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Efficacy of systemic therapy in breast cancer with CNS metastases: “Real-world” experience
No full textBackground: The incidence of CNS metastases in breast cancer is rising. While local therapies such as surgery and radiation remain standard, data on upfront systemic therapies for active brain metastases, especially HER2-negative patients, is limited. This study examines upfront systemic therapy efficacy for CNS metastases in breast cancer patients at a single institution, including a majority African American (AA) population. Methods: A retrospective chart review included breast cancer patients with CNS metastases treated at Henry Ford Health (January 2014-July 2024). Eligible patients had not received concurrent local therapy; prior local therapy was permitted if unrelated to the studied lesions. CNS response was to be assessed using RANOBM (defines measurable disease as lesions \u3e 10 mm) for parenchymal and modified RANO-LM criteria for leptomeningeal disease (LMD). Results: Among 35 patients (20 AA, 13 Caucasian), with a median age of 54 years, HER2-positive was the most common receptor type (49%), followed by HR-positive (37%) and triple-negative (14%); nearly half (46%) had HER2-low disease. Parenchymal metastases were predominant (86%); three had co-existing LMD, and two others had only LMD. Most metastases were multiple; 91% had lesions \u3c 10 mm. 43% had prior WBRT or SRS to unrelated lesions. HER2-positive patients had the highest CNS overall response rate (ORR, 53%) and disease control rate (DCR, 94%), followed by HR-positive (ORR 31%, DCR 69%) and triple-negative (ORR and DCR 20%). Median PFS did not significantly differ between receptor groups (p = 0.130). Trastuzumab-deruxtecan (T-Dxd) was the most common regimen (10/35) and within HER2-positive and HR-positive groups. T-Dxd achieved CNS ORR of 60%, DCR of 90%, and median PFS of 16 months. Tucatinib-based regimens showed a 100% DCR with median PFS of six months. Other therapies, including sacituzumab, abemaciclib, and trastuzumab-emtansine, showed stable disease as the best response. Among AAs, HR-positive was the most common receptor type (50%). These patients had ORR of 35% and DCR of 65%. TDxd maintained ORR of 60% and DCR of 80%. Of five patients with LMD, three were HER2- positive, and two were HR-positive, with an ORR of 60%, and DCR of 80%. Conclusions: This “real-world” experience highlights that, at our institution, most patients with breast cancer and CNS metastases considered for upfront systemic therapy lack measurable disease (91% having lesions \u3c 10 mm) typically required for clinical trials. Nonetheless, the response rate aligns with published experiences. In addition, we included patients with LMD, who are often excluded in trials. Our data also suggests impressive CNS responses with T-Dxd, both overall and in AA patients. The management of brain metastases and LMD in these patients is best approached in a multidisciplinary format
A phase II trial of tobemstomig (tobe) plus platinum-based chemotherapy (chemo) vs pembrolizumab (pembro) plus chemo in patients (pts) with untreated locally advanced or metastatic non-small cell lung cancer (NSCLC)
No full textBackground: Tobemstomig (tobe) is a novel bispecific antibody targeting programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3). BO44178 (NCT05775289) is a randomised, double-blind, phase II study evaluating tobe + chemo vs pembro + chemo in pts with NSCLC who are ineligible for surgery or definitive chemoradiotherapy. Methods: Eligible pts with previously untreated, locally advanced unresectable or metastatic NSCLC were randomised 1:1 to receive either induction tobe + chemo (carboplatin + paclitaxel/pemetrexed) or pembro + chemo for four 21-day cycles, followed by maintenance tobe or pembro with/without pemetrexed every 3 weeks until disease progression, toxicity or loss of clinical benefit. Pts were stratified by PD ligand 1 expression, histology and smoking status. Primary endpoints: confirmed objective response rate (ORR); progression-free survival (PFS). Secondary endpoints included overall survival (OS), duration of response (DoR) and safety. Results: At data cutoff (20 June 2024), 181 pts were randomised to receive tobe + chemo (n = 90) or pembro + chemo (n = 91). Median duration of follow-up was 6 months. Baseline characteristics were similar across treatment arms; median age was 66 years. There was no improvement in confirmed ORR with tobe + chemo (41.1%) vs pembro + chemo (46.2%) and no PFS difference was observed between treatment arms (HR 0.99; 95% CI 0.63, 1.56; Table). OS data were immature at this analysis. Efficacy results were consistent across subgroups. The rates of grade 3/4 adverse events (AEs), serious AEs and immune-mediated AEs were higher with tobe + chemo vs pembro + chemo; however, the rate of treatment withdrawal due to AEs was similar between arms. Conclusions: At this interim analysis, no ORR or PFS benefit was observed in pts with untreated locally advanced or metastatic NSCLC receiving tobe + chemo over pembro + chemo. OS data remain immature
Status 1 Listing Post Allocation Change: Center Level Variation in Exception Use and Ongoing Disparities Limit Equitable Access to Transplant
