POLE Mutation Spectra Are Shaped by the Mutant Allele Identity, Its Abundance, and Mismatch Repair Status.

Human tumors with exonuclease domain mutations in the gene encoding DNA polymerase ε (POLE) have incredibly high mutation burdens. These errors arise in four unique mutation signatures occurring in different relative amounts, the etiologies of which remain poorly understood. We used CRISPR-Cas9 to engineer human cell lines expressing POLE tumor variants, with and without mismatch repair (MMR). Whole-exome sequencing of these cells after defined numbers of population doublings permitted analysis of nascent mutation accumulation. Unlike an exonuclease active site mutant that we previously characterized, POLE cancer mutants readily drive signature mutagenesis in the presence of functional MMR. Comparison of cell line and human patient data suggests that the relative abundance of mutation signatures partitions POLE tumors into distinct subgroups dependent on the nature of the POLE allele, its expression level, and MMR status. These results suggest that different POLE mutants have previously unappreciated differences in replication fidelity and mutagenesis.

Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome.

Abundant ribonucleoside-triphosphate (rNTP) incorporation into DNA by DNA polymerases in the form of ribonucleoside monophosphates (rNMPs) is a widespread phenomenon in nature, resulting in DNA-structural change and genome instability. The rNMP distribution, characteristics, hotspots and association with DNA metabolic processes in human mitochondrial DNA (hmtDNA) remain mostly unknown. Here, we utilize the ribose-seq technique to capture embedded rNMPs in hmtDNA of six different cell types. In most cell types, the rNMPs are preferentially embedded on the light strand of hmtDNA with a strong bias towards rCMPs; while in the liver-tissue cells, the rNMPs are predominately found on the heavy strand. We uncover common rNMP hotspots and conserved rNMP-enriched zones across the entire hmtDNA, including in the control region, which links the rNMP presence to the frequent hmtDNA replication-failure events. We show a strong correlation between coding-sequence size and rNMP-embedment frequency per nucleotide on the non-template, light strand in all cell types, supporting the presence of transient RNA-DNA hybrids preceding light-strand replication. Moreover, we detect rNMP-embedment patterns that are only partly conserved across the different cell types and are distinct from those found in yeast mtDNA. The study opens new research directions to understand the biology of hmtDNA and genomic rNMPs.

Melanoma-Specific Clinical Outcomes of Inpatient Immune Checkpoint Blockade Treatment.

BACKGROUND: Little is known about patient outcomes with advanced melanoma following inpatient initiation or continuation of immune checkpoint blockade (ICB). METHODS AND RESULTS: We conducted a single institution retrospective case series of advanced melanoma patients who initiated ICB as an inpatient (initial inpatient cohort, n = 9), or continued ICB as an inpatient after previously starting as an outpatient (outpatient then inpatient cohort, n = 5). One patient had a partial response to ICB initiated as an inpatient, but ultimately died of melanoma after 13.5 months. Median overall survival for initial inpatient cohort was 1.0 month (95% CI: 0.2-11.2), and 1.4 months (95% CI: 0.4-58.0) for the outpatient then inpatient cohort. Three patients were alive >6 months after inpatient ICB administration. CONCLUSION: Despite overall poor outcomes, some patients may benefit from inpatient ICB. This study provides additional information for clinicians to appropriately counsel patients on expectations following inpatient ICB.

US, Mammography, and Histopathologic Evaluation to Identify Low Nuclear Grade Ductal Carcinoma in Situ.

