Citations

Abstract Purpose: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded Early Detection Research Network–defined phase II biomarker bakeoff study of blood-based biomarker panels. The aims were to evaluate panel performance, to compare the panels’ performance with that of cancer antigen 19-9 (CA19-9) alone, and to evaluate the performance of new combinations of the individual biomarkers. Experimental Design: Ten biomarkers representing eight biomarker panels and CA19-9 were evaluated using plasma, serum, and germline DNA from 140 stage I to IV pancreatic ductal adenocarcinoma (PDAC) cases and 140 controls from three tertiary care institutions, with controls frequency matched to cases on age and sex. LASSO regression was employed to explore new biomarker combinations. The primary metric was area under the receiver operating characteristic curve (AUC). Results: The study population was 51% female, with median age 67.3 (minimum: 45, maximum: 90) years. Biomarker panel AUCs ranged from 89.9 to 96.3; the AUC for serum CA19-9 alone was 91.7 [95% confidence interval (CI), 87.8–95.6]. Two panels had significantly higher AUCs than serum CA19-9 alone, the CA19-9/FUT2/3 panel (AUC = 96.3, P = 0.002), and the tissue factor pathway inhibitor/tenascin C (TFPI/TNC-FNIII-C) panel (AUC = 95, P = 0.01). Exploratory models to recombine biomarkers retained all but two biomarkers [optimism-corrected AUC = 96.4 (94–98.9)]. Conclusions: The CA19-9/FUT2/3 panel was the best performing panel in this biomarker bakeoff. Its evaluation in larger studies is warranted. Biomarker bakeoffs are an effective strategy for comparing the performance of promising biomarkers for pancreatic cancer early detection, and the PCDC is well poised to conduct such studies. Recommendations for performing such studies are provided.

PURPOSE To compare mortality risk among long-term survivors of high-grade serous ovarian cancer (HGSOC) with that of the general US population and to examine how mortality and recurrence trends have evolved under changing treatment approaches. MATERIALS AND METHODS This is a retrospective cohort study including patients with histologically confirmed HGSOC treated at a single referral cancer center from 1991 to 2022. Mortality risk, expressed as standardized mortality ratios (SMRs, ratio of observed deaths in the study population to expected deaths in an age-matched US population), was assessed at diagnosis and yearly on patients without events (disease persistence, recurrence, or death from any cause). RESULTS A total of 2,074 consecutive patients were included. The median follow-up was 12.5 years (IQR, 11.7-13.8). Most patients were stage III (1,396, 69.2%), 1,299 (62.8%) underwent primary cytoreductive surgery, and 1,688 (87.4%) received platinum-taxane as first-line therapy. At diagnosis, the mortality rate was 7.40 times higher than that in the general population (95% CI, 7.04 to 7.77). By 7 event-free years, the 95% CI for the SMR included 1 for the first time, and at 10 years, the SMR was 1.05 (95% CI, 0.72 to 1.49), indicating no statistically significant excess mortality compared with the general population. In those event-free at 10 years, the 5-year cumulative incidence of ovarian cancer–related deaths (8.2% [95% CI, 4.2 to 16.0]) was comparable with that of non–ovarian cancer–related deaths (6.3% [95% CI, 2.9 to 13.8]). CONCLUSION In this cohort, mortality risk steadily declined for patients who remained event-free, approaching that of the general population by 7 years after diagnosis. These results emphasize the importance of individualized, long-term follow-up to address both recurrence risk and survivorship needs.

INTRODUCTION: Chronic gastrointestinal (GI) conditions, including irritable bowel syndrome and other disorders of gut-brain interaction, are prevalent and costly, and fragmented care contributes to suboptimal outcomes. Virtual and multidisciplinary care models may improve outcomes. Objectives: We aimed to (i) characterize patients receiving virtual GI care, (ii) report patient engagement with and patient-reported outcomes after virtual multidisciplinary care, and (iii) report healthcare utilization and costs from a payer perspective among patients vs propensity score-matched controls identified from claims data. METHODS: We collected descriptive data on patient demographics, clinic provider visits, symptoms, and patient-reported outcomes from 3/2021 to 9/2022. To evaluate healthcare utilization and costs, we conducted difference-in-difference analyses using claims data compared with a propensity score-matched control group. RESULTS: Among 234 patients (71% women, mean age 45.4 ± 13.2 years), 51% received a new GI diagnosis, predominately disorders of gut-brain interaction (63%). Engagement criteria were met by 80% (n = 187), who completed a mean of 10 visits and median time-to-first appointment of 6 days. Dietitians (93%), psychologists (76%), and health coaches (64%) were frequently used. Engaged patients exhibited significant improvements from preclinic to postclinic in irritable bowel syndrome severity (226.7–145.6), symptom control (20.2%–86.6%), quality-of-life dysphoria (27.5–32.8), missed workdays (1.0–0.7), and satisfaction (37.4%–96.3%) (all P < 0.05). Compared with matched controls, a significantly smaller percent of patients had imaging (15% vs 44%; P < 0.0001) and GI-related emergency department visits (4% vs 10%; P = 0.0028), which contributed to reductions in GI-related costs ($443 per member per month; P = 0.047) and all-cause costs ($676 per member per month; P = 0.043), equating to annualized savings of $5,316 and $8,112, respectively. DISCUSSION: Virtual multidisciplinary GI care was associated with high engagement, improved clinical outcomes, and reduced healthcare utilization and costs.

