Publications by authors named "Kristin Jensen"

79 Publications

Iterative reconstruction improves image quality and reduces radiation dose in trauma protocols; A human cadaver study.

Acta Radiol Open 2021 Oct 18;10(10):20584601211055389. Epub 2021 Nov 18.

Department of Radiology and Nuclear Medicine, Oslo University Hospital Ullevål, Oslo, Norway.

Background: Radiation-related cancer risk is an object of concern in CT of trauma patients, as these represent a young population. Different radiation reducing methods, including iterative reconstruction (IR), and spilt bolus techniques have been introduced in the recent years in different large scale trauma centers.

Purpose: To compare image quality in human cadaver exposed to thoracoabdominal computed tomography using IR and standard filtered back-projection (FBP) at different dose levels.

Material And Methods: Ten cadavers were scanned at full dose and a dose reduction in CTDIvol of 5 mGy (low dose 1) and 7.5 mGy (low dose 2) on a Siemens Definition Flash 128-slice computed tomography scanner. Low dose images were reconstructed with FBP and Sinogram affirmed iterative reconstruction (SAFIRE) level 2 and 4. Quantitative image quality was analyzed by comparison of contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). Qualitative image quality was evaluated by use of visual grading regression (VGR) by four radiologists.

Results: Readers preferred SAFIRE reconstructed images over FBP at a dose reduction of 40% (low dose 1) and 56% (low dose 2), with significant difference in overall impression of image quality. CNR and SNR showed significant improvement for images reconstructed with SAFIRE 2 and 4 compared to FBP at both low dose levels.

Conclusions: Iterative image reconstruction, SAFIRE 2 and 4, resulted in equal or improved image quality at a dose reduction of up to 56% compared to full dose FBP and may be used a strong radiation reduction tool in the young trauma population.
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http://dx.doi.org/10.1177/20584601211055389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619783PMC
October 2021

Authors' Response to "Importance of Oral Health for Adolescents and Adults With Down Syndrome".

Am J Prev Med 2021 10;61(4):e213

Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; The Kempe Center for the Prevention and Treatment of Child Abuse and Neglect, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

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http://dx.doi.org/10.1016/j.amepre.2021.04.002DOI Listing
October 2021

Quantitative benchmarking of iodine imaging for two CT spectral imaging technologies: a phantom study.

Eur Radiol Exp 2021 Jun 23;5(1):24. Epub 2021 Jun 23.

Department of Life Sciences and Health, Oslo Metropolitan University, Box 4, St. Olavs plass, 0130, Oslo, Norway.

Background: The aim of this study was to quantitatively benchmark iodine imaging across specific virtual monoenergetic energy levels, iodine maps and virtual non-contrast images with different phantom sizes and iodine concentrations, using a rapid switching dual-energy CT (DECT) and a dual source DECT, in order to investigate accuracy and potential differences between the technologies.

Methods: Solutions of iodine contrast (10, 20, 30, 50, and 100 mg/mL), sterile water and saline were scanned in a phantom on a rapid switching single-source and dual-source DECT scanners from two different vendors. The phantom was equipped with polyurethane rings simulating three body sizes. The datasets were reconstructed in virtual monoenergetic energy levels (70, 80, 90, 100, 110, 120, 130, and 140 keV), virtual non-contrast images and iodine maps. HU and iodine concentrations were measured by placing ROIs in the iodine solutions.

Results: The iodine concentrations were reproduced with a high degree of accuracy for the single-source DECT (1.8-9.0%), showing a slight dependence on phantom size. The dual source DECT technique showed deviant values (error -33.8 to 12.0%) for high concentrations. In relation to the virtual non-contrast measurements, the images from both vendors were affected by the iodine concentration and phantom size (-127.8 to 539.1 HU). Phantom size did not affect the calculated monoenergetic attenuation values, but the attenuation values varied between the scanners.

Conclusions: Quantitative measurements of post-processed images are dependent on the concentration of iodine, the phantom size and different technologies. However, our study indicates that the iodine maps are reliable for quantification of iodine.
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http://dx.doi.org/10.1186/s41747-021-00224-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219825PMC
June 2021

Implementation of Collection of Patients' Disability Status by Centralized Scheduling.

Jt Comm J Qual Patient Saf 2021 10 24;47(10):627-636. Epub 2021 May 24.

Background: Collection of disability status in electronic health records (EHRs) is critical to addressing the significant health care disparities experienced by patients with disabilities. Despite this, little evidence exists to inform implementation.

Methods: This pilot trial evaluated the implementation of collection of patients' disability status during primary care new patient registration by centralized call center staff. The study took place over six weeks at an academic hospital system in Colorado. Staff received a 30-minute training on how to ask and document disability status in the EHR. Completion rate of collection, fidelity, and concordance were assessed through chart reviews and recordings of patient registration calls. Focus groups with staff and phone interviews with patients assessed the experience of including disability screeners in patient registration.

Results: A total of 3,673 new patients were registered at one of the 53 primary care clinics during the study period. Completion of disability status in the EHR increased from 9.5% at baseline to 53.5% by the last week of the trial, which was then maintained for eight weeks. Challenges were identified in the recorded calls with fidelity of if and how the questions were asked. No patient complaints were reported, and patients reported no concerns regarding collection of disability status during interviews.

Conclusion: Documenting disability status during patient registration was effective and was not concerning to patients. To make initial steps to providing equitable care, efforts should be made to implement this type of screening universally across the clinical encounter.
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http://dx.doi.org/10.1016/j.jcjq.2021.05.007DOI Listing
October 2021

Predictors of Receipt of Clinical Preventive Services in Adolescents and Adults with Down Syndrome Accessing Medicaid.

Disabil Health J 2021 04 6;14(2):101016. Epub 2020 Nov 6.

University of Colorado School of Medicine, Department of Internal Medicine, Division of General Internal Medicine, 12631 E. 17th Ave., Mailstop B180, 80045, Aurora, CO, USA. Electronic address:

Background: Persons with Down syndrome (DS) require preventive care that addresses their age-/gender- and syndrome-specific needs. Yet, adolescents and adults with DS do not receive these preventive care services as recommended.

