Recent ucla_radonc items

Therapeutic efficacy of dendritic cell vaccination in a novel syngeneic mouse model of diffuse hemispheric glioma, H3 G34-mutant

Wed, 22 Apr 2026 00:00:00 +0000

PurposeThe prognosis for pediatric high-grade gliomas associated with mutations in the H3-3A gene is very poor. To investigate whether tumor lysate-pulsed dendritic cells (DC) together with checkpoint blockade might be a potential treatment modality for diffuse hemispheric glioma H3 G34-mutant (DHG), we have developed a novel syngeneic mouse model.MethodsWe used the RCAS/tv-A system to target the expression of H3G34R and PDGFβ and knock out p53 in neural progenitors in C57BL/6 neonatal mice. Three independent cell lines were obtained that expressed transcripts associated with oligodendrocyte and interneuron lineages. Lethal tumor developed following intracranial injection.ResultsTwo cycles of DC vaccination with PD-1 blockade decreased tumor burden and increased survival. In treatment resistant tumors we found higher expression of several genes involved in remodeling the extracellular matrix compared with tumors from untreated animals, suggesting a causal link to resistance to...

Adversarial AI reveals mechanisms and treatments for disorders of consciousness

Tue, 21 Apr 2026 00:00:00 +0000

Understanding disorders of consciousness (DOC) remains one of the most challenging problems in neuroscience, hindered by the lack of experimental models for probing mechanisms or testing interventions. Here, to address this, we introduce a generative adversarial artificial intelligence (AI) framework that pits deep neural networks—trained to detect consciousness across more than 680,000 ten-second neuroelectrophysiology samples and validated on 565 patients, healthy volunteers and animals—against interpretable, machine learning-driven neural field models. This adversarial architecture produces biologically realistic simulations of both conscious and comatose brains that recapitulate empirical neurophysiological features across humans, monkeys, rats and bats. Without explicit programming, the AI model retrodicts known DOC responses to brain stimulation and generates testable predictions about the mechanisms of unconsciousness. Two such predictions are validated here: selective...

Vaccine therapy for pediatric high-grade glioma: current landscape, challenges, and future directions

Mon, 16 Feb 2026 00:00:00 +0000

BackgroundPediatric high-grade gliomas (pHGG) are among the most aggressive childhood brain tumors, with limited treatment options and poor prognosis. Vaccine-based immunotherapy offers a promising strategy by leveraging tumor-specific or associated antigens to stimulate durable anti-tumor immune responses with minimal toxicity.DiscussionThis review outlines the scientific rationale for vaccine therapies in pHGG, detailing key targets such as glioma-associated antigens (EphA2, IL-13Rα2, survivin), driver mutation–derived neoantigens (H3.3K27M, TP53, IDH1), and viral antigens (CMV pp65). We evaluate current vaccine platforms, including peptide vaccines, dendritic cell vaccines, mRNA-based vaccines, and neoantigen-personalized approaches, highlighting early-phase clinical trial results that demonstrate safety and immunogenicity. Despite encouraging preliminary data, several challenges hinder clinical translation, including the distinct immune environment in the central nervous system,...

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons of the Transcriptomic Landscapes Across Mouse Models.

Wed, 10 Sep 2025 00:00:00 +0000

Lung cancer, the leading cause of cancer mortality, exhibits diverse histologic subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMM), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, enhancing the fidelity of the genetic landscape it depicts. The LCAMGDB aligned 859 tumors from GEMMs with human lung cancer mutations, enabling comparative analysis and revealing a pressing need to broaden the diversity of genetic aberrations modeled in the GEMMs....

Stereotactic radiosurgery for brain metastases: evolving practice patterns from the national cancer database (2004–2020)

Wed, 10 Sep 2025 00:00:00 +0000

PurposeStereotactic radiosurgery (SRS) offers less neurotoxicity and comparable survival to whole-brain radiation therapy (WBRT) for brain metastases (BM). Current SRS practice patterns are understudied. We examined national trends in SRS and WBRT utilization.MethodsWe queried the National Cancer Database for patients with BM from twelve cancers (≥ 18 years; diagnosed 2004–2020) treated with radiotherapy. Patients were grouped by first-course radiotherapy modality (SRS:1–5 fractions; WBRT:5–15 fractions). Multivariable logistic regression assessed SRS predictors, adjusting for sociodemographic and clinical variables. A race*diagnosis year interaction evaluated temporal trends. Difference-in-differences analysis assessed Medicaid expansion impact.ResultsOf 89,984 patients, 24,174 (27%) received SRS. SRS utilization rose from 8 to 54% between 2004 and 2020 (P < 0.001). SRS was more likely in patients diagnosed in recent years (aOR = 3.85 [95% CI = 3.70–4.01]), who received prior...

