Analysis Of Outcomes Research Articles

Implementation of the WHO Safe Childbirth Checklist: a scoping review protocol

IntroductionThe WHO Safe Childbirth Checklist (WHO SCC) was developed to accelerate adoption of essential practices that prevent maternal and neonatal morbidity and mortality during childbirth. This study aims to summarise...

Comparative evaluation of postoperative outcomes and expenditure between robotic and conventional single-level lumbar fusion surgery: a comprehensive analysis of nationwide inpatient sample data.

In this study, we investigate the evolution of lumbar fusion surgery with robotic assistance, specifically focusing on the impact of robotic technology on pedicle screw placement and fixation. Utilizing data from the Nationwide Inpatient Sample (NIS) covering 2016 to 2019, we conduct a comprehensive analysis of postoperative outcomes and costs for single-level lumbar fusion surgery. Traditionally, freehand techniques for pedicle screw placement posed risks, leading to the development of robotic-assisted techniques with advantages such as reduced misplacement, increased precision, smaller incisions, and decreased surgeon fatigue. However, conflicting study results regarding the efficacy of robotic assistance in comparison to conventional techniques have prompted the need for a thorough evaluation. With a dataset of 461,965 patients, our aim is to provide insights into the impact of robotic assistance on patient care and healthcare resource utilization. Our primary goal is to contribute to the ongoing discourse on the efficacy of robotic technology in lumbar fusion procedures, offering meaningful insights for optimizing patient-centered care and healthcare resource allocation. This study employed data from the Nationwide Inpatient Sample (NIS) spanning the years 2016 to 2019 from USA, 461,965 patients underwent one-level lumbar fusion surgery, with 5770 of them having the surgery with the assistance of robotic technology. The study focused primarily on one-level lumbar fusion surgery and excluded non-elective cases and those with prior surgeries. The analysis encompassed the identification of comorbidities, surgical etiologies, and complications using specific ICD-10 codes. Throughout the study, a constant comparison was made between robotic and non-robotic lumbar fusion procedures. Various statistical methods were applied, with a p value threshold of < 0.05, to determine statistical significance. Robotic-assisted lumbar fusion surgeries demonstrated a significant increase from 2016 to 2019, comprising 1.25% of cases. Both groups exhibited similar patient demographics, with minor differences in payment methods, favoring Medicare in non-robotic surgery and more private payer usage in robotic surgery. A comparison of comorbid conditions revealed differences in the prevalence of hypertension, dyslipidemia, and sleep apnea diagnoses-In terms of hospitalization outcomes and costs, there was a slight shorter hospital stay of 3.06days, compared to 3.13days in non-robotic surgery, showcasing a statistically significant difference (p = 0.042). Robotic surgery has higher charges, with a mean charge of $154,673, whereas non-robotic surgery had a mean charge of $125,467 (p < 0.0001). Robotic surgery demonstrated lower rates of heart failure, acute coronary artery disease, pulmonary edema, venous thromboembolism, and traumatic spinal injury compared to non-robotic surgery, with statistically significant differences (p < 0.05). Conversely, robotic surgery demonstrated increased post-surgery anemia and blood transfusion requirements compared to non-robotic patients (p < 0.0001). Renal disease prevalence was similar before surgery, but acute kidney injury was slightly higher in the robotic group post-surgery (p = 0.038). This is the first big data study on this matter, our study showed that Robotic-assisted lumbar fusion surgery has fewer post-operative complications such as heart failure, acute coronary artery disease, pulmonary edema, venous thromboembolism, and traumatic spinal injury in comparison to conventional methods. Conversely, robotic surgery demonstrated increased post-surgery anemia, blood transfusion and acute kidney injury. Robotic surgery has higher charges compared to non-robotic surgery.

Histological Outcomes of Pharmacological Interventions in Eosinophilic Esophagitis for Adults and Children: A Network Meta-analysis of Randomized Controlled Trials.

Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children. We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes. Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5mg twice daily, fluticasone 3mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3mg daily, cendakimab 180mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5mg daily, OVB low dose, reslizumab 3mg/kg, reslizumab 1mg/kg, and reslizumab 2mg/kg. Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.

