Real-world Database Research Articles

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation – A real-world database study in Japan: The CReGYT-01 EGFR study

ObjectivesTo clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. MethodsWe conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. ResultsOf 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2–3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. ConclusionThe efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Activity and resolution aware privacy protection for smart water meter databases

Identifying water end-uses from household meter readings yields valuable commercial and environmental insights for both customers and water providers. However, smart water meter databases may expose sensitive information about the activities of metered households, thus raising privacy concerns that limit the possibility of making smart meter data available for research and planning. This paper considers the case where a water provider wishes to publish a database of household water meter traces to be used by water analysts, who are often external entities. This scenario presents privacy risks should an adversary gain access to this database, with the threat of uniquely identifying a household of interest and exposing its water use activities. To mitigate such risks, this paper proposes a process for activity-aware privacy protection and evaluates its effectiveness using real-world and synthetic databases. Our experimental analysis shows that water meter privacy protection is strongly dependent on the type of activity, temporal resolution, and population size. For example, in the case of a high-resolution database, we found that a large base population, small published sample, and 30-second resolution provided optimal trade-offs between privacy and information value. For a low-resolution database with a population of over 3500 households, 1-hour resolution provided strong information value and customisable privacy guarantees depending on the published sample size.

Adult genitourinary sarcoma: analysis using hospital-based cancer registry data in Japan

BackgroundGenitourinary sarcomas are rare in adults and few large-scale studies on adult genitourinary sarcoma are reported. We aimed to elucidate the clinical characteristics, survival outcomes, and prognostic factors for overall survival of adult genitourinary sarcoma in Japan.MethodsA hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with genitourinary sarcoma in 2013. The datasets were registered from 121 institutions.ResultsA total of 116 men and 39 women were included, with a median age of 66 years. The most common primary site was the kidney in 47 patients, followed by the paratestis in 36 patients. The most common histological type was liposarcoma in 54 patients, followed by leiomyosarcoma in 25 patients. The 5-year overall survival rates were 57.6%. On univariate analysis, male gender, paratestis as primary organ, and histological subtype of liposarcoma were predictive of favorable survival while primary kidney, bladder, or prostate gland location were predictive of unfavorable survival. On multivariate analysis, primary paratestis was an independent predictor of favorable survival while primary kidney, bladder, or prostate gland were independent predictors of unfavorable survival.ConclusionsThis is the first report showing the clinical characteristics and survival outcomes of adult genitourinary sarcoma in Japan using a real-world large cohort database.

Developing predictive precision medicine models by exploiting real-world data using machine learning methods

Computational Medicine encompasses the application of Statistical Machine Learning and Artificial Intelligence methods on several traditional medical approaches, including biochemical testing which is extremely valuable both for early disease prognosis and long-term individual monitoring, as it can provide important information about a person's health status. However, using Statistical Machine Learning and Artificial Intelligence algorithms to analyze biochemical test data from Electronic Health Records requires several preparatory steps, such as data manipulation and standardization. This study presents a novel approach for utilizing Electronic Health Records from large, real-world databases to develop predictive precision medicine models by exploiting Artificial Intelligence. Furthermore, to demonstrate the effectiveness of this approach, we compare the performance of various traditional Statistical Machine Learning and Deep Learning algorithms in predicting individuals' future biochemical test outcomes. Specifically, using data from a large real-world database, we exploit a longitudinal format of the data in order to predict the future values of 15 biochemical tests and identify individuals at high risk. The proposed approach and the extensive model comparison contribute to the personalized approach that modern medicine aims to achieve.

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

Kidney Failure Events, Cardiovascular Disease Events, and All-Cause Mortality in Patients with IgA Nephropathy in a Real-World Database.