Impact of postoperative fluorodeoxyglucose positron emission tomography/computed tomography on adjuvant head and neck cancer treatment

Wed, 27 Aug 2025 00:00:00 +0000

BACKGROUND: Residual or recurrent cancer after surgery but prior to adjuvant therapy occurs in a proportion of patients with head and neck cancer and may warrant treatment changes. 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) may help to identify residual or recurrent disease but is not routinely obtained. We evaluated the relevance of postoperative FDG-PET/CT in this clinical context. METHODS: This single-institution, retrospective study identified patients with head and neck cancer who underwent definitive surgery between January 1, 2013, and April 1, 2023, and received a postoperative FDG-PET/CT prior to adjuvant treatment. We measured the rates of management changes resulting from postoperative FDG-PET/CT findings and the association between having a postoperative FDG-PET/CT which resulted in a management change and oncologic outcomes with selected multivariable competing-risks and proportional hazards regressions. RESULTS: Of 150 patients,...

Ray-Bundle Based X-ray Representation and Reconstruction: an Alternative to Classic Tomography on Voxelized Volumes

Wed, 20 Aug 2025 00:00:00 +0000

Tomography recovers internal volume from projection measurements. Formulated as inverse problems, classic computed tomography generally reconstructs attenuation property in a preset cartesian grid coordinate. While this is intuitive and convenient for digital display, such discretization leads to forward-backward projection inconsistency, and discrepancy between digital and effective resolution. We take a different perspective by considering the image volume as continuous and modelling forward projection as a hybrid continuous-to-discrete mapping from volume to detector elements, which we call "ray bundles". The ray bundle can be regarded as an unconventional heterogenous coordinate. Projections are modeled as line integrations along ray bundles in the continuous volume space and approximated by numerical integration using customized sample points. This modeling approach is conveniently supported with an implicit neural representation approach. By representing the volume as a...

An ultra-high performance parallel (UHPP) framework for complex 4π radiotherapy planning

Thu, 14 Aug 2025 00:00:00 +0000

Purpose. In radiotherapy, dose distribution conformity and compactness are critical to patient outcomes. Advanced techniques like4πradiotherapy leverage non-coplanar beams for superior dosimetry by exploring additional degrees of freedom. However,4πplanning is computationally intensive due to large dose-loading matrices for candidate beams. This work presents an ultra-high performance parallel (UHPP) framework to accelerate high-dimensional treatment planning.Methods. For dose calculation, we developed: (1) a two-step total energy released per unit mass (TERMA) computation module calculating the TERMA array once per beam, enabling reuse across convolution directions; (2) a synchronized dose calculation module based on collapsed-cone convolution superposition (CCCS), arranging rays in dedicated sequences to preserve thread efficiency and minimize memory access; (3) a scattering-based coordinate transformation mapping dose from beamlet to patient Cartesian coordinates,...

Cold atmospheric plasma effectively kills chordoma cells through induction of intracellular reactive oxygen species

Wed, 30 Jul 2025 00:00:00 +0000

Chordomas remain one of the most difficult-to-treat of skull base tumors. The best chance of survival and cure to date is with en bloc radical surgical resection, followed by adjuvant radiotherapy. Oftentimes, tumor infiltration into functionally critical, or difficult-to-access areas, precludes optimal resection. The median overall survival for these tumors is 116 months. Cold atmospheric plasma (CAP) is generated by applying a high voltage electric field to helium or argon feed gases, resulting in reactive atmospheric species. Over the past decade, CAP has been applied experimentally in a number of oncologic conditions and has demonstrated anti-tumor effects both in vitro and in vivo. Additionally, CAP has been shown to increase cancer cells’ sensitivity to radiation and could therefore be a useful tool in improving chordoma recurrence rates as an intraoperative adjuvant therapy to the current standard of care. To date, there are no studies in the literature examining the efficacy...

Cerebrovascular longitudinal atlas: Changes in cerebral arteries in unruptured intracranial aneurysm patients followed with MRA

Fri, 11 Apr 2025 00:00:00 +0000

BACKGROUND: Patterns of change in cerebrovascular (CV) morphology associated with aging are highly relevant to the incidence and progression of CV disease, particularly stroke. Intracranial aneurysms (IA), a leading cause of hemorrhagic stroke, are linked with factors such as blood flow, arterial stiffness, and inflammation that may also drive other changes in CV morphology. We worked with a cohort of longitudinally-imaged IA patients to construct the first longitudinal atlas of CV morphology and studied its relationship with disease. METHODS: 110 IA patients, ranging from 19 to 84 years old at IA detection, were monitored using 3D magnetic resonance angiography (MRA) for a mean of 6.11 (2.60) years with 3.6 (1.3) scans per patient. Using 405 image studies, we applied a machine learning diffeomorphic shape analysis to construct a longitudinal atlas of the cerebral arteries which defined a general trajectory of CV morphological change vs. age. This was paired with a centerline...

