Publications by authors named "Mark Rosen"

179 Publications

Adaptive convolutional neural networks for accelerating magnetic resonance imaging via k-space data interpolation.

Med Image Anal 2021 Aug 16;72:102098. Epub 2021 May 16.

Center for Biomedical Image Computing and Analytics (CBICA), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Deep learning in k-space has demonstrated great potential for image reconstruction from undersampled k-space data in fast magnetic resonance imaging (MRI). However, existing deep learning-based image reconstruction methods typically apply weight-sharing convolutional neural networks (CNNs) to k-space data without taking into consideration the k-space data's spatial frequency properties, leading to ineffective learning of the image reconstruction models. Moreover, complementary information of spatially adjacent slices is often ignored in existing deep learning methods. To overcome such limitations, we have developed a deep learning algorithm, referred to as adaptive convolutional neural networks for k-space data interpolation (ACNN-k-Space), which adopts a residual Encoder-Decoder network architecture to interpolate the undersampled k-space data by integrating spatially contiguous slices as multi-channel input, along with k-space data from multiple coils if available. The network is enhanced by self-attention layers to adaptively focus on k-space data at different spatial frequencies and channels. We have evaluated our method on two public datasets and compared it with state-of-the-art existing methods. Ablation studies and experimental results demonstrate that our method effectively reconstructs images from undersampled k-space data and achieves significantly better image reconstruction performance than current state-of-the-art techniques. Source code of the method is available at https://gitlab.com/qgpmztmf/acnn-k-space.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.media.2021.102098DOI Listing
August 2021

Occult Hepatocellular Carcinoma Associated With Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients.

Liver Transpl 2021 Apr 14. Epub 2021 Apr 14.

Division of Transplant, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA.

Transplant eligibility for hepatocellular carcinoma (HCC) is determined by the imaging identification of tumor burden within the Milan criteria. Transjugular intrahepatic portosystemic shunt(s) (TIPS) reduce portal hypertension but may impact HCC visualization. It was hypothesized that the presence of pretransplant TIPS would correlate with occult HCC and reduced survival. A single-center, retrospective, case control study was performed among liver transplant recipients with HCC (2000-2017). The primary endpoint was occult disease on explant pathology. Backward stepwise logistic regression was performed. The secondary endpoints disease-free survival (DFS) and overall survival (OS) were evaluated with Kaplan-Meier curves and Cox regression analysis. Of 640 patients, 40 had TIPS and more frequently exhibited occult disease (80.0% versus 43.1%; P < 0.001; odds ratio [OR], 4.16; P < 0.001). Portal vein thrombosis (PVT) similarly correlated with occult disease (OR, 1.97; P = 0.02). Explant tumor burden was equivalent between TIPS subgroups; accordingly, TIPS status was not independently associated with reduced DFS or OS. However, exceeding the Milan criteria was associated with reduced DFS (hazard ratio, 3.21; P = 0.001), and TIPS status in patients with a single suspected lesion (n = 316) independently correlated with explant tumor burdens beyond these criteria (OR, 13.47; P = 0.001). TIPS on pretransplant imaging are associated with occult HCC on explant pathology. Comparable occult disease findings in patients with PVT suggest that the mechanism may involve altered hepatic perfusion, obscuring imaging diagnosis. TIPS are not independently associated with reduced DFS or OS but are associated with exceeding the Milan criteria for patients with a single suspected lesion. The presence of TIPS may necessitate a higher index of suspicion for occult HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.26073DOI Listing
April 2021

Respiratory Motion Mitigation and Repeatability of Two Diffusion-Weighted MRI Methods Applied to a Murine Model of Spontaneous Pancreatic Cancer.

Tomography 2021 Feb 20;7(1):66-79. Epub 2021 Feb 20.

Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Respiratory motion and increased susceptibility effects at high magnetic fields pose challenges for quantitative diffusion-weighted MRI (DWI) of a mouse abdomen on preclinical MRI systems. We demonstrate the first application of radial k-space-sampled (RAD) DWI of a mouse abdomen using a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) on a 4.7 T preclinical scanner equipped with moderate gradient capability. RAD DWI was compared with the echo-planar imaging (EPI)-based DWI method with similar voxel volumes and acquisition times over a wide range of -values (0.64, 535, 1071, 1478, and 2141 mm/s). The repeatability metrics are assessed in a rigorous test-retest study ( = 10 for each DWI protocol). The four-shot EPI DWI protocol leads to higher signal-to-noise ratio (SNR) in diffusion-weighted images with persisting ghosting artifacts, whereas the RAD DWI protocol produces relatively artifact-free images over all -values examined. Despite different degrees of motion mitigation, both RAD DWI and EPI DWI allow parametric maps of apparent diffusion coefficients (ADC) to be produced, and the ADC of the PDAC tumor estimated by the two methods are 1.3 ± 0.24 and 1.5 ± 0.28 × 10 mm/s, respectively ( = 0.075, = 10), and those of a water phantom are 3.2 ± 0.29 and 2.8 ± 0.15 × 10 mm/s, respectively ( = 0.001, = 10). Bland-Altman plots and probability density function reveal good repeatability for both protocols, whose repeatability metrics do not differ significantly. In conclusion, RAD DWI enables a more effective respiratory motion mitigation but lower SNR, while the performance of EPI DWI is expected to improve with more advanced gradient hardware.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/tomography7010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048371PMC
February 2021

Quantification of abdominal fat from computed tomography using deep learning and its association with electronic health records in an academic biobank.

J Am Med Inform Assoc 2021 Jun;28(6):1178-1187

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: The objective was to develop a fully automated algorithm for abdominal fat segmentation and to deploy this method at scale in an academic biobank.

Materials And Methods: We built a fully automated image curation and labeling technique using deep learning and distributive computing to identify subcutaneous and visceral abdominal fat compartments from 52,844 computed tomography scans in 13,502 patients in the Penn Medicine Biobank (PMBB). A classification network identified the inferior and superior borders of the abdomen, and a segmentation network differentiated visceral and subcutaneous fat. Following technical evaluation of our method, we conducted studies to validate known relationships with visceral and subcutaneous fat.