IgA nephropathy (IgAN) associated glomerular injury leads to proteinuria, hematuria, and progressive loss of glomerular filtration rate, with progression to kidney failure (KF). This retrospective study evaluated the prognostic effects of proteinuria and progression to KF on cardiovascular disease (CVD)/mortality events and KF/mortality events in the United States. We conducted a non-interventional, retrospective cohort study in adult IgAN patients using Optum's de-identified Market Clarity Data (01/01/2007 to 03/31/2021). Adult (≥18 years old) patients with at least two signs, disease, symptoms natural language processing term entries for IgAN, within 180 days and ≥30 days apart within the identification period were included. Outcomes were assessed by time-dependent proteinuria (≥1 g/day vs. <1 g/day) and KF status (pre vs. post). Descriptive statistics were used for categorical and continuous variables. Multivariable Cox proportional hazard models with time-dependent predictors were used to estimate differences across groups. Pre-KF patients with proteinuria ≥1 g/day were more likely to have a CVD/mortality event during follow-up (adjusted hazard ratio [HR; 95% CI]: 1.80 [1.12-2.89]; p<0.001) or a KF/mortality event (adjusted HR [95% CI]: 2.10 [1.73-2.56]; p<0.001). Post-KF patients were more likely to have a CVD/mortality event during follow-up (adjusted HR [95% CI]: 3.28 [2.82-3.81]; p<0.001). Elevated proteinuria and progression to KF was associated with higher risk of CVD/mortality events. Elevated pre-KF proteinuria was also associated with progression to KF/mortality events. Based on our real-world retrospective database analysis, we hypothesize that novel IgAN therapies that reduce proteinuria and slow the rate of progression to KF have the potential to reduce CVD risk, improve kidney outcomes and prolong/increase overall survival.

Risk Factors for Respiratory Depression Associated with Tramadol Based on the Global Pharmacovigilance Database (VigiBase).

Tramadol, a weak μ-opioid receptor agonist, has been used worldwide for pain management. It is considered to have a favorable safety profile without serious adverse events; however, safety issues of respiratory depression were proposed by regulatory governments. We aimed to examine the risk and contributing factors associated with tramadol-related respiratory depression using a real-world database, VigiBase. Disproportionality analysis of tramadol and tramadol/paracetamol was performed using proportional reporting ratios, reporting odds ratios, and information components for all drugs and opioids. Factors related to respiratory depression, including sex, age, presence of abuse, death, and various concomitant medications, were evaluated. Among 140,721 tramadol reports, respiratory depression was reported in 1126 cases, 81.3% of which were deemed serious. Five adverse events were detected as signals of tramadol-related acute central respiratory depression (ACRD) in 882 reports. A higher proportion of ACRD cases in children and adolescents was observed than all adverse events cases of tramadol. Concomitant users of CYP2D6 inhibitors, opioids, benzodiazepines, and anti-depressant drugs showed a higher proportion in ACRD cases than non-ACRD cases. ACRD was related to drug abuse and death. This pharmacovigilance study, using VigiBase, confirmed a high risk of respiratory depression (a serious, potentially fatal adverse event) secondary to the use of tramadol, especially in pediatric patients, drug abusers, or during concomitant use of opioids, benzodiazepines, or antidepressants.

(269) Analysis of Sexual Dysfunction Development Among Male and Female Living Kidney Donors

Abstract Introduction The need for kidney donations in patients with end-stage kidney disease has continued to exceed the number of deceased donor transplants, signifying the need for the continued growth, sustainability, and success of living kidney donation. Following donation, living kidney donors have excellent survival rates with mixed data regarding long-term outcomes of renal failure, hypertension, and proteinuria. However, no studies to our knowledge have looked at differences in the development of long-term sexual dysfunction following living kidney donation, a potentially serious quality of life issue. Objective To analyze differences in five-year sexual dysfunction outcomes among male and female living kidney donors using the US Collaborative Network within the TriNetX database, a federated network of EMR data from multiple healthcare organizations across the United States. Methods We used the TriNetX database to perform a propensity score-matched cohort study comparing five-year outcomes of sexual dysfunction development among adult (≥18) male living kidney donors (Male) and female living kidney donors (Female) from December 2013 to December 2022. Living kidney donors were defined as the presence of one diagnostic code and one procedural code. Patients were excluded from the study if they had any instance of diagnosed transplant status (by ICD-10) or transplantation procedures (by CPT) prior to the kidney donor status. Patients were matched on age, sex, race, ethnicity, marital status, diabetes mellitus, cardiovascular disease, personal history of genitourinary disease, presence of urogenital implants, mood disorders, BMI, tobacco and alcohol use, and problems related to lifestyle and socioeconomic circumstances. Primary outcomes analysis included 5-year hazard ratio of diagnosed decreased libido, sexual dysfunction (composite of new diagnosed male ED, vaginismus/dyspareunia, infertility, orgasmic disorders, arousal/desire disorders, or unspecified), UTI, and STDs. Secondary outcomes included sex counseling or problems in relationship with spouse or partner. Results There were 2,821 patients in each cohort after matching (Male, Female). Mean age of the cohort was 42.7 ± 12.7, 73.3% were White, and 10.8% were Hispanic/Latino (p &amp;gt;0.05). At 5-years, Kaplan-Meier analysis revealed that the Male donor cohort had a significantly higher hazard ratio (HR) than Female donors for sexual dysfunction (HR: 3.006, 95% Confidence Interval [CI]: 1.761,5.131). Between the cohorts, 39 (1%) Male patients developed ED and ~10 (&amp;lt;1%) Female patients developed vaginismus/dyspareunia within 5 years. No significant difference was found for the development of sexual arousal disorders/desire disorders (0.17% vs 0.06%, p = 0.052), orgasmic disorders (0.03% vs 0.03%, p = 0.99), decreased libido (0.48% vs 0.85%, p =0.94) and STD’s (0.72% vs 0.89%, p = 0.70). For secondary outcomes, no significant difference was found for the 5-year hazard of need for sex counseling or interpersonal relationship issues. Conclusions In our analysis of this large, real-world database, we found that male living kidney donors had higher rates of sexual dysfunction development 5-years post-living kidney donation. While living kidney donation is a safe, viable, and excellent alternative to deceased kidney donation, clinicians and living donors should both be aware about the potential association of developing sexual dysfunction post-donation. Disclosure No.