ECG‐free cine MRI with data‐driven clustering of cardiac motion for quantification of ventricular function

Wed, 9 Apr 2025 00:00:00 +0000

BACKGROUND: Despite the widespread use of cine MRI for evaluation of cardiac function, existing real-time methods do not easily enable quantification of ventricular function. Moreover, segmented cine MRI assumes periodicity of cardiac motion. We aim to develop a self-gated, cine MRI acquisition scheme with data-driven cluster-based binning of cardiac motion. METHODS: A Cartesian golden-step balanced steady-state free precession sequence with sorted k-space ordering was designed. Image data were acquired with breath-holding. Principal component analysis and k-means clustering were used for binning of cardiac phases. Cluster compactness in the time dimension was assessed using temporal variability, and dispersion in the spatial dimension was assessed using the Caliński-Harabasz index. The proposed and the reference electrocardiogram (ECG)-gated cine methods were compared using a four-point image quality score, SNR and CNR values, and Bland-Altman analyses of ventricular function. RESULTS:...

Cerebellar Vascular Malformation of Unknown Aetiology with Recent COVID-19 Infection

Wed, 9 Apr 2025 00:00:00 +0000

Cerebellar Vascular Malformation of Unknown Aetiology with Recent COVID-19 Infection

Trends in racial and ethnic disparities in the health-related quality of life of older adults with breast cancer: a SEER-MHOS national database study

Mon, 7 Apr 2025 00:00:00 +0000

PurposeTo examine racial and ethnic disparities in Health-Related Quality of Life (HRQOL) in older adults with breast cancer, both pre- and post-diagnosis.MethodsUsing the SEER-MHOS database, we included patients ≥ 65 years old with breast cancer who completed the Health Outcomes Survey within 24 months pre- and post-diagnosis, and who were non-Hispanic White, non-Hispanic Asian or Pacific Islander, non-Hispanic Black or African American, or Hispanic. HRQOL data was measured via the Physical and Mental Component Summary (PCS, MCS). Univariable and multivariable linear regression models were fitted to assess for potential disparities between races and ethnicities.ResultsOn univariable regression models, a numerical drop in mean scores of PCS and MCS was found among all racial/ethnic groups between pre- and post-diagnosis. Among patients in the pre-diagnosis cohort who would be diagnosed with stage IV breast cancer, race was found to be a predictor of PCS with overall significance...

Radiation-induced cellular plasticity primes glioblastoma for forskolin-mediated differentiation

Wed, 2 Apr 2025 00:00:00 +0000

Glioblastoma (GBM) is the deadliest brain cancer in adults, and all patients succumb to the tumor. While surgery followed by chemoradiotherapy delays disease progression, these treatments do not lead to tumor control, and targeted therapies or biologics have failed to further improve survival. Utilizing a transient radiation-induced state of multipotency, we used the adenylcyclase activator forskolin to alter the fate of irradiated glioma cells. The effects of the combined treatment on neuronal marker expression, cell cycle distribution, and proliferation were studied. Gene expression profiling was conducted using bulk RNA-seq. Changes in cell populations were investigated using single-cell RNA-seq. Effects on glioma stem cells (GSCs) were studied in extreme limiting dilution assays, and the effects on median survival were studied in both syngeneic and PDOX mouse models of GBM. The combined treatment induced the expression of neuronal markers in glioma cells, reduced proliferation,...

Metastatic secondary gliosarcoma: patient series

Wed, 2 Apr 2025 00:00:00 +0000

BACKGROUND: Gliosarcoma is a rare and highly malignant cancer of the central nervous system with the ability to metastasize. Secondary gliosarcoma, or the evolution of a spindle cell-predominant tumor after the diagnosis of a World Health Organization grade IV glioblastoma, has also been shown to metastasize. There is little information on metastatic secondary gliosarcoma. OBSERVATIONS: The authors present a series of 7 patients with previously diagnosed glioblastoma presenting with recurrent tumor and associated metastases with repeat tissue diagnosis consistent with gliosarcoma. The authors describe the clinical, imaging, and pathological characteristics in addition to carrying out a systematic review on metastases in secondary gliosarcoma. LESSONS: The present institutional series and the systematic review of the literature show that metastatic secondary gliosarcoma is a highly aggressive disease with a poor prognosis.

