Care-seeking experiences of unattached patients in the Canadian health care system: Qualitative study.

OBJECTIVE: To understand how lack of attachment to a regular primary care provider influences patients' outlooks on primary care, ability to address their health care needs, and confidence in the health care system. DESIGN: Qualitative descriptive study using semistructured interviews. SETTING: Canadian provinces of Nova Scotia, Ontario, and Quebec. PARTICIPANTS: Patients aged 18 years or older who were unattached or had become attached within 1 year of being interviewed and who resided in the province in which they were interviewed. METHODS: Forty-one semistructured interviews were conducted, during which participants were asked to describe how they had become unattached, their searches to find new primary care providers, their perceptions of and experiences with the centralized waiting list in their province, their experiences seeking care while unattached, and the impact of being unattached on their health and on their perceptions of the health care system. Interviews were transcribed and analyzed using a thematic approach. MAIN FINDINGS: Two main themes were identified in interviews with unattached or recently attached patients: unmet needs of unattached patients and the impact of being unattached. Patients' perceived benefits of attachment included access to care, longitudinal relationships with health care providers, health history familiarity, and follow-up monitoring and care coordination. Being unattached was associated with negative effects on mental health, poor health outcomes, decreased confidence in the health care system, and greater pre-existing health inequities. CONCLUSION: Having a regular primary care provider is essential to having access to high-quality care and other health care services. Attachment also promotes health equity and confidence in the public health care system and has broader system-level, social, and policy implications.

An analysis of policies supporting the roles of family physicians in four regions in Canada during the COVID-19 pandemic.

Policy supports are needed to ensure that Family Physicians (FPs) can carry out pandemic-related roles. We conducted a document analysis in four regions in Canada to identify regulation, expenditure, and public ownership policies during the COVID-19 pandemic to support FP pandemic roles. Policies supported FP roles in five areas: FP leadership, Infection Prevention and Control (IPAC), provision of primary care services, COVID-19 vaccination, and redeployment. Public ownership polices were used to operate assessment, testing and vaccination, and influenza-like illness clinics and facilitate access to personal protective equipment. Expenditure policies were used to remunerate FPs for virtual care and carrying out COVID-19-related tasks. Regulatory policies were region-specific and used to enact and facilitate virtual care, build surge capacity, and enforce IPAC requirements. By matching FP roles to policy supports, the findings highlight different policy approaches for FPs in carrying out pandemic roles and will help to inform future pandemic preparedness.

A Method for Reducing Variability Across Dual-Energy CT Manufacturers in Quantification of Low Iodine Content Levels.

BACKGROUND. Clinical use of the dual-energy CT (DECT) iodine quantification technique is hindered by between-platform (i.e., across different manufacturers) variability in iodine concentration (IC) values, particularly at low iodine levels. OBJECTIVE. The purpose of this study was to develop in an anthropomorphic phantom a method for reducing between-platform variability in quantification of low iodine content levels using DECT and to evaluate the method's performance in patients undergoing serial clinical DECT examinations on different platforms. METHODS. An anthropomorphic phantom in three body sizes, incorporating varied lesion types and scanning conditions, was imaged with three distinct DECT implementations from different manufacturers at varying radiation exposures. A cross-platform iodine quantification model for correcting between-platform variability at low iodine content was developed using the phantom data. The model was tested in a retrospective series of 30 patients (20 men, 10 women; median age, 62 years) who each underwent three serial contrast-enhanced DECT examinations of the abdomen and pelvis (90 scans total) for routine oncology surveillance using the same three DECT platforms as in the phantom. Estimated accuracy of phantom IC values was summarized using root-mean-square error (RMSE) relative to known IC. Between-platform variability in patients was summarized using root-mean-square deviation (RMSD). RMSE and RMSD were compared between platform-based IC (ICPB) and cross-platform IC (ICCP). ICPB was normalized to aorta and portal vein. RESULTS. In the phantom study, mean RMSE of ICPB across platforms and other experimental conditions was 0.65 ± 0.18 mg I/mL compared with 0.40 ± 0.08 mg I/mL for ICCP (38% decrease in mean RMSE; p < .05). Intrapatient between-platform variability across serial DECT examinations was higher for ICPB than ICCP (RMSD, 97% vs 88%; p < .001). Between-platform variability was not reduced by normalization of ICPB to aorta (RMSD, 97% vs 101%; p = .12) or portal vein (RMSD, 97% vs 97%; p = .81). CONCLUSION. The developed cross-platform method significantly decreased between-platform variability occurring at low iodine content with platform-based DECT iodine quantification. CLINICAL IMPACT. With further validation, the cross-platform method, which has been implemented as a web-based app, may expand clinical use of DECT iodine quantification, yielding meaningful IC values that reflect tissue biologic viability or treatment response in patients who undergo serial examinations on different platforms.

