Position statement on opportunistic genomic screening from the Association of Genetic Nurses and Counsellors (UK and Ireland)

The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest ‘opportunistic genomic screening'' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.     

The Genome Clinic: A Multidisciplinary Approach to Assessing the Opportunities and Challenges of Integrating Genomic Analysis into Clinical Care

Our increasing knowledge of how genomic variants affect human health and the falling costs of whole‐genome sequencing are driving the development of individualized genetic medicine. This new clinical paradigm uses knowledge of an individual's genomic variants to guide health care decisions throughout life, to anticipate, diagnose, and manage disease. While individualized genetic medicine offers the promise of transformative change in health care, it forces us to reconsider existing ethical, scientific, and clinical paradigms. The potential benefits of presymptomatic identification of at risk individuals, improved diagnostics, individualized therapy, accurate prognosis, and avoidance of adverse drug reactions coexist with the potential risks of uninterpretable results, psychological harm, outmoded counseling models, and increased health care costs. Here, we review the challenges of integrating genomic analysis into clinical practice and describe a prototype for implementing genetic medicine. Our multidisciplinary team of bioinformaticians, health economists, ethicists, geneticists, genetic counselors, and clinicians has designed a “Genome Clinic” research project that addresses multiple challenges in genomic medicine—ranging from the development of bioinformatics tools for the clinical assessment of genomic variants and the discovery of disease genes to health policy inquiries, assessment of clinical care models, patient preference, and the ethics of consent.     

False‐positive Extra‐Mammary Findings in Breast MRI: Another Cause for Concern

Breast magnetic resonance imaging (MRI) has been repeatedly shown to have a high false‐positive rate for additional findings in the breast resulting in additional breast imaging and biopsies. We hypothesize that breast MRI is also associated with a high rate of false‐positive findings outside of the breast requiring additional evaluation, interventions, and delays in treatment. We performed a retrospective review of all breast MRIs performed on breast cancer patients in 2010 at a single institution. MRI reports were analyzed for extra‐mammary findings. The timing and yield of the additional procedures was also analyzed. Three hundred and twenty‐seven breast cancer patients (average age = 53.53 ± 11.08 years) had a breast MRI. Incidental, extra‐mammary findings were reported in 35/327 patients (10.7%) with a total of 38 incidental findings. The extra‐mammary findings were located in the liver (n = 21, 60.0%), thoracic cavity (n = 12, 34.3%), kidneys (n = 1, 2.9%), musculoskeletal system (n = 3, 8.6%), and neck (n = 1, 2.9%). Eighteen of the 35 patients (51.4%) received additional radiographic imaging, 3 (8.6%) received additional laboratory testing, 2 (5.7%) received additional physician referrals and 2 (5.7%) received a biopsy of the finding. The average time to additional procedures in these patients was 14.5 days. None of the incidental, extra‐mammary findings were associated with breast cancer or other malignancy. Breast MRI was associated with a high rate (10.7%) of extra‐mammary findings, which led to costly additional imaging studies, referrals, and tests. These findings were not associated with breast cancer or other malignancies. Extra‐mammary findings highlight an unrecognized adverse consequence of breast MRI.     

Detection of Extrapulmonary Malignancy During Lung Cancer Screening: 5-Year Analysis at a Tertiary Hospital

PurposeThe aims of this study were to determine the prevalence and outcomes of extrapulmonary malignancies identified on lung cancer screening (LCS) and to determine the cost associated with the investigation of these lesions.MethodsThis retrospective study included 7,414 low-dose CT studies performed between June 2014 and December 2019 on 4,160 patients as part of an established LCS program. Patients with indeterminate extrapulmonary lesions were identified, and the diagnostic workup, management, and outcomes of the lesions were determined. Costs related to diagnostic evaluation were estimated using 2020 total facility relative value units and the 2020 Medicare conversion factor. Out-of-pocket costs were extracted from billing records.ResultsThere were 20 extrapulmonary malignancies among 241 reported lesions in 225 patients (mean age, 66.1 ± 6.4 years; 109 men, 116 women). The prevalence of extrapulmonary malignancy was 20 of 4,160 (0.48%). Early-stage cancers were detected in 13 of 20 (65%). No cancer-specific mortality was observed. The predictive value for malignancy varied by organ (P = .03) and was highest in the chest wall and axilla (36.4%), followed by bone (25%). The average cost on the basis of Medicare reimbursement for diagnosis of an extrapulmonary malignancy on LCS was $1,316.03 ($6.33 per participant and $109.21 per indeterminate incidental lesion). Most patients (203 of 225 [90.2%]) did not have out-of-pocket costs related to diagnostic workup. In those who did, the median cost was $160.60 (range, $75-$606.76).ConclusionsLow-dose CT for LCS detects extrapulmonary malignancy with high predictive value for certain locations. There is cost associated in the workup related to these incidental lesions, but most malignancies are detected at early stages and have good outcomes.     

Carotid Artery Calcification on Orthopantomograms (CACO Study) – is it indicative of carotid stenosis?

It is unclear whether incidental carotid artery calcification (CAC) on radiographs has a defined relationship to clinically significant carotid artery stenosis, and therefore risk of stroke. The primary objective of this study was to ascertain the relationship between dental radiograph detected carotid calcification and carotid artery stenoses ≥50% on carotid duplex ultrasound. We carried out an observational study of patients undergoing routine dental orthopantomogram (OPG) examinations. Consecutive patients with CAC on OPG were prospectively matched to those without CAC based on age and gender. Ultrasound of the carotid arteries was performed to determine the presence of stenosis (≥50%) in either vessel. Of 5780 consecutive OPG examinations with suitable images for analysis, CAC was detected in 10.8%. A total of 233 patients underwent carotid ultrasound (130 with and 103 without CAC on OPG). The prevalence of a clinically significant (≥50%) carotid stenosis on ultrasound was 15.4% (20/130) in those with CAC and 5.8% (6/103) for those without CAC on OPG. Incidental CAC detected on routine OPG requires both radiological reporting and clinical follow‐up since 1 in 7 patients will have a clinically significant carotid artery stenosis as compared with 1 in 20 patients who do not have CAC. Trial Registration: Australian and New Zealand Clinical Trials Registry website (U1111‐1148‐1066). http://www.ANZCTR.org.au/ACTRN12613001038785.aspx     

A significant incidental finding on cone beam computed tomography: multiple myeloma

Cone beam computed tomography is widely used in dentistry. Incidental findings are common, with many requiring intervention or monitoring. We present a rare case of previously undiagnosed, asymptomatic multiple myeloma first identified incidentally on cone beam computed tomography and panoramic radiography. This case highlights the diverse range of lesions that may appear on cone beam computed tomography and the importance of radiologic interpretation.