Travel Burden of Radiation Therapy in the Philippines

Wed, 2 Apr 2025 00:00:00 +0000

Purpose: Travel burden negatively impacts the stage at diagnosis, treatment, outcome, and quality of life among patients with cancer. Travel burden-quantified as distance, time, and cost of travel-is magnified in low- and middle-income countries like the Philippines, where radiation therapy (RT) resources are lacking and are inequitably distributed. Methods and Materials: We compared Philippine Radiation Oncology Society data and the population census to determine the distribution and density of RT facilities across the country's 17 regions. For distance and travel time, we used the Google Maps route planner to determine the best routes from each province to the nearest private and government RT facility. Travel cost was calculated by multiplying distance by the local price of diesel per liter and the mean fuel economy of passenger vehicles in the Philippines. Results: There are only 54 RT facilities in the Philippines (0.5 per 1 million population). More than a third are in the...

Metabolic differences in breast cancer stem cells and differentiated progeny

Thu, 27 Mar 2025 00:00:00 +0000

In general, tumor cells display a more glycolytic phenotype compared to the corresponding normal tissue. However, it is becoming increasingly clear that tumors are composed of a heterogeneous population of cells. Breast cancers are organized in a hierarchical manner, with the breast cancer stem cells (BCSCs) at the top of the hierarchy. Here, we investigate the metabolic phenotype of BCSCs and their differentiated progeny. In addition, we determine the effect of radiation on the metabolic state of these two cell populations. Luminal, basal, and claudin-low breast cancer cell lines were propagated as mammospheres enriched in BCSCs. Lactate production, glucose consumption, and ATP content were compared with differentiated cultures. A metabolic flux analyzer was used to determine the oxygen consumption, extracellular acidification rates, maximal mitochondria capacity, and mitochondrial proton leak. The effect of radiation treatment of the metabolic phenotype of each cell population...

An implicit neural deformable ray model for limited and sparse view‐based spatiotemporal reconstruction

Wed, 26 Mar 2025 00:00:00 +0000

BACKGROUND: Continuous spatiotemporal volumetric reconstruction is highly valuable, especially in radiation therapy, where tracking and calculating actual exposure during a treatment session is critical. This allows for accurate analysis of treatment outcomes, including patient response and toxicity in relation to delivered doses. However, continuous 4D imaging during radiotherapy is often unavailable due to radiation exposure concerns and hardware limitations. Most setups are limited to acquiring intermittent portal projections or images between treatment beams. PURPOSE: This study addresses the challenge of spatiotemporal reconstruction from limited views by reconstructing patient-specific volume with as low as 20 input views and continuous-time dynamic volumes from only two orthogonal x-ray projections. METHODS: We introduce a novel implicit neural deformable ray (INDeR) model that uses a ray bundle coordinate system, embedding sparse view measurements into an implicit neural...

In-clinic Versus Online Recruitment of Women With a History of Cervical Intraepithelial Neoplasia or Cervical Cancer to a Smoking Cessation Trial: A Post hoc Comparison of Participant Characteristics, Study Retention, and Cessation Outcomes

Thu, 20 Mar 2025 00:00:00 +0000

INTRODUCTION: Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment. AIMS AND METHODS: Participants were recruited from clinics within a university-based NCI-designated cancer center (n = 87) and online nationally via Facebook (n = 115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors. RESULTS: Participants recruited online (vs. in-clinic) had higher educational attainment (p = .01) and health literacy...

Personalized Accelerated ChEmoRadiation (PACER) for Lung Cancer: Protocol for a Bayesian Optimal Phase I/II Trial

Tue, 18 Mar 2025 00:00:00 +0000

INTRODUCTION: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs). METHODS: Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping...

Analysis of Oncology and Radiation Therapy Representation on the National Board of Medical Examiners Official Practice Material for the United States National Standardized Medical Board Examinations

Sat, 1 Mar 2025 00:00:00 +0000

Radiation therapy (RT) is a critical component of multidisciplinary cancer care, but has inconsistent curricular exposure. We characterize the radiation oncology (RO) content on the standardized undergraduate medical examinations by comparing its context and prevalence with other domains in oncology. National Board of Medical Examiners (NBME) self-assessments and sample questions for the United States Medical Licensing Exam (USMLE) Steps 1–3 and NBME clinical science shelf examinations were accessed (n = 3878). Questions were inductively analyzed for content pertaining to oncology and treatment modalities of RT, systemic therapy (ST), and surgical intervention (SI). Questions were coded using USMLE Physician Tasks/Competencies and thematic analysis. Descriptive statistics and analyses using the Kruskal–Wallis test are reported. A total of 337 questions (8.6%) within the USMLE and shelf exams included oncology content, with 101 questions (2.6%) referencing at least one cancer treatment...

