Citations

Abstract Background Opioid stewardship policies could adversely affect pain management for patients with cancer. Yet patients with cancer are also at risk for opioid‐related harms. This study sought to determine trends in opioid prescribing by clinical stratum and pain for patients with cancer from 2016 to 2020. Methods A retrospective study was conducted of opioid‐naive adults with newly diagnosed cancer from 2016 to 2020 ( N = 10,232) in a large Connecticut health system. Logistic regression was used to calculate changes in the predicted probability of opioid prescribing from 2016 to 2020. Two subpopulations were examined: patients treated surgically ( n = 4405) and patients with metastatic cancer ( n = 2158). Flowsheet pain scores for patients with metastatic cancer were used to stratify by no pain (all scores, 0) versus any pain. The main outcomes were new (≥1 prescription in the 0–6 months after diagnosis) and additional (0–6 and 7–9 months) opioid prescriptions. Results A decline was observed in the predicted probability of new (71.1% to 64.6%; p < .001) and additional prescribing (27.2% to 24.2%; p = .07 [not significant]) declined. Among surgical patients, the predicted probability of new opioid prescribing fell (96.0% to 88.6%; p < .001), whereas additional prescribing was stable (13%). For patients with metastatic cancer with pain, new opioid prescribing was stable (56%). For those reporting no pain, the predicted probability of new opioid prescribing declined from 61.6% to 36.1% ( p < .001). Conclusions In the context of widespread policy changes, this study showed a modest decline in new and additional opioid prescribing for patients with cancer. In metastatic cancer, prescribing remained stable for patients reporting pain and declined steeply for those reporting no pain.

Background Endovascular thrombectomy (EVT) has transformed acute ischemic stroke (AIS) care, with onset-to-puncture (OTP) time widely recognized as a critical determinant of outcome. However, emerging evidence suggests that in-hospital procedure time (PT)—from arterial puncture to final recanalization—may have an equally or more significant impact. This study examines the relative contribution of PT versus OTP to functional outcomes in patients with AIS undergoing EVT. Methods A retrospective analysis was conducted of 6644 patients with AIS treated at 44 international stroke centers from the Stroke Thrombectomy and Aneurysm Registry (STAR; 2016–2023). Multivariable regression, time-equivalence analysis, and marginal effects modeling were used to assess associations between PT, OTP, and 90-day modified Rankin Scale (mRS) outcomes. Centers were stratified by procedural efficiency and compared using propensity score matching (PSM). Mediation analysis evaluated whether PT accounted for inter-center differences. Results PT and OTP were independently associated with functional outcomes; however, PT had a significantly stronger effect (adjusted OR for mRS 0–2: PT=0.56 vs OTP=0.96 per hour). Each 5 min increase in PT was equivalent to 78–100 min of additional OTP in outcome impact. Centers with faster average PT had higher rates of functional independence (number needed to treat (NNT)=10), fewer complications, and lower symptomatic intracranial hemorrhage rates. PT significantly mediated the relationship between center tier and outcomes (Sobel’s P<0.001). Conclusion While minimizing OTP remains important, PT exerts a greater influence on outcomes after EVT. Procedural efficiency should be emphasized in stroke systems of care and included in center performance metrics to improve patient outcomes.

BACKGROUND AND OBJECTIVES: Flow-diverting stents (FDSs) have improved treatment options for intracranial aneurysms. Although FDS have proven successful in treating aneurysms that would previously have required complex microsurgical or endovascular repairs, treatment failures remain a concern. In this multicenter study, we aim to analyze the predictors of residual aneurysmal filling at early angiographic follow-up. METHODS: A retrospective analysis of a prospectively maintained neuroendovascular database at 14 high-volume US centers was conducted for all patients who underwent FDS placement for intracranial aneurysms between 2011 and 2019. Aneurysms were graded on the O'Kelly-Marotta scale (OKM). RESULTS: A total of 2277 patients underwent FDS embolization for intracranial aneurysms during the study period. The patient's mean age was 55 (SD ± 13.5) years, and 82% were female. The median maximal aneurysm diameter was 6.7 mm (IQR 4.10-11 mm). Complete aneurysm obliteration (OKM grade 4) occurred in 1109 patients (68%), and 146 (9%) were OKM grade 3, 188 (12%) were OKM grade 2, and 174 (11%) were OKM grade 1. In the adjusted multivariate analysis, individuals in the 65-74 years and 75+ years age groups had significantly increased risk of residual aneurysm filling at 6-month follow-up compared with the 18-44 years age group (odds ratio [OR] 1.92 (95% CI: 1.33-2.78) and 2.92 (95% CI: 1.79-4.77), respectively). Aneurysms arising from the superior cerebellar artery, the basilar artery, and the carotid terminus were more likely to have a residual filling (OR 12.6, 95% CI: 1.39–14.7; OR 4.27, 95% CI: 1.39–14.7; OR 3.16, 95% CI: 1.24–8.06, respectively). CONCLUSION: As the utilization of FDS for intracranial aneurysms becomes more widespread, the efficacy of aneurysm obliteration needs to be assessed. Our results indicate that several patient-dependent factors, such as age, aneurysm location, and size, predict the likelihood of residual aneurysm filling 6 months post-treatment.