Objective/hypothesis: To identify factors that predict receipt of age-/gender- and syndrome-specific preventive healthcare among adolescents and adults with DS. We hypothesized that more healthcare encounters and greater medical complexity would increase receipt of preventive care due to more opportunities to complete these activities.

Methods: Using Medicaid claims (2006-2010) for California, Colorado, Michigan, and Pennsylvania, we conducted a retrospective cohort study of adolescents and adults with DS (≥12 years old). We modeled receipt of both ≥1 wellness examination and ≥1 thyroid function test (TFT) in 2009-2010 as a function of receipt of those same healthcare activities in 2006-08, adjusting for demographics, key comorbidities, and medical complexity using multivariable logistic regression.

Results: In this cohort of 3487 adolescents and adults with DS accessing Medicaid, 17% received both ≥1 wellness examination and ≥1 TFT in 2006-2008, 15% in 2009-2010, and only 7% during both time periods. Despite medical complexity and frequent healthcare interactions, the best predictor of future receipt of these activities was past receipt. State of residence variably impacted receipt of these preventive activities.

Conclusions: Although past receipt of wellness examination and TFT was the best predictor of future receipt of these activities, overall rates were quite low in this cohort of adolescents and adults with DS. Further work is needed to improve preventive healthcare delivery to this vulnerable population.
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http://dx.doi.org/10.1016/j.dhjo.2020.101016DOI Listing
April 2021

Low Rates of Preventive Healthcare Service Utilization Among Adolescents and Adults With Down Syndrome.

Am J Prev Med 2021 01 12;60(1):1-12. Epub 2020 Nov 12.

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado; Kempe Center for the Prevention of Child Abuse and Maltreatment, University of Colorado School of Medicine, Aurora, Colorado.

Introduction: People with Down syndrome have health risks that require specific lifelong preventive health care. With increasing life expectancy, people with Down syndrome also face health conditions typical of their unaffected peers and thus need coordinated health care. The purpose of this study is to describe rates of age/sex- and Down syndrome-specific preventive healthcare activities among adolescents and adults with Down syndrome.

Methods: Using Medicaid claims (2006-2010) in California, Colorado, Michigan, and Pennsylvania, the cohort was defined as people with Down syndrome aged ≥12 years seen by primary care providers and enrolled in Medicaid for ≥45 of 60 months without dual Medicare enrollment (n=3,501). Age focus-consistent primary care providers were defined as having a focus concordant with a patient's age: 12-17 years, child or mixed-focus; ≥26 years, adult or mixed-focus; 18-25 years, any focus. Differences in healthcare activities were evaluated using Pearson's chi-square, Fisher's exact, and Kruskal-Wallis tests. Analyses were performed in 2015-2017.

Results: Of the cohort, 79% had an age focus-consistent primary care provider. However, 40% of adults aged ≥26 years received care from a child-focused primary care provider. Only 43% with an age focus-consistent provider had ≥1 well examination (age focus-inconsistent primary care provider: 35%, p<0.001). Most preventive activities had poor rates (<50%) regardless of age focus consistency between provider and patient age or whether they were age/sex- or Down syndrome-specific (well examinations; vaccinations; sleep apnea; hearing; and breast, cervical, and colon cancer screenings). Lipids, vision, and thyroid screenings reached moderate levels (50% to <80%).

Conclusions: Rates of age/sex- and Down syndrome-specific preventive recommendations were low among adolescents and adults with Down syndrome, regardless of the age focus consistency of their primary care provider. This represents a significant opportunity to improve primary care in this vulnerable population.
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http://dx.doi.org/10.1016/j.amepre.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750281PMC
January 2021

BENCHMARKING OF A NEW AUTOMATIC CT RADIATION DOSE CALCULATOR.

Radiat Prot Dosimetry 2020 Dec;191(3):361-368

Department of Diagnostic Physics, Oslo University Hospital, 0424 Oslo, Norway.

Information on patient radiation dose is essential to meet the radiation protection regulations and the demands of dose optimization. Vendors have developed different tools for patient dose assessment for radiological purposes. In this study, estimated effective doses derived from a new image-based software tool (DoseWatch, GE Healthcare) was benchmarked against the corresponding doses from a dose calculator (CT-Expo, SASCRAD) and a conversion coefficient method. Dose data from 150 adult patients (66 male and 84 female), who underwent CT head, abdominopelvic or chest examinations, were retrospectively collected using DoseWatch. Effective dose estimated by DoseWatch was significantly lower than that of CT-Expo and DLP-E (k) (p ≤ 0.001). For the organ doses, DoseWatch resulted in lower dose than CT-Expo for all the organs with the exception of testis (p ≤ 001) and eye lenses (p ≤ 0.026).
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http://dx.doi.org/10.1093/rpd/ncaa167DOI Listing
December 2020

Evaluation of Image Quality for 7 Iterative Reconstruction Algorithms in Chest Computed Tomography Imaging: A Phantom Study.

J Comput Assist Tomogr 2020 Sep/Oct;44(5):673-680

Department of Radiology and Nuclear Medicine, Ullevål, Oslo University Hospital.

Objectives: This study aimed to evaluate the image quality of 7 iterative reconstruction (IR) algorithms in comparison to filtered back-projection (FBP) algorithm.

Methods: An anthropomorphic chest phantom was scanned on 4 computed tomography scanners and reconstructed with FBP and IR algorithms. Image quality of anatomical details-large/medium-sized pulmonary vessels, small pulmonary vessels, thoracic wall, and small and large lesions-was scored. Furthermore, general impression of noise, image contrast, and artifacts were evaluated. Visual grading regression was used to analyze the data. Standard deviations were measured, and the noise power spectrum was calculated.

