Cox Proportional Hazards Analysis Research Articles

Machine learning-derived prognostic signature for progression-free survival in non-metastatic nasopharyngeal carcinoma.

Early detection of high-risk nasopharyngeal carcinoma (NPC) recurrence is essential. We created a machine learning-derived prognostic signature (MLDPS) by combining three machine learning (ML) models to predict progression-free survival (PFS) in patients with non-metastatic NPC. A cohort of 653 patients with non-metastatic NPC was divided into a training (n = 457) and validation (n = 196) dataset (7:3 ratio). The study included clinicopathological characteristics, hematologic markers, and MRI findings in three machine learning models-random forest (RF), extreme gradient boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO)-to predict progression-free survival (PFS). A Venn diagram identified the overlapping signatures from the three ML algorithms. Cox proportional hazard analysis determined the MLDPS for PFS. The RF, XGBoost, and LASSO algorithms identified six consensus factors from the 33 signatures. Cox proportional hazards analysis showed that the MLDPS includes age, lymphocyte count, number of positive lymph nodes, and regional lymph node density. Additionally, MLDPS effectively stratified prognosis, with low-risk individuals showing better PFS than high-risk individuals (p < 0.001). MLDPS, based on clinicopathological characteristics, hematologic markers, and MRI findings, is crucial for guiding clinical management and personalizing treatments for patients with non-metastatic NPC.

Outcome 1 year after ICH: Data from the Tranexamic acid for IntraCerebral Haemorrhage 2 (TICH-2) trial.

The Tranexamic acid for IntraCerebral Haemorrhage-2 (TICH-2) trial reported no significant improvement in death and dependency at day 90 despite reductions in haematoma expansion, early neurological deterioration and early death. However, significant recovery after stroke, particularly intracerebral haemorrhage (ICH), may take more than 3 months. Here we report the participant outcomes at 1 year after stroke. TICH-2 was a prospective randomised controlled trial that tested the efficacy and safety of tranexamic acid in spontaneous ICH when given within 8 h of onset. Patients with ICH on anticoagulation were excluded. Centralised blinded telephone follow up was performed for patients from the United Kingdom at 1 year. The primary outcome was modified Rankin Scale at 1 year. Secondary outcomes included Barthel index, Telephone Interview Cognitive Status-modified, EuroQoL-5D and Zung Depression Scale. This was a prespecified secondary analysis of the TICH-2 trial. About 2325 patients were recruited into the trial (age 68.9 ± 13.8 years; 1301 male, 56%). About 1910 participants (82.2%) were eligible for day 365 follow up. 57 patients (3.0%) were lost to follow up. Tranexamic acid did not reduce the risk of poor functional outcome at 1 year (adjusted OR 0.91 95% CI 0.77-1.09; p = 0.302). However, Cox proportional hazard analysis revealed significant survival benefit in the tranexamic acid group (adjusted HR 0.83, 95% CI 0.70-0.99; p = 0.038). There was no difference in functional outcome at 1 year after ICH. Tranexamic acid may reduce mortality at 1 year without an increase in severely dependent survivors. But this should be interpreted with caution as this is a result of secondary analysis in a neutral trial.

The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score-Matched Study.

Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.

Albumin corrected anion gap for predicting in-hospital death among patients with acute myocardial infarction: A retrospective cohort study

ObjectiveTo explore the relationship between Anion Gap (AG), Albumin Corrected AG (ACAG), and in-hospital mortality of Acute Myocardial Infarction (AMI) patients and develop a prediction model for predicting the mortality in AMI patients. MethodsThis was a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC)-Ⅲ, MIMIC-IV, and eICU Collaborative Study Database (eICU). A total of 9767 AMI patients who were admitted to the intensive care unit were included. The authors employed univariate and multivariable cox proportional hazards analyses to investigate the association between AG, ACAG, and in-hospital mortality; p < 0.05 was considered statistically significant. A nomogram incorporating ACAG and clinical indicators was developed and validated for predicting mortality among AMI patients. ResultsBoth ACAG and AG exhibited a significant association with an elevated risk of in-hospital mortality in AMI patients. The C-index of ACAG (C-index = 0.606) was significantly higher than AG (C-index = 0.589). A nomogram (ACAG combined model) was developed to predict the in-hospital mortality for AMI patients. The nomogram demonstrated a good predictive performance by Area Under the Curve (AUC) of 0.763 in the training set, 0.744 and 0.681 in the external validation cohort. The C-index of the nomogram was 0.759 in the training set, 0.756 and 0.762 in the validation cohorts. Additionally, the C-index of the nomogram was obviously higher than the ACAG and age shock index in three databases. ConclusionACAG was related to in-hospital mortality among AMI patients. The authors developed a nomogram incorporating ACAG and clinical indicators, demonstrating good performance for predicting in-hospital mortality of AMI patients.

