No significant differences were observed in grade 3-4 treatment-related adverse events between the two groups (39.5% vs 30.7%, p = 0.162).

Compared with CRT alone, the addition of anlotinib to CRT was safe and provided survival benefits in ESCC patients with lymph node recurrence after radical resection.

rhIL-7-hyFc (Efineptakin alfa) is a novel, long-acting recombinant human interleukin-7 developed to enhance immune responses by correcting T-cell deficiencies through increased lymphocyte counts. This study aimed to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model to support selection of the recommended Phase 2 dose (RP2D) through optimization of dosing regimens.

Serum rhIL-7-hyFc concentrations and absolute lymphocyte counts (ALC) were collected from 35 patients with solid tumors enrolled in a Phase Ib clinical trial (NCT03478995), who received multiple intramuscular administrations of rhIL-7-hyFc at doses ranging from 0.06 to 1.7 mg/kg every 3 or 6 weeks. A sequential mixed-effects PK-PD model was developed using NONMEM^® (version 7.4.3) based on individual PK parameters. Monte Carlo simulations with extended dosing intervals up to 12 weeks were conducted to explore serum concentration profiles, ALC dynamics over time, and exposure-response relationships.

The PK data were best described by a two-compartment model with first-order absorption from two depot compartments, and inter-occasional variability in clearance was incorporated in the final model. To account for the time-delayed response, the PD model utilized a series of transit compartments representing lymphocyte maturation. The stimulatory effect of rhIL-7-hyFc on progenitor cell proliferation was described using a simple maximum effect model. The estimated half-maximum effective concentration (EC₅₀) was 0.066 ng/mL, indicating a high potency in increasing serum lymphocyte levels. Monte-Carlo simulation based on the final PK-PD model showed a dose-dependent increase in ALC. A dose range of 0.6-1.2 mg/kg administered at intervals of 6 to 12 weeks was suggested as feasible for the RP2D in further clinical trials.

A population PK-PD modeling and simulation results demonstrated a strong exposure-response relationship for ALC across dosing intervals, underscoring the mechanism-based therapeutic potential of rhIL-7-hyFc in cancer immunotherapy.

Venous thromboembolism (VTE), especially pulmonary embolism (PE), can be treated in an outpatient setting after appropriate risk assessment. However, front-door physicians may be resistant to follow this practice. The possibility of cancer-associated VTE complicates the outpatient management of PE. This study aimed to assess the morbidity and mortality in patients with PE who were managed in an emergency/acute medicine-led outpatient clinic as per risk stratification as well as detecting diagnoses of new cancer sites (NCSs) in these patients.

This retrospective study included all patients with confirmed PE managed in an acute medicine outpatient setting at Queens Hospital, Burton-on-Trent, United Kingdom, from 2019 to 2022. Biochemical findings, radiological findings, mortality and morbidity rates, treatment administered, simplified Pulmonary Embolism Severity Index (sPESI) scores, complications and NCS diagnosis were obtained.

A total of 82 patients were included in this study; their mean age was 63.3 ± 16.7 years and 56.1% (n = 46) were male. The two commonest presenting complaints were new shortness of breath (25.6%, n = 21) and pleuritic chest pain (19.5%, n = 16). Unprovoked PE was observed in 52.4% (n = 43) of patients. Increased sPESI scores were related to increased mortality rates; sPESI scores of 0 and 3 were associated with 0% and 50% mortality rates within 90 days, respectively. NCS was reported in 13.4% (n = 11). Statistical analyses using logistic regression and classification tree methods revealed that NCS can be predicted with 70.6% sensitivity and 97% specificity using 2 variables (history of cancer and age >73 years).

The sPESI can help in the risk stratification of patients with PE showing poor outcomes; patients at a high risk of NCS development can be identified using the classification tree method.