A Retrospective Analysis of the First Clinical 5DCT Workflow

Fri, 28 Feb 2025 00:00:00 +0000

BACKGROUND/OBJECTIVES: 5DCT was first proposed in 2005 as a motion-compensated CT simulation approach for radiotherapy treatment planning to avoid sorting artifacts that arise in 4DCT when patients breathe irregularly. Since March 2019, 5DCT has been clinically implemented for routine use at our institution to leverage this technological advantage. The clinical workflow includes a quality assurance report that describes the output of primary workflow steps. This study reports on the challenges and quality of the clinical 5DCT workflow using these quality assurance reports. METHODS: We evaluated all thoracic 5DCT simulation datasets consecutively acquired at our institution between March 2019 and December 2022 for thoracic radiotherapy treatment planning. The 5DCT datasets utilized motion models constructed from 25 fast-helical free-breathing computed tomography (FHFBCTs) with simultaneous respiratory bellows signal monitoring to reconstruct individual, user-specified breathing-phase...

Distinct Urinary Metabolite Signatures Mirror In Vivo Oxidative Stress-Related Radiation Responses in Mice

Thu, 27 Feb 2025 00:00:00 +0000

Exposure to ionizing radiation disrupts metabolic pathways and causes oxidative stress, which can lead to organ damage. In this study, urinary metabolites from mice exposed to high-dose and low-dose whole-body irradiation (WBI HDR, WBI LDR) or partial-body irradiation (PBI BM2.5) were analyzed using targeted and untargeted metabolomics approaches. Significant metabolic changes particularly in oxidative stress pathways were observed on Day 2 post-radiation. By Day 30, the WBI HDR group showed persistent metabolic dysregulation, while the WBI LDR and PBI BM2.5 groups were similar to control mice. Machine learning models identified metabolites that were predictive of the type of radiation exposure with high accuracy, highlighting their potential use as biomarkers for radiation damage and oxidative stress.

Longitudinal varying coefficient single-index model with censored covariates

Wed, 26 Feb 2025 00:00:00 +0000

It is of interest to health policy research to estimate the population-averaged longitudinal medical cost trajectory from initial cancer diagnosis to death, and understand how the trajectory curve is affected by patient characteristics. This research question leads to a number of statistical challenges because the longitudinal cost data are often non-normally distributed with skewness, zero-inflation, and heteroscedasticity. The trajectory is nonlinear, and its length and shape depend on survival, which are subject to censoring. Modeling the association between multiple patient characteristics and nonlinear cost trajectory curves of varying lengths should take into consideration parsimony, flexibility, and interpretation. We propose a novel longitudinal varying coefficient single-index model. Multiple patient characteristics are summarized in a single-index, representing a patient's overall propensity for healthcare use. The effects of this index on various segments of the cost...

Characterization of facial nerve outcomes following radiosurgery for vestibular schwannoma: a meta-analysis

Fri, 14 Feb 2025 00:00:00 +0000

PurposeGamma Knife radiosurgery (GKRS) is a precise and efficacious treatment modality for vestibular schwannoma (VS) with favorable cranial nerve preservation rates. This study aims to better characterize facial nerve (FN) outcomes in VS after GKRS.MethodsA query of six medical databases was conducted following PRISMA guidelines. Eligible studies exclusively reported VS managed with single-fraction GKRS and included House-Brackmann (HB) scale assessments prior to and following GKRS. Data was analyzed using random-effects modeling, and FN preservation was defined as HB I or II at last follow-up.ResultsData was analyzed from 15 articles with 3,155 patients at an mean age of 55.0 years. Mean tumor volume, radiation dose, follow-up, tumor control, and hearing preservation were 4.28 cm3, 13.3 Gy, 59.4 months, 92.7%, and 62.6%, respectively. The pooled FN preservation rate was 92.9%. Mean preoperative tumor volume > 2.5 cm3 and age > 60 years were significantly...

Toward a Computable Phenotype for Determining Eligibility of Lung Cancer Screening Using Electronic Health Records

Fri, 14 Feb 2025 00:00:00 +0000

PURPOSE: Lung cancer screening (LCS) has the potential to reduce mortality and detect lung cancer at its early stages, but the high false-positive rate associated with low-dose computed tomography (LDCT) for LCS acts as a barrier to its widespread adoption. This study aims to develop computable phenotype (CP) algorithms on the basis of electronic health records (EHRs) to identify individual's eligibility for LCS, thereby enhancing LCS utilization in real-world settings. MATERIALS AND METHODS: The study cohort included 5,778 individuals who underwent LDCT for LCS from 2012 to 2022, as recorded in the University of Florida Health Integrated Data Repository. CP rules derived from LCS guidelines were used to identify potential candidates, incorporating both structured EHR and clinical notes analyzed via natural language processing. We then conducted manual reviews of 453 randomly selected charts to refine and validate these rules, assessing CP performance using metrics, for example,...