Results: Iterative reconstruction algorithms showed significantly better results when compared with FBP for these criteria (regression coefficients/P values in parentheses): vessels (FIRST: -1.8/0.05, AIDR Enhanced: <-2.3/0.01, Veo: <-0.1/0.03, ADMIRE: <-2.1/0.04), lesions (FIRST: <-2.6/0.01, AIDR Enhanced: <-1.9/0.03, IMR1: <-2.7/0.01, Veo: <-2.4/0.02, ADMIRE: -2.3/0.02), image noise (FIRST: <-3.2/0.004, AIDR Enhanced: <-3.5/0.002, IMR1: <-6.1/0.001, iDose: <-2.3/0.02, Veo: <-3.4/0.002, ADMIRE: <-3.5/0.02), image contrast (FIRST: -2.3/0.01, AIDR Enhanced: -2.5/0.01, IMR1: -3.7/0.001, iDose: -2.1/0.02), and artifacts (FIRST: <-3.8/0.004, AIDR Enhanced: <-2.7/0.02, IMR1: <-2.6/0.02, iDose: -2.1/0.04, Veo: -2.6/0.02). The iDose algorithm was the only IR algorithm that maintained the noise frequencies.

Conclusions: Iterative reconstruction algorithms performed differently on all evaluated criteria, showing the importance of careful implementation of algorithms for diagnostic purposes.
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http://dx.doi.org/10.1097/RCT.0000000000001037DOI Listing
September 2020

Molecular profiling of a primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid.

J Cutan Pathol 2020 Sep 15;47(9):860-864. Epub 2020 Jun 15.

Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

Primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid is a rare and aggressive neoplasm. Fewer than 50 cases have been reported in the literature, and the genetic driving mutations are unknown. Herein, we present a case of this rare disease along with the results of molecular profiling via targeted next-generation sequencing. The patient is an 85-year-old man who presented with left eyelid swelling initially thought to be a chalazion. After no response to incision and drainage and antibiotics, an incisional biopsy was performed. Histopathologic sections revealed a proliferation of cells with signet-ring and histiocytoid morphology arranged singly and in cords infiltrating the dermis, subcutaneous tissue, and muscle. The lesional cells strongly expressed cytoplasmic cytokeratin 7 and nuclear androgen receptor. Next-generation sequencing revealed a CDH1 mutation, which is known to confer signet-ring morphology in other carcinomas. Pathogenic mutations in NTRK3, CDKN1B, and PIK3CA were also detected. To our knowledge, this is the first documented genetic analysis of this rare disease with findings that offer insights into disease pathogenesis and potential therapeutic targets.
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http://dx.doi.org/10.1111/cup.13733DOI Listing
September 2020

Integrating genomic features for non-invasive early lung cancer detection.

Nature 2020 04 25;580(7802):245-251. Epub 2020 Mar 25.

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.

Radiologic screening of high-risk adults reduces lung-cancer-related mortality; however, a small minority of eligible individuals undergo such screening in the United States. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq), a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.
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http://dx.doi.org/10.1038/s41586-020-2140-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230734PMC
April 2020

Goblet cell carcinoid of the appendix - diagnostic challenges and treatment updates: a case report and review of the literature.

J Med Case Rep 2018 Sep 24;12(1):275. Epub 2018 Sep 24.

Department of Medicine, Veterans Affairs Central California Health Care System, University of California San Francisco, 2615 E Clinton Ave, Fresno, CA, 93703, USA.

Background: Goblet cell carcinoid is a rare but distinct entity of appendiceal tumors which is a hybrid or mixed tumor consisting of both epithelial (glandular) and neuroendocrine elements containing goblet cells. This entity is important to recognize and appropriately grade as it tends to be more aggressive than typical carcinoid tumors, often presenting with metastatic disease. As a result, the 5-year overall survival is 14-22% in stage III-IV disease. GCC therefore warrants more aggressive surgical and medical (chemotherapy) interventions than typical carcinoid tumors. Through this case report we give a brief update on GCC pathological features, staging, surgical management, and review the literature as a guide to indications for chemotherapy and choice of agents.

Case Presentation: We present the case of a 77-year-old Caucasian man with a history of stage I adenocarcinoma of transverse colon status post transverse colectomy who was incidentally found on surveillance colonoscopy to have an abnormal appendiceal orifice lesion. A biopsy revealed an appendiceal goblet cell carcinoid and he underwent a right hemicolectomy which revealed a pathologic stage III GCC for which he received eight cycles of adjuvant chemotherapy with capecitabine.

Conclusions: It is essential that patients who have tumors > 2 cm, are pT3 or pT4, have higher grade histology with signet ring (Tang grade B or grade C), locally advanced, or with positive surgical margins on appendectomy undergo a right hemicolectomy. Although there is no category 1 evidence, consensus recommendations are that patients with stage II (particularly Tang B and C) and stage III GCC be offered adjuvant chemotherapy with a regimen based on 5-fluorouracil, as these patients are known to have high rates of relapse.
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http://dx.doi.org/10.1186/s13256-018-1789-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151924PMC
September 2018

Adults with Communication Disabilities Experience Poorer Health and Healthcare Outcomes Compared to Persons Without Communication Disabilities.

J Gen Intern Med 2018 12 24;33(12):2147-2155. Epub 2018 Aug 24.

Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS), Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Background: Persons with speech, language, and/or voice disabilities (collectively referred to as communication disabilities (CD)) represent 10% of the US population, yet their healthcare outcomes have not been described. Generally, research shows that persons with disabilities have poorer health and healthcare outcomes than their non-disabled peers.

Objectives: To examine the health and healthcare outcomes of persons with CD compared to persons without CD.

Design: Retrospective cohort study of the 2012 National Health Interview Survey, which contained the first supplemental questions on CD. We compared proportional differences in outcomes; logistic and ordered logistic regression assessed the outcome measures across CD categories, controlling for demographics, non-communication disabilities, and chronic conditions. Findings are weighted to permit national inferences.

Participants: Adults (≥ 18 years old) were divided into 4 mutually exclusive groups: people with voice disabilities only; speech/language disabilities only; speech/language and voice disabilities; and people without CD.

