From Bench to Bedside: A Team's Approach to Multidisciplinary Strategies to Combat Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is diagnosed in more than 71,000 patients each year in the United States, with nearly 16,000 associated deaths. One significant hurdle in the treatment of HNSCC is acquired and intrinsic resistance to existing therapeutic agents. Over the past several decades, the University of Wisconsin has formed a multidisciplinary team to move basic scientific discovery along the translational spectrum to impact the lives of HNSCC patients.

MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer.

Purpose: The objective of this study was to investigate the effects of inhibiting the MET receptor with capmatinib, a potent and clinically relevant ATP-competitive tyrosine kinase inhibitor, in combination with radiation in MET exon 14-mutated and MET-amplified non-small cell lung (NSCLC) cancer models.

Methods And Materials: effects of capmatinib and radiation on cell proliferation, colony formation, MET signaling, apoptosis, and DNA damage repair were evaluated. tumor responses were assessed in cell line xenograft and patient-derived xenograft models.

"I Want to Know Everything ... ": The Return of Research Results and the Importance of Transparency in the Acceptability of Lumbar Punctures for African American Older Adults.

Background: Although African Americans experience the highest risk of Alzheimer's disease (AD), they are dramatically underrepresented in preclinical biomarker research. This is especially true for studies involving lumbar puncture as it may involve more perceived risk even for those participants who are otherwise supportive of research.

Objective: To understand the unique concerns of African American participants regarding biomarker studies involving lumbar puncture who demonstrate support for AD research.

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. As such, HNC patients stand to benefit from the conformal targeting of primary and remnant disease achievable with radiopharmaceutical therapies. In this study, the authors investigated the tumor targeting capacity of I-CLR1404 (iopofosine I-131) in various HNC xenograft mouse models and the impact of partial volume correction (PVC) on theranostic dosimetry based on I-CLR1404 (CLR 124) positron emission tomography (PET)/computed tomography (CT) imaging.

Skeletal Muscle Adiposity and Lung Function Trajectory in the Severe Asthma Research Program.

Extrapulmonary manifestations of asthma, including fatty infiltration in tissues, may reflect systemic inflammation and influence lung function and disease severity. To determine if skeletal muscle adiposity predicts lung function trajectory in asthma. Adult SARP III (Severe Asthma Research Program III) participants with baseline computed tomography imaging and longitudinal postbronchodilator FEV% predicted (median follow-up 5 years [1,132 person-years]) were evaluated.

A comparison study of microwave ablation vs. histotripsy for focal liver treatments in a swine model.

Objective: To compare the acute and chronic safety and treatment effects of non-invasive hepatic histotripsy vs. percutaneous microwave (MW) ablation in a healthy porcine model.

Methods: This was a dual-arm study in which each animal (n = 14) received either a single hepatic microwave (n = 6) or histotripsy (n = 6 single treatment; n = 2 double treatment) under ultrasound guidance.

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis.

Purpose: To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant.

Materials And Methods: This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques.

AXL regulates neuregulin1 expression leading to cetuximab resistance in head and neck cancer.

Background: The receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR) is overexpressed and an important therapeutic target in Head and Neck cancer (HNC). Cetuximab is currently the only EGFR-targeting agent approved by the FDA for treatment of HNC; however, intrinsic and acquired resistance to cetuximab is a major problem in the clinic. Our lab previously reported that AXL leads to cetuximab resistance via activation of HER3.

Evaluation of staging systems to predict prognosis in hepatocellular carcinoma patients treated with radioembolization.

Purpose: To compare the prognostic accuracy of nine staging systems, some of which are well-known and some of which have only been more recently described, for patients with unresectable HCC treated with radioembolization (RE).

Materials And Methods: Individual scores or classes for the following staging systems were recorded or calculated for patients (n = 89) with unresectable HCC who underwent RE at a single tertiary care center from January 2008 to October 2016: Eastern Cooperative Oncology Group, Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, Okuda, Cancer of the Liver Italian Program (CLIP), Model for End Stage Liver Disease, Child-Pugh (CP) Categorical and Numeric, and Albumin-Bilirubin. For each staging system, a cox proportional hazards regression model was fit to the data and log-rank test statistics, concordance indices, Akaike Information Criteria (AIC) and other diagnostic statistics were calculated.

Screening Digital Breast Tomosynthesis: Radiation Dose Among Patients With Breast Implants.

Objective: To compare the mean glandular dose (MGD), cancer detection rate (CDR), and recall rate (RR) among screening examinations of patients with breast implants utilizing various digital breast tomosynthesis (DBT)-based imaging protocols.

Methods: This IRB-approved retrospective study included 1998 women with breast implants who presented for screening mammography between December 10, 2013, and May 29, 2020. Images were obtained using various protocol combinations of DBT and 2D digital mammography.

Proton density water fraction as a reproducible MR-based measurement of breast density.

Purpose: To introduce proton density water fraction (PDWF) as a confounder-corrected (CC) MR-based biomarker of mammographic breast density, a known risk factor for breast cancer.

Methods: Chemical shift encoded (CSE) MR images were acquired using a low flip angle to provide proton density contrast from multiple echo times. Fat and water images, corrected for known biases, were produced by a six-echo CC CSE-MRI algorithm.

Microwave ablation for colorectal cancer metastasis to the liver: a single-center retrospective analysis.

Background: The purpose of this study is to evaluate the safety and intermediate-term efficacy of percutaneous microwave (MW) ablation for the treatment of colorectal liver metastases (CRLM) at a single institution.

