TriNetX (United States)

Abstract Background The potential oncologic risks associated with medically assisted procreation (MAP) remain a concern, particularly in young women undergoing hormonal stimulation. Although previous studies have suggested no significant increase in breast cancer (BC) risk after MAP, data remain limited for ovarian (OC) and endometrial (EC) cancers. Moreover, the protective role of pregnancy against BC is well established but less explored for other gynecologic malignancies. This study aimed to evaluate the risk of BC, OC, and EC in women under 45 undergoing MAP compared with women who had a delivery, and to assess the impact of pregnancy compared with nulliparity. Methods This was a retrospective analysis using real-world data from the TriNetX Global Collaborative Network. Two propensity-matched comparisons were performed: (1) MAP vs. a cohort of parous women undergoing mammographic screening (n=878 per group); (2) parous vs. nulliparous women undergoing mammographic screening (n=1,322 per group). Matching was performed on age, race, body mass index (BMI), genetic predisposition to malignancies, and previous oral contraceptive use. Outcomes included the incidence of BC, OC, and EC. Risk ratios (RR), odds ratios (OR), hazard ratios (HR), and cumulative incidence curves were calculated. The observation period extended up to 20 years. Results In the first analysis, no significant difference was found in BC risk (3.6% vs. 4.3%; RR=0.84; HR=1.005; p=0.985). OC cases were absent in both cohorts. EC incidence was significantly higher in the MAP group, although the number of cases was low (1.1% vs. none; p=0.002). In the second analysis, parous women had a significantly lower BC incidence (3.3% vs. 7.3%; RR=0.45; HR=0.42; p=0.010). OC occurred only in nulliparous women (0.8% vs. none; p=0.002). Conversely, EC was higher in parous women (0.8% vs. none; p=0.002). Conclusions This real-world study suggests that MAP in women under 45 does not increase the risk of BC or OC compared with parous women. However, a possible increased risk of EC, although based on few cases, warrants attention. Moreover, pregnancy appears to confer a significant protective effect against BC and OC compared with nulliparity. Pending further long-term studies, these data support the oncologic safety of MAP for BC and OC, while highlighting the importance of individualized risk counseling regarding EC. Citation Format: G. Miserocchi, A. Farolfi, F. Merloni, C. Gianni, N. Gentili, M. Mariotti, G. Di Menna, O. Serra, C. Casadei, F. Rusconi, A. Andalò, S. Sabbioni, A. Carlini, D. Montanari, M. Sirico, R. Maltoni, L. Cecconetto, S. Sarti, M. Palleschi, A. Musolino. Impact of medically assisted procreation and pregnancy on breast and gynecologic cancer risk in women under 45: a real-world, propensity-matched analysis using the trinetx network [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-01.

Abstract Background: Combination therapy involving anastrozole or fulvestrant with fam-trastuzumab deruxtecan-nxki (TDX-d) has demonstrated promising antitumour activity in chemotherapy-naïve, HER2-low, hormone receptor-positive (HR+) metastatic breast cancer (mBC) patients, as evidenced by the phase 1b DESTINY-Breast08 trial (NCT04556773). Although this regimen is not currently established as a standard of care, it is being utilized in several oncology centers. However, real-world evidence supporting this strategy remains limited. Methods: Applying the TriNetX Global Collaborative Network, we retrospectively identified two cohorts comprising 658 mBC patients, stratified by receipt of TDX-d monotherapy or TDX-d in combination with endocrine therapy (ET). Propensity score matching (1:1) was performed to balance the cohorts (TDX-d plus ET, n=85; TDX-d alone, n=85) for age, race, and body mass index, all of whom had prior exposure to CDK4/6 inhibitors and chemotherapy. Hazard ratios (HRs) were calculated to compare overall survival (OS) between groups. Results: Following matching, the median age was 57.3 years (±13.9) in the TDX-d plus ET group and 56.7 years (±14.1) in the TDX-d monotherapy group. Median follow-up was 87.9 months for the combination cohort and 46.1 months for the monotherapy cohort. The combination group demonstrated a trend towards improved overall survival compared to TDX-d alone (HR=0.79; 95% CI, 0.465-1.344; p=0.384), although statistical significance was not achieved. Conclusions: This represents the first large-scale real-world cohort analysis evaluating the addition of endocrine therapy to TDX-d in patients with HER2-low, HR+ mBC. While these preliminary findings suggest a potential survival benefit with the combination approach, the limited follow-up duration preclude definitive conclusions. Further prospective studies are warranted to elucidate the clinical utility of combining TDX-d with ET in this patient population. Our research aims to perform ongoing follow-up of these patients to generate more robust data, thereby further clarifying the clinical benefit of combining TDX-d with ET in this population. Key-words (max 5): Trastuzumab deruxtecan; metastatic breast cancer; endocrine therapies; TrineTX; real world evidence Citation Format: M. Palleschi, A. Farolfi, C. Gianni, G. Miserocchi, M. Corianò, N. Gentili, M. Mariotti, G. Di Menna, O. Serra, C. Casadei, F. Rusconi, A. Andalò, S. Sabbioni, A. Carlini, D. Montanari, M. Sirico, R. Maltoni, L. Cecconetto, S. Sarti, F. Merloni, A. Musolino. Real-world outcomes of trastuzumab deruxtecan with or without endocrine therapy in her2-low, hormone receptor-positive metastatic breast cancer: a propensity-matched analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-04-06.