Main Measures: Chronic health conditions; self-rated health; access to care; unmet needs for care; healthcare utilization.

Key Results: Adults with CD more frequently had ≥ 1 chronic condition (voice 67.9%, speech/language 68.6%, speech/language and voice 79.9%, no CD 50.1%, p < 0.001) and reported fair/poor health (voice 19.5%, speech/language 32.5%, speech/language and voice 48.3%, no CD 11.2%, p < 0.001) compared to those without CD. Adults with CD more frequently utilized healthcare compared to those without CD. However, persons with CD endorsed greater difficulties accessing care than those without CD, including identifying a usual source of care, trouble finding a physician, and delaying or foregoing care (e.g., delayed due to availability of care: voice 26.1%, speech/language 37.2%, speech/language and voice 30.8% no CD 16.1%, p < 0.001).

Conclusions: Persons with CD are medically complex and experience greater challenges accessing healthcare than persons without CD. Healthcare providers need support and tools to provide equitable care that addresses the medical needs of persons with CD.
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http://dx.doi.org/10.1007/s11606-018-4625-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258615PMC
December 2018

Homologous recombination deficiency (HRD) status predicts response to standard neoadjuvant chemotherapy in patients with triple-negative or BRCA1/2 mutation-associated breast cancer.

Breast Cancer Res Treat 2018 Apr 23;168(3):625-630. Epub 2017 Dec 23.

Division of Oncology, Department of Medicine, Stanford University School of Medicine, 875 Blake Wilbur Drive, CC 2241, Stanford, CA, 94305-5826, USA.

Purpose: Defects in the homologous recombination (HR) DNA repair pathway sensitize tumors to therapeutics that target this pathway. A significant proportion of triple-negative breast cancers (TNBC) carry HR defects. The HRD assay is highly associated with sensitivity to neoadjuvant platinum-based chemotherapy in TNBC. Standard chemotherapy consists of some combination of an anthracycline, cyclophosphamide, and taxane. This study assesses the association of HR deficiency status with response to standard neoadjuvant chemotherapy in TNBC or BRCA1/2 mutation-associated breast cancer.

Methods: Tumor samples were retrospectively obtained from 45 TNBC patients and 2 BRCA1/2 mutant, hormone receptor-positive/HER2-negative breast cancer patients who received anthracycline- and/or taxane-based neoadjuvant chemotherapy at Stanford University or Cedars-Sinai Medical Centers. The HRD score and tumor BRCA1/2 mutation status were determined from baseline tumor biopsies. HR deficient tumors were those with a HRD score of ≥ 42 or a tumor BRCA1/2 mutation. Response was categorized by the residual cancer burden (RCB) index.

Results: HR deficient patients were more likely to achieve a pathologic complete response (pCR) compared with non-deficient patients (OR 13.06, CI 1.52-11.241, p = 0.0028). Among BRCA1/2 mutation wild-type patients, HR deficient patients were more likely to achieve a pCR (OR 16, 95% CI 1.65-160.41, p = 0.0041) compared with HR non-deficient patients. Further, HRD scores were highly concordant pre- and post-therapy (Spearman correlation > 99%).

Conclusions: HR deficiency status is significantly associated with response to standard neoadjuvant chemotherapy in TNBC. This observation is consistent with the mechanisms of action of doxorubicin and cyclophosphamide as DNA damaging agents.
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http://dx.doi.org/10.1007/s10549-017-4624-7DOI Listing
April 2018

Quantitative Measurements Versus Receiver Operating Characteristics and Visual Grading Regression in CT Images Reconstructed with Iterative Reconstruction: A Phantom Study.

Acad Radiol 2018 Apr 29;25(4):509-518. Epub 2017 Nov 29.

Department of Diagnostic Physics, Oslo University Hospital, P.O. Box, 0454 Oslo, Norway; Department of Physics, University of Oslo, P. O. Box 1048 Blindern, N-0316 Oslo, Norway.

Rationale And Objectives: This study aimed to evaluate the correlation of quantitative measurements with visual grading regression (VGR) and receiver operating characteristics (ROC) analysis in computed tomography (CT) images reconstructed with iterative reconstruction.

Materials And Methods: CT scans on a liver phantom were performed on CT scanners from GE, Philips, and Toshiba at three dose levels. Images were reconstructed with filtered back projection (FBP) and hybrid iterative techniques (ASiR, iDose, and AIDR 3D of different strengths). Images were visually assessed by five readers using a four- and five-grade ordinal scale for liver low contrast lesions and for 10 image quality criteria. The results were analyzed with ROC and VGR. Standard deviation, signal-to-noise ratios, and contrast-to-noise ratios were measured in the images.

Results: All data were compared to FBP. The results of the quantitative measurements were improved for all algorithms. ROC analysis showed improved lesion detection with ASiR and AIDR and decreased lesion detection with iDose. VGR found improved noise properties for all algorithms, increased sharpness with iDose and AIDR, and decreased artifacts from the spine with AIDR, whereas iDose increased the artifacts from the spine. The contrast in the spine decreased with ASiR and iDose.

Conclusions: Improved quantitative measurements in images reconstructed with iterative reconstruction compared to FBP are not equivalent to improved diagnostic image accuracy.
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http://dx.doi.org/10.1016/j.acra.2017.10.020DOI Listing
April 2018

Characteristics and clinical outcomes of pleomorphic lobular carcinoma in situ of the breast.

Breast J 2018 01 19;24(1):66-69. Epub 2017 Sep 19.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.

Pleomorphic lobular carcinoma in situ (PLCIS) of the breast is a rare variant of lobular carcinoma in situ (LCIS). We reviewed 78 cases of PLCIS diagnosed at our institution from 1998 to 2012. Among all cases, 47 (60%) were associated with invasive carcinoma and/or ductal carcinoma in situ (DCIS) after final surgical excision. Of the 20 cases with PLCIS alone on core needle biopsy (CNB), 6 (30%) were upgraded to invasive carcinoma or DCIS after final surgical excision. Our findings support a recommendation for complete surgical excision of PLCIS when diagnosed on CNB.
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http://dx.doi.org/10.1111/tbj.12843DOI Listing
January 2018

Regional Variability in Percentage of Breast Cancers Reported as Positive for HER2 in California: Implications of Patient Demographics on Laboratory Benchmarks.