Abstract AI-powered pathology foundation models provide general-purpose representations of histopathological images by encoding image tiles into numerical embeddings. However, these embeddings are not directly interpretable in biological or clinical terms and must be translated into biologically meaningful features, such as cell-type composition or gene expression, to enable downstream clinical applications. To bridge this gap, we developed STpath, a framework that integrates histopathology image embeddings derived from existing pathology foundation models with matched, spatially resolved transcriptomics data. STpath consists of cancer-specific XGBoost models trained to infer cell-type compositions and gene expression from histopathology image tiles. We evaluated STpath in colorectal and breast cancer datasets and showed that it provides accurate estimates of the composition of major cell types and the expression of a subset of genes, with further performance gains achieved by combining embeddings from multiple foundation models. Finally, we demonstrated that STpath inferred features that can be used in downstream studies to evaluate their associations with clinical outcomes.

Background: ASCO recommends extended venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) following cancer surgery. However, these recommendations were based on trials using routine venography, which detects asymptomatic VTEs, and real-life efficacy is not well studied. We aimed to assess the association of extended VTE prophylaxis with the incidence of clinically significant VTE after elective cancer surgery. Patients and Methods: In this retrospective, population-based cohort study, we identified patients who underwent surgical resection for lung, breast, esophageal, gastric, pancreas, and colon cancer from 2010 to 2017 using the SEER–Medicare linked dataset. Patients were divided into 1 of 2 main groups for comparative analyses: those who received extended VTE prophylaxis after cancer surgery and those who did not. Patients who received extended VTE prophylaxis after cancer surgery were identified as those prescribed prophylactic doses of LMWH or a DOAC within 7 days of discharge, as captured in Medicare Part D files. Results: A total of 113,739 Medicare beneficiaries were identified, of whom 1,570 (1.4%) received extended VTE prophylaxis. There was a year-over-year increase in the use of extended VTE prophylaxis during the study period, rising from 0.6% in 2010 to 3.3% in 2017. The overall incidence of VTE was 1.6% at 1 month, 4.3% at 6 months, 5.7% at 12 months, with significant differences observed across cancer types ( P <.001). However, patients who received extended VTE prophylaxis had a higher 1-year cumulative incidence of postoperative VTE compared with those who did not (11.4% vs 5.3%; P <.001), an association that was consistent across cancer sites. In adjusted analyses, extended VTE prophylaxis was independently associated with an increased risk of VTE (hazard ratio, 1.6; 95% CI, 1.3–2.0; P <.001). Extended prophylaxis was also associated with a higher 1-year incidence of bleeding events compared with patients who did not receive prophylaxis (12.0% vs 8.5%; P <.001). Conclusions: The utilization of extended VTE prophylaxis after cancer surgery remains low, although it has increased every year. Paradoxically, patients who received extended VTE prophylaxis had higher incidences of clinically significant VTE and bleeding compared with those who did not, likely reflecting patient selection and surveillance bias after surgery. In light of these findings, national guidelines recommending postoperative extended VTE prophylaxis, and its use as a surrogate for quality of care, should continue to be re-examined.

BACKGROUND Bertolotti syndrome is an underrecognized cause of chronic low back pain. Back pain generated from Bertolotti syndrome is believed to result from altered weight dissipation mechanics and/or instability of the pseudoarticulation, while local nerve root compression may result in radiculopathy. Here, the authors describe the findings of a patient with treatment-refractory low back pain found to have a cystic lesion arising from a Bertolotti joint causing L5 nerve root compression. To their knowledge, this has not been previously described in the literature. OBSERVATIONS Despite early recognition of Bertolotti syndrome, the patient’s back pain remained resistant to many years of both conservative and surgical management. The novel finding of a cyst arising from the pseudoarticulation complicated the management. The patient is scheduled to undergo further surgery this year. LESSONS This case highlights a pseudocyst associated with a Bertolotti joint. The cyst introduced additional clinical uncertainty to what is already an uncommon and difficult to treat condition. Resection of the Bertolotti joint failed to improve the patient’s symptoms. Postoperatively, a complex hemorrhagic pseudocyst was seen on imaging, possibly due to the pseudoarticulation with persistent motion. Ongoing efforts to characterize Bertolotti syndrome and its associated imaging findings are necessary to better optimize management strategies in these patients. https://thejns.org/doi/10.3171/CASE25948

