Citations

Abstract Clinical interventions and neuroimaging in the subcortex require anatomical definitions that exceed the resolution and anatomical detail of currently available deformable brain atlases. Here, we introduce a high-resolution human brain atlas comprising 95 manually segmented grey and white matter structures as well as 82 white matter tracts compiled from a multitude of resources including ex-vivo MRI, histology, fibre dissections, and neuroanatomy textbooks. The atlas is defined at an isotropic resolution of 100 μm and can be precisely deformed to individual subject brain anatomy. By providing precise definitions of both grey and white matter structures within and around the basal ganglia, thalamus, subthalamus, midbrain and cerebellum, the atlas provides a foundational resource for stereotactic surgery and subcortical brain imaging research, as well as for development of next-generation neuromodulation strategies.

Importance Patients with recurrent prostate cancer after previous radiotherapy typically have poor survival. Those with recurrences prostate confined might be suitable for salvage focal therapy (sFT) or salvage radical prostatectomy (sRP). sFT may offer good cancer control with comparatively less toxic effects, but outcomes beyond 5 years have not been reported, and no study has compared sFT to sRP. Objective To compare cancer control and perioperative complications among patients after sFT vs sRP. Design, Setting, and Participants In this international, multicenter cohort study of matched comparison data, patients undergoing sFT were derived from the prospective UK HIFU (high-intensity focused ultrasound) Evaluation and Treatment and International Cryotherapy Evaluation registries (9 centers; 2006-2024) and the prospective UK Focal Recurrent Assessment and Salvage Treatment cohort study (6 centers; 2014-2018). Patients undergoing sRP were derived from an international retrospective registry (12 centers in 8 countries; 2000-2021). Patients with biopsy-confirmed, localized recurrent prostate cancer postradiotherapy, either external beam radiotherapy, brachytherapy, or both, were included. Data were analyzed from March to July 2025. Exposures sFT using HIFU or cryotherapy vs sRP. Main Outcomes and Measures The primary outcome was cancer-specific survival up to 10 years. Secondary outcomes were overall survival, any perioperative complications (Clavien-Dindo grades 1-5), and major perioperative complications (Clavien-Dindo grades 3-5). Comparisons were made on matched patients following 1:1 cardinality matching within individual multiply-imputed datasets. Matching variables used were radiotherapeutic treatment, years between primary and salvage treatments, European Association of Urology recurrence risk group, and presalvage age, prostate-specific antigen, prostate volume, grade group, T stage, and androgen-deprivation therapy use. Results A total of 923 patients were eligible for matching (419 undergoing sFT and 504 undergoing sRP). Of the patients undergoing sFT, 325 (77.6%) underwent HIFU and the remainder cryotherapy, with 241 (57.5%) treated with quadrant ablation. Of patients treated with sRP, 376 (74.6%) underwent open surgery and the remainder robot-assisted surgery. For sFT vs sRP, 10-year cancer-specific survival was 92% (95% CI, 86%-98%) vs 99% (95% CI, 97%-100%), with no statistically significant difference (restricted mean time lost, −0.09 years; 95% CI, −0.22 to 0.03 years; P = .15; subdistribution hazard ratio, 0.45; 95% CI, 0.05-4.00; P = .47). There was no statistically significant difference in 10-year overall survival (restricted mean survival time, −0.13 years; 95% CI, −0.86 to 0.60 years; P = .72). Undergoing sRP was associated with statistically significant higher odds of any complication (adjusted odds ratio, 24.20; 95% CI, 12.94-45.27; P < .001) and major complication (adjusted odds ratio, 9.31; 95% CI, 3.42-25.36; P < .001). Conclusions and Relevance In this cohort study, sFT and sRP were effective for treating localized radiorecurrent prostate cancer, while sFT was associated with fewer perioperative complications. sFT may provide a favorable therapeutic ratio for many patients with localized radiorecurrent prostate cancer.

ABSTRACT Background Patients with gastric dysmotility exhibit abnormal transit and reduced contractility, for which quantification is limited with current methodologies. The Atmo Capsule is a wireless motility capsule that measures regional gastrointestinal transit. We tested its technical capabilities to evaluate gastric contractility by detecting changes in capsule acceleration during transit. Methods Data from 91 healthy controls and 182 patients with suspected dysmotility who ingested the Atmo Capsule following a standardized protocol were included. Gastric emptying times (GET) ≥ 5 h were considered delayed. Contraction frequencies (cycles per minute [cpm]) and amplitudes (as arbitrary units [au]) were identified following Fast Fourier Transformation of accelerometer data using 5‐min windows and were assessed in 30‐min windows post‐ingestion (early gastric phase) and before gastric emptying (late gastric phase). Data were compared via ANOVA, using Bonferroni corrections, between healthy controls, patients with normal gastric emptying, and patients with delayed gastric emptying. Key Results Gastric emptying was delayed in 53/182 (29%) patients. Three cpm contraction frequencies were identified across both gastric phases in controls and patients. Contraction amplitudes did not differ between groups in the early gastric phase. In the late phase, mean amplitudes were lower in patients with delayed gastric emptying (6.4 au) compared with subjects with normal gastric emptying (controls, 9.7 au, p < 0.0001; patients, 8.6 au, p < 0.0001). Conclusions & Inference The Atmo Capsule enables precise quantification of gastric contraction profiles, permitting differentiation of normal from pathological motor patterns. Findings of this technical assessment support its potential for evaluating gastric physiology and detecting pathophysiological patterns of gastric dysmotility.