Preoperative Breast MRI for Newly Diagnosed Ductal Carcinoma in Situ: Imaging Features and Performance in a Multicenter Setting (ECOG-ACRIN E4112 Trial).

Background There are limited data from clinical trials describing preoperative MRI features and performance in the evaluation of mammographically detected ductal carcinoma in situ (DCIS). Purpose To report qualitative MRI features of DCIS, MRI performance in the identification of additional disease, and associations of imaging features with pathologic, genomic, and surgical outcomes from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E4112 trial. Materials and Methods Secondary analyses of a multicenter prospective clinical trial from the ECOG-ACRIN Cancer Research Group included women with DCIS diagnosed with conventional imaging techniques (mammography and US), confirmed via core-needle biopsy (CNB), and enrolled between March 2015 and April 2016 who were candidates for wide local excision (WLE) based on conventional imaging and clinical examination results. DCIS MRI features and pathologic features from CNB and excision were recorded. Each woman without invasive upgrade of the index DCIS at WLE received a 12-gene DCIS score. MRI performance metrics were calculated. Associations of imaging features with invasive upgrade, dichotomized DCIS score (<39 vs ≥39), and single WLE success were estimated in uni- and multivariable analyses. Results Among 339 women (median age, 60 years; interquartile range, 51-66 years), most DCIS cases showed nonmass enhancement (NME) (195 of 339 [58%]) on MRI scans with larger median size than on mammograms (19 mm vs 12 mm; P < .001). Positive predictive value of MRI-prompted CNBs was 32% (21 of 66) (95% CI: 22, 44), yielding an additional cancer detection rate of 6.2% (21 of 339) (95% CI: 4.1, 9.3). MRI false-positive rate was 14.2% (45 of 318) (95% CI: 10.7, 18.4). No imaging features were associated with invasive upgrade or DCIS score (P = .05 to P = .95). Smaller size and focal NME distribution at MRI were linked to single WLE success (P < .001). Conclusion Preoperative MRI depicted ductal carcinoma in situ (DCIS) diagnosed with conventional imaging most commonly as nonmass enhancement, with larger median span than mammography, and additional cancer detection rate of 6.2%. MRI features of this subset of DCIS did not enable prediction of pathologic or genomic outcomes. Clinical trial registration no. NCT02352883 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kuhl in this issue. An earlier incorrect version of this article appeared online. This article was corrected on August 4, 2021.

Dynamic contrast-enhanced breast MRI features correlate with invasive breast cancer angiogenesis.

Angiogenesis is a critical component of breast cancer development, and identification of imaging-based angiogenesis assays has prognostic and treatment implications. We evaluated the association of semi-quantitative kinetic and radiomic breast cancer features on dynamic contrast-enhanced (DCE)-MRI with microvessel density (MVD), a marker for angiogenesis. Invasive breast cancer kinetic features (initial peak percent enhancement [PE], signal enhancement ratio [SER], functional tumor volume [FTV], and washout fraction [WF]), radiomics features (108 total features reflecting tumor morphology, signal intensity, and texture), and MVD (by histologic CD31 immunostaining) were measured in 27 patients (1/2016-7/2017). Lesions with high MVD levels demonstrated higher peak SER than lesions with low MVD (mean: 1.94 vs. 1.61, area under the receiver operating characteristic curve [AUC] = 0.79, p = 0.009) and higher WF (mean: 50.6% vs. 22.5%, AUC = 0.87, p = 0.001). Several radiomics texture features were also promising for predicting increased MVD (maximum AUC = 0.84, p = 0.002). Our study suggests DCE-MRI can non-invasively assess breast cancer angiogenesis, which could stratify biology and optimize treatments.

Virtual Unenhanced Dual-Energy CT Images Obtained with a Multimaterial Decomposition Algorithm: Diagnostic Value for Renal Mass and Urinary Stone Evaluation.