(178) Exploring Intraoperative and Postoperative Penile Prosthetic Complications in the Solid Organ Transplant Population: A Propensity-Score Matched Analysis

Abstract Introduction Solid-organ transplant (SOT) patients are highly susceptible to adverse post-operative outcomes given they are on one or multiple immunosuppressant medications. This makes surgeons performing elective surgeries, such as penile prosthetic implant surgery, understandably concerned given the higher risk of potential infection and perioperative complications. However, data regarding the safety and efficacy related to the penile prosthesis in the SOT population is mixed. Our study aimed to analyze adverse intraoperative and post-operative complications related to the penile prosthesis using the TriNetX database. Objective To observe whether SOT patients experienced more intraoperative and postoperative penile prosthetic complications when compared to the general population using the TriNetX US Collaborative Network, a large real-world database consisting of deidentified patient data from 56 healthcare organizations across the United States. Methods We used the TriNetX database to perform a propensity score-matched cohort study comparing five-year outcomes between SOT patients (kidney, heart, lung, liver, pancreas, and intestine by ICD-10) who underwent either an inflatable or non-inflatable penile prosthetic procedure (SOT) and non-SOT patients who underwent a similar procedure(s) (non-SOT). Patients were excluded from the analysis if they had any instance of priapism (treatment or dx) or Peyronie disease (treatment or diagnosis) in their medical record prior to the penile prosthetic procedure. Cohorts were matched on age, race/ethnicity, CKD, diseases of the prostate or prostatectomy, overweight and obesity status, T2DM, cardiovascular disease, psychiatric disorders, substance-use disorders, and spinal cord injury. Outcomes of interest included intraoperative and perioperative complications as well as post-operative complications related to the prosthetic implant (mechanical malfunction, fibrosis, displacement, hemorrhage, pain, stenosis, removal with or without replacement, and complex [all post-operative complications]). Results There were 223 patients in each group after matching (SOT, non-SOT). Mean age at penile prosthesis procedure 60.4 ± 10.2, 52% were White, and 8.9% were Hispanic/Latino. Kaplan-Meier analysis revealed that there was no significant difference found for the incidences of intraoperative complications (0.49% vs 0.53%, p = 0.99). In regards to postoperative complications, we found significantly higher incidences of complex prosthetic complications (28.76% vs 18.28%, p = 0.01) and mechanical malfunction of the penile prosthesis (8.56% vs 3.45%, p = 0.03) in the SOT cohort when compared to the non-SOT cohort. No significant difference was found between the cohorts for 5-year incidences of fibrosis (p = 0.81), hemorrhage (p = 0.97), pain (p = 0.69), stenosis (p = 0.81), infection (p =0.34), displacement (p = 0.68), removal with replacement (p = 0.72), and removal without replacement (p = 0.91). Conclusions In our analysis of this large, real-world database, we found that SOT patients were more likely to experience complex penile prosthetic complications as well as mechanical malfunction of the penile prosthesis. However, we observed no difference in 5-yr incidences of stenosis, fibrosis, hemorrhage, pain, infection, displacement, and prosthesis removal between the cohorts. Our analysis reveals that surgeons performing penile prosthetic surgeries, should be aware of potential long-term mechanical malfunction complications related to the penile prosthesis in the SOT population. Disclosure No.