Abstract The phase 1/2 Intergroup study E4412 investigated checkpoint blockade with nivolumab (Nivo) and ipilimumab (Ipi) combined with the CD30 targeting antibody-drug conjugate brentuximab vedotin (BV) in relapsed/refractory classic Hodgkin lymphoma. A total of 147 patients aged ≥12 years were randomized between BV/Nivo and BV/Ipi/Nivo; 132 patients were included in the primary efficacy analysis. The complete response (CR) rate, was 64.7% (52.2, 75.9) for BV/Nivo and 70.3% (57.6, 81.1) for BV/Ipi/Nivo (1-sided P = .29). The median survival follow-up was 38.0 months (interquartile range, 32.6-48.1). Progression-free survival (PFS) did not significantly differ between the 2 arms (hazard ratio [HR], 0.78, confidence interval [CI], 0.39-1.57; 1-sided P = .24). Treatment-related grade 3+ toxicities in the adult cohort, excluding rash, were similar between both arms (38.5% BV/Nivo and 39.3% BV/Ipi/Nivo); there was a higher frequency of grade 3 rash with BV/Ipi/Nivo (24.6%) compared with BV/Nivo (9.2%). We compared PFS by stem cell transplantation (SCT) status in a planned before hoc comparison; 58 patients received SCT, and 36-month PFS (from SCT) was &gt;90% for both arms. Sixty-six patients were progression free after the first scan and did not undergo SCT. The 36-month PFS was 73.0% (54.5, 85.0) for BV/Ipi/Nivo compared with 45.8% (26.3, 63.4) for BV/Nivo (HR, 0.45; CI, 0.19-1.08; 1-sided P = .03). The study did not meet its primary end point of superior CR rate for the triplet, but it supports the use of checkpoint antibody-drug conjugate induction prior to auto SCT, and there is an intriguing signal of disease control for patients wishing to defer or avoid SCT with the triplet of BV/Ipi/Nivo. This trial was registered at www.clinicaltrials.gov as NCT01896999.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

Background: Upfront resectable pancreatic ductal adenocarcinoma (PDAC) is defined by the NCCN as disease with ≤180° portomesenteric vein (PMV) abutment. However, the clinical significance of PMV abutment in this cohort remains unexplored, and we sought to investigate its impact. Methods: This multi-institutional study included patients who underwent pancreatoduodenectomy (PD) for upfront resectable PDAC from 2002 to 2023. Patients with PDAC with ≤180° PMV abutment were compared with those without. Overall survival (OS) was compared and stratified based on whether patients underwent upfront surgery or neoadjuvant therapy (NAT). Results: Among 1,446 patients included, 521 (36.0%) had PMV abutment. Median OS for patients with PMV abutment was 28.8 months compared with 31.2 months for those without ( P =.17). In a stratified analysis of patients who underwent upfront surgery, patients with PMV abutment had worse OS (19.2 vs 27.6 months; P <.05) and lower R0 resection rates (63.1% vs 87.2%; P <.05) compared with those without. However, in patients who underwent NAT, this difference in R0 resection rate was not observed (91.4% vs 94.0%, respectively; P =.27). Furthermore, there was no significant difference in median OS with NAT (42.5 vs 51.6 months, respectively; P =.48). Conclusions: In this largest cohort to date of patients with upfront resectable PDAC, PMV abutment was associated with worse OS compared with no PMV abutment when an upfront resection strategy was used. The use of NAT in patients with PMV abutment mitigated this survival difference with increased R0 resection rates. These findings suggest that patients with upfront resectable PDAC with PMV abutment benefit from a NAT approach for optimal survival outcomes, and that the current criteria guidelines need to be redefined.

Background: Aggressive non-Hodgkin lymphoma (aNHL) commonly occurs in older adults. However, geriatric assessments (GAs), which are associated with both survival and treatment-related toxicity, are infrequently performed due to logistical constraints. In this study, we examined how the brief, self-reported Vulnerable Elders Survey-13 (VES-13) screening tool and a comprehensive GA relate to clinical outcomes in this population. Methods: We conducted a longitudinal study of 105 adults aged ≥65 years who were initiating upfront chemoimmunotherapy for aNHL at 2 academic medical centers and their community affiliates between September 2020 and January 2023. Baseline frailty was evaluated using the Fondazione Italiana Linfomi (FIL) GA, which classifies patients as fit, unfit, or frail. The VES-13 was assessed both continuously and by categorizing patients as vulnerable (score ≥3). Using logistic regression controlling for covariates, we examined the association of VES-13 with grade ≥3 nonhematologic toxicity (toxicity), unplanned hospitalization within 6 months of treatment initiation, decline in quality of life (QoL) 1 year after therapy initiation, and death within 1 year of treatment initiation. In addition, we calculated the sensitivity and specificity of both the VES-13 and the FIL GA in identifying patients at risk for these outcomes. Results: The median patient age was 73 years (range, 64–99 years), with 42% aged ≥75 years. GA classified 40% of patients as fit, 10% as unfit, and 51% as frail, while 46% of patients had a VES-13 score ≥3, indicating vulnerability. VES-13 score was significantly associated with toxicity (odds ratio [OR], 1.18; P =.026), unplanned hospitalization (OR, 1.16; P =.043), QoL decline at 1 year (OR, 1.22; P =.027), and death within 1 year (OR, 1.49; P =.010). Using the VES-13 to define vulnerability (score ≥3), sensitivity and specificity were 59% and 61% for predicting toxicity, and 100% and 59% for predicting death within 1 year, respectively. FIL GA frailty had a sensitivity of 63% and specificity of 56% for predicting toxicity, and 100% sensitivity and 54% specificity for predicting death within 1 year. Conclusions: We found that VES-13 score was associated with survival, toxicity, health care utilization, and QoL decline, demonstrating similar sensitivity and specificity to the FIL GA. These findings underscore the potential utility of VES-13 as a screening instrument to identify older patients with aNHL at risk for adverse clinical outcomes.