Am J Clin Pathol 2017 Sep;148(3):199-207

Department of Pathology.

Objectives: The expected regional variability in percent human epidermal growth factor receptor 2 (HER2)-positive breast cancers is not currently clear.

Methods: Data from the 2006 to 2011 California Cancer Registry were examined by county and health service area. The influence of demographic and pathologic features was used in a multivariable logistic regression model to compare expected with observed HER2-positive percentages by region.

Results: There was significant geographic variation by California counties (11.6%-26%). The reported HER2-positive percentage was higher when the population had higher stage, tumor size, grade, percent estrogen receptor negative, younger age, or lower socioeconomic status. Ethnic distribution of the population also influenced HER2-positive percentages. Using a multivariable logistic regression model, most regions had expected values based on their population characteristics; however, "outlier" regions were identified.

Conclusions: These results deepen our understanding of population characteristics' influence on the distribution of HER2-positive breast cancers. Taking these factors into account can be useful when setting laboratory benchmarks and assessing test quality.
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http://dx.doi.org/10.1093/ajcp/aqx063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848426PMC
September 2017

Non-Small Cell Lung Cancer Radiogenomics Map Identifies Relationships between Molecular and Imaging Phenotypes with Prognostic Implications.

Radiology 2018 01 20;286(1):307-315. Epub 2017 Jul 20.

From the Stanford Center for Biomedical Informatics Research, Department of Medicine (M.Z., O.G.), Department of Radiology (A.L., S.E., A.G., S.K.P., D.L.R., S.N.), Division of Thoracic Surgery, Department of Cardiothoracic Surgery (J.B.S.), and Department of Pathology (K.C.J., G.J.B.), Stanford University, 1265 Welch Rd, Stanford, CA 94305-5479.

Purpose To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Materials and Methods A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. For example, nodule attenuation and margins are associated with the late cell-cycle genes, and a metagene that represents the EGF pathway was significantly correlated with the presence of ground-glass opacity and irregular nodules or nodules with poorly defined margins. Conclusion Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways, and it can result in noninvasive identification of molecular properties of NSCLC. Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2017161845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749594PMC
January 2018

Comparison of Estrogen and Progesterone Receptor Antibody Reagents Using Proficiency Testing Data.

Arch Pathol Lab Med 2017 Oct 17;141(10):1402-1412. Epub 2017 Jul 17.

Context: - Immunohistochemical analysis of estrogen receptor (ER) and progesterone receptor (PgR) expression in breast cancer is the current standard of care and directly determines therapy. In 2010 the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) published guidelines for ER and PgR predictive testing, encompassing preanalytic, analytic, postanalytic factors; antibody validation; and proficiency testing.

Objective: - To compare the performance of different antibody reagents for ER and PgR immunohistochemical analysis by using CAP proficiency testing data.

Design: - The CAP PM2 survey uses tissue microarrays of ten 2-mm cores per slide. We analyzed survey data from 80 ER and 80 PgR cores by antibody clone from more than 1200 laboratories.

Results: - Laboratories used the ER antibodies SP1 (72%), 6F11 (17%), 1D5 (3%), and the PgR antibodies 1E2 (61%), 16 (12%), PgR-636 (13%), PgR-1294 (8%) in 2015. While 63 of 80 ER cores (79%) were scored similarly using each of the 3 antibodies, there were significant differences for others, with SP1 yielding more positive interpretations. Four cores were scored as ER negative by more than half of the laboratories using 1D5 or 6F11, while SP1 produced positive results in more than 70% of laboratories using that antibody. Despite the greater variety of PgR antibody reagents and greater PgR tumor heterogeneity, 61 of 80 cores (76%) were scored similarly across the 4 PgR antibodies.

Conclusions: - Accurate ER and PgR testing in breast cancer is crucial for appropriate treatment. The CAP proficiency testing data demonstrate differences in staining results by ER clone, with SP1 yielding more positive results.
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http://dx.doi.org/10.5858/arpa.2016-0497-OADOI Listing
October 2017

Low bone mineral density risk factors and testing patterns in institutionalized adults with intellectual and developmental disabilities.

J Appl Res Intellect Disabil 2018 Jan 1;31 Suppl 1:157-164. Epub 2017 Mar 1.

Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado, Aurora, CO, USA.

Background: Adults with intellectual or developmental disability (ID/DD) have multiple risks for low bone mineral density (BMD) without formal guidelines to guide testing. We sought to identify risk factors and patterns of BMD testing among institutionalized adults with ID/DD.

Methods: We evaluated risk factors for low BMD (Z-/T-score < -1) and patterns of BMD testing among adults with ID/DD receiving care at a state-run residential facility. Kruskal-Wallis, Fisher's exact and Pearson's chi-squared tests were used as appropriate.

Results: Of the 140 eligible patients, only 44% ever had BMD testing of which 89% had low BMD. Median age at diagnosis was 42 years old. Individuals with low BMD were more likely to be older, non-weight bearing, Caucasian and have severe cognitive delay.

Conclusions: Adults with ID/DD in this facility had a high prevalence of low BMD. Further studies are needed to better characterize risk factors and inform screening within this high-risk population.
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http://dx.doi.org/10.1111/jar.12341DOI Listing
January 2018

Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics.

Clin Cancer Res 2017 Jul 13;23(14):3700-3710. Epub 2017 Feb 13.

Department of Urology, Stanford University School of Medicine, Stanford, California.

