Citations

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions for patients with prostate cancer across the disease spectrum. The Guidelines sections included in this article focus on metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). For patients with mCSPC, disease characteristics, such as whether metastases arose synchronously or metachronously and the degree of metastatic burden, impact therapy decisions, including how much treatment intensification is appropriate and when prostate-directed and/or metastasis-directed therapy should be considered. In the mCRPC setting, androgen deprivation therapy is continued with the sequential or concurrent addition of certain androgen receptor pathway inhibitors, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, biomarkers, the extent and location of metastases, symptoms, and potential side effects.

Background The Woven EndoBridge (WEB) device represents an innovative solution for cerebral aneurysm occlusion, particularly for challenging wide-neck bifurcation aneurysms. However, factors affecting sustained occlusion remain poorly understood. We utilized machine learning to attempt to identify predictors of favorable long-term outcomes following WEB treatment. Methods In this multicenter retrospective study, we collected patient demographics, aneurysm characteristics, procedural details, and clinical outcomes. The primary endpoint was improvement in occlusion status, defined as maintained Raymond-Roy Occlusion Classification (RROC) grade 1, or improvement from grade 2 to 1, or from grade 3 to either 2 or 1 on final angiographic follow up. The dataset was split into training (75%) and validation (25%) sets. The CatBoost algorithm was selected based on performance metrics, with Shapley Additive exPlanations (SHAP) values calculated to determine feature importance. Furthermore, a multivariable binomial logistic regression model was performed to validate machine learning findings. Results Among 720 aneurysms from 36 hospitals, 84% showed improvement in occlusion at follow up. Both machine learning and multivariable logistic regression identified aneurysm height as the most consistent correlate of nonimprovement (odds ratio (OR) 0.90 per mm, p = 0.022). In the CatBoost model, the highest-ranking features by SHAP included aneurysm height, patient age, treatment acuity, ACom location, WEB-SLS device, bifurcation anatomy, aneurysm multiplicity, baseline modified Rankin Scale, access route, and partial thrombosis. Conclusions Machine-learning and regression analyses identified consistent predictors of occlusion improvement after WEB treatment, with aneurysm height most strongly linked to nonimprovement. These insights may guide patient selection and follow up. Findings require cautious interpretation and external validation in larger cohorts.

Abstract Purpose: Relapse is a major cause of failure in human papillomavirus–independent head and neck squamous cell carcinoma. Clinicopathologic criteria for adjuvant treatment remain imprecise and have not changed for decades. We investigated whether ctDNA in lymphatic exudate collected via surgical drains (“lymph”) 24 hours after surgery identified molecular residual disease (MRD) and compared its performance with time-matched plasma. Experimental Design: Using an ultra-sensitive tumor-informed sequencing approach, tumor variants were called in lymph and plasma to classify patients as ctDNA positive or ctDNA negative, trained in an initial cohort of 36 patients, and replicated in an independent cohort of 37 patients. Progression-free survival was compared in ctDNA(+) versus ctDNA(–) patients. Results: Lymph identified MRD in two independent multi-site cohorts (initial cohort sensitivity = 76% and specificity = 63%; log-rank P = 0.01; replication cohort sensitivity = 65% and specificity = 70%; log-rank P = 0.04). Lymph performance was enhanced in locoregional relapse (sensitivity = 78% and specificity = 67%; log-rank P = 0.0004) and generalized to early-stage patients. Analysis of matched plasma collected at this early timepoint was not predictive of recurrence (sensitivity = 35% and specificity = 72%; log-rank P = 0.7). In patients with intermediate-risk pathology, lymph ctDNA was associated with recurrence (sensitivity = 88% and specificity = 67%; log-rank P = 0.0008), suggesting an opportunity for improved stratification of patients who may benefit from additional adjuvant treatment. Conclusions: Postoperative lymph is a novel, proximal, and early source of MRD with the potential to introduce more precision into adjuvant therapy decision-making and improve outcomes, especially for patients with intermediate-risk human papillomavirus–independent head and neck squamous cell carcinoma.

