Real-world Cohort Study Research Articles

Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence insitu hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Glycemic control of once-weekly and other administration frequencies for DPP-4 inhibitor in patients with type 2 diabetes: a real-world retrospective cohort study.

To assess the glycemic control of once-weekly (QW) and other administration frequencies for dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes in a real-world setting. A retrospective cohort study used Japanese medical claims data and medical check-up data between December 2015 and February 2020. Patients with type 2 diabetes had been newly prescribed a DPP-4i regimen of once-daily (QD), twice-daily (BID), or QW administration and had hemoglobin A1c (HbA1c) values from regular medical check-ups. HbA1c values and proportion of patients achieving their HbA1c target were assessed. Multivariable analyses were conducted to examine the association between DPP-4i regimen and achievement of HbA1c target. Of the analysis population (N = 7229), 6098 patients were prescribed the QD regimen, 772 BID, and 359 QW. Mean HbA1c before exposure to DPP-4i was 7.31 ± 1.20% (mean ± standard deviation) for QD, 7.64 ± 1.47% for BID, and 7.06 ± 0.96% for QW, decreasing after DPP-4i exposure to 6.71 ± 0.78%, 6.77 ± 0.84%, and 6.59 ± 0.67%, respectively. HbA1c < 7% was achieved in 72.1% of patients for QD, 69.0% for BID, and 79.1% for QW. On multivariable analysis, the odds ratio (95% confidence interval) for HbA1c < 7.0% in patients < 65years of age was 0.97 (0.73-1.30) for BID and 0.90 (0.57-1.42) for QW compared to QD. Similar achievement of HbA1c target was noted in each regimen for patients age ≥ 65years and for age ≥ 65years with multimorbidity. In this study under real-world conditions, glycemic control for the DPP-4i QW regimen was similar to that for QD and BID. The online version contains supplementary material available at 10.1007/s13340-024-00718-5.

Risk of Intracranial Hemorrhage in Persons with Hemophilia A in the United States: Real-World Retrospective Cohort Study Using the ATHNdataset.

Intracranial hemorrhage (ICH), a serious complication in persons with hemophilia A (PWHA), causes high rates of mortality and morbidity. Identified ICH risk factors from patient data spanning 1998-2008 require reassessment in light of changes in the current treatment landscape. PWHA identified in the ATHNdataset were evaluated retrospectively to assess incidence of ICH and determine the association between ICH risk and key characteristics using time-to-event analyses (Cox proportional-hazards models, survival curves, and sensitivity analyses). Over a median follow-up time of 10.7 patient-years, 135 of 7837 PWHA over 2 years of age in the ATHNdataset (1.7%) experienced an ICH. Stratification by prophylaxis status and inhibitor status resulted in an incidence rate (IR) ratio (IRR) (IR+/IR-) of 0.63 (95% confidence interval [CI], 0.43-0.94; P=0.020) and 1.76 (95% CI, 0.97-3.20; P=0.059), respectively. Characteristics associated with greater risk of developing ICH include being aged 2-12 years; being covered by Medicaid; having had HIV, hepatitis C, or hypertension; and never having received factor VIII or prophylactic treatment. In multivariable analysis with interaction, the estimated hazard ratio for PWHA never receiving prophylaxis was 7.67 (95% CI, 2.24-26.30), which shrunk to 2.03 (95% CI, 1.30-9.12) in bootstrapping analysis and 3.09 in the highest-penalty ridge-regression analysis but was still significant. Inhibitor status was found not to be statistically associated with ICH in all analyses. These results align with previous studies demonstrating that prophylaxis confers a protective effect against ICH. Previously, inhibitor positivity had been shown to increase risk for ICH; however, this study did not corroborate those findings.