Chimeric antigen receptor (CAR)-based therapies have become an integral part of modern cancer care, delivering durable responses in patients with otherwise refractory hematologic malignancies. As their use has expanded, it has become increasingly clear that these immune-based treatments exert important effects on the cardiovascular system. Rather than reflecting isolated cardiac injury, CAR-associated cardiovascular complications arise from a broader inflammatory process in which immune activation, cytokine release, endothelial dysfunction, and myocardial stress are closely interconnected. Pro-inflammatory mediators such as interleukin-6, interleukin-1β, tumor necrosis factor-α, and interferon-γ play central roles in shaping these responses, particularly during cytokine release syndrome. From a clinical perspective, cardiovascular manifestations often include hypotension, arrhythmias, and transient reductions in left ventricular function, with more severe presentations occurring in patients who develop high-grade inflammatory toxicity. At the same time, advances in immune engineering are reshaping how these platforms are viewed, extending their relevance beyond toxicity alone. Preclinical studies now suggest that CAR-based approaches may be adapted to modulate cardiac fibrosis and promote myocardial repair, highlighting a potential shift from purely oncologic applications toward broader cardiovascular benefit. Placing these developments within a cardio-oncology framework emphasizes the need for careful cardiovascular assessment, longitudinal monitoring, and close collaboration between specialties.

ABSTRACT Background Patients with gastroparesis (Gp) can have a variety of symptoms. Apart from use of prokinetics, symptomatic therapies for the predominant symptom (PrS) are used. Aims (1) To classify Gp patients based on their PrS; (2) To determine differences in Gp symptoms, gastric emptying (GE), quality of life (QOL), treatments, and symptom improvement among Gp patients with different PrS. Methods Gp patients were enrolled in a multicenter registry and followed for 96‐weeks. Patients recorded their PrS and completed questionnaires assessing symptoms and QOL at enrollment and at follow up visits. Results Of 1013 Gp patients (361 diabetic, 607 idiopathic, 45 post‐fundoplication), the PrS were nausea (31%), vomiting (20%), abdominal pain (20%), bloating (9%), fullness (4%), GERD (4%), constipation (3%). Abdominal pain was more often a PrS in idiopathics, whereas vomiting was more often a PrS in diabetics. QOL scores were lower in the abdominal pain PrS group. PrS was associated with greater use of directed symptomatic treatment (antiemetic agents and gastric electrical stimulation for nausea and vomiting, prokinetic agents for vomiting and fullness, and constipation medications for constipation). Of 555 patients followed over 48 weeks, GCSI improved by ≥ 1 in 26% overall, more often in patients with initial PrS of nausea (32%) and bloating (35%) and less often for initial PrS of fullness (13%) or abdominal pain (15%). Conclusions In Gp patients, the most common PrS were nausea, vomiting, and abdominal pain. PrS is associated with QOL, treatments utilized, and patient outcomes. Thus, the PrS of a patient with Gp provides useful information about their present condition and future outcome.

Abstract Background Genetic testing is increasingly used in presurgical evaluation, but the yield of resection across germline genetic epilepsies remains uncertain. Methods We conducted a systematic review of MEDLINE (PubMed) and Scopus and added cases from three institutional cohorts and the Pediatric Epilepsy Research Consortium (PERC) databases, including individuals with pathogenic/likely pathogenic germline variants besides tuberous sclerosis and neurofibromatosis who underwent resection or laser ablation. Etiologies were grouped into biologically informed categories (GATORopathies, vascular, overgrowth, CNVs, channelopathies, synaptopathies, other). Primary outcome was seizure freedom (Engel I) at last follow-up. Group comparisons used Fisher’s exact and Kruskal–Wallis tests (α=0.05; Bonferroni when applicable). Prespecified sensitivity analyses stratified by lesional status, excluded GATORopathies, and restricted to literature-only cases. Results We included 223 literature cases (64 studies), 35 institutional cases, and 11 PERC cases (n=269). Median follow-up was 24 months (IQR 12–48.0). Seizure freedom was achieved in: vascular disorders 14/19 (73.6%), GATORopathies 79/120 (67.5%), CNVs 18/31 (66.7%), overgrowth 7/13 (53.8%), other 16/25 (41.7%), channelopathies 13/43 (33.3%), and synaptopathies 4/18 (22.2%) (overall p<0.001). Among cases with known imaging, 208/253 (82.2%) had epileptogenic MRI lesions, including 64% of channelopathies and 80% of the synaptopathies. In univariate contrasts (each category vs all others), odds of seizure freedom were higher for vascular disorders (2.66-fold, 95% CI 0.87–9.72) and GATORopathies (2.46-fold, 95% CI 1.46–4.18), and lower for synaptopathies (∼4.2-fold lower, OR 0.24, 95% CI 0.05– 0.78) and channelopathies (∼4.5-fold lower, OR 0.22, 95% CI 0.09–0.48). Direction and magnitude were consistent across prespecified sensitivity analyses (lesional-only, literature-only, exclusion of GATORopathies). Conclusions Resective surgeries can be effective in germline genetic epilepsies, but outcomes vary by pathway. Disorders with discrete, lesional substrates (GATORopathies, vascular) show the highest likelihood of seizure freedom, whereas channelopathies and synaptopathies, despite the presence of MRI lesions, have substantially lower yields even in lesional cases. Prospective, genotype-aware surgical registries with standardized reporting (EEG, imaging, pathology) and time-to-event outcomes are needed to refine the selection of surgical candidates and quantify seizure and non-seizure-related outcomes.