Brain tumor-related epilepsy (BTRE) is a common and debilitating symptom of central nervous system (CNS) tumors. The epileptogenic zone, defined as cortex responsible for seizure generation, is located at the peritumoral region for most tumors, and lower-grade intrinsic brain tumors have the highest seizure incidence. Surgery is often the most effective treatment for the reduction in seizures in BTRE. However, surgical decisions have historically often been made exclusively for oncologic reasons, with less emphasis on seizure control. Surgical approaches for all tumor types are reviewed, highlighting relevant risk factors. Adjunctive tools during surgery, such as intraoperative electrocorticography (ECoG), may help identify and remove surrounding brain areas which are epileptogenic. Minimally invasive surgery is also gaining traction, given its utility in treating seizures deep-seated tumors. This review explores epileptogenic brain tumors, surgery for BTRE, and emerging strategies to better achieve seizure control.

Introduction: Apolipoprotein B (ApoB) and coronary artery calcium score (CAC) are well-established risk factors for coronary heart disease (CHD). However, the interaction between these risk factors on CHD risk has not been well-studied. We investigated the association between ApoB levels and CAC with CHD risk. Methods: We analyzed 4,649 participants from the Multiethnic Study of Atherosclerosis cohort (median follow-up 13.9 years) without baseline CHD or statin use. High ApoB was defined as ≥120 mg/dL. Participants were divided into 6 groups; group 1: CAC = 0 with normal ApoB, group 2: CAC = 0 with high ApoB, group 3: CAC 1-99 with normal ApoB, group 4: CAC 1-99 with high ApoB, group 5: CAC ≥100 with normal ApoB, group 6: CAC ≥100 with high ApoB. CHD was defined as myocardial infarction, resuscitated cardiac arrest, or CHD death. Survival analysis using Kaplan-Meier and multivariable Cox proportional hazard models were performed to assess the relationship between ApoB, CAC, and time to first CHD event. Results: In an adjusted model, high ApoB, CAC (1-99), and CAC (≥100) were independently associated with CHD (HR: 1.48; 95% CI: 1.04, 2.11; HR: 2.54; 95% CI: 1.78, 3.64; and HR: 4.41; 95% CI: 3.08, 6.31, respectively). Compared to group 1 (CAC 0 with normal ApoB), CAC 0 and high ApoB (group 2) was not associated with increased risk of CHD (HR: 1.15; 95% CI: 0.59, 2.23). However, a statistically significant greater risk of CHD was observed in those with CAC 1-99 and normal ApoB (group 3) (HR: 2.12; 95% CI: 1.37, 3.28), CAC 1-99 and high ApoB (group 4) (HR: 4.12; 95% CI: 2.42, 7.00), CAC ≥100 and normal ApoB (group 5) (HR: 4.20; 95% CI: 2.78, 6.34), CAC ≥100 and high ApoB (group 6) (HR: 5.72; 95% CI: 3.40, 9.63). Conclusions: In this analysis, ApoB and CAC are independently associated with CHD risk. Individuals with high ApoB and CAC ≥100 had the highest risk of CHD. In contrast, individuals with CAC = 0 and high ApoB had no significant increase in CHD risk compared to individuals with normal ApoB levels. These findings suggest that ApoB and CAC may be complementary tools for CHD risk stratification in the context of primary prevention.