(859) - Treatment Patterns for Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in Finland Between 2008 and 2020 - A Descriptive Real-World Cohort Study (FINPAH)

(859) - Treatment Patterns for Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in Finland Between 2008 and 2020 - A Descriptive Real-World Cohort Study (FINPAH)

Abstract 2533: In-depth multi-omic profiling of immune cells in cancer patients developing immune-related adverse events

Abstract Background: The clinical efficacy of immune-checkpoint inhibitors is complicated by the risk for immune-related adverse events (irAEs) that can involve any organ systems. To date, (1) we cannot predict irAE risk reliably at patient level and (2) irAEs remain a diagnosis of exclusion as there are no specific clinical or biological markers. The goal of this study was to elucidate intricate transcriptomic and proteomic signatures of immune cells in patients evolving irAEs. Methods: This pilot trial was conducted as part of a prospective multicenter cohort study (NCT04631731). The study cohort consisted of n=71 patients who were treated with ICIs across Blacktown and Westmead Hospitals, NSW, Australia. Peripheral blood mononuclear cells (PBMCs) were collected from both pre-treatment and after 6-8 weeks post-ICI commencement. Samples were further utilized for RNA sequencing, flow cytometry and Chromium 3’ gene expression analysis (10x Genomics). Results: The median age was 67 years old with the 78% (n=56) of Caucasian origin. The predominant number of patients were treated with dual ICIs. N=21 patients experienced irAEs. Firstly, a differential analysis established a set of genes which were significantly (FDR&amp;lt;0.01) dysregulated between patients with (group A) and without irAEs (group B) and were mostly related to cell cycle and regulation. Notably, phospholipase D signaling pathway was exclusively upregulated in group A and is known to be linked to B cell expansion. Secondly, a cell enrichment analysis within the group A revealed a significant increase of CD4+ and CD8+ T central memory (Tcm) cells upon the toxicity onset as compared to baseline stage. Thirdly, the flow cytometry data established that group A had (1) higher expression of CD27 on CD4+ T cells, a member of Traf-linked tumor necrosis factor receptor family essential for T cells’ maturation and (2) lower expression of inhibitory receptor LAG3 (CD223) which is crucial for maintaining homeostasis of immune system through suppression of T cell proliferation. Finally, we sequenced CD45+ cells from n=4 patients from group A and n=4 from group B at both pre- and post-treatment stages. The unsupervised clustering established 17 different clusters in our single cell dataset with cluster 11 was unique only to patients from group A. The differential analysis established that a set of n=62 genes was significantly upregulated (p&amp;lt;0.05) in cluster 11. Functional annotation established that B cell activation and proliferation pathways were enriched by those genes further stressing B cells’ role in irAEs development. Conclusions: Our real-world cohort study established significant molecular and cellular differences between patients with and without irAEs. Further research in larger cohorts is imperative to validate the established findings and to elucidate the precise mechanisms contributing to the development of irAEs. Citation Format: Dmitrii Shek, Bo Gao, Joey Lai, Brian Gloss, Adnan Nagrial, Ines Pires da Silva, Matteo S. Carlino, Scott A. Read, Golo Ahlenstiel. In-depth multi-omic profiling of immune cells in cancer patients developing immune-related adverse events [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2533.

Abstract 2543: Evaluating biomarkers of immunotherapy response in a real-world metastatic NSCLC cohort