Results: When compared with 100 manually annotated cases, the classification network was on average within one 5-mm slice for both the superior (0.4 ± 1.1 slice) and inferior (0.4 ± 0.6 slice) borders. The segmentation network also demonstrated excellent performance with intraclass correlation coefficients of 1.00 (P < 2 × 10-16) for subcutaneous and 1.00 (P < 2 × 10-16) for visceral fat on 100 testing cases. We performed integrative analyses of abdominal fat with the phenome extracted from the electronic health record and found highly significant associations with diabetes mellitus, hypertension, and renal failure, among other phenotypes.

Conclusions: This work presents a fully automated and highly accurate method for the quantification of abdominal fat that can be applied to routine clinical imaging studies to fuel translational scientific discovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jamia/ocaa342DOI Listing
June 2021

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

NPJ Breast Cancer 2020 Nov 27;6(1):63. Epub 2020 Nov 27.

University of Pennsylvania, Philadelphia, PA, USA.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-020-00203-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695723PMC
November 2020

Effect of contrast dose on diagnostic performance in DCE-MR breast imaging.

J Appl Clin Med Phys 2020 Nov 22;21(11):188-194. Epub 2020 Oct 22.

Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Objective: To assess the diagnostic performance of breast magnetic resonance (MR) imaging as a function of gadolinium contrast dose using a retrospective reader study.

Material And Methods: IRB approval was obtained prior to the start of this study and was HIPAA compliant. One-hundred and fifty MR breast examinations were included that were acquired between January 2001 and December 2006. Seventy-five patients received contrast doses (gadopentetate dimeglumine) by weight of 0.10 mmol/kg and 75 patients were imaged using fixed volumes of 20 ml. The images were assessed by two radiologists with performance calculated for each reader as well as a combined assessment. Dose response was measured by comparing performance between cases binned by dose: <=0.10; >0.10; and >0.13 mmol/kg. Statistical significance was calculated using a one-sided Z-test for differences in proportions with interobserver agreement calculated using Cohen's kappa statistics.

Results: In the combined reader assessment with equivocal lesions classified as negative, sensitivity rose from 66% (19/29) to 92% (24/26, P < 0.01) and 95% (18/19, P < 0.01) with the specificity also increasing from 65% (32/49) to 87% (40/46, P < 0.01) and 86% (32/37, P = 0.01) corresponding to doses <=0.10, >0.10, >0.13 mmol/kg. With equivocal lesions classified as positive, sensitivity rose from 79% (23/29) to 92% (24/26, P < 0.10) and 95% (18/19, P < 0.10) Specificity also increased from 53% (26/49) to 72% (33/46, P < 0.05) and 70% (26/37, P = 0.05) with increasing dose. Interobserver agreement also improved at the higher doses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acm2.13010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701107PMC
November 2020

Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial.

Lancet Oncol 2020 08 20;21(8):1110-1122. Epub 2020 Jul 20.

Department of Radiology and Medical Imaging, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Background: Outcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone.

Methods: In this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and <18 years) from 57 hospitals in the USA and Canada with unresected, newly diagnosed trunk or extremity chemotherapy-sensitive soft tissue sarcoma, which were larger than 5 cm in diameter and of intermediate or high grade. Eligible patients had Lansky (if aged ≤16 years) or Karnofsky (if aged >16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m per dose intravenously on days 1-3 with mesna) and doxorubicin (37·5 mg/m per dose intravenously on days 1-2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients <18 years 350 mg/m once daily; if patients ≥18 years 600 mg once daily) or not (control group), with pazopanib not given immediately before or after surgery at week 13. The study projected 100 randomly assigned patients were needed to show an improvement in the number of participants with a 90% or higher pathological response at week 13 from 40% to 60%. Analysis was done per protocol. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02180867.

Findings: Between July 7, 2014, and Oct 1, 2018, 81 eligible patients were enrolled and randomly assigned to the pazopanib group (n=42) or the control group (n=39). At the planned second interim analysis with 42 evaluable patients and a median follow-up of 0·8 years (IQR 0·3-1·6) in the pazopanib group and 1 year (0·3-1·6) in the control group, the number of patients with a 90% pathological response or higher was 14 (58%) of 24 patients in the pazopanib group and four (22%) of 18 patients in the control group, with a between-group difference in the number of 90% or higher pathological response of 36·1% (83·8% CI 16·5-55·8). On the basis of an interim analysis significance level of 0·081 (overall one-sided significance level of 0·20, power of 0·80, and O'Brien-Fleming-type cumulative error spending function), the 83·8% CI for response difference was between 16·5% and 55·8% and thus excluded 0. The improvement in pathological response rate with the addition of pazopanib crossed the predetermined boundary and enrolment was stopped. The most common grade 3-4 adverse events were leukopenia (16 [43%] of 37 patients), neutropenia (15 [41%]), and febrile neutropenia (15 [41%]) in the pazopanib group, and neutropenia (three [9%] of 35 patients) and febrile neutropenia (three [9%]) in the control group. 22 (59%) of 37 patients in the pazopanib group had a pazopanib-related serious adverse event. Paediatric and adult patients had a similar number of grade 3 and 4 toxicity. There were seven deaths (three in the pazopanib group and four in the control group), none of which were treatment related.

Interpretation: In this presumed first prospective trial of soft tissue sarcoma spanning nearly the entire age spectrum, adding pazopanib to neoadjuvant chemoradiotherapy improved the rate of pathological near complete response, suggesting that this is a highly active and feasible combination in children and adults with advanced soft tissue sarcoma. The comparison of survival outcomes requires longer follow-up.

Funding: National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30325-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745646PMC
August 2020

Dextran-Coated Cerium Oxide Nanoparticles: A Computed Tomography Contrast Agent for Imaging the Gastrointestinal Tract and Inflammatory Bowel Disease.

ACS Nano 2020 08 28;14(8):10187-10197. Epub 2020 Jul 28.

Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

Computed tomography (CT) is an X-ray-based medical imaging technique commonly used for noninvasive gastrointestinal tract (GIT) imaging. Iodine- and barium-based CT contrast agents are used in the clinic for GIT imaging; however, inflammatory bowel disease (IBD) imaging is challenging since iodinated and barium-based CT agents are not specific for sites of inflammation. Cerium oxide nanoparticles (CeNP) can produce strong X-ray attenuation due to cerium's k-edge at 40.4 keV but have not yet been explored for CT imaging. In addition, we hypothesized that the use of dextran as a coating material on cerium oxide nanoparticles would encourage accumulation in IBD inflammation sites in a similar fashion to other inflammatory diseases. In this study, therefore, we sought to develop a CT contrast agent, , dextran-coated cerium oxide nanoparticles (Dex-CeNP) for GIT imaging with IBD. We synthesized Dex-CeNP, characterized them using various analytical tools, and examined their biocompatibility, CT contrast generation, and protective effect against oxidative stress. CT imaging was done with both healthy mice and a dextran sodium sulfate induced colitis mouse model. Dex-CeNP's CT contrast generation and accumulation in inflammation sites were compared with iopamidol, an FDA approved CT contrast agent. Dex-CeNP was found to be protective against oxidative damage. Dex-CeNP produced strong CT contrast and accumulated in the colitis area of large intestines. In addition, >97% of oral doses were cleared from the body within 24 h. Therefore, Dex-CeNP can be used as a potential CT contrast agent for imaging GIT with IBD while protecting against oxidative damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c03457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484129PMC
August 2020

Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation.

Br J Cancer 2020 02 2;122(3):333-339. Epub 2019 Dec 2.

Division of Hematology-Oncology, Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined.

Methods: Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS.

Results: The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25-0.74; 0.0068).

Conclusion: Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-019-0582-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000723PMC
February 2020

Multisite evaluation of radiomic feature reproducibility and discriminability for identifying peripheral zone prostate tumors on MRI.

J Med Imaging (Bellingham) 2019 Apr 14;6(2):024502. Epub 2019 Jun 14.

Case Western Reserve University, Department of Biomedical Engineering, Cleveland, Ohio, United States.

Recent advances in the field of radiomics have enabled the development of a number of prognostic and predictive imaging-based tools for a variety of diseases. However, wider clinical adoption of these tools is contingent on their generalizability across multiple sites and scanners. This may be particularly relevant in the context of radiomic features derived from T1- or T2-weighted magnetic resonance images (MRIs), where signal intensity values are known to lack tissue-specific meaning and vary based on differing acquisition protocols between institutions. We present the first empirical study of benchmarking five different radiomic feature families in terms of both reproducibility and discriminability in a multisite setting, specifically, for identifying prostate tumors in the peripheral zone on MRI. Our cohort comprised 147 patient T2-weighted MRI datasets from four different sites, all of which are first preprocessed to correct for acquisition-related artifacts such as bias field, differing voxel resolutions, and intensity drift (nonstandardness). About 406 three-dimensional voxel-wise radiomic features from five different families (gray, Haralick, gradient, Laws, and Gabor) were evaluated in a cross-site setting to determine (a) how reproducible they are within a relatively homogeneous nontumor tissue region and (b) how well they could discriminate tumor regions from nontumor regions. Our results demonstrate that a majority of the popular Haralick features are reproducible in over 99% of all cross-site comparisons, as well as achieve excellent cross-site discriminability (classification accuracy of ). By contrast, a majority of Laws features are highly variable across sites (reproducible in of all cross-site comparisons) as well as resulting in low cross-site classifier accuracies ( ), likely due to a large number of noisy filter responses that can be extracted. These trends suggest that only a subset of radiomic features and associated parameters may be both reproducible and discriminable enough for use within machine learning classifier schemes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/1.JMI.6.2.024502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566001PMC
April 2019

Beyond Traditional Structure-Based Drug Design: The Role of Iron Complexation, Strain, and Water in the Binding of Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylase 2.

ACS Omega 2019 Apr 12;4(4):6703-6708. Epub 2019 Apr 12.

Janssen Research & Development, San Diego, California 92121, United States.

A combination of structure-based drug design and medicinal chemistry efforts led us from benzimidazole-2-carboxamide with modestly active hypoxia-inducible factor prolyl hydroxylase 2 inhibition to certain benzimidazole-2-pyrazole carboxylic acids that were more potent as well as orally efficacious stimulators of erythropoietin secretion in our in vivo mouse model. To better understand the structure-activity relationship, it was necessary to account for (i) the complexation of the ligand with the active site Fe, (ii) the strain incurred by the ligand upon binding, and (iii) certain key water interactions identified by a crystal structure analysis. With this more complete computational model, we arrived at an overarching paradigm that accounted for the potency differences between benzimidazole-2-carboxamide and benzimidazole-2-pyrazole carboxylic acid enzyme inhibitors. Moreover, the computational paradigm allowed us to anticipate that the bioisostere replacement strategy (amide → pyrazole), which had shown success in the benzimidazole series, was not generally applicable to other series. This illustrates that to fully reconcile the important ligand-active site interactions for certain targets, one often needs to move beyond traditional structure-based drug design (such as crystallographic analysis, docking, etc.) and appeal to a higher level of computational theory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.9b00199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547624PMC
April 2019

Diffusion-weighted MRI in Multicenter Trials of Breast Cancer.

Radiology 2019 05 2;291(2):546. Epub 2019 Apr 2.

Department of Radiology, University of California, San Francisco, San Francisco, Calif †.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2019190446DOI Listing
May 2019

Comparing radiomic classifiers and classifier ensembles for detection of peripheral zone prostate tumors on T2-weighted MRI: a multi-site study.

BMC Med Imaging 2019 02 28;19(1):22. Epub 2019 Feb 28.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.

Background: For most computer-aided diagnosis (CAD) problems involving prostate cancer detection via medical imaging data, the choice of classifier has been largely ad hoc, or been motivated by classifier comparison studies that have involved large synthetic datasets. More significantly, it is currently unknown how classifier choices and trends generalize across multiple institutions, due to heterogeneous acquisition and intensity characteristics (especially when considering MR imaging data). In this work, we empirically evaluate and compare a number of different classifiers and classifier ensembles in a multi-site setting, for voxel-wise detection of prostate cancer (PCa) using radiomic texture features derived from high-resolution in vivo T2-weighted (T2w) MRI.