Background Virtual unenhanced (VUE) images obtained by using a dual-energy CT (DECT) multimaterial decomposition algorithm hold promise for diagnostic use in the abdomen in lieu of true unenhanced (TUE) images. Purpose To assess VUE images obtained from a DECT multimaterial decomposition algorithm in patients undergoing renal mass and urinary stone evaluation. Materials and Methods In this retrospective Health Insurance Portability and Accountability Act-compliant study, DECT was performed in patients undergoing evaluation for renal mass or urinary stone. VUE images were compared quantitatively to TUE images and qualitatively assessed by four independent radiologists. Differences in attenuation between VUE and TUE images were summarized by using 95% limits of agreement. Diagnostic performance in urinary stone detection was summarized by using area under the receiver operating characteristic curve, sensitivity, and specificity. Results A total of 221 patients (mean age ± standard deviation, 61 years ± 14; 129 men) with 273 renal masses were evaluated. Differences in renal mass attenuation between VUE and TUE images were within 3 HU for both enhancing masses (95% limits of agreement, -3.1 HU to 2.7 HU) and nonenhancing cysts (95% limits of agreement, -2.9 HU to 2.5 HU). Renal mass classification as enhancing mass versus nonenhancing cyst did not change (reclassification rate of enhancing masses, 0% [0 of 78]; 95% CI: 0, 5; reclassification rate of nonenhancing cysts, 0% [0 of 193]; 95% CI: 0, 2) with use of VUE in lieu of TUE images. Among 166 urinary stones evaluated, diagnostic performance of VUE images for stone detection was lower compared with that of TUE images (area under the receiver operating characteristic curve, 0.79 [95% CI: 0.73, 0.84] vs 0.93 [95% CI: 0.91, 0.95]; P < .001) due to reduced sensitivity of VUE for detection of stones 3 mm in diameter or less compared with those greater than 3 mm (sensitivity, 23% [25 of 108; 95% CI: 12, 40] vs 88% [126 of 144; 95% CI: 77, 94]; P < .001). Conclusion Compared with true unenhanced images, virtual unenhanced (VUE) images were unlikely to change renal mass classification as enhancing mass versus nonenhancing cyst. Diagnostic performance of VUE images remained suboptimal for urinary stone detection due to subtraction of stones 3 mm or less in diameter. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sosna in this issue.

Frequency and Outcomes of Incidental Breast Lesions Detected on Abdominal MRI Over a 7-Year Period.

OBJECTIVE: Our aim was to evaluate the frequency and outcomes of incidental breast lesions detected on abdominal MRI examinations. MATERIALS AND METHODS: Abdominal MRI reports for 11,462 women imaged at our institution from November 2007 through December 2014 were reviewed to identify those reporting an incidental breast lesion. Available breast imaging and pathology results were assessed to identify outcomes in these lesions. RESULTS: Incidental breast lesions were described in the MRI reports of 292 (3%) patients who underwent abdominal MRI during the study period; breast imaging was recommended for 192 of these 292 (66%) patients. Sixty-three of the 192 (33%) patients for whom follow-up breast imaging was recommended underwent such imaging at our institution. Twenty-one of these 63 (33%) lesions underwent biopsy or surgery; histologic sampling of these lesions yielded seven incidental cancers (invasive ductal, n = 6; invasive lobular, n = 1) and 14 benign diagnoses. Three additional cancers (invasive ductal, n = 2; invasive lobular, n = 1) and three benign diagnoses were discovered at pathology at outside institutions. Of the remaining 165 patients without a histologic diagnosis, the lesions in 95 (58%) patients were presumed to be benign because of stability over time. Seven of the 10 patients with a diagnosis of incidental cancer (age range, 53-86 years; mean ± SD, 67.0 ± 10.6 years) had not undergone screening mammography at our institution. The frequency of incidental breast cancer was 11% of patients subsequently undergoing follow-up breast imaging at our institution, 3% of all patients with reported breast lesions, and 0.09% of patients undergoing abdominal MRI examinations. CONCLUSION: Although incidental breast lesions were rarely detected on abdominal MRI, a considerable number of these lesions were found to represent breast cancer, particularly when leading to a recommendation for follow-up breast imaging. Therefore, it is important for radiologists interpreting abdominal MRI examinations to carefully evaluate for the presence of breast abnormalities.

18F-FDG PET/CT Metabolic Tumor Volume and Intratumoral Heterogeneity in Pancreatic Adenocarcinomas: Impact of Dual-Time Point and Segmentation Methods.

