Introduction: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and has a propensity to metastasize to the brain. It is incredibly difficult to distinguish between a primary brain lesions and a solitary metastasis from distant occult disease using current imaging techniques. Further, complications arise from the shifting paradigm in how medicine views NSCLC brain metastasis due to contemporary nonsurgical curative treatments and the recent increase in the number of multiple primary malignancy (MPM) diagnoses associated with NSCLC.
View Article and Find Full Text PDFBackground: It is common in outcome analysis to work with a large set of candidate prognostic features. However, such high-dimensional input and relatively small sample size leads to risk of overfitting, low generalizability, and correlation bias.
Purpose: This study addresses the issue of correlation bias mitigation in the context of predicting genitourinary (GU) toxicity in prostate cancer patients underwent MRI-guided stereotactic body radiation therapy (SBRT).
Purpose: Although radiotherapy (RT) is one of the primary treatment modalities used in the treatment of cancer, patients often experience toxicity during or after treatment. RT-induced genitourinary (GU) toxicity is a significant survivorship challenge for patients with prostate cancer, but identifying those at risk has been challenging. Herein, we attempt (i) to validate a previously identified biomarker of late RT-induced GU toxicity, PROSTOX, consisting primarily of miRNA-based germline biomarkers (mirSNPs), and (ii) investigate the possibility of temporally and genetically defining other forms of RT-associated GU toxicity.
View Article and Find Full Text PDFIt has been shown that magnetic resonance imaging (MRI) guidance versus computed tomography (CT) guidance for aggressive margin-reduction (AMR) for stereotactic body radiotherapy (SBRT) in prostate cancer reduces acute toxicity, but the longer-term benefits are unknown. We performed a secondary analysis of MIRAGE, a phase 3 randomized clinical trial of MRI-guided SBRT for prostate cancer, to determine whether AMR with MRI guidance significantly reduced 2-yr physician-scored or patient-reported toxic effects in comparison to CT guidance. The cumulative incidence of 2-yr physician-scored toxicity, defined as grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxic effects according to Common Terminology Criteria for Adverse Events v4.
View Article and Find Full Text PDFUnlabelled: Prostate cancer is frequently treated with radiotherapy. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation).
View Article and Find Full Text PDFImportance: Intrathoracic progression remains the predominant pattern of failure in patients treated with concurrent chemoradiation followed by a consolidation immune checkpoint inhibitor for locally advanced, unresectable non-small cell lung cancer (NSCLC).
Objective: To determine the maximum tolerated dose (MTD) and use of hypofractionated concurrent chemoradiation with an adaptive stereotactic ablative radiotherapy (SABR) boost.
Design, Setting, And Participants: This was an early-phase, single-institution, radiation dose-escalation nonrandomized controlled trial with concurrent chemotherapy among patients with clinical stage II (inoperable/patient refusal of surgery) or III NSCLC (American Joint Committee on Cancer Staging Manual, seventh edition).
Background: MR-guided radiation therapy (MRgRT) systems provide superior soft tissue contrast than x-ray based systems and can acquire real-time cine for treatment gating. These features allow treatment planning margins to be reduced, allowing for improved critical structure sparing and reduced treatment toxicity. Despite this improvement, genitourinary (GU) toxicity continues to affect many patients.
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
March 2024
Purpose: Emerging data suggest that trigone dosimetry may be more associated with poststereotactic body radiation therapy (SBRT) urinary toxicity than whole bladder dosimetry. We quantify the dosimetric effect of interfractional displacement and deformation of the whole bladder and trigone during prostate SBRT using on-board, pretreatment 0.35T magnetic resonance images (MRI).
View Article and Find Full Text PDFJuvenile nasopharyngeal angiofibroma (JNA) is a relatively uncommon, benign neoplasm of the nasopharynx that can be very difficult to diagnose early due to inconspicuous and seemingly harmless presenting symptoms. Early diagnosis and treatment of JNA are essential for a good prognosis. JNA typically responds well to radiation therapy (RT), but when it does not, the most appropriate next course of action has not been readily defined due to the limited occurrence and experience with this neoplasm.
View Article and Find Full Text PDFBackground: A majority of breast cancer tumors express estrogen receptor (ER) and/or progesterone receptor (PR); however, the percentage of cancer cells expressing these receptors can range from 0-100%. The prognostic and therapeutic impact of the percentage of cells expressing hormone receptors in breast cancer is not fully understood.