Methods: A retrospective review was performed of all CRLM treated with MW ablation from 3/2011 to 7/2020 (102 tumors; 72 procedures; 57 patients). Mean age was 60 years (range, 36-88) and mean tumor size was 1.

Measuring interdisciplinarity of biomedical research, medical specialty performance, and implications for radiology: A retrospective review of 2.6 million citations.

Purpose: To assess and determine the overall interdisciplinarity and impact of radiology and imaging sciences research.

Methods: Utilizing the Thomson Reuters Web of Science, the top 15 journals rank-ordered by impact factor in each of 10 major medical subspecialties were identified. The 2012 impact factors for these journals were noted.

Real-time respiratory motion compensated roadmaps for hepatic arterial interventions.

Purpose: During hepatic arterial interventions, catheter or guidewire position is determined by referencing or overlaying a previously acquired static vessel roadmap. Respiratory motion leads to significant discrepancies between the true position and configuration of the hepatic arteries and the roadmap, which makes navigation and accurate catheter placement more challenging and time consuming. The purpose of this work was to develop a dynamic respiratory motion compensated device guidance system and evaluate the accuracy and real-time performance in an in vivo porcine liver model.

Impact of immediate cryopreservation on the establishment of patient derived xenografts from head and neck cancer patients.

Background: Patient-derived xenografts established from human cancers are important tools for investigating novel anti-cancer therapies. Establishing PDXs requires a significant investment and many PDXs may be used infrequently due to their similarity to existing models, their growth rate, or the lack of relevant mutations. We performed this study to determine whether we could efficiently establish PDXs after cryopreservation to allow molecular profiling to be completed prior to implanting the human cancer.

Mammary Tumors Growing in the Absence of Growth Hormone Are More Sensitive to Doxorubicin Than Wild-Type Tumors.

Previously, we reported that N-methyl-N-nitrosourea (MNU)-induced mammary tumors could be established in mutant spontaneous dwarf rats (SDRs), which lack endogenous growth hormone (GH) by supplementing with exogenous GH, and almost all such tumors regressed upon GH withdrawal. When the highly inbred SDR line was outcrossed to wild-type (WT) Sprague-Dawley rats, MNU-induced mammary tumors could still be established in resulting outbred SDRs by supplementing with exogenous GH. However, unlike tumors in inbred SDRs, 65% of mammary tumors established in outbred SDRs continued growth after GH withdrawal.

A technique for intra-procedural blood velocity quantitation using time-resolved 2D digital subtraction angiography.

Background: 2D digital subtraction angiography (DSA) is utilized qualitatively to assess blood velocity changes that occur during arterial interventions. Quantitative angiographic metrics, such as blood velocity, could be used to standardize endpoints during angiographic interventions.

Purpose: To assess the accuracy and precision of a quantitative 2D DSA (qDSA) technique and to determine its feasibility for in vivo measurements of blood velocity.

A Quantitative Digital Subtraction Angiography Technique for Characterizing Reduction in Hepatic Arterial Blood Flow During Transarterial Embolization.

Objective: There is no standardized and objective method for determining the optimal treatment endpoint (sub-stasis) during transarterial embolization. The objective of this study was to demonstrate the feasibility of using a quantitative digital subtraction angiography (qDSA) technique to characterize intra-procedural changes in hepatic arterial blood flow velocity in response to transarterial embolization in an in vivo porcine model.

Materials And Methods: Eight domestic swine underwent bland transarterial embolizations to partial- and sub-stasis angiographic endpoints with intraprocedural DSA acquisitions.

Interobserver agreement for the direct and indirect signs of pulmonary embolism evaluated using contrast enhanced magnetic angiography.

Background: Accurate diagnosis of pulmonary embolism (PE) using contrast enhanced MRA (CE-MRA) requires awareness of both the direct and indirect findings of PE.

Purpose: To evaluate reader agreement of the direct and indirect findings of PE on CE-MRA.

Methods: We evaluated pulmonary artery diameter, right ventricle/left ventricle ratio, and clot/vessel lumen signal intensity ratio.

Complex confounder-corrected R2* mapping for liver iron quantification with MRI.

Objectives: MRI-based R2* mapping may enable reliable and rapid quantification of liver iron concentration (LIC). However, the performance and reproducibility of R2* across acquisition protocols remain unknown. Therefore, the objective of this work was to evaluate the performance and reproducibility of complex confounder-corrected R2* across acquisition protocols, at both 1.

Optimization of quantitative time-resolved 3D (4D) digital subtraction angiography in a porcine liver model.

Background: Time-resolved three-dimensional digital subtraction angiography (4D-DSA) can be used to quantify blood velocity. Contrast pulsatility, a major discriminant on 4D-DSA, is yet to be optimized. We investigated the effects of different imaging and injection parameters on sideband ratio (SBR), a measure of contrast pulsatile strength, within the hepatic vasculature of an in vivo porcine model.

AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer.

Purpose: Radiation and cetuximab are therapeutics used in management of head and neck squamous cell carcinoma (HNSCC). Despite clinical success with these modalities, development of both intrinsic and acquired resistance is an emerging problem in the management of this disease. The purpose of this study was to investigate signaling of the receptor tyrosine kinase AXL in resistance to radiation and cetuximab treatment.

FGFR Inhibition Enhances Sensitivity to Radiation in Non-Small Cell Lung Cancer.

FGFRs are commonly altered in non-small cell lung cancer (NSCLC). FGFRs activate multiple pathways including RAS/RAF/MAPK, PI3K/AKT, and STAT, which may play a role in the cellular response to radiation. We investigated the effects of combining the selective FGFR 1-3 tyrosine kinase inhibitor AZD4547 with radiation in cell line and xenograft models of NSCLC.