Eigenrank by committee: Von-Neumann entropy based data subset selection and failure prediction for deep learning based medical image segmentation

Thu, 13 Feb 2025 00:00:00 +0000

Manual delineation of anatomy on existing images is the basis of developing deep learning algorithms for medical image segmentation. However, manual segmentation is tedious. It is also expensive because clinician effort is necessary to ensure correctness of delineation. Consequently most algorithm development is based on a tiny fraction of the vast amount of imaging data collected at a medical center. Thus, selection of a subset of images from hospital databases for manual delineation - so that algorithms trained on such data are accurate and tolerant to variation, becomes an important challenge. We address this challenge using a novel algorithm. The proposed algorithm named 'Eigenrank by Committee' (EBC) first computes the degree of disagreement between segmentations generated by each DL model in a committee. Then, it iteratively adds to the committee, a DL model trained on cases where the disagreement is maximal. The disagreement between segmentations is quantified by the maximum...

PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging

Wed, 12 Feb 2025 00:00:00 +0000

Importance: The phase 3 randomized EMBARK trial evaluated enzalutamide with or without leuprolide in high-risk nonmetastatic hormone-sensitive prostate cancer. Eligibility relied on conventional imaging, which underdetects metastatic disease compared with prostate-specific membrane antigen-positron emission tomography (PSMA-PET). Objective: To describe the staging information obtained by PSMA-PET/computed tomography (PSMA-PET/CT) in a patient cohort eligible for the EMBARK trial. Design, Setting, and Participants: This post hoc, retrospective cross-sectional study included 182 patients from 4 prospective studies conducted from September 15, 2016, to September 27, 2021. All patients had recurrent prostate cancer after radical prostatectomy (RP), definitive radiotherapy (dRT), or salvage radiotherapy (SRT). Analysis was performed from January 2023 to July 2024. Exposures: Patients included had increasing prostate-specific antigen (PSA) levels greater than 1.0 ng/mL (after RP and...

Small pretreatment lesion size and high sphericity as favorable prognostic factors after laser interstitial thermal therapy in brain metastases.

Wed, 5 Feb 2025 00:00:00 +0000

OBJECTIVE: The objective of this study was to identify baseline clinical and radiological characteristics of brain metastases (BMs) associated with a higher probability of lesion-specific progression-free survival (PFS-L) after laser interstitial thermal therapy (LITT). METHODS: A total of 47 lesions in 42 patients with BMs treated with LITT were retrospectively examined, including newly diagnosed BM, suspected recurrent BM, and suspected radiation necrosis. The association of baseline clinical and radiological features with PFS-L was assessed using survival analyses. Radiological features included lesion size measurements, diffusion and perfusion metrics, and sphericity, which is a radiomic feature ranging from 1 (perfect sphere) to 0. RESULTS: The probability of PFS-L for the entire cohort was 88.0% at 3 months, 70.6% at 6 months, 67.4% at 1 and 2 years, and 62.2% at 3 years. For lesions progressing after LITT (n = 13), the median time to progression was 3.9 months, and most...

Patient-reported quality of life and adherence outcomes after integrating exclusive liquid meal replacement in patients with head and neck cancer undergoing chemoradiation: results from a phase II study

Fri, 31 Jan 2025 00:00:00 +0000

Objectives: Preventing malnutrition during chemoradiation (CRT) for head and neck cancer is critical maximizing quality of life (QOL). We sought to assess patient-reported QOL outcomes after integrating exclusive liquid meal replacement with Soylent, a novel meal replacement agent, in patients with head and neck cancer undergoing CRT. Methods: Patients undergoing definitive or adjuvant concurrent CRT for locally advanced head and neck cancer enrolled on our single-institution, prospective phase II protocol evaluating nutritional replacement with Soylent. Patients who reached 5% body weight loss during CRT were transitioned to Soylent meal replacement for all nutritional needs. Patients who reached 10% body weight loss were recommended for gastrostomy tube (G-tube) placement. UW-QOL and FACT-H&N questionnaires assessed patient-reported QOL prior to the receipt of CRT and following conclusion of CRT. Paired t-test or Wilcoxon signed-rank test were performed to assess for differences...