Underutilization of androgen deprivation therapy (ADT) intensification for the treatment of men with metastatic hormone-sensitive prostate cancer (mHSPC): A systematic review of real-world database studies.

66 Background: In the last decade, intensification of ADT with chemotherapy or androgen receptor pathway inhibitors (ARPi) has shown clinical benefits for men with mHSPC compared to ADT alone and has been recommended for mHSPC in clinical guidelines. The transition of these guidelines into real-world practice was investigated by several studies; however, these data have not been systematically summarized across the globe. Thus, we conducted a systematic literature review of real-world database (RWD) studies to summarize treatment patterns in mHSPC. Methods: An electronic search was performed in PubMed and Embase (covering citations until July 2023) and for relevant conferences of the past 2 years to identify RWD studies examining treatment patterns in men with mHSPC. Treatment patterns were summarized by overall study population across major geographies and factors associated with ADT intensification were described. Results: Of 2,325 retrieved citations, 29 studies met the inclusion criteria, with a total of 344,473 men with mHSPC covering study periods from 2014 to 2021. Most were cohort studies (n=26), utilizing electronic medical records (EMR)/chart reviews (n=18), and with RWDs from the United States (US) (n=21), followed by Europe (n=8), and Asia (n=6). Most studies included men with a median age of ≥70 years (n=23) and &gt;80% of men had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1 (n=5 of 8). In the US, most studies showed that ADT monotherapy was predominantly utilized (&gt;50%), followed by ADT/ARPi (20-40%), and ADT/chemotherapy (10-20%). Abiraterone was the most frequently used ARPi followed by enzalutamide. In Europe, most studies also reported ADT monotherapy (&gt;45%), followed by ADT/ARPi (11-25%), or ADT/chemotherapy (12-34%). In Asia, ADT monotherapy (&gt;62%) was the most common treatment in most studies, with low use of ADT/ARPIs (&lt;20%), and ADT/chemotherapy (&lt;15%). A few studies with recent EMR data (covering the 2020-21 data period) from cancer centers/registries showed high use of ADT/ARPi (&gt;40%) in both the US and Europe. Reported quantitative factors (n=13) associated with intensification beyond ADT were high disease burden (spread of metastases, high volume), young age, ECOG PS 0/1, low comorbidities, and treating physician specialty-oncologist; qualitative factors (n=2) were patient preference, unsatisfactory response to ADT treatment, ability to tolerate adverse events, and lack of cost barriers. Conclusions: This comprehensive review shows ADT monotherapy remained highly utilized across major geographies until 2021 despite new evidence and updated guideline recommendations. However, the utilization of intensified treatment with ARPi combinations is slowly increasing after the recent approvals in mHSPC.

The association between losartan potassium prescription and postoperative outcomes following total knee arthroplasty: A TriNetX analysis

BackgroundTotal knee arthroplasty (TKA) is a common surgical procedure performed to alleviate pain and improve functional outcomes in patients with knee osteoarthritis and rheumatoid arthritis who have failed conservative treatments. Arthrofibrosis has been extensively studied due to its negative impact on TKA outcomes. Losartan, an angiotensin receptor blocker (ARB), has the potential to improve TKA outcomes by inhibiting TGF-β and decreasing fibrosis. This study aims to analyze a large-scale, real-world healthcare database to investigate the association between losartan potassium prescription and postoperative outcomes such as readmissions, ED visits, and the need for MUA or revision TKA. HypothesisBased on previous literature and the nature of ARBs, it is expected that the addition of losartan will aid in better outcomes for patients following a primary TKA. Patients and methodsIn this retrospective observational study, the TriNetX Research Network (TriNetX) database was queried as of June 21, 2023. All patients who underwent a primary total knee arthroplasty (TKA) prior to June 21, 2022 were included. Patients were then divided into two cohorts by whether they had an active losartan potassium prescription within the year prior to their surgery to within 90days postoperatively. Patients were then propensity-matched to eliminate differences in demographics and comorbidities. ResultsLosartan TKA patients were 1.18 [OR: 0.85 (95% CI: 0.79–0.90), p<0.001] times less likely to be readmitted within 90days and were 1.15 (OR: 0.87 (95% CI: 0.79–0.96); p=0.009) times less likely to undergo a manipulation under anesthesia (MUA) within the 1-year postoperative period. There were no statistically significant differences in rates of emergency department (ED) visits at 90days postoperatively or revision TKAs at 1year postoperatively. DiscussionIn conclusion, patients with an active losartan prescription prior to TKA had a significantly lower likelihood of readmission within 90days and a lower likelihood of undergoing MUA within the 1-year postoperative period compared to patients not taking losartan. This presents an opportunity for further clinical investigation to explore the value of losartan in TKA. Level of evidenceIII; an observational cohort study.