Methods: A retrospective analysis of 411 breast cancer patients who were treated at the University of Nebraska Medical Center between 2010 and 2017 was performed.
This case of sarcoidosis mimicking metastatic breast cancer serves as a reminder of the need to consider differential diagnoses even when the clinical scenario and imaging findings are highly suggestive of metastases.
View Article and Find Full Text PDFGenome-wide, loss-of-function screening can be used to identify novel vulnerabilities upon which specific tumor cells depend for survival. Functional Signature Ontology (FUSION) is a gene expression-based high-throughput screening (GE-HTS) method that allows researchers to identify functionally similar proteins, small molecules, and microRNA mimics, revealing novel therapeutic targets. FUSION uses cell-based high-throughput screening and computational analysis to match gene expression signatures produced by natural products to those produced by small interfering RNA (siRNA) and synthetic microRNA libraries to identify putative protein targets and mechanisms of action (MoA) for several previously undescribed natural products.
View Article and Find Full Text PDFReproductive toxicity is common after total body irradiation (TBI) and has major quality of life implications for patients. In that context, this is the first report of gonadal-sparing volumetric-modulated arc therapy (VMAT) TBI, successfully delivered in a boy and a girl with aplastic anemia. Both patients' VMAT TBI plans demonstrated improved gonadal sparing versus simulated conventional 2-dimensional (2D) approach (mean testes dose, 0.
View Article and Find Full Text PDFA gene expression-based siRNA screen was used to evaluate functional similarity between genetic perturbations to identify functionally similar proteins. A siRNA library (siGenome library, Dharmacon) consisting of multiple siRNAs per gene that have been pooled in to one well per gene was arrayed in a 384-well format and used to individually target 14,335 proteins for depletion in HCT116 colon cancer cells. For each protein depletion, the gene expression of eight genes was quantified using the multiplexed Affymetrix Quantigene 2.
View Article and Find Full Text PDFGene expression signature-based inference of functional connectivity within and between genetic perturbations, chemical perturbations, and disease status can lead to the development of actionable hypotheses for gene function, chemical modes of action, and disease treatment strategies. Here, we report a FuSiOn-based genome-wide integration of hypomorphic cellular phenotypes that enables functional annotation of gene network topology, assignment of mechanistic hypotheses to genes of unknown function, and detection of cooperativity among cell regulatory systems. Dovetailing genetic perturbation data with chemical perturbation phenotypes allowed simultaneous generation of mechanism of action hypotheses for thousands of uncharacterized natural products fractions (NPFs).
View Article and Find Full Text PDFBackground And Objectives: Carbon monoxide is one of the most common causes of fatal intoxications in the United States, and multiple previous studies have demonstrated that cigarette smokers have higher levels of carbon monoxide in their blood. However, the potential negative effects due to acute carbon monoxide poisoning from excessive cigarette smoking have not been well established.
Methods: This is a single patient case report.
Background: Despite the fact that stereotactic body radiation therapy (SBRT) is the only recommended first-line therapy for inoperable early-stage non-small cell lung cancer (NSCLC), several thermal ablative procedures (TAPs; defined herein as laser/cryoablation and electrocautery) are available. Studies showing outcomes of these procedures and how they compare with SBRT are scarce. We sought to evaluate the comparative efficacy of SBRT versus TAPs using the National Cancer Database (NCDB).
View Article and Find Full Text PDFBackground: Pituitary tumors typically remain silent unless interaction with nearby structures occurs. Rare subsets of pituitary tumors display aggressive phenotypes: highly mitotic, locally invasive, metastatic, chemotherapy and radiation resistant, etc. Disease progression and response to therapy is ill-defined in these subtypes, and their true prognostic potential is debated.
View Article and Find Full Text PDFBackground: Nuclear protein in testis midline carcinoma is a rare, highly metastatic undifferentiated carcinoma that typically arises in midline structures and is characterized by having a fusion involving the nuclear protein in testis, NUT, gene. Nuclear protein in testis midline carcinoma has been identified in patients of all ages and is often initially misdiagnosed due to the rapid timeline of symptom onset.
Case Presentation: Here we report the case of a 47-year-old Caucasian woman with a nuclear protein in testis midline carcinoma that was initially mistaken for a sinus infection.
Importance: Currently, rates of referral of patients with peritoneal metastasis in the United States who qualify for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are low, in part because of the misperception of high morbidity and mortality rates. However, patients requiring major gastrointestinal surgical procedures with similar complication rates are routinely referred.
Objective: To evaluate the relative safety of CRS/HIPEC.