Necessity and impact of specialization of large foundation model for medical segmentation tasks

Thu, 16 Jan 2025 00:00:00 +0000

BACKGROUND: Large foundation models, such as the Segment Anything Model (SAM), have shown remarkable performance in image segmentation tasks. However, the optimal approach to achieve true utility of these models for domain-specific applications, such as medical image segmentation, remains an open question. Recent studies have released a medical version of the foundation model MedSAM by training on vast medical data, who promised SOTA medical segmentation. Independent community inspection and dissection is needed. PURPOSE: Foundation models are developed for general purposes. On the other hand, stable delivery of reliable performance is key to clinical utility. This study aims at elucidating the potential advantage and limitations of landing the foundation models in clinical use by assessing the performance of off-the-shelf medical foundation model MedSAM for the segmentation of anatomical structures in pelvic MR images. We also explore the simple remedies by evaluating the dependency...

Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort.

Thu, 16 Jan 2025 00:00:00 +0000

Glioblastoma is immunologically cold and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that...

Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma

Mon, 6 Jan 2025 00:00:00 +0000

Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates...

Molecular Hallmarks of Prostate-specific Membrane Antigen in Treatment-naïve Prostate Cancer

Sat, 28 Dec 2024 00:00:00 +0000

BACKGROUND AND OBJECTIVE: We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer. METHODS: We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts. We validated those associations in independent cohorts (18 total; 5684 tumor samples) to characterize the pathways and treatment responses associated with PSMA. KEY FINDINGS AND LIMITATIONS: PSMA RNA abundance correlates moderately with SUVmax (ρ = 0.41). In independent cohorts, androgen receptor signaling is more active in tumors with high PSMA. Accordingly, patients with high PSMA tumors experienced longer cancer-specific survival when...

A quantitative CBCT pipeline based on 2D antiscatter grid and grid‐based scatter sampling for image‐guided radiation therapy

Wed, 11 Dec 2024 00:00:00 +0000

BACKGROUND: Quantitative accuracy is critical for expanding the role of cone beam CT (CBCT) imaging from target localization to quantitative treatment monitoring and plan adaptations in radiation therapy. Despite advances in CBCT image quality improvement methods, quantitative accuracy gap between CBCT and multi-detector CT (MDCT) remains. PURPOSE: In this work, a physics-driven approach was investigated that combined robust scatter rejection, raw data correction and iterative image reconstruction to further improve CBCT image quality and quantitative accuracy, referred to as quantitative CBCT (qCBCT). METHODS: QCBCT approach includes tungsten 2D antiscatter grid hardware, residual scatter correction with grid-based scatter sampling, image lag, and beam hardening correction for offset detector geometry linac-mounted CBCT. Images were reconstructed with iterative image reconstruction to reduce image noise. qCBCT was evaluated using a variety of phantoms to investigate the effect...

MRI and pathology comparisons in Rasmussen’s encephalitis: a multi-institutional examination of hemispherotomy outcomes relative to imaging and histological severity

Sat, 7 Dec 2024 00:00:00 +0000

PurposeRasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers.MethodsThis multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution’s review board. Data was collected from all known pediatric cases of peri-insular functional hemispherotomy from the earliest available electronic medical records. Mean follow-up time was 4.9 years. Clinical outcomes were measured by last follow-up visit using both Engel and...

Simplified methods for variance estimation in microbiome abundance count data analysis

Thu, 5 Dec 2024 00:00:00 +0000

The complex nature of microbiome data has made the differential abundance analysis challenging. Microbiome abundance counts are often skewed to the right and heteroscedastic (also known as overdispersion), potentially leading to incorrect inferences if not properly addressed. In this paper, we propose a simple yet effective framework to tackle the challenges by integrating Poisson (log-linear) regression with standard error estimation through the Bootstrap method and Sandwich robust estimation. Such standard error estimates are accurate and yield satisfactory inference even if the distributional assumption or the variance structure is incorrect. Our approach is validated through extensive simulation studies, demonstrating its effectiveness in addressing overdispersion and improving inference accuracy. Additionally, we apply our approach to two real datasets collected from the human gut and vagina, respectively, demonstrating the wide applicability of our methods. The results highlight...

Costs and Access Barriers to Ondansetron in the US

Wed, 4 Dec 2024 00:00:00 +0000

This cross-sectional study compares the use of management tools and plan-level total costs for oral ondansetron between Part D independent prescription drug plans and Medicare Advantage prescription drug plans.