Chronic Pulmonary Aspergillosis after Surgical Treatment for Non-Small Cell Lung Cancer—An Analysis of Risk Factors and Clinical Outcomes

Chronic Pulmonary Aspergillosis after Surgical Treatment for Non-Small Cell Lung Cancer—An Analysis of Risk Factors and Clinical Outcomes

A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.

Win statistics offer a new approach to the analysis of outcomes in clinical trials, allowing the combination of time-to-event and longitudinal measurements and taking into account the clinical importance of the components of composite outcomes, as well as their relative timing. We examined this approach in a post hoc analysis of two trials that compared dapagliflozin to placebo in patients with heart failure and reduced ejection fraction (DAPA-HF) and mildly reduced or preserved ejection fraction (DELIVER). The effect of dapagliflozin on a hierarchical composite kidney outcome was assessed, including the following: (1) all-cause mortality; (2) end-stage kidney disease; (3) a decline in estimated glomerular filtration rate (eGFR) of ≥57%; (4) a decline in eGFR of ≥50%; (5) a decline in eGFR of ≥40%; and (6) participant-level eGFR slope. For this outcome, the win ratio was 1.10 (95% confidence interval (CI) = 1.06-1.15) in the combined dataset, 1.08 (95% CI = 1.01-1.16) in the DAPA-HF trial and 1.12 (95% CI = 1.05-1.18) in the DELIVER trial; that is, dapagliflozin was superior to placebo in both trials. The benefits of treatment were consistent in participants with and without baseline kidney disease, and with and without type 2 diabetes. In heart failure trials, win statistics may provide the statistical power to evaluate the effect of treatments on kidney as well as cardiovascular outcomes.

An Outcome Analysis of Pediatric Diaphyseal Fractures Treated Surgically With the Titanium Elastic Nailing System

An Outcome Analysis of Pediatric Diaphyseal Fractures Treated Surgically With the Titanium Elastic Nailing System

Comparison of Maternal and Neonatal Complications in Women with and without Gestational Diabetes Mellitus

Background: Gestational Diabetes Mellitus (GDM) is a common pregnancy-related metabolic disorder associated with adverse maternal and neonatal outcomes. Gestational Diabetes Mellitus is characterized by glucose intolerance that develops during pregnancy. It affects approximately 7% of all pregnancies and has been linked to an increased risk of maternal and neonatal complications. Objective: The study was aimed to provide a comprehensive comparison of maternal and neonatal complications in women with and without GDM involving a thorough examination of medical records and clinical data to identify patterns and associations between GDM and various complications. Methods: A retrospective cohort study was conducted, including pregnant women with and without GDM who received prenatal care and underwent hospital delivery at the Department of Obstetrics and Gynecology, Enam Medical College and Hospital, Dhaka, Bangladesh from June 2022 to June 2023. Clinical data, including maternal age, gestational age at diagnosis, parity, and antenatal care were collected. Pregnancy outcomes, such as maternal complications, and live birth complications were also assessed. Result: A total of 60 pregnant women were included in the analysis, 30 were diagnosed with GDM and 30 without GDM. Analysis of pregnancy outcomes revealed a higher incidence of cesarean section deliveries in the GDM group (p&lt;.05). Additionally, infants born to mothers with GDM had a higher risk of neonatal complications. Conclusions: Women diagnosed with GDM demonstrated distinct clinical characteristics and experienced a higher incidence of adverse pregnancy outcomes. These findings underscore the importance of effective management and close monitoring of pregnant women with GDM to optimize maternal and neonatal health. J Rang Med Col. March 2024; Vol. 9, No. 1: 28-32

A DBT-Informed, Inclusive Treatment Program for College Students With Severe Mental Health Issues: Outcome Analysis of In-Person and Telehealth Services

ABSTRACT Treatment options for college students with significantly functionally impairing mental illnesses are often limited. The Intensive Clinical Services (ICS) program is a Dialectical Behavior Therapy (DBT)-informed, inclusive outpatient treatment option offered within a large Midwestern university’s counseling and psychiatric services center. The present study investigated the treatment effectiveness of the ICS program as well as the comparative effectiveness of telehealth and in-person service offerings. Statistical analyses demonstrated a significant reduction of symptoms associated with borderline personality disorder and trauma-associated anxiety as well as reduction in overall emotional distress. While statistically equivalent symptom reduction was observed on most measures, telehealth service demonstrated greater reduction in overall distress compared with in-person treatment. These results suggest the potential utility of similar programs in university counseling centers, the adoption of which may ultimately expand access to collegiate education by encouraging recovery in place for students with functionally-impairing psychological disorders.