Abstract Background: Non-small cell lung cancer (NSCLC) is the leading cause of global cancer deaths, since a large proportion of cases are initially diagnosed at advanced stages. Therapeutic developments have shifted first-line (1L) therapy in the metastatic setting to immunotherapy (IO)-based regimens, albeit with heterogeneity in response. Patients harboring KEAP1 and STK11 mutations have been reported to exhibit both poorer outcomes and IO treatment resistance. Recent work suggests gene expression signatures which characterize mutant phenotypes may better identify those with compromised IO response. Leveraging a molecular real-world dataset of metastatic NSCLC patients treated with 1L IO, we aimed to evaluate gene expression signatures representing KEAP1 and STK11-mutated phenotypes and their impact on real-world outcomes. Methods: Metastatic NSCLC patients who received 1L anti-PD(L)1 as a monotherapy or in combination were identified from the multimodal real-world database of Tempus Labs, Inc. All patients in the analytical cohort had tissue biopsies sequenced on Tempus targeted DNA and whole transcriptome RNA assays within 90 days prior to the start of the 1L IO regimen. Patients were negative for actionable mutations with record duration of at least 30 days from 1L initiation. KEAP1 and STK11 mutants were identified with likely pathogenic and/or pathogenic mutations as annotated by Tempus bioinformatic pipelines. Gene expression signatures related to these mutations were obtained from recently published literature. Evaluation of mutations or signatures as genomic markers for IO non-response were conducted using real-world progression-free survival (rwPFS) and overall survival (rwOS). Results: A total of 332 patients were included in the study (45% IO monotherapy, 55% IO combination therapy). Previously validated biomarkers, including tumor mutation burden, T-cell inflamed GEP signature, and PD(L)1 expression, were associated with prolonged rwPFS. KEAP1 mutations were observed in 9% of analytical cohort with a higher proportion in non-squamous (11%) compared with squamous (4%) samples. For STK11, 10% were identified as mutants with a similar histology distribution (12% vs. 3%). Neither KEAP1 mutations nor related gene signatures evaluated in this study were significantly associated with real-world survival outcomes. Patients harboring STK11 mutations trended towards poor outcomes; furthermore, those with higher STK11 inactivation signature score were associated with shorter rwPFS and rwOS. Conclusions: STK11 inactivation phenotype described by a gene expression signature was able to distinguish patients with significantly poorer survival outcomes. This finding would need validation in independent cohorts. This real-world cohort study adds supporting evidence for the utility of gene expression signatures encompassing mutant phenotypes for patient stratification. Citation Format: Katherina C. Chua, Assieh Saadatpour, Ariel Chen, Aisha Hasan, Bevan Emma Huang, Stewart Bates. Evaluating biomarkers of immunotherapy response in a real-world metastatic NSCLC cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2543.

Effectiveness and Safety of Edoxaban Compared With Apixaban in Elderly Patients With Nonvalvular Atrial Fibrillation: A Real-World Population-Based Cohort Study.

The very elderly (≥80 years) are at high risk of nonvalvular atrial fibrillation and thromboembolism. Given its recent approval, the comparative effectiveness and safety of edoxaban in this population, relative to the commonly used apixaban, remain unknown. Using the United Kingdom Clinical Practice Research Datalink, we identified a cohort of patients aged ≥80 with incident nonvalvular atrial fibrillation and newly treated with edoxaban or apixaban between 2015 and 2021. Cohort entry was defined as the first prescription for one of the 2 drugs. We used propensity score fine stratification and weighting for confounding adjustment. A weighted Cox proportional hazards model was used to estimate the hazard ratios (HR) with 95% CI of ischemic stroke/transient ischemic attack/systemic embolism (primary effectiveness outcome) and of major bleeding (primary safety outcome) associated with edoxaban compared with apixaban. We also assessed the risk of all-cause mortality and a composite outcome of ischemic stroke/transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage as secondary outcomes. The cohort included 7251 new-users of edoxaban and 39 991 of apixaban. Edoxaban and apixaban had similar incidence rates of thromboembolism (adjusted rates, 20.38 versus 19.22 per 1000 person-years; adjusted HR, 1.06 [95% CI, 0.89-1.26]), although the rates of major bleeding were higher with edoxaban (adjusted rates, 45.57 versus 31.21 per 1000 person-years; adjusted HR, 1.42 [95% CI, 1.26-1.61]). The risk of the composite outcome was 21% higher with edoxaban (adjusted HR, 1.21 [95% CI, 1.07-1.38]). All-cause mortality was similar between edoxaban and apixaban (adjusted HR, 1.04 [95% CI, 0.96-1.12]). In very elderly patients with nonvalvular atrial fibrillation, edoxaban resulted in similar thromboembolism prevention as apixaban, although it was associated with a higher risk of major bleeding. These findings may improve the management of nonvalvular atrial fibrillation by informing physicians on the choice of anticoagulant for this vulnerable population.