Methods: Twelve different supervised classifier schemes: Quadratic Discriminant Analysis (QDA), Support Vector Machines (SVMs), naïve Bayes, Decision Trees (DTs), and their ensemble variants (bagging, boosting), were compared in terms of classification accuracy as well as execution time. Our study utilized 85 prostate cancer T2w MRI datasets acquired from across 3 different institutions (1 for discovery, 2 for independent validation), from patients who later underwent radical prostatectomy. Surrogate ground truth for disease extent on MRI was established by expert annotation of pre-operative MRI through spatial correlation with corresponding ex vivo whole-mount histology sections. Classifier accuracy in detecting PCa extent on MRI on a per-voxel basis was evaluated via area under the ROC curve.

Results: The boosted DT classifier yielded the highest cross-validated AUC (= 0.744) for detecting PCa in the discovery cohort. However, in independent validation, the boosted QDA classifier was identified as the most accurate and robust for voxel-wise detection of PCa extent (AUCs of 0.735, 0.683, 0.768 across the 3 sites). The next most accurate and robust classifier was the single QDA classifier, which also enjoyed the advantage of significantly lower computation times compared to any of the other methods.

Conclusions: Our results therefore suggest that simpler classifiers (such as QDA and its ensemble variants) may be more robust, accurate, and efficient for prostate cancer CAD problems, especially in the context of multi-site validation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12880-019-0308-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396464PMC
February 2019

Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer.

Clin Cancer Res 2019 04 11;25(7):2072-2079. Epub 2019 Jan 11.

Department of Medicine, Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: The CDK 4/6 inhibitor palbociclib rapidly and reversibly inhibits the cell cycle. The goal of this study was to exploit the cell cycle through intermittent, alternating dosing with palbociclib/paclitaxel to enhance efficacy. We determined the combination dose-limiting toxicity (DLT) in patients with Rb protein-expressing, advanced breast cancer.

Patients And Methods: This open-label, phase I trial (NCT01320592) enrolled patients to sequential cohorts of palbociclib orally dosed intermittently between days 1 and 19 of a 28-day cycle alternating with weekly paclitaxel. Dose escalation proceeded in a standard 3 + 3 design. Ten additional patients received the combination at the recommended phase II dose (RP2D). Those who reached response plateau ≥6 cycles could continue on palbociclib alone on a 3 week on/1 week off schedule at one dose level above their combination dose.

Results: Twenty-seven patients enrolled. Although there was only 1 DLT (grade 3 alanine aminotransferase/aspartate aminotransferase at 125 mg), neutropenia (NTP) requiring dose modification in cycle 1 (C1) resulted in an RP2D of 75 mg palbociclib/80 mg/m paclitaxel. During C1, the most common adverse event was NTP, occurring in 15 patients (55.6%); grade 1 or 2 nausea and peripheral neuropathy were also observed in 8 patients each (29.6%). The clinical benefit rate was 55% at the RP2D; benefit was observed across all receptor subtypes.

Conclusions: Alternating sequential palbociclib/paclitaxel in patients with Rb advanced breast cancer is feasible and safe, without evidence of additive toxicity. This represents a new application for CDK 4/6 inhibitors in Rb breast cancer regardless of subtype; efficacy trials are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-0790DOI Listing
April 2019

Dynamic Contrast-enhanced MRI Detects Responses to Stroma-directed Therapy in Mouse Models of Pancreatic Ductal Adenocarcinoma.

Clin Cancer Res 2019 04 26;25(7):2314-2322. Epub 2018 Dec 26.

Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: The dense stroma underlies the drug resistance of pancreatic ductal adenocarcinoma (PDA) and has motivated the development of stroma-directed drugs. Our objective is to test the concept that dynamic contrast-enhanced (DCE) MRI using FDA-approved contrast media, an imaging method sensitive to the tumor microenvironment, can detect early responses to stroma-directed drug.

Experimental Design: Imaging studies were performed in three mouse models exhibiting high desmoplastic reactions: the autochthonous PDA in genetically engineered mice (KPC), an orthotopic model in syngeneic mice, and a xenograft model of human PDA in athymic mice. An investigational drug, PEGPH20 (pegvorhyaluronidase alfa), which degrades hyaluronan (HA) in the stroma of PDA, was injected alone or in combination with gemcitabine.

Results: At 24 hours after a single injection of PEGPH20, , a DCE-MRI-derived marker that measures how fast a unit volume of contrast media is transferred from capillaries to interstitial space, increased 56% and 50% from baseline in the orthotopic and xenograft tumors, respectively, compared with a 4% and 6% decrease in vehicle groups (both < 0.05). Similarly, after three combined treatments, in KPC mice increased 54%, whereas it decreased 4% in controls treated with gemcitabine alone ( < 0.05). Consistently, after a single injection of PEGPH20, tumor HA content assessed by IHC was reduced substantially in all three models while drug delivery (measured by paclitaxel accumulation in tumor) was increased by 2.6-fold.

Conclusions: These data demonstrated a DCE-MRI marker, , can detect early responses to stroma-directed drug and reveal the sustained effect of combination treatment (PEGPH20+ gemcitabine).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-2276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445712PMC
April 2019

Quantitative imaging biomarkers alliance (QIBA) recommendations for improved precision of DWI and DCE-MRI derived biomarkers in multicenter oncology trials.

J Magn Reson Imaging 2019 06 19;49(7):e101-e121. Epub 2018 Nov 19.

Departments of Medical Physics, Radiology, and Human Oncology, University of Wisconsin School of Medicine, Madison, Wisconsin, USA.

Physiological properties of tumors can be measured both in vivo and noninvasively by diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging. Although these techniques have been used for more than two decades to study tumor diffusion, perfusion, and/or permeability, the methods and studies on how to reduce measurement error and bias in the derived imaging metrics is still lacking in the literature. This is of paramount importance because the objective is to translate these quantitative imaging biomarkers (QIBs) into clinical trials, and ultimately in clinical practice. Standardization of the image acquisition using appropriate phantoms is the first step from a technical performance standpoint. The next step is to assess whether the imaging metrics have clinical value and meet the requirements for being a QIB as defined by the Radiological Society of North America's Quantitative Imaging Biomarkers Alliance (QIBA). The goal and mission of QIBA and the National Cancer Institute Quantitative Imaging Network (QIN) initiatives are to provide technical performance standards (QIBA profiles) and QIN tools for producing reliable QIBs for use in the clinical imaging community. Some of QIBA's development of quantitative diffusion-weighted imaging and dynamic contrast-enhanced QIB profiles has been hampered by the lack of literature for repeatability and reproducibility of the derived QIBs. The available research on this topic is scant and is not in sync with improvements or upgrades in MRI technology over the years. This review focuses on the need for QIBs in oncology applications and emphasizes the importance of the assessment of their reproducibility and repeatability. Level of Evidence: 5 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;49:e101-e121.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.26518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526078PMC
June 2019

The Importance of Imaging in Radiation Oncology for National Clinical Trials Network Protocols.