Delivering a sleep intervention across a youth mental health service using non-expert practitioners: A service evaluation.

Poor sleep is highly prevalent in young people and increases risk of mental health difficulties, yet access to sleep interventions remains limited. This paper evaluates the use of a sleep intervention delivered by non-expert practitioners in a secondary care youth mental health service. Assistant psychologists were trained to deliver a six-session 1:1 cognitive-behavioural sleep intervention adapted for use with young people with mental health difficulties. A within-subject design assessed clinical outcomes relating to sleep (Insomnia Severity Index), psychological distress and personal goals (Goal Based Outcome Measures) at four time points. High referral, intervention take-up (82.82%) and completion (70%) rates were reported, together with high baseline levels of insomnia (Insomnia Severity Index mean 20.47, SD 3.68) and poor sleep efficiency (56.36%, SD 17.23). Fifty-six young people (average age 19.2 years, SD 3.25) were included in the outcome analysis. Statistically and clinically significant improvements were seen across all outcome measures, with 68% no longer meeting clinical threshold (ISI ≥15) for insomnia at endpoint. This study demonstrates exceptionally high levels of clinical need and engagement with a sleep intervention adapted specifically for young people with mental health difficulties. Whilst limited by the uncontrolled design, large improvements in insomnia and psychological distress support its effectiveness and utility in clinical settings. More robust implementation and evaluation is warranted in broader youth mental health services to promote earlier access.

Robotic sectionectomy versus robotic hemihepatectomy for anatomic liver resection: a comparative analysis of perioperative outcomes.

Sectionectomy is a parenchma-sparing alternative to (extended) right or left hemihepatectomy. However, the effectiveness and safety of robotic sectionectomy (RS) versus robotic (extended) hemihepatectomy (RH) for the treatment of liver tumors remains unclear. We reviewed our prospective database for consecutive patients who had undergone robotic hepatectomies between March 2021 and July 2023 and included all patients with RS and RH. Demographic data, perioperative outcomes and long-term outcomes were analyzed and compared between both groups. Thirty patients met our inclusion criteria, of whom 16 patients underwent RS as opposed to 14 patients who underwent RH. Baseline characteristics were comparable between the study groups. The duration of Pringle maneuver was significantly longer in the RS group, while the remaining operative details were comparable. There were no significant differences in posthepatectomy outcomes between the study groups. All patients had negative resection margins. RS is a safe and effective parenchyma-sparing treatment modality.

Ankle fracture surgery performed by orthopaedic residents without supervision has comparable outcomes to surgery performed by fellowship trained orthopaedic surgeons.

Unstable fractures often necessitate open reduction and internal fixation (ORIF), which generally yield favourable outcomes. However, the impact of surgical trainee autonomy on healthcare quality in these procedures remains uncertain. We hypothesized that surgery performed solely by residents, without supervision or participation of an attending surgeon, can provide similar outcomes to surgery performed by trauma or foot and ankle fellowship-trained orthopaedic surgeons. A single-center cohort of an academic level-1 trauma center was retrospectively reviewed for all ankle ORIF between 2015 and 2019. Data were compared between surgery performed solely by post-graduate-year 4 to 6 residents, and surgery performed by trauma or foot and ankle fellowship-trained surgeons. Demographics, surgical parameters, preoperative and postoperative radiographs, and primary (mortality, complications, and revision surgery) and secondary outcome variables were collected and analyzed. Univariate analysis was performed to evaluate outcomes. A total of 460 ankle fractures were included in the study. Nonoperative cases and cases operated by senior orthopaedic surgeons who are not trauma or foot and ankle fellowship-trained orthopaedic surgeons were excluded. The average follow-up time was 58.4 months (SD ± 12.5). Univariate analysis of outcomes demonstrated no significant difference between residents and attendings in complications and reoperations rate (p = 0.690, p = 0.388). Sub-analysis by fracture pattern (Lauge-Hansen classification) and the number of malleoli involved and fixated demonstrated similar outcomes. surgery time was significantly longer in the resident group (p < 0.001). The current study demonstrates that ankle fracture surgery can be performed by trained orthopaedic surgery residents, with similar results and complication rates as surgery performed by fellowship-trained attendings. These findings provide valuable insights into surgical autonomy in residency and its role in modern clinical training and surgical education. Level III - retrospective cohort study.