The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients ( = 13) and controls ( = 10). Eight bladder cancer specific and 3 reference genes identified by RNA-seq were quantitated by qPCR in a training cohort of 102 urine samples. A diagnostic model based on the training cohort was constructed using multiple logistic regression. The model was further validated in an independent cohort of 101 urines. A total of 418 genes were found to be differentially expressed between bladder cancer and controls. Validation of a subset of these genes was used to construct an equation for computing a probability of bladder cancer score (P) based on expression of three markers (, and ). Setting P = 0.45 as the cutoff for a positive test, urine testing using the three-marker panel had overall 88% sensitivity and 92% specificity in the training cohort. The accuracy of the three-marker panel in the independent validation cohort yielded an AUC of 0.87 and overall 83% sensitivity and 89% specificity. Urine-based molecular diagnostics using this three-marker signature could provide a valuable adjunct to cystoscopy and may lead to a reduction of unnecessary procedures for bladder cancer diagnosis. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-2610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873297PMC
July 2017

Tumor Reversion Mutation Arising during Neoadjuvant Platinum-Based Chemotherapy in Triple-Negative Breast Cancer Is Associated with Therapy Resistance.

Clin Cancer Res 2017 07 13;23(13):3365-3370. Epub 2017 Jan 13.

Department of Medicine, Stanford, University School of Medicine, Stanford, California.

In germline or () mutation carriers, restoration of tumor function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed patients with -mutant breast cancer with poor response to neoadjuvant platinum-based therapy. PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin, and iniparib in patients with stage I-IIIA triple-negative or mutation-associated breast cancer ( = 80). All patients underwent comprehensive genotyping. For mutation carriers with moderate or extensive residual disease after neoadjuvant therapy, status was resequenced in the residual surgical breast tumor tissue. Nineteen patients had a deleterious germline mutation, and four had moderate residual disease at surgery. sequencing of residual tissue was performed on three patients. These patients had 1479delAG, 3374insGA, and W1712X mutations, respectively, with LOH at these loci in the pretreatment tumors. In the first case, a new mutation was detected in the residual disease. This resulted in a 14-amino acid deletion and restoration of the reading frame. A local relapse biopsy 4 months later revealed the identical reversion mutation, and the patient subsequently died from metastatic breast cancer. We report a reversion mutation in a patient newly diagnosed with triple-negative breast cancer that developed over 18 weeks of platinum-based neoadjuvant therapy. This was associated with poor therapy response, early relapse, and death. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-2174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496787PMC
July 2017

[Radiation-induced cataracts].

Tidsskr Nor Laegeforen 2016 Nov 22;136(21):1809-1812. Epub 2016 Nov 22.

Intervensjonssenteret Oslo universitetssykehus, Rikshospitalet og Fysisk institutt Universitetet i Oslo.

The dose limit for the lens of the eye for occupationally exposed workers that is stipulated in the Norwegian Regulation on radiation protection is based on outdated threshold doses for radiation-induced cataracts. Recent studies have shown that injuries may occur at significantly lower radiation doses than previously assumed. The results from the new studies will impact upon future legislation and recommendations regarding radiation hygiene for personnel in x-ray laboratories and operating theatres who may be exposed to significant radiation doses in the course of their work.
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http://dx.doi.org/10.4045/tidsskr.16.0307DOI Listing
November 2016

The molecular basis of breast cancer pathological phenotypes.

J Pathol 2017 Feb 29;241(3):375-391. Epub 2016 Dec 29.

Cancer Research Institute, Beth Israel Deaconess Cancer Center, Boston, MA, USA.

The histopathological evaluation of morphological features in breast tumours provides prognostic information to guide therapy. Adjunct molecular analyses provide further diagnostic, prognostic and predictive information. However, there is limited knowledge of the molecular basis of morphological phenotypes in invasive breast cancer. This study integrated genomic, transcriptomic and protein data to provide a comprehensive molecular profiling of morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases from The Cancer Genome Atlas (TCGA). Morphological features were significantly associated with genomic alteration, DNA methylation subtype, PAM50 and microRNA subtypes, proliferation scores, gene expression and/or reverse-phase protein assay subtype. Marked nuclear pleomorphism, necrosis, inflammation and a high mitotic count were associated with the basal-like subtype, and had a similar molecular basis. Omics-based signatures were constructed to predict morphological features. The association of morphology transcriptome signatures with overall survival in oestrogen receptor (ER)-positive and ER-negative breast cancer was first assessed by use of the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset; signatures that remained prognostic in the METABRIC multivariate analysis were further evaluated in five additional datasets. The transcriptomic signature of poorly differentiated epithelial tubules was prognostic in ER-positive breast cancer. No signature was prognostic in ER-negative breast cancer. This study provided new insights into the molecular basis of breast cancer morphological phenotypes. The integration of morphological with molecular data has the potential to refine breast cancer classification, predict response to therapy, enhance our understanding of breast cancer biology, and improve clinical management. This work is publicly accessible at www.dx.ai/tcga_breast. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.4847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499709PMC
February 2017

'Non-classical' HER2 FISH results in breast cancer: a multi-institutional study.

Mod Pathol 2017 02 14;30(2):227-235. Epub 2016 Oct 14.

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with 'monosomy', 'co-amplification/polysomy', low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or 'non-classical' HER2 FISH results. Breast cancers (2001-2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected. HER2 FISH was interpreted using the updated recommendations. Amplified cases with non-classical results were grouped into the following categories: (1) 'monosomy' (ratio ≥2.0, mean HER2/cell<4.0); (2) 'co-amplified' (ratio<2.0, mean HER2/cell ≥6.0); (3) 'low amplified' (ratio ≥2.0, mean HER2/cell 4.0-5.9). Heterogeneous cases with clustered HER2-positive cells were also included. Of 8068 cases, 5.2% were equivocal and 4.6% had a 'non-classical' HER2 amplified result; 1.4% 'monosomy', 0.8% 'co-amplified', 2.1% 'low amplified', and 0.3% clustered heterogeneity. These cancers had a high frequency of ER positive (80.4%), Nottingham grade 3 (52.1%) results. The highest percentage of grade 3 cancers (66.7%) and positive HER2 immunohistochemistry (31.7%) was in the 'co-amplified' group. The 'monosomy' group had the highest percent grade 1 cancers (13.3%) and was most frequently HER2 immunohistochemistry negative (30.1%). Equivocal cases had very similar characteristics to the 'low-amplified' category. Cases with non-classical HER2 amplification or equivocal results are typically ER positive, higher grade cancers. 'Co-amplified' cases have the highest frequencies of aggressive characteristics and 'monosomy' cases the highest frequencies of lower risk features. With little clinical outcomes data currently available on these non-classical HER2 results, these results support the current classification scheme for HER2 FISH, with case-by-case correlation with additional clinical-pathologic factors when evaluating whether to offer HER2-targeted therapies in these non-classical cases.
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http://dx.doi.org/10.1038/modpathol.2016.175DOI Listing
February 2017

Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

Sci Rep 2016 Sep 23;6:33924. Epub 2016 Sep 23.

Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.

Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently used proximal V, D and J genes in complete IGH gene rearrangements, despite normal Ig locus contraction. Fewer N-nucleotides were added in IGH gene rearrangements in the context of low TdT and XRCC4 expression. Moreover, fetal progenitor-B cells expressed lower levels of IL7Rα than their pediatric counterparts. Analysis of progenitor-B cells from IL7Rα-deficient patients revealed that TdT expression and N-nucleotides additions in Dh-Jh junctions were dependent on functional IL7Rα. Thus, IL7Rα affects TdT expression, and decreased expression of this receptor underlies at least in part the skewed Ig repertoire formation in fetal B-cell precursors. These new insights provide a better understanding of the formation of adaptive immunity in the developing fetus.
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http://dx.doi.org/10.1038/srep33924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034271PMC
September 2016

Radiation exposure in patients treated with endovascular aneurysm repair: what is the risk of cancer, and can we justify treating younger patients?

Acta Radiol 2017 Mar 19;58(3):323-330. Epub 2016 Jul 19.

2 Medical faculty, University of Oslo, Oslo, Norway.

Background Endovascular aneurysm repair (EVAR) is becoming the mainstay treatment of abdominal aortic aneurisms (AAA). The postoperative follow-up regime includes a lifelong series of CT angiograms (CTAs) at different intervals in addition to EVAR, which will confer significant cumulative radiation exposure over time. Purpose To examine the impact of age and follow-up regime over time on cumulative radiation exposure and attributable cancer risk after EVAR. Material and Methods We calculated a mean effective dose (ED) for the EVAR procedure, CTA, and plain abdominal X-rays (PAX). Cumulative ED was calculated for standard, complex, and simplified surveillance over 5, 10, and 15 years for different age groups. Results For EVAR, the mean ED was 34 mSv (range, 12-75 mSv) per procedure. For PAX, the ED was 1.1 mSv (range, 0.3-4.4 mSv), and for CTA it was 8.0 mSv (range, 2-20 mSv). For a 55-year-old man, an attributable cancer risk (ACR) in standard surveillance at 5 and 15 years of follow-up was 0.35% and 0.65%, respectively. The corresponding values were 0.22% and 0.37% for a 75-year-old man. When using a simplified follow-up, the ACRs for a 55-year-old at 5 and 15 years were 0.30% and 0.37%, respectively. These values were 0.18% and 0.21% for a 75-year-old man. A complex follow-up with half-yearly CTA over similar age and time span doubled the ACR. Conclusion Treating younger patients with EVAR poses a low ACR of 0.65% (15-year standard surveillance) compared to a lifetime cancer risk of 44%. A simplified surveillance should be used if treating younger patients, which will halve the ACR over 15 years.
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http://dx.doi.org/10.1177/0284185116651002DOI Listing
March 2017

A Liver Phantom Study: CT Radiation Dose Reduction and Different Image Reconstruction Algorithms Affect Diagnostic Quality.

J Comput Assist Tomogr 2016 Sep-Oct;40(5):735-9

From the *Section for Radiology Radiumhospitalet, Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo; †Department of Radiology, Ostfold Hospital Trust, Fredrikstad; ‡Institute of Physics, University of Oslo; and §The Intervention Centre, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Objective: The aim of this study was to evaluate whether iterative reconstruction techniques for different dose levels and/or reduction of tube potential can increase liver lesion detectability.

Methods: An anthropomorphic liver phantom was scanned at different dose levels (CTDIvol 15 mGy, 7.5 mGy, 5 mGy, and 2.6 mGy) and tube potential levels (120 kV, 100 kV, and 80 kV). Images were reconstructed with the following algorithms: filtered back projection (FBP), adaptive statistical iterative reconstruction (ASiR) 40%, and a model-based iterative reconstruction (Veo). The presence or absence of lesions was assessed independently on a 4-point scale by 4 readers. The areas under the receiver operating characteristic curve were calculated.

Results: Veo improved detectability of hyperdense liver lesions compared with both FBP and ASiR 40% at most dose levels (15 mGy, 7.5 mGy, and 5 mGy with P < 0.05). Veo also improved detectability at reduced tube potential compared with FBP (120 kV, 100 kV, and 80 kV at 5 mGy with P < 0.05) and ASiR 40% (120 kV and 100 kV at 5 mGy with P < 0.05). For ASiR 40%, the area under the receiver operating characteristic curve was significantly larger compared with FBP only at dose levels 7.5 mGy and 2.6 mGy at 120 kV. In general, the reduction of tube potential reduced the lesion detectability.

Conclusions: This study shows that iterative reconstruction algorithms, in particular Veo, improve lesion detectability in a liver phantom. However, a too aggressive dose reduction may result in poorer image quality. Results considering different tube potentials diverged, thus careful consideration is necessary upon tube potential reduction.
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http://dx.doi.org/10.1097/RCT.0000000000000433DOI Listing
January 2017

Image Quality in Oncologic Chest Computerized Tomography With Iterative Reconstruction: A Phantom Study.