Background Low nuclear grade ductal carcinoma in situ (DCIS) identified at biopsy can be upgraded to intermediate to high nuclear grade DCIS at surgery. Methods that confirm low nuclear grade are needed to consider nonsurgical approaches for these patients. Purpose To develop a preoperative model to identify low nuclear grade DCIS and to evaluate factors associated with low nuclear grade DCIS at biopsy that was not upgraded to intermediate to high nuclear grade DCIS at surgery. Materials and Methods In this retrospective study, 470 women (median age, 50 years; interquartile range, 44-58 years) with 477 pure DCIS lesions at surgical histopathologic evaluation were included (January 2010 to December 2015). Patients were divided into the training set (n = 330) or validation set (n = 147) to develop a preoperative model to identify low nuclear grade DCIS. Features at US (mass, nonmass) and at mammography (morphologic characteristics, distribution of microcalcification) were reviewed. The upgrade rate of low nuclear grade DCIS was calculated, and multivariable regression was used to evaluate factors for associations with low nuclear grade DCIS that was not upgraded later. Results A preoperative model that included lesions manifesting as a mass at US without microcalcification and no comedonecrosis at biopsy was used to identify low nuclear grade DCIS, with a high area under the receiver operating characteristic curve of 0.97 (95% CI: 0.94, 1.00) in the validation set. The upgrade rate of low nuclear grade DCIS at biopsy was 38.8% (50 of 129). Ki-67 positivity (odds ratio, 0.04; 95% CI: 0.0003, 0.43; P = .005) was inversely associated with constant low nuclear grade DCIS. Conclusion The upgrade rate of low nuclear grade ductal carcinoma in situ (DCIS) at biopsy to intermediate to high nuclear grade DCIS at surgery occurred in more than a third of patients; low nuclear grade DCIS at final histopathologic evaluation could be identified if the mass was viewed at US without microcalcifications and had no comedonecrosis at histopathologic evaluation of biopsy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Rahbar in this issue. An earlier incorrect version appeared online. This article was corrected on April 14, 2022.

Immune-Related Adverse Events Among COVID-19-Vaccinated Patients With Cancer Receiving Immune Checkpoint Blockade.

BACKGROUND: Whether COVID-19 vaccination and the associated immune response increases susceptibility to immune-related adverse events (irAEs) among patients treated with immune checkpoint inhibition (ICI) remains unknown. Short-term follow-up can assess the safety of concurrent administration of the vaccine and ICI treatment. METHODS: We conducted an electronic health record analysis of a cohort of 408 patients with cancer receiving ICI therapy and who were vaccinated for COVID-19 between January 16 and March 27, 2021. Patients were seen in follow-up for 90 days from the day of the first dose in this single-institution tertiary care center. We evaluated the incidence of irAEs and the frequency of each event type and grade among patients who experienced an irAE. We also evaluated the incidence of irAEs in patients who began a new immunotherapy agent after vaccination. RESULTS: Among 408 patients with cancer receiving ICI therapy (median age, 71 years; 217 [53%] male), administration of a COVID-19 mRNA vaccine within 90 days of ICI treatment was not associated with an increased incidence of irAEs. A total of 27 (7%) patients experienced a new irAE within the observation period. Among patients with previous irAEs from ICIs (n=54), 3 (6%) experienced a recurrent irAE, and of those initiating a new immunotherapy (n=52), 9 (17%) experienced an irAE. No excess risk of COVID-19 diagnosis was seen in this subset of patients receiving ICI therapy, and no breakthrough COVID-19 cases were seen after full COVID-19 vaccination. CONCLUSIONS: These findings should reassure providers that COVID-19 vaccination during ICI therapy is safe and efficacious.

Ultrafast dynamic contrast-enhanced breast MRI: association with pathologic complete response in neoadjuvant treatment of breast cancer.