Int J Radiat Oncol Biol Phys 2018 11 18;102(4):775-782. Epub 2018 Oct 18.

Imaging and Radiation Oncology Core QA Center Rhode Island, University of Massachusetts Medical School, Lincoln, Rhode Island.

Imaging is essential in successfully executing radiation therapy (RT) in oncology clinical trials. As technically sophisticated diagnostic imaging and RT were incorporated into trials, quality assurance in the National Clinical Trials Network groups entered a new era promoting image acquisition and review. Most trials involving RT require pre- and post-therapy imaging for target validation and outcome assessment. The increasing real-time (before and during therapy) imaging and RT object reviews are to ensure compliance with trial objectives. Objects easily transmit digitally for review from anywhere in the world. Physician interpretation of imaging and image application to RT treatment plans is essential for optimal trial execution. Imaging and RT data sets are used to credential RT sites to confirm investigator and institutional ability to meet trial target volume delineation and delivery requirements. Real-time imaging and RT object reviews can be performed multiple times during a trial to assess response to therapy and application of RT objects. This process has matured into an effective data management mechanism. When necessary, site and study investigators review objects together through web media technologies to ensure the patient is enrolled on the appropriate trial and the intended RT is planned and executed in a trial-compliant manner. Real-time imaging review makes sure: (1) the patient is entered and eligible for the trial, (2) the patient meets trial-specific adaptive therapy requirements, if applicable, and (3) the intended RT is according to trial guidelines. This review ensures the study population is uniform and the results are believable and can be applied to clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2018.08.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510266PMC
November 2018

The Influence of Imaging in the Modern Practice of Radiation Oncology.

Int J Radiat Oncol Biol Phys 2018 11 18;102(4):680-682. Epub 2018 Oct 18.

Imaging and Radiation Oncology Core (IROC) Rhode Island/University of Massachusetts Medical School, Worcester, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2018.08.028DOI Listing
November 2018

Test-retest repeatability and reproducibility of ADC measures by breast DWI: Results from the ACRIN 6698 trial.

J Magn Reson Imaging 2019 06 22;49(6):1617-1628. Epub 2018 Oct 22.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.

Background: Quantitative diffusion-weighted imaging (DWI) MRI is a promising technique for cancer characterization and treatment monitoring. Knowledge of the reproducibility of DWI metrics in breast tumors is necessary to apply DWI as a clinical biomarker.

Purpose: To evaluate the repeatability and reproducibility of breast tumor apparent diffusion coefficient (ADC) in a multi-institution clinical trial setting, using standardized DWI protocols and quality assurance (QA) procedures.

Study Type: Prospective.

Subjects: In all, 89 women from nine institutions undergoing neoadjuvant chemotherapy for invasive breast cancer.

Field Strength/sequence: DWI was acquired before and after patient repositioning using a four b-value, single-shot echo-planar sequence at 1.5T or 3.0T.

Assessment: A QA procedure by trained operators assessed artifacts, fat suppression, and signal-to-noise ratio, and determine study analyzability. Mean tumor ADC was measured via manual segmentation of the multislice tumor region referencing DWI and contrast-enhanced images. Twenty cases were evaluated multiple times to assess intra- and interoperator variability. Segmentation similarity was assessed via the Sørenson-Dice similarity coefficient.

Statistical Tests: Repeatability and reproducibility were evaluated using within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), agreement index (AI), and repeatability coefficient (RC). Correlations were measured by Pearson's correlation coefficients.

Results: In all, 71 cases (80%) passed QA evaluation: 44 at 1.5T, 27 at 3.0T; 60 pretreatment, 11 after 3 weeks of taxane-based treatment. ADC repeatability was excellent: wCV = 4.8% (95% confidence interval [CI] 4.0, 5.7%), ICC = 0.97 (95% CI 0.95, 0.98), AI = 0.83 (95% CI 0.76, 0.87), and RC = 0.16 * 10 mm /sec (95% CI 0.13, 0.19). The results were similar across field strengths and timepoint subgroups. Reproducibility was excellent: interreader ICC = 0.92 (95% CI 0.80, 0.97) and intrareader ICC = 0.91 (95% CI 0.78, 0.96).

Data Conclusion: Breast tumor ADC can be measured with excellent repeatability and reproducibility in a multi-institution setting using a standardized protocol and QA procedure. Improvements to DWI image quality could reduce loss of data in clinical trials.

Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1617-1628.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.26539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524146PMC
June 2019

Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial.

Radiology 2018 12 4;289(3):618-627. Epub 2018 Sep 4.

From the Department of Radiology, University of Washington, 825 Eastlake Ave E, G2-600, Seattle, WA 98109 (S.C.P.); Department of Biostatistics (Z.Z.) and Center for Statistical Sciences (Z.Z., H.S.M., J.R.), Brown University, Providence, RI; American College of Radiology Imaging Network (ACRIN), Reston, Va (Z.Z., H.S.M., J.R.); Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, Calif (D.C.N., J.E.G., B.N.J., L.J.E., N.M.H.); Department of Radiology/MRI, University of Michigan, Ann Arbor, Mich (T.L.C.); Department of Radiology, University of Pennsylvania, Philadelphia, Pa (M.A.R.); Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minn (P.J.B.); American College of Radiology and ECOG-ACRIN Cancer Research Group, Reston, Va (L.C.); Department of Radiology, University of Alabama, Birmingham, Birmingham, Ala (H.R.U.); Department of Radiology, University of California, San Diego, San Diego, Calif (H.O.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex and the University of Texas Southwestern Medical Center, Dallas, Tex (B.D.); Department of Radiology, Oregon Health and Science University, Portland, Ore (K.O.); Department of Radiology, University of Chicago, Chicago, Ill (H.A.); and Department of Diagnostic Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla and Department of Women's Imaging, St Joseph's Women's Hospital, Tampa, Fla (J.S.D.).