Biomarker Testing, Targeted Therapy and Clinical Trial Participation by Race Among Patients With Lung Cancer: A Real-World Medicaid Database Study

IntroductionBiomarker testing in oncology is fundamental for targeted therapy use and clinical trial participation. Factors contributing to previously identified racial disparities in biomarker testing remain unclear. This study investigated biomarker testing, clinical trial participation, and targeted therapy by race among patients with metastatic lung cancer with Medicaid coverage in the United States. MethodsThe Merative MarketScan Medicaid claims database was used for this study to identify patients diagnosed with having metastatic lung cancer between 2017 and 2019 with at least 121 days of follow-up. Racial differences in biomarker testing, clinical trial enrollment, and targeted therapy use were analyzed using chi-square/t tests followed by logistic regression for confounding covariates. ResultsA total of 3845 patients were eligible. A total of 970 (25.2%) patients included in this study were Black. Biomarker testing was observed among 57.0%, targeted therapy among 4.6%, and 2.6% of the study cohort had evidence of clinical trial participation. No significant disparities between Black and White races were identified. Younger age and metastatic disease at initial diagnosis were the strongest independent factors associated with increased biomarker testing. Biomarker testing was positively associated with targeted therapy use (OR = 1.69, p = 0.005). ConclusionsPatients with metastatic lung cancer with Medicaid coverage were found to have exceedingly low biomarker testing rates; only 57% had evidence of any biomarker testing. Although no consistent differences between Black and White races were identified, this study calls attention to care experienced by socioeconomically disadvantaged patients with metastatic lung cancer in the United States.

Characteristics and outcomes of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) showing a primary resistance (PR) to docetaxel (DOC): Results from a large real-world database.

158 Background: ECHOS trial is a large real-world study, which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, &gt; 1500 pts were included in the study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed the characteristics and outcomes of mCSPC pts progressing within 6 mos from the start of DOC. Methods: We retrospectively and prospectively reviewed the clinical records of a consecutive series of mCSPC pts treated with DOC in the daily clinical practice in 69 Italian Hospitals. The treatment mostly consisted of DOC at the standard dose of 75 mg/sqm every 3 wks for six courses. For each pt we recorded the pre and post-DOC clinical history, the baseline characteristics of the pts, the treatment details and clinical outcomes. For the purpose of the present study, we considered only pts who ended chemotherapy by September 2022. PR was defined as the onset of progressive disease within 6 mos from the DOC start. Results: Among 920 mCSPC pts treated with DOC, 122 (14.3%) were PR. Most of them (95.6%) presented a de novo (DN) disease, which showed mostly high volume (HV) features (82.3%). Compared to the pts without PR, those showing PR presented more frequently a visceral involvement (26.2% vs 18.2%; p = 0.038), had lower baseline levels of hemoglobin (12.8 g/dl vs 13.4 g/dl; p &lt; 0.0001), and higher baseline levels of lactate dehydrogenase (266 U/L vs 220,5 U/L; p &lt; 0.002). No other significant differences were observed in terms of baseline PSA and alkaline phosphatase levels, symptoms degree, disease volume and timing of mets presentation between PR e no-PR pts. The median number of life prolonging agents administered after DOC progression was 1 in pts with PR as well as in pts without PR. The median overall survival was 11.9 mos and 44.9 mos in PR and no-PR pts, respectively (p &lt; 0.0001). Conclusions: Our data suggest that PR led a significant worsening of prognosis with a relevant shortening of life expectancy in pts who receive DOC for mCSPC.