A real-world retrospective cohort study comparing two bilateral stimulation protocols of add-on rTMS in patients with treatment resistant depression and severe anxiety

BackgroundTranscranial magnetic stimulation (TMS) has been shown to improve response and remission in patients with treatment resistant depression. The objective of this study was to compare the efficacy of two bilateral rTMS protocols with different protocols in patients with treatment resistant depression and comorbid severe anxiety. MethodsA retrospective cohort study involving 67 patients who underwent two different bilateral TMS protocols and who met the specified eligibility criteria was conducted. Group 1 received stimulation with 85% RMT intermittent theta burst (iTBS) in the left DLPFC + 120% RMT (1 Hz) in the right DLPFC. Group 2 received stimulation with 100% RMT (iTBS) in the left DLPFC + 110% RMT (1 Hz) in the left DLPFC. ResultsAfter the magnetic stimulation treatment, 55% (n=22) achieved response to depression symptoms in group 1 and 62% (n=18) in group 2. Remission of depression symptoms was achieved in 13% in group 1 (n=5) and 24% in group 2 (n=7). There were no significant differences between the two protocols after TMS ConclusionsDifferent bilateral protocol parameters in individuals undergoing TMS may have an impact on symptom response and remission. Further studies with larger sample sizes are needed.

Characteristics and Outcomes of Patients With Relapsed/Refractory Multiple Myeloma After Exposure to Lenalidomide in First Line of Therapy: A Single Center Database Review in Greece

BackgroundThe increasing use of lenalidomide (Len) in first-line (1L) therapy of multiple myeloma (MM) has led to a significant proportion of patients becoming Len-refractory following 1L treatment. However, there are limited real-world data on treatment strategies and outcomes of patients who become Len-refractory following 1L therapy. Patients and MethodsThis real-world retrospective cohort study analyzed Len-refractory and non-Len-refractory patients who received 1L Len and initiated second-line (2L) therapy at a Greek MM center. The Len-exposed cohort (n = 249) included 55.4% Len-refractory patients after 1L. ResultsCompared to non-Len-refractory patients, Len-refractory patients more frequently had high-risk cytogenetics and Revised-International Staging System-3 disease stage at diagnosis, and had shorter progression-free survival (PFS) following 1L therapy. Len-refractory versus non-Len-refractory patients more frequently received triplets (59% vs. 40%), anti-CD38 agents (20% vs. 9%) and pomalidomide (22% vs. 13%). The overall response rate was 53% for Len-refractory patients and 64% for non-Len-refractory patients in 2L therapy; median PFS was 10.7 vs. 18.3 months, respectively. Median overall survival (OS) was shorter for Len-refractory patients vs non-Len-refractory patients (23.8 vs. 53.6 months). Len refractoriness was an independent prognostic factor for both PFS and OS in Len-exposed patients. ConclusionIn this real-world Len-exposed cohort, Len-refractory patients receiving 1L Len experienced poorer survival outcomes than non-Len-refractory patients, highlighting the unmet need in this patient population which has driven the development of novel therapies.

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial

IntroductionFrailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown.Methods and analysisThis prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition.DiscussionThis study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05635877, NCT05635877.

Long-term benefits of EPs® 7630 in patients with acute sinusitis: a real-world cohort study.

Background: We evaluated whether EPs® 7630 prescription in patients with acute sinusitis (AS) is associated with less frequent recurrence of AS, occurrence of chronic sinusitis or nasal polyps, or fewer antibiotic prescriptions. Methods: This retrospective cohort study used electronic medical records from the IQVIA Disease Analyzer database. Associations between initial therapy [EPs® 7630, antibiotics, intranasal corticosteroid (INCS), or corticosteroid-free nasal spray within 3days of AS diagnosis] and AS recurrence, incidence of chronic sinusitis or nasal polyps or rate of antibiotic prescription were studied using multivariable Cox or logistic regression models, adjusting for sex, age, insurance status, month of diagnosis, and comorbidity. Results: A total of 216,360 patients were analyzed. INCS prescription was associated with a higher risk of recurrent AS (HR: 1.40; 95% CI: 1.01-1.92) and a higher incidence of chronic sinusitis or nasal polyp diagnosis (HR: 1.39; 95% CI: 1.01-1.92) compared to EPs® 7630. Initial antibiotic therapy was significantly associated with higher risk of new antibiotic prescription in the period of 31-365days after the index date compared to EPs® 7630 (OR: 2.20; 95% CI: 1.66-2.92). Conclusion: EPs® 7630 prescription is associated with long-term benefits in AS patients. EPs® 7630 can help to reduce inappropriate antibiotic use and might reduce the risk of chronic sinusitis or nasal polyps.

Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study

BackgroundTo investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP).MethodsThis multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected.ResultsA total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories.ConclusionSLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.

The hidden epidemic: Uncovering incidental fatty liver disease and its metabolic comorbidities by datamining in a hospital data lake – A real-world cohort study

AimsTo identify individuals with incidental fatty liver disease (FLD), and to evaluate its prevalence, metabolic co-morbidities and impact on follow-up. MethodsWe leveraged the data-lake of Helsinki Uusimaa Hospital district (Finland) with a population of 1.7 million (specialist and primary care). A phrase recognition script on abdominal imaging reports (2008–2020) identified/excluded FLD or cirrhosis; we extracted ICD-codes, laboratory and BMI data. ResultsExcluding those with other liver diseases, the prevalence of FLD was 29% (steatosis yes/no, N=61,271/155,521; cirrhosis, N=3502). The false positive and negative rates were 5–6%. Only 1.6% of the FLD cases had the ICD code recorded and 32% had undergone full clinical evaluation for associated co-morbidities. Of the 35–65-year-old individuals with FLD, 20% had diabetes, 42% prediabetes and 28% a high liver fibrosis index. FLD was independently predicted by diabetes (OR 1.56, CI 1.46–1.66, p = 2.3 * 10^-41), BMI (1.46, 1.42–1.50, p = 1.7 * 10^-154) and plasma triglyceride level (1.5, 1.43–1.57, p = 3.5 * 10^-68). Alanine aminotransferase level mildly increased (1.12, 1.08–1.16, p = 2.2 * 10^-9) and high age decreased the risk (0.92, 0.89–0.94, p = 4.65*10^-09). Half of the cases had normal ALT. ConclusionsThe incidental radiological finding of FLD is reliable and associated with metabolic risks but largely ignored, although it should lead to metabolic and hepatic follow-up.

Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment. Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment. Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study

BackgroundThere are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy.MethodsUsing electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher’s exact test. ROC curve and surv_cutpoint function of ‘survminer’ package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors.ResultsA total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy.ConclusionsThird-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

Comparison of safety and effectiveness between etanercept biosimilar LBEC0101 and reference in patients with rheumatoid arthritis in real-world data using the KURAMA cohort.

Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021. Serum ETN levels were measured using liquid chromatography-tandem mass spectrometry. The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice.

Effectiveness and safety of edaravone dexborneol in acute ischemic stroke (EXPAND): Study protocol for a prospective, multicenter, real-world cohort study

Background: Edaravone dexborneol has been confirmed as a novel neuroprotective agent by acting on multiple active targets of antioxidation and anti-inflammation. Objectives: This study aims to evaluate the effectiveness and safety of edaravone dexborneol in patients with acute ischemic stroke (AIS) within 14 days of symptom onset in real-world clinical practice. Methods: This prospective, multicenter, 2-arm, parallel, real-world cohort study will involve 72 stroke centers in China and plans to recruit 4750 exposed/unexposed patients with a 2:1 ratio to gather additional safety information on edaravone dexborneol. Patients eligible of the Effectiveness and Safety of Edaravone Dexborneol in Acute Ischemic Stroke (EXPAND) are diagnosed with AIS within 14 days of symptom onset. The eligible patients who receive edaravone dexborneol will be assigned to the exposed group, while those without using edaravone dexborneol will be assigned to the unexposed group. All participants will be followed up for 90 days. The primary outcome is a favorable functional outcome as defined by a modified Rankin Scale (mRS) score 0–1 at 90 days. Primary efficacy in the 2 groups will be compared using multivariable logistic regression. Results: EXPAND is the first real-world study to elucidate the efficacy and safety of edaravone dexbornel in AIS, which has the potential to extend the therapeutic time window of neuroprotective treatment and propose a multiple-target approach for AIS. Conclusions: The protocol was approved by the Ethics Committee at all participating sites [the reference number of central ethic committee: (2022)090] and by the local Institutional Review Board of each participating center. The findings of the study will be published in peer-reviewed scientific journals and presented at national and international conferences. This cohort study only collects real-world patient data during the diagnosis and treatment process. The refusal of a patient to participate or the decision to withdraw from the study will not interfere with the clinical decision-making. Thus, no additional risk will be imposed. Trial registration number: NCT05644223.