OBJECTIVES: We aimed to determine the consistency of quantitative PET measurements of metabolic tumor volume (MTV) and intratumoral heterogeneity index for primary untreated pancreatic adenocarcinomas, when using dual-time point F-FDG PET/CT imaging. METHODS: This is an institutional review board-approved, retrospective study including 71 patients with pancreatic adenocarcinoma, who underwent dual-time point F-FDG PET/CT imaging, at approximately 1 hour (early) and 2 hours (delayed), after injection. Automated gradient-based and 50% SUVmax-threshold segmentation methods were used to assess the primary tumor MTV and metabolic intratumoral heterogeneity index, calculated as the area under cumulative SUV-volume histograms (AUC-CSH), with lower AUC-CHS indexes corresponding to higher degrees of tumor heterogeneity. We defined that more than a ±10% change in MTV or AUC-CSH, compared with baseline, as clinically significant. RESULTS: Seventy-one FDG-avid pancreatic tumors were identified, with an average tumor diameter of 3.4 ± 0.9 cm (range, 1.5-6.4 cm). Metabolic tumor volume values remained consistent between early and delayed imaging when using the gradient PET segmentation method (P = 0.086), whereas statistically significant change was seen when using 50% SUVmax-threshold segmentation (P < 0.001). A decrease in more than 10% change in MTV (% ΔMTV) was observed in 70.4% (50/71) tumors, and 7.0% (5/71) of the tumors showed an increase more than 10 % ΔMTV, when using the 50% SUVmax-threshold segmentation. AUC-CSH indexes showed statistically significant differences between early and delayed time points (P < 0.001), when using the gradient segmentation. AUC-CSH index decreased by 10% or greater in 40.8% (29/71) of the tumors. AUC-CSH index remained stable between early and delayed when using the 50% SUVmax-threshold segmentation (P = 0.148) with percentage of change of less than 10% for all tumors. CONCLUSIONS: Metabolic tumor volume was relatively stable between early and delayed time points when PET gradient segmentation was used but changed greater than 10% in 77.4% of the tumors at delayed time point when threshold segmentation was used. The tumor heterogeneity index (AUC-CSH) changed greater than 10% in 40.8% of tumors at delayed imaging, when gradient segmentation was used but remained stable when threshold segmentation was used. It is important to standardize uptake time and segmentation methods to use FDG PET MTV and heterogeneity index as imaging biomarkers.

FDG-PET/CT and MRI for Evaluation of Pathologic Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer: A Meta-Analysis of Diagnostic Accuracy Studies.

INTRODUCTION: This study compared the diagnostic test accuracy of magnetic resonance imaging (MRI) with that of (18)F-fluoro-2-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging in assessment of response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: A systematic search was performed in PubMed and EMBASE (last updated in June 2015). Studies investigating the performance of MRI and FDG-PET or FDG-PET/CT imaging during or after completion of NAC in patients with histologically proven breast cancer were eligible for inclusion. We considered only studies reporting a direct comparison between these imaging modalities to establish precise summary estimates in the same setting of patients. Pathologic response was considered as the reference standard. Two authors independently screened and selected studies that met the inclusion criteria and extracted the data. RESULTS: A total of 10 studies were included. The pooled estimates of sensitivity and specificity across all included studies were 0.71 and 0.77 for FDG-PET/CT (n = 535) and 0.88 and 0.55 for MRI (n = 492), respectively. Studies were subgrouped according to the time of therapy assessment. In the intra-NAC setting, FDG-PET/CT imaging outperformed MRI with fairly similar pooled sensitivity (0.91 vs. 0.89) and higher specificity (0.69 vs. 0.42). However, MRI appeared to have higher diagnostic accuracy than FDG-PET/CT imaging when performed after the completion of NAC, with significantly higher sensitivity (0.88 vs. 0.57). CONCLUSION: Analysis of the available studies of patients with breast cancer indicates that the timing of imaging for NAC-response assessment exerts a major influence on the estimates of diagnostic accuracy. FDG-PET/CT imaging outperformed MRI in intra-NAC assessment, whereas the overall performance of MRI was higher after completion of NAC, before surgery. IMPLICATIONS FOR PRACTICE: The timing of therapy assessment imaging exerts a major influence on overall estimates of diagnostic accuracy. (18)F-fluoro-2-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) imaging outperformed magnetic resonance imaging (MRI) in intra-neoadjuvant chemotherapy assessment with fairly similar pooled sensitivity and higher specificity. However, MRI appeared to be more accurate than FDG-PET/CT in predicting pathologic response when used in the post-therapy setting.