Symptom-associated alterations in functional connectivity in primary and secondary provoked vestibulodynia

Fri, 22 Nov 2024 00:00:00 +0000

ABSTRACT: Primary provoked vestibulodynia (PVD) is marked by the onset of symptoms at first provoking vulvar contact, whereas secondary PVD refers to symptom onset after some period of painless vulvar contact. Different pathophysiological processes are believed to be involved in the development and maintenance of primary PVD and secondary PVD. The primary aim of this study was to test the hypotheses that the resting state functional connectivity of the brain and brain stem regions differs between these subtypes. Deep clinical phenotyping and resting state brain imaging were obtained in a large sample of a women with primary PVD (n = 46), those with secondary PVD (n = 68), and healthy control women (n = 94). The general linear model was used to test for differences in region-to-region resting state functional connectivity and psychosocial and symptom assessments. Direct statistical comparisons by onset type indicated that women with secondary PVD have increased dorsal attention-somatomotor...

Glioblastomas: Hijacking Metabolism to Build a Flexible Shield for Therapy Resistance

Tue, 19 Nov 2024 00:00:00 +0000

Significance: Glioblastomas (GBMs) are among the most lethal tumors despite the almost exclusive localization to the brain. This is largely due to therapeutic resistance. Radiation and chemotherapy significantly increase the survival for GBM patients, however, GBMs always recur, and the median overall survival is just over a year. Proposed reasons for such intractable resistance to therapy are numerous and include tumor metabolism, in particular, the ability of tumor cells to reconfigure metabolic fluxes on demand (metabolic plasticity). Understanding how the hard-wired, oncogene-driven metabolic tendencies of GBMs intersect with flexible, context-induced metabolic rewiring promises to reveal novel approaches for combating therapy resistance. Recent Advances: Personalized genome-scale metabolic flux models have recently provided evidence that metabolic flexibility promotes radiation resistance in cancer and identified tumor redox metabolism as a major...

The Association of Organizational Readiness With Lung Cancer Screening Utilization

Wed, 13 Nov 2024 00:00:00 +0000

INTRODUCTION: Lung cancer screening is widely underutilized. Organizational factors, such as readiness for change and belief in the value of change (change valence), may contribute to underutilization. The aim of this study was to evaluate the association between healthcare organizations' preparedness and lung cancer screening utilization. METHODS: Investigators cross-sectionally surveyed clinicians, staff, and leaders at10 Veterans Affairs from November 2018 to February 2021 to assess organizational readiness to implement change. In 2022, investigators used simple and multivariable linear regression to evaluate the associations between facility-level organizational readiness to implement change and change valence with lung cancer screening utilization. Organizational readiness to implement change and change valence were calculated from individual surveys. The primary outcome was the proportion of eligible Veterans screened using low-dose computed tomography. Secondary analyses...

Nicotinamide Adenine Dinucleotide Phosphate Oxidase Promotes Glioblastoma Radiation Resistance in a Phosphate and Tensin Homolog-Dependent Manner

Wed, 13 Nov 2024 00:00:00 +0000

Aims: The goal of this study was to determine whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-produced reactive oxygen species (ROS) enhance brain tumor growth of glioblastoma (GBM) under hypoxic conditions and during radiation treatment. Results: Exogenous ROS promoted brain tumor growth in gliomasphere cultures that expressed functional phosphate and tensin homolog (PTEN), but not in tumors that were PTEN deficient. Hypoxia induced the production of endogenous cytoplasmic ROS and tumor cell growth via activation of NOX. NOX activation resulted in oxidation of PTEN and downstream protein kinase B (Akt) activation. Radiation also promoted ROS production via NOX, which, in turn, resulted in cellular protection that could be abrogated by knockdown of the key NOX component, p22. Knockdown of p22 also inhibited tumor growth and enhanced the efficacy of radiation in PTEN-expressing GBM cells. Innovation:...

Cost-Effectiveness of Metastasis-Directed Therapy in Oligorecurrent Hormone-Sensitive Prostate Cancer

Fri, 8 Nov 2024 00:00:00 +0000

PURPOSE: Oligorecurrent prostate cancer has historically been treated with indefinite androgen deprivation therapy (ADT), although many patients and providers opt to defer this treatment at the time of recurrence given quality-of-life and/or comorbidity considerations. Recently, metastasis-directed therapy (MDT) has emerged as a potential intermediary between surveillance and immediate continuous ADT. Simultaneously, advanced systemic therapy in addition to ADT has also been shown to improve survival in metastatic hormone-sensitive disease. This study aimed to compare the cost-effectiveness of treating oligorecurrent patients with upfront MDT before standard-of-care systemic therapy. METHODS AND MATERIALS: A Markov-based cost-effectiveness analysis was constructed comparing 3 strategies: (1) upfront MDT → salvage abiraterone acetate plus prednisone (AAP) + ADT → salvage docetaxel + ADT; (2) upfront AAP + ADT → salvage docetaxel + ADT; and (3) upfront docetaxel + ADT → salvage...

SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson’s disease in human dopaminergic neurons and a mouse model