Background: Lipoprotein(a) [Lp(a)] and metabolic syndrome (MetS) are well-established risk factors for cardiovascular disease. Recent evidence suggests that high Lp(a) levels may increase the risk of coronary heart disease (CHD) in patients with diabetes, raising the question of whether similar interactions exist between Lp(a) and metabolic syndrome. We aimed to evaluate the joint association of Lp(a) and MetS with incident CHD risk in a large, multi-ethnic, prospective cohort. Methods: We analyzed 6,664 participants from the MESA (Multiethnic Study of Atherosclerosis) cohort (median follow-up 14.0 years) without baseline CHD. MetS was defined as ≥3 of the following criteria: waist circumference ≥102 cm (men), or ≥88 cm (women), triglycerides ≥150 mg/dL or use of a fibrate medication, HDL-C <40 (men) or <50 (women) or use of a fibrate medication, SBP ≥130 mm Hg and/or DBP ≥85 mm Hg or use of antihypertensive medication, fasting glucose ≥100 mg/dL or use of antidiabetic medication (4). Elevated Lp(a) was defined as a level ≥50 mg/dL. CHD was defined as myocardial infarction, resuscitated cardiac arrest, or CHD death. Participants were divided into four groups: group 1: Normal Lp(a) without MetS, group 2: elevated Lp(a) without MetS, group 3: normal Lp(a) with MetS, group 4: elevated Lp(a) with MetS. Survival analysis using Kaplan-Meier and multivariable Cox proportional hazard models were performed to assess the relationship between Lp(a), MetS, and time to CHD. Results: In an adjusted model, log [Lp(a)] and MetS were both independently associated with CHD (HR: 1.14; 95% CI: 1.03, 1.25) and (HR: 1.75; 95% CI: 1.35, 2.27). Compared to the reference group (normal Lp(a) without MetS), those with elevated Lp(a) without MetS (group 2) did not have increased risk of CHD (HR: 1.30; 95% CI: 0.94, 1.80). However, those with normal Lp(a) with MetS (group 3) had greater risk of CHD (HR: 1.56; 95% CI: 1.18, 2.05). The highest risk for CHD were in those with elevated Lp(a) with MetS (group 4) (HR: 2.37; 95% CI: 1.66, 3.37). Conclusions: In this analysis. elevated Lp(a) and MetS independently increase CHD risk. MetS alone significantly increases risk, whereas elevated Lp(a) without MetS does not demonstrate a significant effect. However, their combination confers the highest risk, suggesting a synergistic interaction. These results emphasize the value of assessing Lp(a) in individuals with MetS to improve cardiovascular risk stratification and guide targeted prevention.

Background: We investigated the impact of genetic risk factors for coronary heart disease (CHD) -polygenic risk score (PRS), familial hypercholesterolemia (FH), and family history (FamHx)- on CHD risk estimates, across the age spectrum, in two diverse cohorts of US adults -eMERGE IV (eIV) and All of Us (AoU). Methods: CHD was defined as myocardial infarction, unstable angina, and coronary revascularization. Self-identified race/ethnicity (SIRE) was used as a population descriptor. We calculated a PRS for CHD (PRS CHD , PGS004698), ascertained FH as the presence of pathogenic/likely pathogenic variants in FH genes, and defined FamHx as early-onset CHD in first-degree relatives. We employed Pooled Cohort Equations (PCE) to estimate the 10y risk of CHD for adults ≥40y and modeled the association of conventional risk factors with CHD in adults <40y. AoU served as the training set, and eIV as the testing set. We analyzed the impact of PRS CHD and FamHx on CHD risk estimates by a) using multivariable logistic regression and Cox proportional hazard models, assessing discrimination and the extent of risk reclassification; and b) net benefit analysis and decision curves to assess the performance of prediction models across actionable thresholds. Results: We analyzed data for 19348 participants from eIV (age 50±15, 68% female, 41% non-White) and 239645 participants from AoU (age 55±17, 61% female, 48% non-White). Genetic risk factors were significantly associated with CHD. PRS CHD performance varied by SIRE groups, while FamHx was consistent. The effects of PRS CHD and FamHx on CHD were independent and additive (Figure 1). In adults ≥40y, incorporating PRS CHD and FamHx into PCE improved discrimination (C-statistic increased from 0.719 to 0.753; P -diff=9.1×10 -3 , Figure 2) and reclassified risk in 19% and 20% of participants at the 7.5% and 10% 10y CHD risk thresholds, respectively. Between the 7.5% and 10% 10y CHD risk thresholds, incorporating PRS CHD and FamHx into the PCE improved the net benefit of the risk prediction models across White, Black, and Hispanic/Latino groups (Figure 3). Conclusion: PRS CHD and FamHx were independently and additively associated with CHD in two large diverse cohorts in the US. Incorporating PRS CHD and FamHx into PCE improved risk discrimination, reclassified risk in a significant portion of participants, and improved net benefit of the PCE across all three major SIRE groups, motivating the addition of these factors to clinical risk calculators.