Discriminative Regression With Adaptive Graph Diffusion.

In this article, we propose a new linear regression (LR)-based multiclass classification method, called discriminative regression with adaptive graph diffusion (DRAGD). Different from existing graph embedding-based LR methods, DRAGD introduces a new graph learning and embedding term, which explores the high-order structure information between four tuples, rather than conventional sample pairs to learn an intrinsic graph. Moreover, DRAGD provides a new way to simultaneously capture the local geometric structure and representation structure of data in one term. To enhance the discriminability of the transformation matrix, a retargeted learning approach is introduced. As a result of combining the above-mentioned techniques, DRAGD can flexibly explore more unsupervised information underlying the data and the label information to obtain the most discriminative transformation matrix for multiclass classification tasks. Experimental results on six well-known real-world databases and a synthetic database demonstrate that DRAGD is superior to the state-of-the-art LR methods.

A High-Fidelity Combined ATC-Rxnorm Drug Hierarchy for Large-Scale Observational Research.

Observational research utilizes patient information from many disparate databases worldwide. To be able to systematically analyze data and compare the results of such research studies, information about exposure to drugs or classes of drugs needs to be harmonized across these data. The NLM's RxNorm drug terminology and WHO's ATC classification serve these needs but are currently not satisfactorily combined into a common system. Creating such system is hampered by a number of challenges, resulting from different approaches to representing attributes of drugs and ontological rules. Here, we present a combined ATC-RxNorm drug hierarchy, allowing to use ATC classes for retrieval of drug information in large scale observational data. We present the heuristic for maintaining this resource and evaluate it in a real world database containing drug and drug classification information.

An International Standard RWD Database Designed - Taiwan Experience.

The use of Real-World Data (RWD) in medical data analysis is nowadays required. RWD may come from electronic health records (EHRs), insurance claims, medical products, Internet of Things sensors, health screenings, etc. The goal of RWD is that the data used for analysis should not be affected by environmental variables, experimental control, research context settings, etc. RWD can effectively reduce the cost and improve the accuracy of medical research. The clinical data and patient self-report are integrated, cleaned and pre-processed, and the data format is unified and standardized by international standard formats to provide a structured database for clinical research by this study. An international standard real-world research database was established through the breast cancer database of a medical center in Taipei.

P986 Effectiveness of the adjuvanted recombinant zoster vaccine (RZV) in preventing herpes zoster (HZ) among patients ≥50 years of age with Inflammatory Bowel Disease in the United States: A retrospective real-world database analysis from 2018 to 2021

Abstract Background Patients with inflammatory bowel disease (IBD) are at higher risk of developing HZ compared to general population.1 The US Food and Drug Administration (FDA) approved RZV for adults ≥50 years of age (YOA) in Oct 2017 and for adults ≥18 YOA who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression, as patients with IBD, in Jul 2021. This study addresses an information gap for RZV vaccine effectiveness (VE) in preventing HZ among IBD patients ≥50 YOA. Methods We conducted a retrospective matched cohort study using the Optum Clinformatics Data Mart healthcare administrative claims database from Jan 2018 to Dec 2021. Patients ≥50 YOA with IBD who received 2 RZV doses with dose interval ≥28 days (RZV [2-dose] cohort) were 1:3 matched to their unvaccinated counterparts (non-RZV cohort) by age, medication category, and other confounders (propensity score). The index date for RZV cohort was the date of the second dose and for non-RZV cohort was the same index date as their vaccinated match. Follow-up started from index date +30 days until earliest date of HZ occurrence, end of enrolment, death, receipt of HZ vaccine, or study end. The first HZ episode during follow-up was identified using an algorithm that included ICD-10 diagnosis code, inpatient or outpatient claims and/or HZ antiviral medication used within 7 days pre/post-HZ diagnosis. Incidence rates (IRs) of HZ were calculated overall, stratified by condition (ulcerative colitis [UC], Crohn’s disease [CD]) and age. Cox hazards models were used to estimate overall and stratified hazard ratios (HRs). VE (%) was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose. Results We identified 6501 RZV vaccinated and 19962 matched unvaccinated IBD patients who were included in the 2-dose analysis (Table). The IR of HZ was 2.92/1000 person-years (PY) in the RZV cohort and 10.96/1000 PY in the non-RZV cohort, resulting in a VE of 73.4% (95% confidence intervals [CIs]: 60.8-82.0) for IBD patients (Figure). VE against HZ was 63.5% (95%CIs: 43.0-76.6) and 85.7% (95%CIs: 69.5-93.3) in UC and CD 2-dose cohorts. IRs and VE stratified by condition and age are presented in Figure. Adjusted VE for IBD patients who received 1 RZV dose was 63.4% (95%CIs: 24.9-82.2). Conclusion Our analysis provides real-world evidence that RZV vaccination is effective in preventing HZ in IBD patients ≥50 YOA and reduce the burden in this population with increased risk of HZ. These findings are consistent with the available literature on RZV effectiveness in patients with IBD, suggesting that this population could greatly benefit from RZV vaccination. 1. Yun H et al, Arthritis Rheumatol 2016;68:2328-37 Funding GSK