Prognostic value of blood GRHL2 in patients with non-small-cell lung cancer after radiotherapy and chemotherapy.

Aim: We aimed to investigate the predictive value of the Grainyhead-like 2 (GRHL2) expression from circulating blood for recurrence, metastasis and overall death on patients with non-small-cell lung cancer (NSCLC). Materials & Methods: We collected blood samples from 122 patients who were admitted to our hospital for NSCLC. Results: Multivariable Cox proportional-hazards analysis in adjusted Model II showed that compared with GRHL2-negative expression, positive expression in patients with NSCLC was associated with increased death risk (HR=7.0, 95% CI: 2.1-20.9, p=0.03) and risk for composite end point (HR=8.2, 95% CI: 4.0-27.1, p <0.01). Conclusion: This study supported that elevated circulating GRHL2 expression might be considered as a candidate prognostic biomarker for poor prognosis among these NSCLC patients.

High antinuclear antibody titer is associated with increased mortality risk in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a diagnosis of exclusion, requiring that potential etiologies of interstitial lung disease be ruled out. Antinuclear antibody (ANA) testing is commonly performed in individuals with IPF, but the clinical significance of ANA positivity remains uncertain. A retrospective search identified 161 patients diagnosed with IPF between May 2010 and January 2021. Data on ANA titers at the time of diagnosis were available in all cases. Mean age of the patients was 66.4 ± 9.6 years; 70.8% were male. ANA titers were high (≥ 1:160) in 25.4% of the cohort. Baseline characteristics were comparable between those with high and low ANA titers. During follow-up (median 28 months), 93 patients (57%) died. On Cox proportional-hazards analysis with lung transplantation entered as a competing risk and adjusting for potential confounders (age, sex, and baseline forced vital capacity and diffusing lung capacity for carbon monoxide), ANA ≥ 1:160, as a dichotomized variable, was significantly associated with case-specific mortality (HR 2.25, 95% CI 1.14−4.42, P = 0.02) and older age (for each 10-year increment, HR 1.55, 95% CI 1.07−2.25, P = 0.02). High ANA titers appear to be associated with increased mortality in IPF. This finding emphasizes the potential prognostic value of ANA testing. Further studies are needed to validate these findings and explore their implications for patient management.

Risk Factors for Heart Failure and Coronary Artery Disease Mortality Based on the National Vital Statistics During a 25-Year Follow-up in Japan - NIPPON DATA90.

Prevention of heart failure (HF) is a public health issue. Using the National Vital Statistics, we explored risk factors for HF and coronary artery disease (CAD) mortality. Altogether, 7,556 Japanese individuals aged ≥30 years in 1990 were followed over 25 years; of these, 139 and 154 died from HF and CAD, respectively. In multivariable Cox proportional hazard analysis, common risk factors for CAD and HF mortality were hypertension (hazard ratio [HR] 1.48 [95% confidence interval {CI} 1.00-2.20] and 2.31 [95% CI 1.48-3.61], respectively), diabetes (HR 2.52 [95% CI 1.63-3.90] and 2.07 [95% CI 1.23-3.50], respectively), and current smoking (HR 2.05 [95% CI 1.27-3.31) and 1.86 [95% CI 1.10-3.15], respectively). Specific risk factors for CAD were male sex, chronic kidney disease, history of cardiovascular disease, and both abnormal T and Q waves, with HRs (95% CIs) of 1.75 (1.05-2.92), 1.78 (1.19-2.66), 2.50 (1.62-3.88), and 11.4 (3.64-36.0), respectively. Specific factors for HF were current drinking (HR 0.43; 95% CI 0.24-0.78) and non-high-density lipoprotein cholesterol (non-HDL-C; HR 0.81; 95% CI 0.67-0.98). There was an inverse association between non-HDL-C and HF in those aged ≥65 years (HR 0.71; 95% CI 0.56-0.90), but not in those aged <65 years. We identified common risk factors for HF and CAD deaths; a history of cardiovascular disease was a specific risk for CAD.