A comparative analysis of kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction: AUNOS database study.

The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p<0.001), 3-year (6.0 vs. 4.3%, p<0.001) and 5-year follow-up (7.7 vs. 6.4%, p=0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p=0.0005), 3-year (7.6 vs. 5.5%, p<0.001) and 5-year follow-up (11.5 vs. 8.8%, p<0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p=0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p=0.53) or 5-year follow-up (7.2 vs. 8.1%, p=0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p=0.98) and at 3 years (5.5 vs. 5.4%, p=0.45), respectively. Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.

The effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy

BackgroundFermented soy products have shown to possess inhibitory effects on prostate cancer (PCa). We evaluated the effect of a fermented soy beverage (Q-Can®), containing medium-chain triglycerides, ketones and soy isoflavones, among men with localized PCa prior to radical prostatectomy.MethodsWe conducted a placebo-controlled, double-blind randomized trial of Q-Can®. Stratified randomization (Cancer of the Prostate Risk Assessment (CAPRA) score at diagnosis) was used to assign patients to receive Q-Can® or placebo for 2–5 weeks before RP. Primary endpoint was change in serum PSA from baseline to end-of-study. We assessed changes in other clinical and pathologic endpoints. The primary ITT analysis compared PSA at end-of-study between randomization arms using repeated measures linear mixed model incorporating baseline CAPRA risk strata.ResultsWe randomized 19 patients, 16 were eligible for analysis of the primary outcome. Mean age at enrollment was 61, 9(56.2%) were classified as low and intermediate risk, and 7(43.8%) high CAPRA risk. Among patients who received Q-Can®, mean PSA at baseline and end-of-study was 8.98(standard deviation, SD 4.07) and 8.02ng/mL(SD 3.99) compared with 8.66(SD 2.71) to 9.53ng/mL(SD 3.03), respectively, (Difference baseline – end-of-study, p = 0.36). There were no significant differences in Gleason score, clinical stage, surgical margin status, or CAPRA score between treatment arms (p > 0.05), and no significant differences between treatment arms in end-of-study or change in lipids, testosterone and FACT-P scores (p > 0.05).ConclusionsShort exposure to Q-Can® among patients with localized PCa was not associated with changes in PSA levels, PCa characteristics including grade and stage or serum testosterone. Due to early termination from inability to recruit, study power, was not achieved.

FT4-to-FT3 ratio is a novel prognostic marker in subacute combined spinal cord degeneration patients.

The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD. This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC). About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, P < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; P < 0.001). We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.

Caffeine intake enhances bowel recovery after colorectal surgery: a meta-analysis of randomized and non-randomized studies.