Abstract A blood-based multi-cancer early detection (MCED) test has demonstrated feasibility as a screening tool in large-scale clinical trials. The PATHFINDER 2 (PF2) study (NCT05155605) evaluates safety and performance of the MCED test in a diverse intended-use population. To gauge generalizability of study results, we assessed participant (ppt) baseline characteristics vs general US population data from the National Health and Nutrition Examination Survey (NHANES). PF2, a prospective, multicenter, interventional study, enrolled ppts aged ≥50 y from diverse clinical settings in North America. Enrollment targets for sex and race/ethnicity were established from the 2019 American Community Survey (US Census Bureau). Recruitment strategies were implemented to maximize enrollment for groups historically underrepresented in clinical studies. Exclusion criteria included clinical suspicion of cancer or cancer diagnosis/treatment within 3 y. Data on baseline characteristics and key cancer risk factors were collected at enrollment. We compared the PF2 study population to a nationally representative sample of US adults aged ≥50 y from 2017-2020 NHANES data. NHANES data were weighted using complex, multistage probability sampling to generate a nationally representative sample. There were 35,878 ppts enrolled in PF2; 35,307 clinically eligible and evaluable ppts were included in this analysis. Mean age was 64 y for both PF2 and NHANES; 56.2% were females in PF2 vs 53.6% (95% CI 52.0-55.3%) in NHANES. Race/ethnicity distribution for PF2 vs NHANES was 7.4 vs 11.0% (8.9-13.1%) Hispanic, 74.6 vs 69.7% (65.0-74.5%) non-Hispanic (NH) White, 8.6 vs 10.3% (7.6-13.1%) NH Black, and 5.8 vs 5.1% (3.5-6.8%) NH Asian. In terms of lifestyle characteristics for PF2 vs NHANES, 58.9 vs 29.2% (25.8-32.7%) had at least a bachelor’s degree, 74.8 vs 63.8% (60.6-67.0%) were married/living with a partner, 69.3 vs 53.8% (50.9-56.7%) had never smoked, 66.5 vs 70.4% (68.0-72.8%) were overweight/obese, and 24.2 vs 28.4% (26.4-30.3%) reported never using alcohol. PF2 enrolled a diverse ppt population that is reasonably reflective of the demographics of the US population aged ≥50 y. As is typical for clinical trials, a higher percentage of PF2 vs NHANES ppts reported lifestyle characteristics associated with better health. As the study population largely reflects the MCED test intended-use population, safety and performance results from PF2 are expected to reflect real-world clinical experience. Citation Format: Shirish Gadgeel, Nima Nabavizadeh, Dax Kurbegov, Charles McDonnell, III, James W. Lillard, Jr., Marc Matrana, Alan Roth, Andrea Johnston, Sami Tahhan, Rami Owera, Matthew Margolis, Anuraag Kansal, Margarita Lopatin, Margaret McCusker, Karthik V. Giridhar. Baseline participant characteristics from PATHFINDER 2, a prospective interventional study of a multi-cancer early detection test in a population setting [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C145.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Importance The Implantable Neurostimulator for the Treatment of Parkinson’s Disease (INTREPID) trial was a randomized, double-blind, sham-controlled study of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD). Objective To evaluate the long-term (5-year) outcomes and safety of STN-DBS for PD. Design, Setting, and Participants This was a prospective, randomized (3:1), 12-week double-blind sham-controlled study at 23 movement disorder centers across the US with an open-label 5-year follow-up. Patients were implanted and followed up with the Vercise DBS system from May 2013 to December 2022. Eligibility required diagnosis of bilateral idiopathic PD with more than 5 years of motor symptoms, more than 6 hours per day of poor motor function, modified Hoehn and Yahr Scale scores higher than 2, Unified Parkinson’s Disease Rating Scale (UPDRS-III) score of 30 or higher (medication-off state), and 33% or higher improvement in UPDRS-III medication-on score. Intervention Bilateral STN-DBS for moderate to advanced PD. Main Outcomes and Measures Primary outcomes included changes in UPDRS and dyskinesia scores, quality-of-life measures, and safety assessments. Exploratory analyses included medication reduction and DBS association with motor signs. Results A total of 313 patients were enrolled with 191 receiving the DBS system, and 137 participants (72%) completed the study. The study population had a mean (SD) age of 60 (7.9) years, with 139 (73%) male participants. Motor function without medication as measured by UPDRS-III improved from a mean (SD) of 42.8 (9.4) to 21.1 (10.6) at year 1 (51%; 95% CI, 49%-53%; P &amp;lt; .001) and 27.6 (11.6) at year 5 (36%; 95% CI, 33%-38%; P &amp;lt; .001). Activities of daily living without medication as measured by UPDRS-II improved from a mean (SD) of 20.6 (6.0) to 12.4 (6.1) at year 1 (41%; 95% CI, 38%-42%; P &amp;lt; .001) and 16.4 (6.5) at year 5 (22%; 95% CI, 18%-23%; P &amp;lt; .001). Dyskinesia scores decreased from 4.0 (5.1) to 1.0 (2.1) at year 1 (75%; 95% CI, 73%-75%; P &amp;lt; .001) and to 1.2 (2.1) at year 5 (70%; 95% CI, 63%-75%; P &amp;lt; .001). The levodopa equivalent dose was reduced by 28% at year 1, remaining stable at year 5 (28%; 95% CI, 26%-31%; P &amp;lt; .001). The most common serious adverse event was infection (9 participants). Ten deaths were reported, none related to the study. Conclusions and Relevance Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant improvement in motor and activities of daily living scores, along with a stable reduction in anti-parkinsonian medication over the 5-year follow-up period.