15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

Screening high-risk individuals for primary gastric carcinoma: evaluating overall survival probability score in the presence and absence of lymphatic metastasis post-gastrectomy

ObjectiveThe aim of this study was to develop and validate prognostic models for predicting overall survival in individuals with gastric carcinoma, specifically focusing on both negative and positive lymphatic metastasis.MethodsA total of 1650 patients who underwent radical gastric surgery at Shanxi Cancer Hospital between May 2002 and December 2020 were included in the analysis. Multiple Cox Proportional Hazards analysis was performed to identify key variables associated with overall survival in both negative and positive lymphatic metastasis cases. Internal validation was conducted using bootstrapping to assess the prediction accuracy of the models. Calibration curves were used to demonstrate the accuracy and consistency of the predictions. The discriminative abilities of the prognostic models were evaluated and compared with the 8th edition of AJCC-TNM staging using Harrell’s Concordance index, decision curve analysis, and time-dependent receiver operating characteristic curves.ResultsThe nomogram for node-negative lymphatic metastasis included variables such as age, pT stage, and maximum tumor diameter. The C-index for this model in internal validation was 0.719, indicating better performance compared to the AJCC 8th edition TNM staging. The nomogram for node-positive lymphatic metastasis included variables such as gender, age, maximum tumor diameter, neural invasion, Lauren classification, and expression of Her-2, CK7, and CD56. The C-index for this model was 0.674, also outperforming the AJCC 8th edition TNM staging. Calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis for both nomograms demonstrated excellent prediction ability. Furthermore, significant differences in prognosis between low- and high-risk groups supported the models’ strong risk stratification performance.ConclusionThis study provides valuable risk stratification models for lymphatic metastasis in gastric carcinoma, encompassing both node-positive and negative cases. These models can help identify low-risk individuals who may not require further intervention, while high-risk individuals can benefit from targeted therapies aimed at addressing lymphatic metastasis.

High Intraocular Pressure Is Independently Associated With New-Onset Systemic Hypertension Over a 10-Year Period.

Systemic hypertension (HT) is associated with the development of increased intraocular pressure (IOP), a risk factor for glaucoma. However, it remains unclear whether high IOP is a risk factor for HT.Methods and Results: We investigated 7,487 Japanese individuals (4,714 men, 2,773 women; mean [±SD] age 49±9 years) who underwent annual health checkups in 2006. Over the 10-year follow-up period, 1,232 (24.3%) men and 370 (11.5%) women developed new-onset HT, defined as initiation of antihypertensive drug treatment or blood pressure ≥140/90 mmHg. After dividing IOP into tertiles (T1-T3), Cox proportional hazards analysis (adjusted for age, sex, systolic blood pressure, obesity, current smoking, alcohol consumption, family history of HT, estimated glomerular filtration rate, and diabetes and dyslipidemia diagnoses at baseline) revealed a significantly higher risk of newly developed HT in T3 (IOP ≥14 mmHg; hazard ratio 1.14; 95% confidence interval 1.01-1.29; P=0.038) using T1 (IOP ≤11 mmHg) as the reference group. There was no significant interaction between sex and IOP tertile (P=0.153). A restricted cubic spline model showed a gradual but robust increase in the hazard ratio for new-onset HT with increasing IOP. High IOP is an independent risk factor for the development of HT over a 10-year period.

An Exploratory Randomized Controlled Study to Investigate Concentration-Dependence of Green Tea Catechin Gargling on Acute Upper Respiratory Tract Infections.

Green tea (GT) catechins exhibit antiviral effects in experimental studies. However, we lack clinical evidence on the preventive effects of catechin concentrations in gargling against acute upper respiratory tract infections (URTIs). Therefore, we aimed to investigate the concentration-dependence of GT catechins in gargling on the incidence of URTIs. We conducted an open-label randomized study. The target population consisted of 209 students from the University of Shizuoka and Meiji University, who were randomly assigned to high-catechin (approximate catechin concentration: 76.4 mg/dL), low-catechin (approximate catechin concentration: 30.8 mg/dL), and a control water gargling (catechin concentration: 0 mg/dL) group. All participants gargled water or GT daily for 12 weeks. The symptoms of URTIs were recorded on a daily survey form by participants. The incidences of URTIs occurred in 6 (9.1%), 7 (10.8%), and 11 (15.7%) participants in the high-catechin, low-catechin, and water groups, respectively. Cox proportional hazards analysis, using background factors and prevention status as covariates, revealed a hazard ratio of 0.57 (95% Confidence Interval (CI): 0.21-1.55, p = 0.261) for the high-catechin vs. water group and 0.54 (95% CI: 0.20-1.50, p = 0.341) for the low-catechin vs. water group. Our findings showed the incidence of URTIs in a concentration-dependent GT gargling was not significantly different, partly owing to the low event rates caused by intense precautions against the coronavirus disease 2019 pandemic. Our study would serve as a foundation for the development of an advanced protocol with optimal concentrations and a larger number of participants.