Postoperative ileus (POI) after colorectal surgery is a major problem thataffects both patient recovery and hospital costs highlighting the importance of preventive strategies. Therefore, we aimed to perform a systematic analysis of the effects of postoperative caffeine consumption on bowel recovery and surgical morbidity after colorectal surgery. A comprehensive literature search was conducted through September 2023 for randomized and non-randomized trials comparing the effect of caffeinated versus non-caffeinated drinks on POI by evaluating bowel movement resumption, time to first flatus and solid food intake, and length of hospital stay (LOS). Secondary outcome analysis included postoperative morbidity in both groups. After data extraction and inclusion in a meta-analysis, odds ratios (ORs) for dichotomous variables and standardized mean differences (SMDs) for continuous outcomes with 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed in cases of substantial heterogeneity. Six randomized and two non-randomized trials with a total of 610 patients were included in the meta-analysis. Caffeine intake significantly reduced time to first bowel movement [SMD -0.39, (95% CI -0.66 to -0.12), p = 0.005] and time to first solid food intake [SMD -0.41, (95% CI -0.79 to -0.04), p = 0.03] in elective laparoscopic colorectal surgery, while time to first flatus, LOS, and the secondary outcomes did not differ significantly. Postoperative caffeine consumption may be a reasonable strategy to prevent POI after elective colorectal surgery. However, larger randomized controlled trials (RCTs) with homogeneous study protocols, especially regarding the dosage form of caffeine and coffee, are needed.

Abstract PO4-18-02: Real-world (RW) utilization and patient outcomes across three CDK4/6 inhibitors in metastatic breast cancer (mBC)

Abstract Background: While CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard-of-care first-line (1L) therapy for hormone-positive (HR+), HER2-negative mBC, there is ongoing debate regarding optimal use of the three FDA-approved CDK4/6i drugs. All three drugs have demonstrated significantly improved progression-free survival (PFS), but only two have significantly improved overall survival (OS). These trial data have prompted debate regarding optimal selection and sequencing of these drugs. To further evaluate this, we analyzed a RW clinical-genomic database to explore the use and outcomes associated with each of these CDK4/6i drugs. Methods: RW data were queried using GuardantINFORM, a database combining de-identified genomic results from patients (pts) with cell-free circulating tumor (ctDNA) testing done via Guardant360, with administrative claims data. Pts with BC who had record of metastatic diagnosis, &amp;gt;2 medical or pharmacy claims, and CDK4/6i treatment in the mBC setting between March 2018 and March 2023 were included. In the subset of pts treated with CDK4/6i in the 1L or 2nd line (2L) with at least 12 months of follow-up (f/u) post-CDK4/6i initiation, RW time to next treatment (rwTTNT) and RW time to treatment discontinuation (rwTTD) were used as proxies for PFS. RW overall survival (rwOS), rwTTNT and rwTTD were reported in months (mos) and were measured based on time from first CDK4/6ki treatment claim. Multivariate Cox regressions adjusted for pt age, gender, weighted comorbidity score (Elixhauser Comorbidity Index [ECI]), and year of CDK4/6i start were used to compare outcomes across CDK4/6i drugs. Chi-squared tests were used for comparison of categorical variables, while one-way ANOVA was used for continuous variables. Results: 4556 pts with mBC were included, of whom 65% received palbociclib (palbo), 24% abemaciclib (abema) and 11% ribociclib (ribo). Ribo use increased post-2020, while palbo use decreased and abema remained similar (2020: ribo: 9%, palbo: 63%, abema: 28%; 2022: ribo: 18%, palbo: 54%, abema: 28%). Pts who received ribo were younger and had fewer comorbidities than those receiving palbo and abema [median age: 57, 61, 60 years, respectively (p &amp;lt; 0.001); ECI score: 19.8, 20.1, 21.3, respectively (p &amp;lt; 0.001)]. Median f/u for pts included in outcomes assessment was 24.1 mos for abema, 30.1 mos for palbo, and 28.5 mos for ribo. Adjusted hazard ratios (HR) for rwTTD, rwTTNT, and rwOS for pts treated in the 1L or 2L showed no significant difference between the drugs (Table 1). 1120 pts had ctDNA analysis within +/- 90 days of CDK4/6i treatment end and these data will be shown at the time of presentation. Conclusions: RW analysis shows increased use of ribo and decreased use of palbo in recent years, with potential preferential use of ribo in pts who are younger and have fewer comorbidities. Multivariate Cox regressions adjusted for pt age, gender, co-morbidities, and year of CDK4/6i start found no significant differences in rwTTD and rwTTNT for pts treated in the 1L or 2L between the drugs. While we only included pts with at least 12 months of f/u in the outcomes analysis, it is difficult to make conclusions regarding rwOS data as the median f/u still differs between the drugs at this time. These findings confirm anecdotal evidence suggesting shifting physician preferences in the use of the CDK4/6i drugs in mBC. Further investigation is needed to refine CDK4/6i drug selection in the rapidly changing mBC landscape. Table. Citation Format: Caroline Weipert, Seth Wander, Andrew Davis, Leslie Bucheit, Jayati Saha, Jiemin Liao, Nicole Zhang, Daniel Stover, Aditya Bardia, Massimo Cristofanilli. Real-world (RW) utilization and patient outcomes across three CDK4/6 inhibitors in metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-02.