Real-World Overall Survival and Treatment Patterns by PTEN Status in Metastatic Castration-Resistant Prostate Cancer.

It is estimated that the PTEN tumor suppressor gene is functionally lost in 40%-50% of patients with metastatic castration-resistant prostate cancer (mCRPC). There is limited information on the prognostic significance of PTEN status identified with genomic testing. This real-world cohort study assessed PTEN as a genetic biomarker using data from US-based oncology practices. This retrospective real-world cohort study used a deidentified US-based metastatic prostate cancer clinicogenomic database linked to longitudinal clinical data derived from electronic health records. Patients were aged 18 years and older and diagnosed with mCRPC between January 1, 2018, and June 30, 2021. Comprehensive genomic profiling (CGP) of tumor specimens was performed using next-generation sequencing. First-line (1L) and second-line (2L) treatment patterns were assessed and stratified by PTEN status. Kaplan-Meier methods and a multivariable Cox model were used to compare the real-world overall survival by PTEN status among patients who received 1L novel hormone therapy or taxanes. In patients with mCRPC who underwent CGP, PTEN loss of function (LOF) was associated with decreased survival compared with intact PTEN (hazard ratio, 1.61 [95% CI, 1.07 to 2.42]; P = .024). The results were not influenced by 1L treatment type. 1L treatment patterns were similar between intact PTEN and PTEN LOF subgroups, with abiraterone and enzalutamide being the two most common treatments in both groups. Patients with PTEN LOF were less likely to receive 2L treatments than patients with intact PTEN. PTEN LOF, identified with genomic testing, was associated with decreased survival and negative prognoses in patients with mCRPC.

160P Perioperative and patient reported outcomes of robotic-assisted and video-assisted thoracoscopic surgery for patients with NSCLC receiving neoadjuvant immunotherapy: A real-world cohort study

160P Perioperative and patient reported outcomes of robotic-assisted and video-assisted thoracoscopic surgery for patients with NSCLC receiving neoadjuvant immunotherapy: A real-world cohort study

Construction and validation of machine learning models for predicting distant metastases in newly diagnosed colorectal cancer patients: A large-scale and real-world cohort study.

More accurate prediction of distant metastases (DM) in patients with colorectal cancer (CRC) would optimize individualized treatment and follow-up strategies. Multiple prediction models based on machine learning have been developed to assess the likelihood of developing DM. Clinicopathological features of patients with CRC were obtained from the National Cancer Center (NCC, China) and the Surveillance, Epidemiology, and End Results (SEER) database. The algorithms used to create the prediction models included random forest (RF), logistic regression, extreme gradient boosting, deep neural networks, and the K-Nearest Neighbor machine. The prediction models' performances were evaluated using receiver operating characteristic (ROC) curves. In total, 200,958 patients, 3241 from NCC and 197,717 CRC from SEER were identified, of whom 21,736 (10.8%) developed DM. The machine-learning-based prediction models for DM were constructed with 12 features remaining after iterative filtering. The RF model performed the best, with areas under the ROC curve of 0.843, 0.793, and 0.806, respectively, on the training, test, and external validation sets. For the risk stratification analysis, the patients were separated into high-, middle-, and low-risk groups according to their risk scores. Patients in the high-risk group had the highest incidence of DM and the worst prognosis. Surgery, chemotherapy, and radiotherapy could significantly improve the prognosis of the high-risk and middle-risk groups, whereas the low-risk group only benefited from surgery and chemotherapy. The RF-based model accurately predicted the likelihood of DM and identified patients with CRC in the high-risk group, providing guidance for personalized clinical decision-making.