Sex and the Relationship Between Cardiometabolic Risk Factors and Estimated GFR Decline: A Population-Based Cohort Study

Rationale & ObjectiveFemales have a higher prevalence of chronic kidney disease (CKD) than males, but are less likely to be treated with kidney replacement therapy (KRT). We studied the interaction between sex and the association of cardiometabolic risk factors for the decline in kidney function over time. Study DesignA population-based cohort study. Setting & Participants1,127,731 adults living in Wales, UK, within the Secure Anonymised Information Linkage Databank. ExposuresSex and risk factors including age, estimated glomerular filtration rate (eGFR), cardiometabolic conditions, smoking, and socioeconomic deprivation. These risk factors were defined using primary care records. OutcomesThe yearly declines in eGFR and the risk of incident kidney failure defined as long-term KRT and/or sustained eGFR<15mL/min/1.73m2. Analytical ApproachLinear mixed effects models and Cox proportional hazards analysis. ResultsThe average decline in eGFR age ≤73 was equal in males and females. After age 73, eGFR decline was faster in males than females, particularly for males with heart failure (males -1.22 mL/min/1.73m2 per year: 95% confidence interval (CI) -1.25 to -1.20 versus females -0.87mL/min/1.73m2: CI -0.89 to -0.85) and current smokers (males -1.58 mL/min/1.73m2 per year: CI -1.60 to -1.55 versus females -1.27 mL/min/1.73m2: CI -1.29 to -1.25). Socioeconomic deprivation was one of the most impactful risk factors on eGFR decline among females age >73, whereas cardiometabolic risk factors were more important among males. Older females at baseline were less likely to develop incident kidney failure than older males (p-value for age<0.001). LimitationsStudy of people who were almost exclusively White and who had blood laboratory test data. Reliance on creatinine-based eGFR. Albuminuria and body mass index data were incomplete. ConclusionseGFR decline was faster in males than in females especially in the setting of heart failure and smoking. Socioeconomic deprivation was an important risk factor associated with eGFR decline, particularly for females. While further work is required to explore less well-recognised risk factors these findings may inform clinical management strategies of CKD overall and within sex-specific groups.

Effects of combined morbid insomnia and sleep apnea on long-term cardiovascular risk and all-cause mortality in elderly patients: a prospective cohort study

PurposeIt is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA).MethodsWe included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality.ResultsThere were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349–4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397–6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393–3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022–8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE.ConclusionsOur results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.

The clinical significance assessment of the transverse lymph node metastasis in gastric cancer: The establishment and validation of nomogram from a single clinical medical center

BackgroundLymph node metastasis is an important route for gastric cancer metastasis. The clinical significance of transverse lymph node metastasis (TLNM) is still unclear. AimsThis study investigates effects of TLNM on the prognosis of GC patients and establishes two nomograms for evaluating the prognosis of GC patients and for predicting the risk clinicopathological factors to TLNM based on a Chinese medical database. MethodsA total of 902 GC patients with lymph node metastasis (LNM) who underwent R0 gastrectomy was included in this study. According to results of Cox proportional hazards analyses and logistic regression analyses, the prognostic and the predictive nomograms were established and validated. ResultsThe overall survival of patients with TLNM was significantly worse than those without TLNM (P < 0.001) and similar to patients with extra-gastric LNM (P > 0.05). TLNM independently influenced prognosis of GC patients. Prognostic and predictive nomograms were established and validated. Both nomograms were proven that have high accuracy by calculating each AUC (Area Under Cure) value. Calibration curves aligned well with actual outcomes. DCA (Decision Curve Analyses) analyses indicated the high clinical utility. ConclusionThese nomograms offer precise survival and TLNM occurrence predictions, which may aid clinical decisions.

Assessment of imaging risks for recurrence after stereotactic radiosurgery for brain metastases (IRRaS-BM)