Abstract PO2-04-05: FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES

Abstract Background Brain metastases (BM) are a severe complication of HER2-positive metastatic breast cancer. In the absence of any immediate indication for local therapy, the tyrosine-kinase inhibitor tucatinib combined with trastuzumab and capecitabine (TTC) is regarded as the preferred systemic treatment option for active BM, while data on the activity of antibody-drug conjugates (ADC) is limited. In the primary outcome analysis of TUXEDO-1, an intracranial response rate (RR) of 73.3% was reported with the ADC trastuzumab-deruxtecan (T-DXd). Here, we report final progression-free survival (PFS) and overall survival (OS) results of this study. Patients and Methods: TUXEDO-1 is a prospective, single-centre, single-arm phase 2 trial. Adult patients with HER2-positive BC and active BM (newly diagnosed untreated or progressing after prior local therapy), prior treatment with trastuzumab and pertuzumab, ECOG performance status 0 or 1 without indication for immediate local therapy were accrued and received T-DXd until progression, inacceptable toxicity, or withdrawal for any other reason. The primary endpoint was intracranial RR centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria in the intention-to-treat population; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population (PPP). Results A total number of 15 patients were accrued; one patient was found to have dural metastases only upon restaging, resulting in a PPP of 14 patients. Patients had received a median number of two prior treatment lines (range, 1-5), 60% had progressive brain metastases and 60% had received prior T-DM1. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). A total of 238 cycles of T-DXd were administered (median 11.5 cycles; range 4-42). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event (AE) was fatigue (n=3; 20%). A total of 8 serious AEs were reported in 8 patients. Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL and neurocognitive functioning were maintained over the entire treatment duration and a significant deterioration of global QoL was observed upon progression (p=0.036). Most patients received TTC (n=5) or local therapy (n=4) as next subsequent treatment line. Ancillary biomarker studies are ongoing, and results will be presented at the meeting. Discussion In TUXEDO-1, T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive breast cancer BM. The safety profile was consistent with previous reports. T-DXd did not impair QoL and neurocognitive functioning was maintained. Results therefore support the concept of ADCs as systemic therapy for active BM. Citation Format: Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Angelika Maria Starzer, Maximilian Mair, Heidrun Forstner, Beate Rottenmanner, Marie-Bernadette Aretin, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegül Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Georg Pfeiler, Christian F. Singer, Ansgar Weltermann, Luzia Berchtold, Matthias Preusser. FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-05.