Purpose To determine if the change in tumor apparent diffusion coefficient (ADC) at diffusion-weighted (DW) MRI is predictive of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancer. Materials and Methods In this prospective multicenter study, 272 consecutive women with breast cancer were enrolled at 10 institutions (from August 2012 to January 2015) and were randomized to treatment with 12 weekly doses of paclitaxel (with or without an experimental agent), followed by 12 weeks of treatment with four cycles of anthracycline. Each woman underwent breast DW MRI before treatment, at early treatment (3 weeks), at midtreatment (12 weeks), and after treatment. Percentage change in tumor ADC from that before treatment (ΔADC) was measured at each time point. Performance for predicting pCR was assessed by using the area under the receiver operating characteristic curve (AUC) for the overall cohort and according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype. Results The final analysis included 242 patients with evaluable serial imaging data, with a mean age of 48 years ± 10 (standard deviation); 99 patients had HR-positive (hereafter, HR+)/HER2-negative (hereafter, HER2-) disease, 77 patients had HR-/HER2- disease, 42 patients had HR+/HER2+ disease, and 24 patients had HR-/HER2+ disease. Eighty (33%) of 242 patients experienced pCR. Overall, ΔADC was moderately predictive of pCR at midtreatment/12 weeks (AUC = 0.60; 95% confidence interval [CI]: 0.52, 0.68; P = .017) and after treatment (AUC = 0.61; 95% CI: 0.52, 0.69; P = .013). Across the four disease subtypes, midtreatment ΔADC was predictive only for HR+/HER2- tumors (AUC = 0.76; 95% CI: 0.62, 0.89; P < .001). In a test subset, a model combining tumor subtype and midtreatment ΔADC improved predictive performance (AUC = 0.72; 95% CI: 0.61, 0.83) over ΔADC alone (AUC = 0.57; 95% CI: 0.44, 0.70; P = .032.). Conclusion After 12 weeks of therapy, change in breast tumor apparent diffusion coefficient at MRI predicts complete pathologic response to neoadjuvant chemotherapy. © RSNA, 2018 Online supplemental material is available for this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2018180273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283325PMC
December 2018

MRI, Clinical Examination, and Mammography for Preoperative Assessment of Residual Disease and Pathologic Complete Response After Neoadjuvant Chemotherapy for Breast Cancer: ACRIN 6657 Trial.

AJR Am J Roentgenol 2018 Jun 30;210(6):1376-1385. Epub 2018 Apr 30.

12 Department of Radiology, University of California, 1600 Divisadero St, C255, Box 1667, San Francisco, CA 94115.

Objective: The objective of our study was to determine the accuracy of preoperative measurements for detecting pathologic complete response (CR) and assessing residual disease after neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer.

Subjects And Methods: The American College of Radiology Imaging Network 6657 Trial prospectively enrolled women with ≥ 3 cm invasive breast cancer receiving NACT. Preoperative measurements of residual disease included longest diameter by mammography, MRI, and clinical examination and functional volume on MRI. The accuracy of preoperative measurements for detecting pathologic CR and the association with final pathology size were assessed for all lesions, separately for single masses and nonmass enhancements (NMEs), multiple masses, and lesions without ductal carcinoma in situ (DCIS).

Results: In the 138 women with all four preoperative measures, longest diameter by MRI showed the highest accuracy for detecting pathologic CR for all lesions and NME (AUC = 0.76 and 0.84, respectively). There was little difference across preoperative measurements in the accuracy of detecting pathologic CR for single masses (AUC = 0.69-0.72). Longest diameter by MRI and longest diameter by clinical examination showed moderate ability for detecting pathologic CR for multiple masses (AUC = 0.78 and 0.74), and longest diameter by MRI and longest diameter by mammography showed moderate ability for detecting pathologic CR for tumors without DCIS (AUC = 0.74 and 0.71). In subjects with residual disease, longest diameter by MRI exhibited the strongest association with pathology size for all lesions and single masses (r = 0.33 and 0.47). Associations between preoperative measures and pathology results were not significantly influenced by tumor subtype or mammographic density.

Conclusion: Our results indicate that measurement of longest diameter by MRI is more accurate than by mammography and clinical examination for preoperative assessment of tumor residua after NACT and may improve surgical planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.17.18323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615034PMC
June 2018

Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma: High Rates of Local Control With Low Toxicity.

Am J Clin Oncol 2018 Nov;41(11):1118-1124

Departments of *Radiation Oncology ∥Medical Oncology #Transplant Surgery **Interventional Radiology ††Radiology †Leonard Davis Institute of Health Economics §Perelman School of Medicine ¶Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA ‡Department of Radiation Oncology, Siteman Cancer Center, Washington University in Saint Louis, Saint Louis, MO.

Objectives: Stereotactic body radiotherapy (SBRT) is potentially curative treatment for small hepatocellular carcinomas (HCC), but data are limited on its efficacy and toxicity. We hypothesized that SBRT can achieve excellent local control (LC) with acceptable toxicity treating HCC lesions, even in advanced cirrhosis.

Materials And Methods: Thirty-seven nonmetastatic HCC patients received SBRT to 43 lesions between October 2012 and April 2016. Median dose was 50 Gy/5 fractions. All Child-Pugh (CP) ≥B patients underwent a planned 1-month break after the first 3 fractions to assess hepatic toxicity. Patients were treated without separately placed fiducial markers using Linac-based SBRT with breath-hold (67%) or 4D-computed tomography with compression belt (33%) to reduce motion. Patients underwent magnetic resonance imaging q3 months post-SBRT.