BackgroundThe identification of viable tumors and radiation necrosis after stereotactic radiosurgery (SRS) is crucial for patient management. Tumor habitat analysis involving the grouping of similar voxels can identify subregions that share common biology and enable the depiction of areas of tumor recurrence and treatment-induced change. This study aims to validate an imaging biomarker for tumor recurrence after SRS for brain metastasis by conducting tumor habitat analysis using multi-parametric MRI.MethodsIn this prospective study (NCT05868928), patients with brain metastases will undergo multi-parametric MRI before SRS, and then follow-up MRIs will be conducted every 3 months until 24 months after SRS. The multi-parametric MRI protocol will include T2-weighted and contrast-enhanced T1-weighted imaging, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. Using k-means voxel-wise clustering, this study will define three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) on T1- and T2-weighted images and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable) on apparent diffusion coefficient maps and cerebral blood volume maps. Using RANO-BM criteria as the reference standard, via Cox proportional hazards analysis, the study will prospectively evaluate associations between parameters of the tumor habitats and the time to recurrence. The DICE similarity coefficients between the recurrence site and tumor habitats will be calculated.DiscussionThe tumor habitat analysis will provide an objective and reliable measure for assessing tumor recurrence from brain metastasis following SRS. By identifying subregions for local recurrence, our study could guide the next therapeutic targets for patients after SRS.Trial registrationThis study is registered at ClinicalTrials.gov (NCT05868928).

Efficacy and Safety of Fruquintinib-Based Treatment in Patients with Refractory Bone and Soft Tissue Sarcoma after Developing Resistance to Several TKIs: A Multicenter Retrospective Study.

Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second-line therapy in refractory sarcoma, prolonging progression-free survival (PFS) but with short-lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-1,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib-based treatment in patients with refractory sarcoma after developing several lines of TKI resistance. We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib-based treatment from November 2021 to August 2023. The primary endpoint was the progression-free survival rate at 4 months (4m-PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan-Meier method. A log-rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS-related prognostic factors. We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow-up time of 6.8 (interquartile range [IQR], 4.6-9.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m-PFSR was 58.4% (95% confidence interval [CI], 49.6%-67.1%). The median PFS and OS were 4.4 (95% CI, 3.9-5.0) months and 11.4 (95% CI, 10.3-12.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10-2.93; p = 0.020). Eighty-eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18/124, 14.5%), diarrhea (8/124, 6.5%), oral mucositis (7/124, 5.6%), and thrombocytopenia (7/124, 5.6%). Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.

The pulmonary-vascular-stump filling defect on CT post lung tumor resection: a predictor of cancer progression

BackgroundTo explore the pulmonary-vascular-stump filling-defect on CT and investigate its association with cancer progression.MethodsRecords in our institutional database from 2018 to 2022 were retrospectively analyzed to identify filling-defects in the pulmonary-vascular-stump after lung cancer resection and collect imaging and clinical data of patients.ResultsAmong the 1714 patients analyzed, 95 cases of filling-defects in the vascular stump after lung cancer resection were identified. After excluding lost-to-follow-up cases, a total of 77 cases were included in the final study. Morphologically, the filling-defects were dichotomized as 46 convex-shape and 31 concave-shape cases. Concave defects exhibited a higher incidence of increase compared to convex defects (51.7% v. 9.4%, P = 0.001). Among 61 filling defects in the pulmonary arterial stump, four (6.5%) increasing concave defects showed the nuclide concentration on PET and extravascular extension. The progression-free survival (PFS) time differed significantly among the concave, convex, and non-filling-defect groups (log-rank P < 0.0001), with concave defects having the shortest survival time. Multivariate Cox proportional hazards analysis indicated that the shape of filling-defects independently predicted PFS in early onset on CT (HR: 0.46; 95% CI: 0.39–1.99; P = 0.04). In follow-ups, the growth of filling-effects was an independent predictor of PFS (HR: 0.26; 95% CI: 0.11–0.65; P = 0.004).ConclusionsCertain filling-defects in the pulmonary-arterial-stump post lung tumor resection exhibit malignant growth. In the early onset of filling-defects on CT, the concave-shape independently predicted cancer-progression, while during the subsequent follow-up, the growth of filling-defects could be used independently to forecast cancer-progression.

Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol

To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia with CD123 expression

To investigate the expression of CD123 in children with acute lymphoblastic leukemia (ALL) and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia (B-ALL). A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology, Children's Hospital of Kunming Medical University, from December 2019 to June 2022. According to the expression of CD123 at initial diagnosis, the children were divided into CD123+ group and CD123- group, and the two groups were compared in terms of clinical characteristics and treatment outcome. The factors influencing the prognosis were analyzed. Among the 251 children with ALL, there were 146 children (58.2%) in the CD123+ group. The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group (P<0.05). Compared with the CD123- group, the CD123+ group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years, with a relatively low proportion of children with E2A-PBX1 fusion gene (P<0.05). The multivariate Cox proportional-hazards regression model analysis showed that compared with the >10 years group, the 1-10 years group had a significantly higher overall survival rate (P<0.05), and compared with the high risk group, the moderate risk group had a significantly higher event-free survival rate in children with B-ALL (P<0.05). CD123 is widely expressed in children with B-ALL, and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL, which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.