Abstract PO3-17-02: Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years

Abstract Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years Ahrong Ham1, Sewon Lee1, Jungmin Jo1, Soo Ji Hong2, Ji Eun Lee2, Haena Lee2, Sungchan Gwark2, Jeongshin An2, Hyun Goo Kim2, Jun Woo Lee2, Joohyun Woo2, Woosung Lim2, Byung-In Moon2, Sei Hyun Ahn2, Hye Ah Lee3, Kyoung Eun Lee1 1 Division of Hematology and Oncology, Department of Internal Medicine, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 2 Department of Surgery, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 3 Clinical Trial Center, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea Purpose: Over the last two decades, treatment landscapes for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) have shown remarkable growth with the development of drugs targeting HER2. The standard of care for HER2+ MBC has continued to change with the ongoing development of new anti-HER2 therapies. We aimed to provide a comprehensive analysis of HER2-targeted therapies, clinical characteristics, and treatment outcomes in real-world practice of HER2+ MBC patients over the past 20 years. Methods: Patients who received palliative chemotherapy with HER2+ MBC between 2000 and 2022 were analyzed. We derived cohorts of two groups with or without anti-HER2 containing therapies. Patients receiving multiple anti-HER2 therapies throughout the entire period of treatment were further analyzed according to treatment regimen. The progression-free survival for palliative first-line (PFS1), and overall survival (OS) were compared between groups. A multivariate Cox regression model was used to investigate predictors of survival outcome in HER2+ MBC. Results: A total of 185 patients were analyzed. Median age was 49 years (IQR, 42-56 years). 47 patients (25.4%) were initially diagnosed with de novo stage IV disease. Visceral metastases were found in 95 patients (51.4%). The median PFS1 was 3.9 months (without anti-HER2 therapy) versus 15.6 months (with anti-HER2 therapy) between two groups (P&amp;lt; 0.001). Likewise, the median OS was significantly improved in anti-HER2 therapy group (34.0 months vs. 70.5 months, P=0.010). As a result of confirming the difference in OS according to the type of anti-HER2 therapies during the entire period of treatment by correspondence analysis, significant improvement was found when two or three types of anti-HER2 were used (without anti-HER2 vs. 2 types of anti-HER2, P=0.009; without anti-HER2 vs. 3 types of anti-HER2, P=0.010). Interestingly, when analyzed by treatment regimen, trastuzumab (H) + pertuzumab (P), HP + TDM-1, and H + TDM-1 significantly improved OS over regimens without anti-HER2 (without anti-HER2 vs. HP, P=0.009; without anti-HER2 vs. HP + TDM-1, P=0.013; without anti-HER2 vs. H + TDM-1, P=0.028, respectively). HP + TDM-1 therapies significantly improved survival rate compared to H single containing regimen (P=0.029). Based on our multiple Cox regression model, visceral metastasis was a significant poor OS prognostic factor and two and three types of anti-HER2 therapies were associated better OS prognosis (visceral metastasis: HR=2.40, P=0.003; 2 types of ant-HER2: HR=0.29, P=0.001; 3 types of anti-HER2: HR=0.22, P=0.018, respectively). Conclusions: Anti-HER2 therapies significantly improved PFS1 and OS. Continuing treatment by changing anti-HER2 therapies may act as a better prognostic factor. Further prospective studies are required. Citation Format: Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-02.

Propensity score matched analysis of treatment outcomes in pediatric ureteropelvic junction obstruction: a comparison between horseshoe and non-horseshoe kidneys.

Pediatric hydronephrosis poses distinct challenges, particularly in cases involving horseshoe kidneys (HSK). This retrospective study compares treatment outcomes between HSK and non-horseshoe kidneys (NHSK) in pediatric ureteropelvic junction obstruction (UPJO) patients. A retrospective cohort study included 35 patients with HSK and 790 patients with NHSK undergoing pyeloplasty. Preoperative, intraoperative, and postoperative parameters were evaluated. Propensity score matching (PSM) balanced patient characteristics in the NHSK group. In comparison with NHSK, HSK exhibited a higher crossing vessel incidence (51.6% vs. 5.12%, P < 0.001) and smaller preoperative anteroposterior pelvic diameter (APD). Post 6 and 12months, NHSK maintained a larger APD, with a higher P/C ratio at 12months. PSM retained significantly higher crossing vessel incidence in HSK (51.6 vs. 3.61%, P < 0.001). Laparoscopic pyeloplasty (LP) in HSK showed lower postoperative length of stay (LOS). Postoperative ultrasound parameters favored NHSK. In HSK and NHSK with crossing vessels, HSK demonstrated higher complications even post-PSM (38.5% vs. 0%, P = 0.039). The study emphasizes the importance of recognizing crossing vessels in HSK-related hydronephrosis. Surgical success, although comparable between HSK and NHSK, requires tailored approaches. This investigation contributes valuable insights to pediatric urology, emphasizing personalized management for optimal outcomes.