Anthracyclines are widely used in the treatment of breast cancer. One of the known adverse effects of anthracyclines is anthracycline-induced cardiomyopathy. Studies done worldwide showed that the prevalence of chemotherapy-induced cardiomyopathy is approximately 9%. However, studies evaluating this complication prevalence, risk factors and cumulative dose are lacking in Oman. This study aimed to investigate the prevalence of anthracycline-induced cardiomyopathy among breast cancer patients in Oman.

This retrospective study included all breast cancer patients who received anthracycline-based chemotherapy exclusively between September 2008 and December 2020 at Sultan Qaboos University Hospital in Muscat. Patients with partial treatment, coexisting heart failure and who did not receive anthracycline as part of the chemotherapy regimen were excluded. Chemotherapy-induced cardiomyopathy was defined as a drop of left ventricular ejection fraction >10% from the patient's baseline during or after receiving anthracycline-based chemotherapy.

A total of 385 patients were included in this study of which 39 (10.1%) developed cardiomyopathy after exposure to anthracyclines. The mean cumulative dose of doxorubicin among these patients was 239 mg/m² (epirubicin was converted to doxorubicin equivalent dose). Univariate analysis showed that the risk of anthracycline-induced cardiomyopathy was influenced by cardiovascular risk factors such as hypertension (33.3%), diabetes (25.6%), dyslipidaemia (20.5%) and previous cardiovascular medications use (10.3%). Trastuzumab exposure significantly correlated with an increased risk of developing cardiomyopathy (P < 0.001). However, multivariate analysis did not show any significant association.

Anthracycline-induced cardiomyopathy was influenced by various cardiovascular risk factors as well as trastuzumab exposure. Further studies are recommended to investigate the prevention and management of anthracycline-induced cardiomyopathy.

Immune checkpoint inhibitors (ICIs) represent an effective treatment for various malignant tumors. However, the utilization of ICIs is frequently accompanied by immune-related adverse events (irAEs), among which immune checkpoint inhibitor (ICI)-induced colitis is a notable complication. Current clinical guidelines recommend corticosteroids as the first-line therapy for ICI-induced colitis. Nevertheless, subset of patients fails to respond adequately to corticosteroid therapy, resulting in steroid refractoriness. At present, studies investigating the risk factors for steroid-refractory remain limited.

A retrospective analysis was conducted on patients diagnosed with ICI-induced colitis after malignant tumor treatment with ICIs. Data collected included demographics, tumor and ICIs types, time to colitis onset, number of ICIs treatments, clinical manifestations (diarrhea, abdominal pain, bloody stool, fever), endoscopic findings (ulcerative lesions, extent of lesion distribution), laboratory results, grades of diarrhea and colitis, and corticosteroid treatment response. Patients were stratified into steroid-responsive and steroid-refractory groups. Multivariate logistic regression analysis was employed to identify risk factors related to steroid-refractory. Kaplan-Meier survival analysis and log-rank tests were conducted to compare survival time differences between the two groups.

A total of 57 patients were included, with 45 patients in the steroid-responsive group and 12 patients in the steroid-refractory group. Univariate analysis revealed differences between the two groups in the time to colitis onset (median days: 97 vs. 141, P = 0.037), presence of fever (4.4% vs. 25.0%, P = 0.045), presence of ulcerative lesions (26.9% vs. 34.6%, P = 0.036), grades of colitis (P = 0.011), and serum interleukin-6 (IL-6) level (24.1 ± 20.5 pg/mL vs. 81.7 ± 38.7 pg/mL, P < 0.001). Multivariate regression analysis indicated that serum IL-6 level was an independent risk factor for steroid-refractory. Kaplan-Meier survival analysis showed no significant difference in survival time between the two groups.

For patients with ICI-induced colitis, serum IL-6 level at colitis onset could serve as an independent risk indicator for predicting the efficacy of corticosteroid therapy. Early consideration of selective immunosuppressive therapy (SIT) may be warranted with caution for patients with high serum IL-6 level.

The relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood.

We investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils.

The percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4⁺ (r = 0.43, p = 0.0045) and CD8⁺ T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4⁺ T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8⁺ T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab.

Higher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.

Hepatocellular carcinoma (HCC) imposes a substantial global health burden, while postoperative recurrence remains a pivotal factor contributing to poor prognosis. Although existing prognostic models predominantly focus on patients with HCC with microvascular invasion (MVI), recurrence mechanisms and risk stratification in those with MVI-negative HCC remain underexplored despite their distinct clinicopathological profiles. As such, this study aimed to develop a prognostic nomogram to predict recurrence-free survival (RFS) in patients with MVI-negative HCC.

Data from 547 treatment-naïve patients with MVI-negative HCC were divided into 2 cohorts: training (n=375); and external validation (n=172). Random survival forest and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram prediction model was developed based on risk factors identified in the training cohort and subsequently validated in the external validation cohort.

Key findings revealed that Ki-67, alpha-fetoprotein (AFP)-L3, neutrophil-to-lymphocyte ratio, AFP, and systemic immune-inflammation index significantly impacted RFS, with a concordance-index (C-index) exceeding 0.7 for the nomogram model in the training cohort, and an area under the receiver operating characteristic curve (AUC) of 0.758, 0.769, and 0.779 for 1-, 3-, and 5-year RFS, respectively. The external validation cohort corroborated these findings, achieving C-index values > 0.7 and AUC values of 0.717, 0.735, and 0.756 for the same time points. The calibration curves indicated strong agreement between the predicted and actual outcomes. Decision curve analysis revealed that the nomogram model demonstrated good net benefits for 1-, 3-, and 5-year RFS in both the training and external validation cohorts.

This study developed and validated a prognostic nomogram for predicting postoperative disease recurrence in patients with MVI-negative HCC, highlighting the importance of individualized patient management based on the risk factors identified.

Predicting the treatment efficacy of programmed cell death protein 1 (PD-1) inhibitors is crucial for guiding optimal treatment plans and preventing unnecessary complications for cancer patients. We aimed to develop a prediction model using clinical and body composition parameters to identify gastric cancer (GC) patients who would respond to chemotherapy plus PD-1 antibody.

Clinical data of GC patients treated with chemotherapy plus PD-1 antibody (immunotherapy cohort, n = 120) or chemotherapy alone (chemotherapy cohort, n = 82) following surgical resection were reviewed as the training set. Patients treated with chemotherapy plus PD-1 antibody at an external center were included as the validation set (n = 43). Tumor regression grade (TRG) was recorded and classified as TRG0/1 or TRG2/3 during analysis. Body composition parameters were assessed on computed tomography images at the third lumbar vertebral level using the SliceOmatic software. Univariate and multivariate analyses were performed to identify parameters associated with TRG0/1, and then a logistic regression model was developed to stratify patients into the good and poor response groups.

In the training set, clinical and body composition parameters between the immunotherapy cohort and chemotherapy cohort were similar. Skeletal muscle radiation attenuation (SMRA), neutrophil-to-lymphocyte ratio (NLR), and weight loss were associated with TRG0/1 in the immunotherapy cohort. Subcutaneous adipose tissue index (SATI) and metastasis were identified in the chemotherapy cohort. A logistic regression model was developed to stratify immunotherapy cohort patients into two response groups with an area under the receiver operating characteristic curve (AUC) value of 0.728. In the immunotherapy cohort, patients stratified as good responders showed a higher TRG0/1 rate (37/55, 67.3%) than poor response patients (18/65, 27.7%, p < 0.001) and had better overall survival (p = 0.001). In the external validation set, patients stratified using the clinical model as good responders also showed a higher TRG0/1 rate (14/18, 77.8%) than poor response patients (9/25, 36.0%, p = 0.012).

The prediction model consisting of SMRA, NLR, and weight loss could help identify GC patients who respond well to chemotherapy plus PD-1 antibody.