No full textPurpose: We sought to 1) assess overall trends and center-level heterogeneity in status 1 (highest acuity) heart transplant (HT) listing in the US 2) identify subgroups of status 1 candidates with inequitable outcomes. Methods: Adult waitlist candidates listed for a first time, single organ HT as status 1 in OPTN between 10/2018 until 9/15/2023 were included. Trends in status 1 listing and the proportion of status 1 exception (1E) by center size were plotted. Wait list outcomes by blood group, sex, race, diagnosis type, and exception use were investigated using Fine Gray competing risk analyses. Results: The study cohort consisted of 2,296 candidates who were listed for HT as a Status 1. Status 1 use increased over time (7.0 % in 2018 vs.12.8 % 2023, p \u3c 0.001), including increased in Status1E listing (3.3% - 7.7%, p \u3c 0.001). There was wide variation in exception use by center (5 % to 100 %, Figure). Compared to Status 1 candidates, those listed by exception had a lower rate of delisting for death or deterioration (HR 0.58, 95% CI 0.41 to 0.8, p \u3c 0.001) but a similar at 30 days cumulative incidence of HT. Among status 1 waitlist candidates, disparities in access to transplant were observed for women, blood group O, and Black populations, which persisted after multivariable adjustment (Table). Blood group O (8.5 %) and congenital heart disease (9.5 %) patients suffered the highest rates of delisting for death or clinical deterioration at 30 days compared to other groups (restrictive 3.3% and ischemic 2.8%). Conclusion: Status 1 use has increased over time and wide variation in Status 1 E listing patterns exist by center. Ongoing disparities exist among multiple underserved populations of high acuity patients. These findings suggest that goal of equitable access to HT is not currently being achieved among the highest acuity patients. Monitoring center-level variation in care and including these identified factors in continuous allocation could reduce disparities and promote equitable access. [Formula presented
Postpartum anxiety: a state-of-the-art review
No full textAlthough there has been increasing interest in the study of postpartum anxiety in recent years, it remains an emerging field. We present a state-of-the-art review of postpartum anxiety, with the aim of comprehensively surveying postpartum anxiety literature and presenting a synthesis of the complete body of knowledge around postpartum anxiety. We found an estimated global prevalence of 12·3% for postpartum anxiety. Postpartum anxiety is associated with primiparity and younger maternal age. Multiple screening tools are validated for use in postpartum anxiety, although none of these tools are validated for ongoing assessment. There are very few studies of pharmacotherapy in postpartum anxiety, but cognitive behavioural therapy has promising evidence. Postpartum anxiety is associated with altered offspring biology and mental health, as well as poor maternal psychological outcomes and quality of life. We review gaps in literature, particularly in our understanding of the biology and clinical features of postpartum anxiety, as well as the limitations of current screening tools. This Review should serve as a call to action towards a rigorous and coordinated study of postpartum anxiety
Multiple Versus Single Vessel CTO PCI in the Same Hospitalization: Data From the PROGRESS-CTO Registry
No full textPercutaneous coronary intervention (PCI) of multiple chronic total occlusions (CTOs) during a single procedure is infrequently performed and remains understudied. We compared the characteristics and outcomes of patients who underwent multiple versus single CTO PCIs during the same procedure. We analyzed data from 16,550 patients (16,876 CTO PCIs) from a large, multicenter registry. PCI of multiple CTOs was attempted in 626 lesions (3.7%) in 304 patients: 289 patients (95.1%) underwent PCI of 2 CTOs, 15 patients underwent PCI of 3 CTOs (4.9%) and 1 of 4 CTOs. Single CTO PCI was attempted in 16,246 patients. These patients had more comorbidities and more complex lesions, with higher prevalence of moderate or severe calcification and tortuosity, higher PROGRESS-CTO scores (1.56 vs 1.22, p \u3c 0.001), but similar J-CTO scores (2.46 vs 2.38, p = 0.110). Technical (84.7% vs 87.3%, p = 0.215) and procedural (83.0% vs 86.0%, p = 0.163) success were similar. Patients who underwent PCI of multiple CTOs required longer procedure and fluoroscopy times and higher contrast volume and use of percutaneous ventricular assistance devices (pVAD) (9.2% vs 1.8%, p \u3c 0.001). The incidence of major adverse cardiovascular events (MACE) was similar (2.6% vs 1.9%, p = 0.372). In patients who underwent PCI of multiple CTOs during the same procedure, subsequently treated CTOs had higher complexity compared with the initially treated CTO. Despite higher complexity, attempting PCI of multiple CTOs during the same procedure was associated with similar outcomes, but higher use of radiation, contrast and pVAD compared with PCI of single CTOs
Tricuspid valve replacement outcomes by baseline tricuspid regurgitation severity: the TRISCEND II trial
No full textBACKGROUND AND AIMS: The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy versus medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity.