Results: Median age was 65 (range, 44 to 88). Pre-SBRT mean CP was 6.4 (range, A5 to C11). Nine (24%) had CP≥B8. Thirty-one of 33 patients (93%) had prior liver-directed therapy (median 2). Seventeen (40%) had solitary lesions. Median lesion diameter was 2.7 cm (range, 1.1 to 5.6). Median follow-up was 14 months (range, 2 to 45). There was 1 local failure (multifocal HCC with 3 prior transarterial chemoembolization). LC, freedom from liver progression, and overall survival at 12 months was 95%, 66%, 87% in the full cohort, and 100%, 76%, 93% for patients with solitary lesions. Four had grade 3 toxicity (ascites [n=2]/gastrointestinal bleed [n=1]/capsular pain [n=1]). Eight of 9 CP≥B8 patients had no grade ≥3 hepatic toxicity.

Conclusions: SBRT for HCC is well-tolerated even in patients with advanced cirrhosis and prior liver-directed treatment and provides excellent LC even for larger lesions that cannot be controlled with radiofrequency ablation. LC with SBRT compares favorably to other liver-directed therapies. Prospective studies comparing SBRT with other liver-directed therapies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/COC.0000000000000435DOI Listing
November 2018

The eIF2α Kinase Heme-Regulated Inhibitor Protects the Host from Infection by Regulating Intracellular Pathogen Trafficking.

Infect Immun 2018 03 20;86(3). Epub 2018 Feb 20.

Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA

The host employs both cell-autonomous and system-level responses to limit pathogen replication in the initial stages of infection. Previously, we reported that the eukaryotic initiation factor 2α (eIF2α) kinases heme-regulated inhibitor (HRI) and protein kinase R (PKR) control distinct cellular and immune-related activities in response to diverse bacterial pathogens. Specifically for , there was reduced translocation of the pathogen to the cytosolic compartment in HRI-deficient cells and consequently reduced loading of pathogen-derived antigens on major histocompatibility complex class I (MHC-I) complexes. Here we show that mice, as well as wild-type mice treated with an HRI inhibitor, are more susceptible to listeriosis. In the first few hours of infection, there was much greater pathogen proliferation in the liver of mice than in the liver of mice. Further, there was a rapid increase of serum interleukin-6 (IL-6) levels in mice in the first few hours of infection whereas the increase in IL-6 levels in mice was notably delayed. Consistent with these findings, the rate of listeriolysin O (LLO)-dependent pathogen efflux from infected macrophages and fibroblasts was significantly higher than the rate seen with infected cells. Treatment of cells with an eIF2α kinase activator enhanced both the HRI-dependent and PKR-dependent infection phenotypes, further indicating the pharmacologically malleability of this signaling pathway. Collectively, these results suggest that HRI mediates the cellular confinement and killing of virulent in addition to promoting a system-level cytokine response and that both are required to limit pathogen replication during the first few hours of infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/IAI.00707-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820965PMC
March 2018

The role of Imaging and Radiation Oncology Core for precision medicine era of clinical trial.

Transl Lung Cancer Res 2017 Dec;6(6):621-624

IROC/NCTN, University of Pennsylvania, Philadelphia, PA, USA.

Imaging and Radiation Oncology Core (IROC) services have been established for the quality assurance (QA) of imaging and radiotherapy (RT) for NCI's Clinical Trial Network (NCTN) for any trials that contain imaging or RT. The randomized clinical trial is the gold standard for evidence-based medicine. QA ensures data quality, preventing noise from inferior treatments obscuring clinical trial outcome. QA is also found to be cost-effective. IROC has made great progress in multi-institution standardization and is expected to lead QA standardization, QA science in imaging and RT and to advance quality data analysis with big data in the future. The QA in the era of precision medicine is of paramount importance, when individualized decision making may depend on the quality and accuracy of RT and imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tlcr.2017.09.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709130PMC
December 2017

Cough in Ambulatory Immunocompromised Adults: CHEST Expert Panel Report.

Chest 2017 11 19;152(5):1038-1042. Epub 2017 Aug 19.

UMass Memorial Medical Center, Worcester, MA.

Background: Cough is a common symptom prompting patients to seek medical care. Like patients in the general population, patients with compromised immune systems also seek care for cough. However, it is unclear whether the causes of cough in immunocompromised patients who are deemed unlikely to have a life-threating condition and a normal or unchanged chest radiograph are similar to those in persons with cough and normal immune systems.

Methods: We conducted a systematic review to answer the question: What are the most common causes of cough in ambulatory immunodeficient adults with normal chest radiographs? Studies of patients ≥ 18 years of age with immune deficiency, cough of any duration, and normal or unchanged chest radiographs were included and assessed for relevance and quality. Based on the systematic review, suggestions were developed and voted on using the American College of Chest Physicians (CHEST) methodology framework.

Results: The results of the systematic review revealed no high-quality evidence to guide the clinician in determining the likely causes of cough specifically in immunocompromised ambulatory patients with normal chest radiographs.

Conclusions: Based on a systematic review, we found no evidence to assess whether or not the proper initial evaluation of cough in immunocompromised patients is different from that in immunocompetent persons. A consensus of the panel suggested that the initial diagnostic algorithm should be similar to that for immunocompetent persons but that the context of the type and severity of the immune defect, geographic location, and social determinants be considered. The major modifications to the 2006 CHEST Cough Guidelines are the suggestions that TB should be part of the initial evaluation of patients with cough and HIV infection who reside in regions with a high prevalence of TB, regardless of the radiographic findings, and that specific causes and immune defects be considered in all patients in whom the initial evaluation is unrevealing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2017.07.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026263PMC
November 2017

Disparities in staging prostate magnetic resonance imaging utilization for nonmetastatic prostate cancer patients undergoing definitive radiation therapy.

Adv Radiat Oncol 2016 Oct-Dec;1(4):325-332. Epub 2016 Jul 25.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland.

Purpose: There is growing evidence supporting incorporating multiparametric (mp) magnetic resonance imaging (MRI) scans into risk stratification, active surveillance, and treatment paradigms for prostate cancer. The purpose of our study was to determine whether demographic disparities exist in staging MRI utilization for prostate cancer patients.

Methods And Materials: An institutional database of 705 nonmetastatic prostate cancer patients treated with radiation therapy from 2005 through 2013 was used to identify patients undergoing versus not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable logistic regression evaluated the relationship of clinical and demographic characteristics with MRI utilization.