Introduction: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) typically have low serum transthyretin (sTTR) levels, worsening heart failure, and increased mortality. A recent study has shown the association of sTTR levels ≥20mg/dL with reduced risk of all-cause mortality and cardiovascular mortality (CVM). It has also been shown that regardless of baseline sTTR level, greater increases in sTTR levels are associated with greater improvements in cardiovascular outcomes. Acoramidis, a near-complete (≥90%) TTR stabilizer, demonstrated a rapid and sustained increase from baseline in sTTR by Day 28 and reduced risk of cardiovascular outcomes in patients with ATTR-CM. Hypothesis: Acoramidis-mediated early increase in sTTR levels ≥20 mg/dL (lower limit of normal) at Day 28 reduces risks of CVM and cardiovascular-related hospitalizations (CVH) in patients with ATTR-CM. Methods: Analyses were conducted in the ATTRibute-CM modified intention-to-treat (mITT) population (acoramidis: 409; placebo: 202). The sTTR concentrations (normal range is 20-40 mg/dL) were assessed using an immunoturbidimetric method (Abbott ARCHITECT system) in a central laboratory. The proportion of participants with sTTR levels below normal at baseline and Day 28 were determined. The relationship between sTTR levels <20 or ≥20 mg/dL, at Day 28 across the pooled acoramidis and placebo treatment groups, and subsequent risk of CVM and of CVH over 30 months were analyzed using a stratified log-rank test. Results: At baseline about 25% of study participants had sTTR levels below normal in both treatment groups. At Day 28, less than 2% of participants had sTTR levels <20 mg/dL in the acoramidis arm compared with 26% in the placebo arm ( Table 1 ). When acoramidis and placebo treatment groups were pooled based on sTTR levels <20 or ≥20 mg/dL at Day 28, participants with sTTR ≥20 mg/dL were associated with a lower risk of the composite endpoint of CVM or first CVH at Month 30 in comparison with <20 mg/dL ( p <0.0001) ( Figure 1A ). Comparable findings were observed for the individual components (CVM, first CVH) ( Figure 1B and C ). Conclusion: Across treatment groups, sTTR levels above normal range (≥20 mg/dL) at Day 28 were associated with a lower risk of cardiovascular outcomes at Month 30, when compared with sTTR levels below normal range (<20 mg/dL). Thus, these observations demonstrate that higher sTTR levels over time may have the potential for clinical benefits in both CVM and CVH.

Background: Ultrasound-guided percutaneous fasciotomy and debridement (USPFD) is a minimally invasive treatment for patients with plantar fasciopathy refractory to conservative management. Previous studies have shown clinical improvement with USPFD, but pain relief and patient satisfaction have not been demonstrated beyond 2 years. Methods: This retrospective case series included patients who underwent USPFD at a quaternary academic medical center between April 2013 and January 2018, with refractory plantar fasciopathy and at least 4 years’ follow-up. Patient outcomes were assessed through electronic surveys and telephone interviews. Primary outcome measures included mean changes in visual analog scale pain (VAS-Pain) scores and patient satisfaction via Likert scale. Secondary measures included VAS-Pain with the first 5 steps, VAS-Pain during daily weightbearing, and procedural complications. Results: Seventy unique procedures were identified among 62 patients. Follow-up data were obtained from 51 of 62 patients (82%) who responded to surveys or phone calls. This corresponded to 58 of 70 procedures (83%) at a mean postprocedure follow-up of 6.6 ± 1.4 years. Patients had a mean duration of symptoms of 2.1 ± 3.0 years prior to the procedure. Baseline VAS-Pain was 6.8 ± 2.2 and final follow-up VAS-Pain was 0.7 ± 1.1. At the last follow-up, patient-reported VAS-Pain with first 5 steps was 0.9 ± 1.6 and VAS-Pain with weightbearing through the day was 1.3 ± 1.8. Overall, 91% (53/58) of the procedures were considered successful, where patients responded they were “satisfied” or “very satisfied” and 52 of 58 (90%) procedural responses indicated that based on the outcome, they would recommend the procedure to others. Final follow-up VAS-Pain, VAS-first 5 steps, and VAS-weightbearing, were all improved in the success vs failure groups ( P ≤ .002). No complications were reported. Conclusion: USPFD was associated with high patient satisfaction and durable pain relief for chronic plantar fasciopathy at an average follow-up of 6.6 ± 1.4 years.