De-risking 1st line chemotherapy-free immune checkpoint inhibitor (ICI) use for patients with advanced gastroesophageal cancer (aGEJ) with tumor mutational burden (TMB).

407 Background: ICI + chemotherapy (chemo-ICI) is becoming an increasingly common 1st line regimen for patients with aGEJ. However, direct outcome comparison between biomarker-enriched groups receiving chemo-ICI vs. ICI monotherapy (mono-ICI) is limited in phase III trials. We sought to evaluate if TMB might identify patients for whom mono-ICI vs. chemo-ICI might be de-risked. We prospectively hypothesized that (1) patients with TMB &lt;10 mut/mB would have more favorable outcomes receiving ICI-chemo vs. mono-ICI and (2) patients with TMB ≥10 mut/mB would have diminished additional benefit from chemo-ICI vs. mono-ICI. Methods: This study included patients with aGEJ who received 1st line chemo-ICI or mono-ICI and tumor tissue genomic profiling by Foundation Medicine. Patient data was obtained by the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine gastric real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (January/2011–March/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between patients receiving chemo-ICI vs. mono-ICI by Cox models, adjusted by propensity scores accounting for disease stage at diagnosis, ECOG PS, PD-L1 score and microsatellite instability (MSI) status. Comparisons of the explanatory power of TMB (&lt;10 vs. ≥10 mut/mB) vs. MSI status (MSI-H vs MSS) were performed by likelihood ratio test (LRT). Results: A total of 263 patients (176 receiving chemo-ICI and 87 mono-ICI) were included in the study. Patients with TMB &lt;10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI for rwPFS (median 5.8 vs. 1.9 months, hazard ratio [HR]: 0.44, 95% confidence interval [CI] 0.26-0.76), p=0.0029) and rwOS (median 11.1 vs. 7.9 months, HR: 0.68, 95% CI 0.40-1.15, p=0.1489). Patients with TMB ≥10 mut/mB did not have reduced benefit from mono-ICI; curiously less favorable outcomes were observed with chemo-ICI vs. mono-ICI for rwPFS (HR: 3.27, 95% CI 1.19-8.97, p=0.0212) and rwOS (HR: 3.56, 95% CI 1.14-11.08, p=0.0286). Evaluating only the mono-ICI group, the LRT indicated that when TMB was added to a model evaluating only MSI status, there was an improvement in ICI outcome prediction (p=0.006 for rwPFS and p=0.003 for rwOS), but not when MSI was added to TMB (p=0.91 for rwPFS and p=0.40 for rwOS). Conclusions: aGEJ patients with TMB &lt;10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI. In the TMB ≥10 mut/mB we did not observe more favorable outcomes among patients receiving chemo-ICI vs. mono-ICI. Curiously, we observed more favorable outcomes among those receiving mono-ICI in the TMB ≥10 mut/mB group. Among patients receiving mono-ICI, TMB better predicted mono-ICI outcomes compared to MSI status alone.

Tumor genomics and sidedness to predict outcomes in metastatic colorectal cancer (mCRC).

