Approximately 6-10% of all breast carcinoma is metastatic at diagnosis, termed de novo metastatic breast carcinoma (dnMBC). Systemic therapy remains the first line of treatment in dnMBC, but there is growing evidence that adjuvant locoregional treatment (LRT) of the primary tumor increases progression-free and overall survival (OS). Although selection bias may exist, real-world data from nearly half a million patients show that patients are undergoing primary tumor removal because of the survival benefit. The main question for the advocates for LRT in this patient population is not whether primary surgery is beneficial in dnMBC patients, but rather who is a good candidate for it. Oligometastatic disease (OMD) is a distinct subset of dnMBC that affects a limited number of organs. A better OS can be achieved with LRT in breast cancer patients, especially in those with OMD, bone only, or favorable subtypes. Though there is currently no consensus among breast care specialists on how to treat dnMBC patients, primary surgery for dnMBC should be taken into consideration for a subset of patients following an extensive multidisciplinary discussion.

De novo metastatic breast cancer (dnMBC) accounts for 3–10% of newly diagnosed cases, with 20–40% presenting as a bone-only metastatic disease, which can achieve survival outcomes exceeding 10 years with multimodal therapy. However, the role of multimodal therapy remains controversial in the guidelines. Objective: This study aims to identify dnBOMBC subgroups to develop a pragmatic staging system for guiding locoregional therapy decisions. Materials and Methods: Data from the MF07-01 phase III randomized trial (2021, median follow-up time (mFT): 40 months (range 1–131)) and the BOMET prospective multi-institutional registry trial (2021, mFT: 34 months (range 25–45)) were combined for analysis, including only patients who presented with bone-only metastases. Exclusion criteria were patients under 18 and those with a history of prior cancer or cancer metastases. Patients with missing data and positive surgical margins were excluded. Out of 770 patients, 589 were included. Survival analyses were first conducted according to molecular subgroups, after which patients were further stratified by hormone receptor status, human epidermal human epidermal growth factor receptor 2 (HER2) status, tumor grade, and clinical T (cT) stage. Group A (GrA) included hormone receptor (HR)-positive, low- or intermediate-grade tumors at any cT; HR-positive, high-grade tumors with cT0–3; or any HER2-positive tumors. Group B (GrB) included HR-positive, high-grade tumors with cT4 disease or any triple-negative (TN) tumors. Results: The hazard of death (HoD) was 43% lower in GrA than in GrB. Median OS was 65 months (39–104) for GrA patients and 44 months (28–72) for GrB patients (HR 0.57, 95% CI 0.41–0.78, p = 0.0003). Primary tumor surgery (PTS) significantly improved OS in GrA patients, regardless of the number of metastases (solitary: HR, 0.375, 95% CI 0.259–0.543, p < 0.001; multiple: HR 0.435, 95% CI 0.334–0.615, p < 0.001). Conversely, GrB patients did not experience a significant benefit from PTS. Conclusions: This study demonstrates that GrA patients have better OS than GrB patients, and PTS reduces the HoD in GrA patients compared to systemic therapy alone. These findings support using a modified staging system in dnBOBMC to identify patients who may benefit from multimodal therapy including PTS.

Between 2009 and 2019, drug overdose deaths were linked to ∼42% of growth in deceased organ donors in the US. Recent national data indicate a ∼27% decline in overdose mortality from 2023 to 2024, the most substantial reduction in decades. It is unclear whether this public health achievement was accompanied by unintended consequences on transplantation. Using data from the Organ Procurement and Transplantation Network, we analyzed trends in deceased donor kidney transplant (DD-KT) and deceased donor liver transplant (DD-LT) rates, as well as the active waitlist size, from January 2015 to December 2024. Overdose decedent donor (ODD) transplant rates rose until mid-2023, when they comprised nearly 1 in 5 DD-KTs and DD-LTs nationally. Thereafter, rates declined by 45.1% for DD-KTs and 37.3% for DD-LTs. We observed concurrent disruption in two long-standing national trends - the overall DD-KT rate, rising since 2015, plateaued and the active kidney transplant waitlist size, declining since 2015, expanded. These data indicate that the national overdose mortality decline coincided with a significant deceleration in kidney transplantation activity. As overdose prevention efforts continue, concerted efforts are warranted to prevent long-term impact on waitlist candidates.