Results: All demographic variables assessed, except the other race category, were significantly associated with MRI utilization (all < .05), including age (odds ratio [OR], 0.92), black race (OR, 0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable analysis stratified by D'Amico risk group, age remained significant across all risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95% confidence interval, 0.16-0.86) disparities persisted in the low-risk group. Clinical stage T3 remained associated in the high-risk group. For race specifically, the percentages of whites, blacks, and others undergoing MRI in the overall cohort and by risk group were, respectively: overall, 80% (343/427), 68% (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%, 72%, and 95%; and high risk, 72%, 72%, and 100%.

Conclusions: In this urban, academic center cohort, older patients across all risk groups and black or nonprivate insurance patients in the low risk group were less likely to undergo staging prostate MRI scans. Further research should investigate these differences to ensure equitable utilization across all demographic groups considering the burden of prostate cancer disparities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.adro.2016.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514159PMC
July 2016

Antiangiogenic tyrosine kinase inhibitors in colorectal cancer: is there a path to making them more effective?

Cancer Chemother Pharmacol 2017 Oct 18;80(4):661-671. Epub 2017 Jul 18.

Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19146, USA.

Antiangiogenic therapy has a proven survival benefit in metastatic colorectal cancer. Inhibition of the VEGF pathway using a variety of extracellular antibody approaches has clear benefit in combination with chemotherapy, while intracellular blockade using tyrosine kinase inhibitors (TKIs) such as sorafenib and regorafenib has had more limited success. Pharmacodynamic modeling using modalities such as DCE-MRI indicates potent antiangiogenic effects of these TKIs, yet numerous combination therapies, primarily with chemotherapy, have failed to demonstrate an additive benefit. The sole comparative study of a single agent TKI against placebo showed a survival benefit of regorafenib in patients with advanced, refractory disease. Preclinical data demonstrate synergy between antiantiogenic TKIs and targeted interventions including autophagy inhibition, and together with a renewed effort to define markers of susceptibility, such combinations may be a way to improve the limited efficacy of this once-promising drug class.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-017-3389-3DOI Listing
October 2017

Performance Observations of Scanner Qualification of NCI-Designated Cancer Centers: Results From the Centers of Quantitative Imaging Excellence (CQIE) Program.

Acad Radiol 2017 02 29;24(2):232-245. Epub 2016 Nov 29.

Cancer Imaging Program, National Cancer Institute, Bethesda, Maryland.

We present an overview of the Centers for Quantitative Imaging Excellence (CQIE) program, which was initiated in 2010 to establish a resource of clinical trial-ready sites within the National Cancer Institute (NCI)-designated Cancer Centers (NCI-CCs) network. The intent was to enable imaging centers in the NCI-CCs network capable of conducting treatment trials with advanced quantitative imaging end points. We describe the motivations for establishing the CQIE, the process used to initiate the network, the methods of site qualification for positron emission tomography, computed tomography, and magnetic resonance imaging, and the results of the evaluations over the subsequent 3 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.acra.2016.09.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389125PMC
February 2017

MR spectroscopy of breast cancer for assessing early treatment response: Results from the ACRIN 6657 MRS trial.

J Magn Reson Imaging 2017 07 16;46(1):290-302. Epub 2016 Dec 16.

Department of Radiology, University of California, San Francisco, California, USA.

Purpose: To estimate the accuracy of predicting response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer using MR spectroscopy (MRS) measurements made very early in treatment.

Materials And Methods: This prospective Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol was approved by the American College of Radiology and local-site institutional review boards. One hundred nineteen women with invasive breast cancer of ≥3 cm undergoing NACT were enrolled between September 2007 and April 2010. MRS measurements of the concentration of choline-containing compounds ([tCho]) were performed before the first chemotherapy regimen (time point 1, TP1) and 20-96 h after the first cycle of treatment (TP2). The change in [tCho] was assessed for its ability to predict pathologic complete response (pCR) and radiologic response using the area under the receiver operating characteristic curve (AUC) and logistic regression models.

Results: Of the 119 subjects enrolled, only 29 cases (24%) with eight pCRs provided usable data for the primary analysis. Technical challenges in acquiring quantitative MRS data in a multi-site trial setting limited the capture of usable data. In this limited data set, the decrease in tCho from TP1 to TP2 had poor ability to predict either pCR (AUC = 0.53, 95% confidence interval [CI]: 0.27-0.79) or radiologic response (AUC = 0.51, 95% CI: 0.27-0.75).

Conclusion: The technical difficulty of acquiring quantitative MRS data in a multi-site clinical trial setting led to a low yield of analyzable data, which was insufficient to accurately measure the ability of early MRS measurements to predict response to NACT.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:290-302.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.25560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464996PMC
July 2017

Glutamatergic stimulation induces GluN2B translation by the nitric oxide-Heme-Regulated eIF2α kinase in cortical neurons.

Oncotarget 2016 09;7(37):58876-58892

Laboratory of Molecular Physiology, Faculty of Health and Life Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.

The activation of N-Methyl D-Aspartate Receptor (NMDAR) by glutamate is crucial in the nervous system function, particularly in memory and learning. NMDAR is composed by two GluN1 and two GluN2 subunits. GluN2B has been reported to participate in the prevalent NMDAR subtype at synapses, the GluN1/2A/2B. Here we studied the regulation of GluN2B expression in cortical neurons finding that glutamate up-regulates GluN2B translation through the action of nitric oxide (NO), which induces the phosphorylation of the eukaryotic translation initiation factor 2 α (eIF2α). It is a process mediated by the NO-heme-regulated eIF2α kinase (HRI), as the effect was avoided when a specific HRI inhibitor or a HRI small interfering RNA (siHRI) were used. We found that the expressed GluN2B co-localizes with PSD-95 at the postsynaptic ending, which strengthen the physiological relevance of the proposed mechanism. Moreover the receptors bearing GluN2B subunits upon NO stimulation are functional as high Ca2+ entry was measured and increases the co-localization between GluN2B and GluN1 subunits. In addition, the injection of the specific HRI inhibitor in mice produces a decrease in memory retrieval as tested by the Novel Object Recognition performance. Summarizing our data suggests that glutamatergic stimulation induces HRI activation by NO to trigger GluN2B expression and this process would be relevant to maintain postsynaptic activity in cortical neurons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.11417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312282PMC
September 2016
-->