BackgroundAtrial fibrillation (AF) and low body weight (BW, <60 kg) are common in patients with heart failure (HF). However, the safety and effectiveness of direct oral anticoagulants (DOACs) in this group remain unclear. This study compares the efficacy and safety of apixaban versus vitamin K antagonists (VKAs) in patients with nonvalvular AF, low BW and HF.MethodsWe analysed 155,152 patients with HF and AF, weighing ≤100 kg and treated with oral anticoagulants (apixaban 86,493; VKA 68,659), from the TriNetX Global Research Network. Outcomes included ischaemic stroke/systemic embolism (SEE), clinically relevant bleedings, intracranial haemorrhage (ICH), all‐cause death and net clinical benefit (composite of stroke/SEE, bleedings and all‐cause death) across three BW categories: 60–100 kg (reference), 50–60 kg (low BW) and ≤50 kg (very low BW). Propensity score matching was used to balance the treatment groups.ResultsPatients with low BW had a higher risk of adverse events compared to those with reference BW, regardless of treatment. Apixaban consistently reduced the risk of ischaemic stroke/SEE and bleeding (including ICH) across all BW ranges (all p‐interaction >.10), and improved net clinical benefit compared to VKA (reference BW: HR .82 [95% CI: .80–.84]; low BW: HR .79 [95% CI: .74–.85]; very low BW: HR .86 [95% CI: .78–.95], p‐interaction = .366). However, a significant BW‐treatment interaction was observed for all‐cause mortality, indicating reduced relative effectiveness of apixaban vs. VKA as BW decreases.ConclusionIn this large real‐world analysis, treatment with apixaban was associated with a superior effectiveness and safety profile compared to VKA in patients with AF, HF and low BW. These results remained consistent, albeit slightly attenuated, in patients with very low BW. These findings provide preliminary evidence supporting the use of apixaban in this high‐risk population.

Background: Cytomegalovirus prophylaxis in kidney transplant recipients (KTRs) is limited by post-transplant neutropenia and leukopenia (PTN/PTL). Despite its clinical significance, the healthcare resource utilization (HCRU) related to PTN/PTL remains poorly characterized. Objective: To evaluate HCRU among KTRs taking valganciclovir during their first year post-transplant. Methods: Using TriNetX Dataworks-USA, a federated, de-identified electronic medical record database, we identified adult KTRs who underwent their first kidney transplant from January 2012 to September 2020. All eligible patients were followed for 1 year. PTN/PTL was defined as absolute neutrophil count less than 1000/μL or white blood cell count less than 3500/μL. Multivariable logistic/Poisson regression models were used to assess the association between PTN/PTL and various HCRU types. Results: A total of 8791 KTRs were identified, of whom 6219 (70.7%) developed PTN/PTL at a mean of 5.7 months post-transplantation. Hospitalizations, rehospitalizations, emergency room visits, outpatient appointments, packed red blood cell transfusions, and granulocyte-colony stimulating factor administration were more prevalent among KTRs with PTN/PTL (61.1% vs 49.5%, 24.5% vs 14.1%, 35.2% vs 28.9%, 30.4 vs 26.2 visits, 22.3% vs 17.6%, 23.4% vs 2.2%, respectively; P < .001). Adjusted analyses confirmed that PTN/PTL correlated with increased HCRU across all categories. Conclusions: KTRs who developed PTN/PTL had significantly higher HCRU. Further studies are needed to evaluate strategies addressing PTN/PTL for KTRs.