207 Background: Tumor sidedness is a prognostic factor and predictive parameter for EGFR monoclonal antibody (mAb) treatment in mCRC. Sidedness is believed to be a surrogate for genomic differences. This study aimed to evaluate genomics vs. tumor sidedness in anticipating outcomes in mCRC. Methods: We included patients (pts) with microsatellite stable mCRC tested by Foundation Medicine tissue comprehensive genomic profiling assay. Patient data was obtained by the US-based de-identified Flatiron Health-Foundation Medicine real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (1/2011–3/2023). Genomic alterations (GA) in 324 genes were compared between right and left side tumors using Fisher’s exact test, adjusted for multiple comparisons. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared by Cox proportional hazard models adjusted for prognostic features in pts receiving 1st line chemotherapy (chemo) + EGFR mAb or bevacizumab (bev). Multivariable analyses including prognostic features, sidedness and GA were performed. Comparisons of the explanatory power of genomics vs. sidedness were performed by the likelihood ratio test (LRT). Results: 3845mCRC pts (2584 left and 1261 right) were included. GA in APC, TP53, ARID1A, and FBXW7 were more prevalent in left side, while GA in BRAF, KRAS, AMER1A, PIK3CA, RNF43, BCOR, PTEN, SMAD4, MAP2K1, and BCOR in right side. 2109 pts received chemo + EGFR mAb or bev. Multivariable analyses identified BRAF, KRAS, MAP2K1, and APC as independently associated with outcomes. Pts were classified as having GA in RAS pathway (RASalt: KRAS/NRAS, BRAF, or MAP2K1), APC (APCalt), both RAS pathway and APC (APC/RASalt), and none. RASalt group had less favorable outcomes while APCalt group had more favorable outcomes, regardless of treatment received and sidedness. LRT indicated that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction (p&lt;0.001), but not when sidedness was added to genomics. Conclusions: Tumor genomics better explains differences in outcomes than sidedness in 1st line treatment in mCRC. [Table: see text]

Evaluation of a real-world clinico-genomics database of patients with upper gastrointestinal (GI) malignancies in Japan.

400 Background: The genomic profile of gastrointestinal (GI) cancers provides essential information for precision medicine, however, there is limited availability of real-world data in Asian populations as they are not well-represented in most publicly accessible clinico-genomic databases. In this retrospective study, we evaluated the clinical and genomic characteristics of upper GI cancer patients in the database from an academia-industry collaborative nationwide cancer genome screening project in Japan. Methods: The Screening Projectfor Individualized Medicine in Japan (J-SCRUM) GI-SCREEN enrolled advanced GI cancer patients from 26 sites before planned or during systemic therapy from 2015 to 2019. Archived formalin-fixed paraffin-embedded tumor tissue was analyzed by next-generation sequencing (NGS) using Oncomine Cancer Research Panel and Oncomine Comprehensive Assay. Patients with gastric (GC), esophageal (EC) and pancreatic (PC) cancers were identified in the database. The frequency of key actionable genomic alterations in each cancer cohort was explored and compared to similar upper GI cohorts in The Cancer Genome Atlas (TCGA), a publicly available genomics database initiated in 2005 and concluded sample collection in 2013 with most samples from White cancer patients. Results: A total of 872 GC (mean age at registration [SD]: 64y [12]; percent males: 65%), 265 EC (64y [9]; 78%) and 495 PC (64y [10]; 60%) patients were identified. The majority (&gt;70%) of samples were obtained from primary sites. Adenocarcinoma was the most common histological type for GC (85%) ad PC (76%), while squamous cell (76%) was the most common among EC patients. In the GC cohort, the prevalence of key actionable genomic alterations in J-SCRUM GI-SCREEN vs TCGA (N = 380) was, TP53 mutation (49% vs 49%), ERBB2 amplification (14% vs 13%), PIK3CA mutation (11% vs 14%), MYC amplification (9% vs 12%) and MET amplification (2% vs 3%). In the EC cohort, the prevalence in J-SCRUM vs TCGA (N = 182) was TP53 mutation (77% vs 87%), NFE2L2 mutation (21% vs 10%), PIK3CA mutation (9% vs 9%) and CDKN2A mutation (8% vs 8%). In the PC cohort, the prevalence in J-SCRUM vs TCGA (N = 150) was KRAS hotspot mutation (90% vs 93%), KRAS G12D (43% vs 41%), KRAS G12V (32% vs27%), TP53 mutation (58% vs 64%), BRCA1/2 deleterious mutation (5% vs 5%), ATM deleterious mutation (6% vs 5%) and MYC amplification (5% vs 5%). Conclusions: As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data.