Abstract PS06-08: Longitudinal Neoadjuvant and Post-operative Evaluation of Circulating Tumor DNA in Early Breast Cancer using a Tumor-Informed Assay: Updated Analysis of the TRACER Cohort

Abstract Background: ctDNA is detectable in early breast cancer (EBC) using sensitive assays and treatment-related changes in ctDNA are associated with clinical response. RaDaR® (NeoGenomics), a tumor-informed assay, has been shown to detect circulating tumor DNA (ctDNA) prior to clinical recurrence. We retrospectively quantified ctDNA using RaDaR in serial samples from a large cohort of patients with EBC receiving standard neoadjuvant therapy (NAT). Methods: Unselected patients with EBC were enrolled prior to NAT in the TRACER cohort from 2015 onwards. Plasma samples were collected at baseline, during treatment, perioperatively, and in follow-up. For patients with available tissue for assay generation, RaDaR was performed on all available plasma timepoints. Clinical and pathologic characteristics (assessed on core biopsy), treatment, and outcomes were recorded. Results: Of 128 patients evaluated, 9 (7.0%) were excluded from this analysis due to panel quality control metrics, leaving 119 patients (41 ER+, 32 TNBC, 46 HER2+) with 681 individual timepoints (median=6, range: 1-12). 103/119 patients (86%) received neoadjuvant anthracycline- and taxane-based chemotherapy. Median followup from diagnosis was 3.8 years (range: 0.6-6.3 years) and 16 recurrences have occurred (9 ER+, 6 TN, 1 HER2+). 114 patients had a baseline plasma sample collected prior to NAT, in which the detection rate was 77% (70% ER+, 90% TNBC, 76% HER2+), with a median estimated variant allele frequency (eVAF) of 0.0823% (range: 2.90E-5 - 7.5%). All patients with clinical recurrence had ctDNA detected at baseline. Baseline detection was associated with tumor grade (p=0.050) but not size (p=0.65) or clinical nodal status (p=0.36). There were non-significant associations between eVAF and grade (p=0.097) and eVAF and tumor size (p=0.086). Persistent ctDNA detection midway through neoadjuvant therapy (pre-cycle 5) was associated with an increased risk of recurrence in patients with ER+ (HR: 10.27, 95%CI: 1.61-65.4; p=0.014) and TNBC (HR: 20.17, 95%CI: 1.97-206.4; p=0.011). Residual cancer burden (RCB) status further stratified the risk of recurrence; those with RCB-2/3 disease and ctDNA detected pre-cycle 5 were at the highest risk. Few patients had detectable ctDNA in pre- or initial post-operative specimens, all of which had residual disease (non-pCR). 9/16 patients with clinical recurrence had evaluable post-operative and follow-up samples for lead time calculation; ctDNA was detected prior to recurrence in 7/9 (78 %), with a median lead time of 152 days (range: 13-699 days). Of the 2 patients without a positive test, one had an ipsilateral local recurrence (grade 2, 1.8 mm), the other had a negative, but borderline, test 72 days prior to recurrence (solitary 8 mm lung nodule on PET). Follow up is ongoing for two patients with ctDNA detected but no recurrence at data cutoff (time since last positive test: 0.60 and 1.78 years). Any ctDNA detection postoperatively or in follow-up was strongly associated with disease recurrence (HR: 37.35, 95%CI: 2.7-520.7; p&amp;lt; 0.0001). Conclusion: RaDaR detects ctDNA in most patients prior to the initiation of NAT for EBC. Changes in ctDNA levels during treatment and its presence are associated with clinical outcomes. Prospective evaluation and integration of RaDaR testing into clinical trials are warranted. Further analysis of ctDNA detection, clinical outcomes, and genomic data will be presented at the meeting. Citation Format: Mitchell Elliott, Jesus Fuentes Antras, Philippe Echelard, Aaron Dou, Zachary Veitch, Philippe Bedard, Eitan Amir, Michelle Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Celeste Yu, Nathan Campbell, Christodoulos Pipinikas, Karen Howarth, Lillian Siu, Hal Berman, David Cescon. Longitudinal Neoadjuvant and Post-operative Evaluation of Circulating Tumor DNA in Early Breast Cancer using a Tumor-Informed Assay: Updated Analysis of the TRACER Cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS06-08.