18F-FDG PET/CT and Melanoma: Value of Fourth and Subsequent Posttherapy Follow-up Scans for Patient Management.

PURPOSE: We aimed to evaluate the added value of performing fourth and subsequent follow-up F-FDG-PET/CT scans to clinical assessment and impact on the patient's management in patients with melanoma. METHODS: This was a retrospective study of 232 biopsy-proven melanoma patients who underwent F-FDG-PET/CT scans. Of these, 71 patients had 4 or more follow-up F-FDG-PET/CT scans after completion of primary treatment, with a total of 246 fourth or subsequent follow-up PET/CT scans. The added value of each follow-up PET/CT scan to the patient's clinical assessment and treatment management was established. Kaplan-Meier plots with a Mantel-Cox log-rank test were used to establish the patient's overall survival. RESULTS: Of the 246 fourth and subsequent follow-up PET/CT scans, 61% (150/246) were negative for malignancy, and 39.0% (96/246) were positive for recurrence/metastases. FDG-PET/CT was helpful in identifying malignancy in 6.5% of the scans performed without prior clinical suspicion, which ruled out malignancy in 28.5% of the scans obtained with prior clinical signs suggestive of recurrence or for secondary therapy assessment. The PET/CT scan resulted in change of the patient's management in approximately 16.7% (41/246) of the scans. Change in management was significantly greater in patients whose scans were done with prior clinical signs suggestive of malignancy, or for therapy assessment than without prior clinical suspicion (29.3% vs 4.1%; P < 0.0001). Statistically significant difference was seen in the overall survival between patients with at least 1 positive and all negative fourth and subsequent follow-up PET/CT scans at patient level (P = 0.001). CONCLUSIONS: The fourth and subsequent F-FDG-PET/CT scans obtained after completion of primary treatment added value to clinical assessment in patients with melanoma. Patients with clinical signs suggestive of recurrence or metastases or being monitored for treatment response are more likely to benefit from the fourth or subsequent FDG PET/CT than those without prior clinical suspicion.

FDG PET/CT in the management of colorectal and anal cancers.

OBJECTIVE: CT remains the imaging modality of choice in the diagnosis of colorectal cancer (CRC) and anal cancer. However, advances in imaging have expanded the role of MRI and PET/CT. This article focuses on the evolving role of FDG PET/CT in the diagnosis, radiation therapy planning, therapy assessment, and posttherapy monitoring of CRC and anal cancer. CONCLUSION: FDG PET/CT is a valuable imaging modality that impacts the clinical management of patients with CRC and those with anal cancer.

Both hydrogen peroxide and transforming growth factor beta 1 contribute to endothelial Nox4 mediated angiogenesis in endothelial Nox4 transgenic mouse lines.

Vascular endothelial cells (ECs) are responsible for post-ischemic angiogenesis, a process that is regulated by reactive oxygen species. Recent studies indicate that endothelial Nox4 based NADPH oxidase may have a key role. This study examines the role of endothelial Nox4 in ischemia-induced angiogenesis and explores the potential mechanisms involved. Mouse lines overexpressing human Nox4 wild type (EWT) or its dominant negative form P437H (EDN) specifically in the endothelium were used. Non-transgenic littermate mice (NTg) were used as controls. Following hind limb ischemia, blood flow recovery was enhanced in EWT and was impaired in EDN compared with NTg. The critical angiogenesis regulating genes vascular endothelial growth factor receptor2 (VEGFR2), endothelial nitric oxide synthase (eNOS) and transforming growth factor beta1 (TGFbeta1) were upregulated in EWT both in the ischemic muscle and in heart ECs, while TGFbeta1 was downregulated in EDNECs. In EC, both VEGFA and TGFbeta1 stimulated EC proliferation, migration, and capillary-like network formation in EWT but failed to do so in EDN. Application of TGFbeta1 increased both VEGFR2 and eNOS expression levels,whereas blocking TGFbeta1 or addition of catalase inhibited the phosphorylation of VEGFR2 and eNOS, indicating H2O2 and TGFbeta1 signaling downstream of Nox4 is critical to maintain EC angiogenic functions. Use of cell specific transgenic mice with both upregulation and downregulation of endothelial Nox4 indicate several mechanisms linked to Nox4 play a role in angiogenesis. Endothelial Nox4 regulates ischemia-induced angiogenesis, likely through H2O2- and TGFbeta1-mediated activation of cell signaling pathways essential for endothelial function.