Introduction: The impact of locoregional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (dnBOMBC) is controversial. This study aims to assess the effect of LRT on survival, utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with dnBOMBC were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Further, patients who received LRT were divided into two subgroups: those who received ST after LRT (LRT+ST group) and those who received ST prior to LRT (ST+LRT group). Factors associated with disease progression, including solitary or multiple bone metastases, were analyzed. Results: There was a total of 744 patients with dnBOMBC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32–66, 25–75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs. 55 (44, 66), p = 0.0001]. There were no significant differences in grade, HER2 status, triple-negative status, receipt of hormonal therapy, or intervention to metastatic sites. During follow-up, 58% (n = 217) of patients in the ST group and 32% (n = 120) of patients in the LRT group died (p < 0.001). Local progression was observed in 20% of the patients in the ST group, whereas 9% progressed in the LRT group (p = 0.0001). Systemic progression occurred more in the ST group; 66% (n = 244) compared to 41% (n = 152) of patients in the LRT group (p < 0.001). The hazard of death was 64% lower in the LRT group than in the ST group (HR: 0.36, 95% CI: 0.29–0.45, p < 0.0001). The burden of metastatic disease differed significantly between the two groups, with a higher rate of solitary bone metastases in the LRT group compared to the ST group (50% vs. 24%, p < 0.001). However, the LRT group had better overall survival (OS) for both solitary (HR: 0.38, 95% Cl: 0.26–0.55) and multiple (HR: 0.38, 95% Cl: 0.29–0.51) bone metastasis patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST. Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p < 0.05). Conclusions: Analysis of this large multi-institutional patient cohort provides further evidence that LRT is associated with longer OS and lower locoregional recurrence rates in patients with dnBOMBC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor.

Introduction: Donor age is a key determinant of liver transplant (LT) outcomes, but its impact varies across recipient age groups. Specific donor age thresholds associated with excess risk remain undefined. Methods: Using data from the Scientific Registry of Transplant Recipients (2011–2021; follow‐up through 2024), we analyzed first‐time, single‐organ LT recipients. Donors and recipients were stratified by age. Outcomes included patient, graft, and death‐censored graft survival. Multivariable Cox regression models adjusted for liver disease severity, comorbidities, graft type, and transplant year were used to identify donor age thresholds associated with increased risk in each recipient age group. Results: Among 70 078 recipients (median age, 57 years), mean donor age rose from 39.6 to 40.9 years ( p = .004), while recipient age increased from 50.7 to 51.9 years ( p = .003). Donor age ≥50 years was associated with a sixfold increase in mortality in pediatric recipients (aHR, 6.48; 95% CI, 1.92–21.83; p = .003). For adults aged 18.1–30 years, excess mortality and graft loss were observed with donors >55 years (aHRs >2.5). In recipients aged 40.1–60 years, risk increased progressively with donor age. Among recipients ≥65 years, donor age was not significantly associated with outcomes. These thresholds were consistent across outcomes and robust in sensitivity analyses. Conclusions: This is the first national study to define recipient age‐specific donor age thresholds associated with post‐LT risk. These findings support the development of age‐informed allocation strategies and call for a reassessment of organ discard practices as donor and recipient ages continue to rise.

Background: The prognostic significance of subclinical rejection (SCR) and borderline rejection (BLR) detected on surveillance kidney allograft biopsies remains uncertain. Methods: We performed a systematic review and meta‐analysis of studies enrolling adult kidney transplant (KT) recipients undergoing protocol biopsies. The primary outcome was death‐censored graft loss (DCGL); the secondary outcome was subsequent rejection. Random‐effects models, sensitivity analyses, and meta‐regression were used. Results: Fifteen studies (5428 recipients) were included. SCR was associated with a higher risk of DCGL (RR 2.22; 95% CI 1.67–2.95) and subsequent rejection (RR 3.09; 95% CI 2.34–4.09), with low heterogeneity. Both T cell–mediated rejection (RR 1.82; 95% CI 1.28–2.61) and antibody‐mediated rejection (ABMR) (RR 3.35; 95% CI 2.11–5.33) were associated with increased DCGL. BLR was associated with increased DCGL (RR 2.40; 95% CI 1.67–3.46) and subsequent rejection (RR 2.79; 95% CI 2.10–3.69). Findings were robust across sensitivity analyses, including contemporary Banff‐era definitions. Conclusions: SCR and BLR are associated with inferior long‐term graft outcomes. These findings underscore their prognostic significance and warrant prospective studies to determine optimal management strategies.