J Comput Assist Tomogr 2016 May-Jun;40(3):351-6

From the *Intervention Centre, Rikshospitalet, Nydalen; †Institute of Physics, University of Oslo; ‡Department of Radiology and Nuclear Medicine, Rikshospitalet, Nydalen, Oslo, Norway; §Department of Medical Radiation Physics, Lund University, Skåne University Hospital, Malmö, Sweden; and ∥Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Objective: The purpose of this study was to validate iterative reconstruction technique in oncologic chest computed tomography (CT).

Methods: An anthropomorphic thorax phantom with 4 simulated tumors was scanned on a 64-slice CT scanner with 2 different iterative reconstruction techniques: one model based (MBIR) and one hybrid (ASiR). Dose levels of 14.9, 11.1, 6.7, and 0.6 mGy were used, and all images were reconstructed with filtered back projection (FBP) and both iterative reconstruction algorithms. Hounsfield units (HU) and absolute noise were measured in the tumors, lung, heart, diaphragm, and muscle. Contrast-to-noise ratios (CNRs) and signal-to-noise ratios (SNRs) were calculated.

Results: Model-based iterative reconstruction (MBIR) increased CNRs of the tumors (21.1-192.2) and SNRs in the lung (-49.0-165.6) and heart (3.1-8.5) at all dose levels compared with FBP (CNR, 1.1-23.0; SNR, -7.5-31.6 and 0.2-1.1) and with adaptive statistical iterative reconstruction (CNR, 1.2-33.2; SNR, -7.3-37.7 and 0.2-1.5). At the lowest dose level (0.6 mGy), MBIR reduced the cupping artifact (HU range: 17.0 HU compared with 31.4-32.2). An HU shift in the negative direction was seen with MBIR.

Conclusions: Quantitative image quality parameters in oncologic chest CT are improved with MBIR compared with FBP and simpler iterative reconstruction algorithms. Artifacts at low doses are reduced. A shift in HU values was shown; thus, absolute HU values should be used with care.
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http://dx.doi.org/10.1097/RCT.0000000000000364DOI Listing
January 2017

Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer.

Clin Cancer Res 2016 08 8;22(15):3764-73. Epub 2016 Mar 8.

Harvard Medical School, Boston, Massachusetts. Dana-Farber Cancer Institute, Boston, Massachusetts. Brigham and Women's Hospital, Boston, Massachusetts.

Purpose: BRCA1/2-mutated and some sporadic triple-negative breast cancers (TNBC) have DNA repair defects and are sensitive to DNA-damaging therapeutics. Recently, three independent DNA-based measures of genomic instability were developed on the basis of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST).

Experimental Design: We assessed a combined homologous recombination deficiency (HRD) score, an unweighted sum of LOH, TAI, and LST scores, in three neoadjuvant TNBC trials of platinum-containing therapy. We then tested the association of HR deficiency, defined as HRD score ≥42 or BRCA1/2 mutation, with response to platinum-based therapy.

Results: In a trial of neoadjuvant platinum, gemcitabine, and iniparib, HR deficiency predicted residual cancer burden score of 0 or I (RCB 0/I) and pathologic complete response (pCR; OR = 4.96, P = 0.0036; OR = 6.52, P = 0.0058). HR deficiency remained a significant predictor of RCB 0/I when adjusted for clinical variables (OR = 5.86, P = 0.012). In two other trials of neoadjuvant cisplatin therapy, HR deficiency predicted RCB 0/I and pCR (OR = 10.18, P = 0.0011; OR = 17.00, P = 0.0066). In a multivariable model of RCB 0/I, HR deficiency retained significance when clinical variables were included (OR = 12.08, P = 0.0017). When restricted to BRCA1/2 nonmutated tumors, response was higher in patients with high HRD scores: RCB 0/I P = 0.062, pCR P = 0.063 in the neoadjuvant platinum, gemcitabine, and iniparib trial; RCB 0/I P = 0.0039, pCR P = 0.018 in the neoadjuvant cisplatin trials.

Conclusions: HR deficiency identifies TNBC tumors, including BRCA1/2 nonmutated tumors more likely to respond to platinum-containing therapy. Clin Cancer Res; 22(15); 3764-73. ©2016 AACR.
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http://dx.doi.org/10.1158/1078-0432.CCR-15-2477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773427PMC
August 2016

Improved Liver Lesion Conspicuity With Iterative Reconstruction in Computed Tomography Imaging.

Curr Probl Diagn Radiol 2016 Sep-Oct;45(5):291-6. Epub 2015 Dec 15.

The Intervention Centre, Rikshospitalet, Oslo, Norway; Institute of Physics, University of Oslo, Oslo, Norway.

Studies on iterative reconstruction techniques on computed tomographic (CT) scanners show reduced noise and changed image texture. The purpose of this study was to address the possibility of dose reduction and improved conspicuity of lesions in a liver phantom for different iterative reconstruction algorithms. An anthropomorphic upper abdomen phantom, specially designed for receiver operating characteristic analysis was scanned with 2 different CT models from the same vendor, GE CT750 HD and GE Lightspeed VCT. Images were obtained at 3 dose levels, 5, 10, and 15mGy, and reconstructed with filtered back projection (FBP), and 2 different iterative reconstruction algorithms; adaptive statistical iterative reconstruction and Veo. Overall, 5 interpreters evaluated the images and receiver operating characteristic analysis was performed. Standard deviation and the contrast to noise ratio were measured. Veo image reconstruction resulted in larger area under curves compared with those adaptive statistical iterative reconstruction and FBP image reconstruction for given dose levels. For the CT750 HD, iterative reconstruction at the 10mGy dose level resulted in larger or similar area under curves compared with FBP at the 15mGy dose level (0.88-0.95 vs 0.90). This was not shown for the Lightspeed VCT (0.83-0.85 vs 0.92). The results in this study indicate that the possibility for radiation dose reduction using iterative reconstruction techniques depends on both reconstruction technique and the CT scanner model used.
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http://dx.doi.org/10.1067/j.cpradiol.2015.11.004DOI Listing
April 2017
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