Electronic health records (EHRs), though they are maintained and utilized for clinical and billing purposes, may provide a wealth of information for research. Currently, sources are available that offer insight into the health histories of well over a quarter of a billion people. Their use, however, is fraught with hazards, including introduction or reinforcement of biases, clarity of disease definitions, protection of patient privacy, definitions of covariates or confounders, accuracy of medication usage compared with prescriptions, the need to introduce other data sources such as vaccination or death records and the ensuing potential for inaccuracy, duplicative records, and understanding and interpreting the outcomes of data queries. On the other hand, the possibility of study of rare disorders or the ability to link apparently disparate events are extremely valuable. Strategies for avoiding the worst pitfalls and hewing to conservative interpretations are essential. This article summarizes many of the approaches that have been used to avoid the most common pitfalls and extract the maximum information from aggregated, standardized, and de‐identified EHR data. This article describes 26 topics broken into three major areas: (1) 14 topics related to design issues for observational study using EHR data, (2) 7 topics related to analysis issues when analyzing EHR data, and (3) 5 topics related to reporting studies using EHR data.

IntroductionThe objective of this study was to estimate the risk of PARPi-related MDS/AML according to the line of treatment.MethodsUsing TriNetX Platform, we defined a cohort (experimental A) of 3,527 AOC patients treated with a first-line maintenance treatment with PARPi and a control cohort of 1,503 AOC patients underwent to at least two lines of a platinum-based chemotherapy and never treated with a PARPi. The third (experimental B) cohort included 356 AOC patients treated with PARPi after platinum-sensitive relapse. Cohorts were propensity score matched 1:1 (experimental A versus control and subsequently experimental B versus control) with respect to age, race, bevacizumab treatment and genetic susceptibility to neoplasms. Hazard ratio (HR) was used to compare the incidence of MDS/AML between the matched cohorts. The time window of observation in both analyses was 10 years.ResultsFor the first analyses, propensity scoring generated 1,282 matched pairs, with a mean age of 59.8 (+/-10.2 SD). The overall incidence of MDS/AML showed no significant differences in the experimental A and control groups (1.25% vs 0.86%): HR = 2.06 (95% CI 0.94 - 4.51, p=0.064). For the second analyses, propensity scoring generated 263 matched pairs (mean age 60.2 +/-11.2). The incidence of MDS/AML was the same in experimental B and control cohort (10, 3.8%), HR = 1.76 (95%CI 0.42-7.37, p = 0.432). No differences across PARPi used were seen.Conclusion/ImplicationsOur study shows real-world evidence that the use of PARPi as first-line or second-line maintenance treatment in patients with AOC does not increase the risk of MDS/AML.

It is unknown whether Medicaid expansion under the Affordable Care Act (ACA) or state-level policies mandating Medicaid coverage of the routine costs of clinical trial participation have ameliorated longstanding racial and ethnic disparities in cancer clinical trial enrollment. We conducted a retrospective, cross-sectional difference-in-differences analysis examining the effect of Medicaid expansion on rates of enrollment for Black or Hispanic nonelderly adults in nonobservational, US cancer clinical trials using data from Medidata's Rave platform for 2012-2019. We examined heterogeneity in this effect on the basis of whether states had pre-existing mandates requiring Medicaid coverage of the routine costs of clinical trial participation. The study included 47,870 participants across 1,353 clinical trials and 344 clinical trial sites. In expansion states, the proportion of participants who were Black or Hispanic increased from 16.7% before expansion to 17.2% after Medicaid expansion (0.5 percentage point [PP] change [95% CI, -1.1 to 2.0]). In nonexpansion states, this proportion increased from 19.8% before 2014 (when the first states expanded eligibility under the ACA) to 20.4% after 2014 (0.6 PP change [95% CI, -2.3 to 3.5]). These trends yielded a nonsignificant difference-in-differences estimate of 0.9 PP (95% CI, -2.6 to 4.4). Medicaid expansion was associated with a 5.3 PP (95% CI, 1.9 to 8.7) increase in the enrollment of Black or Hispanic participants in states with mandates requiring Medicaid coverage of the routine costs of trial participation, but not in states without mandates (-0.3 PP [95% CI, -4.5 to 3.9]). Medicaid expansion was not associated with a significant increase in the proportion of Black or Hispanic oncology trial participants overall, but was associated with an increase specifically in states that mandated Medicaid coverage of the routine costs of trial participation.