Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

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

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, 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.

Investigating the role of imaging factors in the variability of CT-based texture analysis metrics.

OBJECTIVE: This study assesses the robustness of first-order radiomic texture features namely interquartile range (IQR), coefficient of variation (CV) and standard deviation (SD) derived from computed tomography (CT) images by varying dose, reconstruction algorithms and slice thickness using scans of a uniform water phantom, a commercial anthropomorphic liver phantom, and a human liver in-vivo. MATERIALS AND METHODS: Scans were acquired on a 16 cm detector GE Revolution Apex Edition CT scanner with variations across three different nominal slice thicknesses: 0.625, 1.25, and 2.5 mm, three different dose levels: CTDIvol of 13.86 mGy for the standard dose, 40% reduced dose and 60% reduced dose and two different reconstruction algorithms: a deep learning image reconstruction (DLIR-high) algorithm and a hybrid iterative reconstruction (IR) algorithm ASiR-V50% (AV50) were explored, varying one at a time. To assess the effect of non-linear modifications of images by AV50 and DLIR-high, images of the water phantom were also reconstructed using filtered back projection (FBP). Quantitative measures of IQR, CV and SD were extracted from twelve pre-selected, circular (1 cm diameter) regions of interest (ROIs) capturing different texture patterns across all scans. RESULTS: Across all scans, imaging, and reconstruction settings, CV, IQR and SD were observed to increase with reduction in dose and slice thickness. An exception to this observation was found when using FBP reconstruction. Lower values of CV, IQR and SD were observed in DLIR-high reconstructions compared to AV50 and FBP. The Poisson statistics were more stringently noted in FBP than DLIR-high and AV50, due to the non-linear nature of the latter two algorithms. CONCLUSION: Variation in image noise due to dose reduction algorithms, tube current, and slice thickness show a consistent trend across phantom and patient scans. Prospective evaluation across multiple centers, scanners and imaging protocols is needed for establishing quality assurance standards of radiomics.

Technical and clinical considerations of a physical liver phantom for CT radiomics analysis.

OBJECTIVE: This study identifies key characteristics to help build a physical liver computed tomography (CT) phantom for radiomics harmonization; particularly, the higher-order texture metrics. MATERIALS AND METHODS: CT scans of a radiomics phantom comprising of 18 novel 3D printed inserts with varying size, shape, and material combinations were acquired on a 64-slice CT scanner (Brilliance 64, Philips Healthcare). The images were acquired at 120 kV, 250 mAs, CTDIvol of 16.36 mGy, 2 mm slice thickness, and iterative noise-reduction reconstruction (iDose, Philips Healthcare, Andover, MA). Radiomics analysis was performed using the Cancer Imaging Phenomics Toolkit (CaPTk), following automated segmentation of 3D regions of interest (ROI) of the 18 inserts. The findings were compared to three additional ROI obtained of an anthropomorphic liver phantom, a patient liver CT scan, and a water phantom, at comparable imaging settings. Percentage difference in radiomic metrics values between phantom and tissue was used to assess the biological equivalency and <10% was used to claim equivalent. RESULTS: The HU for all 18 ROI from the phantom ranged from -30 to 120 which is within clinically observed HU range of the liver, showing that our phantom material (T3-6B) is representative of biological CT tissue densities (liver) with >50% radiomic features having <10% difference from liver tissue. Based on the assessment of the Neighborhood Gray Tone Difference Matrix (NGTDM) metrics it is evident that the water phantom ROI show extreme values compared to the ROIs from the phantom. This result may further reinforce the difference between a structureless quantity such as water HU values and tissue HU values found in liver. CONCLUSION: The 3-D printed patterns of the constructed radiomics phantom cover a wide span of liver tissue textures seen in CT images. Using our results, texture metrics can be selectively harmonized to establish clinically relevant and reliable radiomics panels.

Randomized Controlled Trial Investigating Cold Snare and Forceps Polypectomy Among Small POLYPs in Rates of Complete Resection: The TINYPOLYP Trial.