OBJECTIVE Degenerative lumbar spondylolisthesis is a common cause of back and leg pain influenced by factors like instability, disc degeneration, facet arthropathy, and psychosocial phenotype. Patients’ experience of high-severity pain is complex, with significant implications for surgical planning. The goal of this study was to assess the impact of back pain catastrophizing on long-term outcomes following lumbar spondylolisthesis surgery. METHODS This study uses the Quality Outcomes Database (QOD) lumbar spondylolisthesis dataset and includes prospectively collected data from the 12 highest-enrolling clinical sites participating in the QOD lumbar module. The authors reviewed patients undergoing single-segment surgery for grade 1 degenerative lumbar spondylolisthesis. Severe baseline numeric rating scale for back pain (NRS-BP) scores (≥ 8) were classified as "catastrophizing," and mild to moderate pain scores (< 8) were classified as "non-catastrophizing." Patient-reported outcomes (PROs) were compared for catastrophizing versus non-catastrophizing patients at 60 months. Univariate and multivariate analyses were conducted to assess the impact of catastrophizing on PROs, with multivariate analysis controlling for variables initially reaching a p value < 0.10. RESULTS Of the 608 patients in this analysis, 260 (42.8%) experienced catastrophizing while 348 (57.2%) did not. Catastrophizing patients were significantly younger (59.9 ± 12.2 years vs 63.9 ± 11.7 years, p < 0.001), less often had ≥ 4 years of college education (31.2% vs 42.5%, p = 0.004), and more often used private insurance (58.8% vs 47.7%, p = 0.01). The catastrophizing cohort also had higher rates of depression (24.6% vs 17.0%, p = 0.02) and back pain predominance (45.4% vs 32.2%, p < 0.001). Surgical and perioperative characteristics did not significantly differ between cohorts. Although catastrophizing patients typically reported worse PRO scores at both baseline and 60 months, they demonstrated significantly greater improvement and minimal clinically important difference (MCID) achievement across almost all PROs at 60 months (p < 0.05). However, North American Spine Society (NASS) satisfaction scores at 60 months did not differ significantly between cohorts. Multivariate analysis found that catastrophizing significantly predicted 60-month NRS-BP change (β −1.45, 95% CI −1.81 to −1.09; p < 0.001) and MCID achievement (OR 1.98, 95% CI 1.52–2.58; p < 0.001) but not mean NRS-BP score or other metrics, including NASS satisfaction. CONCLUSIONS Despite presenting with worse baseline symptoms, patients with pain catastrophizing experienced substantial and clinically meaningful improvement following surgery for degenerative lumbar spondylolisthesis. Patient satisfaction was comparable between cohorts, reflecting a nuanced balance between greater absolute improvement and persistence of residual symptoms. These findings underscore that catastrophizing should not be viewed as a barrier to surgical success, while pointing to the need for proactive expectation setting and shared decision-making.

The NCCN Guidelines for Biliary Tract Cancers (BTCs) provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts is convened at least once annually to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. This manuscript focuses on the adjuvant chemotherapy and chemoradiation treatment options for BTCs as well as the systemic treatment recommendations for patients with advanced BTCs.

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of NSCLC. These NCCN Guidelines Insights discuss recent updates to the NCCN Guidelines, with a focus on systemic therapy options for the treatment of patients with nonmetastatic NSCLC and the corresponding molecular testing considerations.