METHODS: The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR and randomised 2:1 to TTVR (n=267) or control (n=133). In a post-hoc analysis, patients were stratified into severe TR (n=172) and massive/torrential TR (n=220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan-Meier estimates for all-cause mortality and heart failure (HF) hospitalisation assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board.
RESULTS: One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe (1.64 [95% CI: 1.11, 2.43]) and massive/torrential (2.20 [1.55, 3.14]). At 18 months, TTVR patients had similar mortality to controls (rate difference: severe 0.2% [-11.6, 11.9], massive/torrential -5.8% [-17.6, 6.0], whereas HF hospitalisation rates favoured TTVR in the massive/torrential cohort (vs. control, severe 9.8% [-3.0, 22.7], massive/torrential -15.2% [-28.9, -1.5]).
CONCLUSIONS: Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease
Percutaneous Closure of Left Ventricular Outflow Tract to Left Atrium Fistula With 3-Dimensional Printing Simulation
No full textCASE SUMMARY: We present a case of a 31-year-old man with a history of aortic valve endocarditis and surgical aortic intervention. Computed tomography revealed a complex serpiginous fistula with 2 openings between the left ventricular outflow tract and the left atrium. Using 3-dimensional printing simulation for device fit testing and planning, the mother-in-daughter system, multimodality guidance with computed tomography angiography C-arm prediction, and 3-dimensional transesophageal echocardiogram guidance successfully guided an 18-mm Cribriform Amplatzer device deployed via a retrograde approach.
TAKE-HOME MESSAGE: Three-dimensional printing simulation significantly enhances preprocedural planning and device selection for this complex fistula closure, facilitating successful percutaneous repairs in high-risk patients
Social Determinants of Health and HIV Diagnosis Rates in U.S. Counties, Comparing Ending the Epidemic (EHE) and Non-EHE Priority Jurisdictions
No full textIn the U.S., HIV diagnoses have remained steady over the past decade - despite the availability of condoms and pre-exposure prophylaxis. Factors such as adverse Social Determinants of Health (SDoH) may contribute to the sustained HIV diagnosis rate. This study sought to identify SDoH factors associated with HIV diagnosis rates in U.S. counties and between Ending the Epidemic (EHE) priority jurisdictions and non-EHE jurisdictions. We obtained county-level data from publicly available sources. We fit Poisson regression models to estimate associations between separate county-level SDoH factors and county-level HIV diagnosis rates among 344 U.S. counties and 82 EHE priority jurisdictions. Among all U.S. counties, five factors were associated with HIV diagnosis rates. In all U.S. counties, higher percent of renter-occupied housing with rent at least 30% of household income, percent of population with no health insurance, presence of medically underserved area, and percent of housing units that are overcrowded were associated with HIV diagnosis rates. For three factors (percent of populations with less than a high school education, Index of Dissimilarity, and number of social organizations), associations with HIV diagnosis rates were significantly different between non-EHE and EHE priority jurisdictions. Future research should examine SDoH drivers of HIV diagnoses, including how they impact HIV prevention efforts. Long term, these efforts can help develop novel interventions to reduce HIV transmission
Treatment of Acquired Dermal Macular Hyperpigmentation With Oral Isotretinoin: A Multi-Institutional Retrospective Study of 121 Cases
No full textThe term acquired dermal macular hyperpigmentation (ADMH) was introduced to unify Riehl\u27s melanosis (RM), lichen planus pigmentosus (LPP), and related entities. These are cosmetically distressing pigmentary disorders that pose therapeutic challenges. To investigate the efficacy and safety of oral isotretinoin in treating ADMH, we conducted a muticenter retrospective study of patients with ADMH treated with oral isotretinoin between 2014 and 2024. Patients from Australia, China, Europe, India, Middle East, North America, and North Africa were included. Patients lost to follow-up before two visits were excluded. The response was graded by a 5-point Investigator\u27s Global Assessment (IGA) scale. A total of 121 patients were included. Most patients (64.5%) were treated with a dose of 20 mg/d for an average of 8 months. Oral isotretinoin improved the severity of pigmentation in all RM and 85 (90.4%) LPP patients, with 17 (63.0%) RM and 31 (33.0%) LPP patients achieving marked improvement. RM patients responded better than LPP patients (p = 0.005). Patients with localized lesions (p = 0.0012), disease duration of less than 5 years (p = 0.046 for RM, p = 0.0272 for LPP), Fitzpatrick skin phototypes III-VI (p = 0.0081), or longer duration of treatment (p = 0.0178) responded better. Oral isotretinoin appears to be a promising treatment modality for ADMH