INTRODUCTION: Optimizing complete resection during colonoscopy is important because residual neoplastic tissue may play a role in interval cancers. The US Multi-Society Task Force recommends diminutive (≤5 mm) and small (6-9 mm) polyps be removed by cold snare polypectomy (CSP). However, evidence is less clear whether CSP retains significant advantage over cold forceps polypectomy (CFP) for polyps ≤3 mm. METHODS: This study is a single-center prospective noninferiority randomized clinical trial evaluating CFP and CSP for nonpedunculated polyps ≤3 mm. Patients 18 years and older undergoing colonoscopy for any indication were recruited. During each colonoscopy, polyps underwent block randomization to removal with CFP or CSP. After polypectomy, 2 biopsies were taken from the polypectomy margin. The primary noninferiority outcome was the complete resection rate, defined by absence of residual polyp in the margin biopsies. RESULTS: A total of 179 patients were included. Patients had similar distribution in age, sex, race/ethnicity, as well as indication of procedure. A total of 279 polyps ≤3 mm were identified, with 138 in the CSP group and 141 in the CFP group. Mean polypectomy time was longer for CSP compared with CFP (42.3 vs 23.2 seconds, P < 0.001), although a higher proportion of polyps removed by CFP were removed in more than 1 piece compared with CSP (15.6 vs 3.6%, P < 0.001). There were positive margin biopsies in 2 cases per cohort, with a complete resection rate of 98.3% in both groups. There was no significant difference in cohorts in complete resection rates (difference in complete resection rates was 0.057%, 95% confidence interval: -4.30% to 4.53%), demonstrating noninferiority of CFP compared with CSP. DISCUSSION: Use of CFP was noninferior to CSP in the complete resection of nonpedunculated polyps ≤3 mm. CSP required significantly more time to perform compared with CFP. CFP should be considered an acceptable alternative to CSP for removal of polyps ≤3 mm.

Randomized controlled trial investigating use of submucosal injection of EverLift™ in rates of complete resection of non-pedunculated 4-9 mm polyps.

INTRODUCTION: Currently, cold snare polypectomy (CSP) without submucosal injection is recommended for removing polyps < 10 mm. Use of viscous submucosal agents has not been previously evaluated in CSP. We investigate the potential role of EverLift™ (GI Supply, Pennsylvania) in CSP. METHODS: The study is a single-center prospective randomized non-inferiority clinical trial evaluating CSP of non-pedunculated 4-9 mm polyps, with or without submucosal injection of EverLift™. Patients 18-80 years of age presenting for colonoscopy were recruited. Eligible polyps underwent block randomization to CSP with or without EverLift™. Following CSP, two biopsies were performed at the CSP site margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies (non-inferiority margin -10%). RESULTS: A total of 291 eligible polyps underwent CSP, with 142 removed using EverLift™. There was similar polyp size and distribution of pathology between the two groups. Overall, there was a low rate of positive margins with (1.4%) or without submucosal injection (2.8%), with no significant difference in complete resection (difference 1.28%, 95% CI: -2.66 to 5.42%), demonstrating non-inferiority of EverLift™ injection. Use of EverLift™ significantly increased CSP time (109.8 vs 38.8 s, p < 0.0001) and frequency of use of hemostatic clips (13.4 vs 3.6%, p = 0.002). CONCLUSION: Submucosal injection of EverLift™ was non-inferior to CSP of 4-9 mm polyps without injection and increased time for resection as well as use of hemostatic clips to control acute bleeding. Our results suggest that polypectomy of 4-9 mm polyps can be safely performed without submucosal injection of EverLift™.

Quality of life and lifetime achievement in adult survivors of pediatric heart transplant.

BACKGROUND: Survival in pediatric heart transplantation has improved since the first successful transplant over 35 years ago leading to increasing numbers of patients entering adulthood. We sought to examine quality of life and various lifetime achievements in our institutional population of long-term adult survivors of pediatric heart transplant. METHODS: Participants ≥18 years of age who received a heart transplant as a pediatric patient (<18 years old), and who have survived ≥10 years post-transplant, completed two self-report surveys: (1) Ferrans and Powers QLI cardiac version which reports a measure of life satisfaction with a range of 0 (very dissatisfied) to 1 (very satisfied); and (2) CHONY Pediatric Heart Transplant Life Achievement Survey to examine lifetime achievement. RESULTS: Sixty-two and sixty-five participants completed the Ferrans and Powers QLI cardiac version and CHONY Pediatric Heart Transplant Life Achievement Survey. The mean overall QLI was 0.75 ± 0.14 with the most satisfaction in the family domain. QLI scores were analyzed by age at initial transplant, gender, indication for transplant, and whether patients currently followed by pediatric or adult providers, with no statistically significant differences noted. Seventy-two percent of participants demonstrated stable employment or schooling. Around thirty percent of participants showed the ability to reach academic milestones including college and post-graduate education and ten percent to start their own families. CONCLUSIONS: Our cohort of long-term adult survivors of pediatric heart transplant report a quality of life with scores thought to be reflective of a satisfactory quality of life, and many demonstrate achievement of major life milestones.

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

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.

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

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.

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

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.

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

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.

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

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.

The molecular basis of breast cancer pathological phenotypes.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

[Radiation-induced cataracts]. / Strålingsindusert katarakt.

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.