OBJECTIVES: The purpose of this study was to investigate whether pretreatment kinetic features from ultrafast DCE-MRI are associated with pathological complete response (pCR) in patients with invasive breast cancer and according to immunohistochemistry (IHC) subtype. METHODS: Between August 2018 and June 2019, 256 consecutive breast cancer patients (mean age, 50.2 years; range, 25-86 years) who underwent both ultrafast and conventional DCE-MRI and surgery following neoadjuvant chemotherapy were included. DCE-MRI kinetic features were obtained from pretreatment MRI data. Time-to-enhancement, maximal slope (MS), and volumes at U1 and U2 (U1, time point at which the lesion starts to enhance; U2, subsequent time point after U1) were derived from ultrafast MRI. Logistic regression analysis was performed to identify factors associated with pCR. RESULTS: Overall, 41.4% of all patients achieved pCR. None of the kinetic features was associated with pCR when including all cancers. Among ultrafast DCE-MRI kinetic features, a lower MS (OR, 0.982; p = 0.040) was associated with pCR at univariable analysis in hormone receptor (HR)-positive cancers. In triple-negative cancers, a higher volume ratio U1/U2 was associated with pCR at univariable (OR, 11.787; p = 0.006) and multivariable analysis (OR, 14.811; p = 0.005). Among conventional DCE-MRI kinetic features, a lower peak enhancement (OR, 0.993; p = 0.031) and a lower percentage of washout (OR, 0.904; p = 0.039) was associated with pCR only in HR-positive cancers at univariable analysis. CONCLUSIONS: A higher volume ratio of U1/U2 derived from ultrafast DCE-MRI was independently associated with pCR in triple-negative invasive breast cancer. KEY POINTS: • The ratio of tumor volumes obtained at the first (U1) and second time points (U2) of enhancement was independently associated with pCR in triple-negative invasive breast cancers. • Ultrafast MRI has the potential to improve accuracy in predicting treatment response and personalizing therapy.

AI-CAD for differentiating lesions presenting as calcifications only on mammography: outcome analysis incorporating the ACR BI-RADS descriptors for calcifications.

OBJECTIVES: To evaluate how AI-CAD triages calcifications and to compare its performance to an experienced breast radiologist. METHODS: Among routine mammography performed between June 2016 and May 2018, 535 lesions detected as calcifications only on mammography in 500 women (mean age, 48.8 years) that were additionally interpreted with additional magnification views were included in this study. One dedicated breast radiologist retrospectively reviewed the magnification mammograms to assess morphology, distribution, and final assessment category according to ACR BI-RADS. AI-CAD analyzed routine mammograms providing AI-CAD marks and corresponding AI-CAD scores (ranging from 0 to 100%), for which values ≥ 10% were considered positive. Ground truth in terms of malignancy or benignity was confirmed with a histopathologic diagnosis or at least 1 year of imaging follow - up. RESULTS: Of the 535 calcifications, 215 (40.2%) were malignant. Calcifications with positive AI-CAD scores showed significantly higher PPVs compared to calcifications with negative scores for all morphology (all p < 0.05). PPVs were significantly higher in calcifications with positive AI-CAD scores compared to those with negative scores for BI-RADS 3, 4a, or 4b assessments (all p < 0.05). AI-CAD and the experienced radiologist did not show significant difference in diagnostic performance; sensitivity 92.1% vs 95.4% (p = 0.125), specificity 71.9% vs 72.5% (p = 0.842), and accuracy 80.0% vs 81.7% (p = 0.413). CONCLUSION: Among calcifications with same morphology or BI-RADS assessment, those with positive AI-CAD scores had significantly higher PPVs. AI-CAD showed similar diagnostic performances to the experienced radiologist for calcifications detected on mammography. KEY POINTS: • Among calcifications with same morphology or BI-RADS assessment, those with positive AI-CAD scores had significantly higher PPVs. • AI-CAD showed similar diagnostic performance to an experienced radiologist in assessing lesions detected as calcifications only on mammography. • Among malignant calcifications, calcifications with positive AI-CAD scores showed higher rates of invasive cancers than calcifications with negative scores (all p > 0.05).

Cancer yield and imaging features of probably benign calcifications at digital magnification view.

OBJECTIVES: To investigate the malignancy rate of probably benign calcifications assessed by digital magnification view and imaging and clinical features associated with malignancy. METHODS: This retrospective study included consecutive women with digital magnification views assessed as probably benign for calcifications without other associated mammographic findings from March 2009 to January 2014. Initial studies rendering a probably benign assessment were analyzed, with biopsy or 4-year imaging follow-up. Fisher's exact test and univariable logistic regression were performed. Cancer yields were calculated. RESULTS: A total of 458 lesions in 422 patients were finally included. The overall cancer yield was 2.2% (10 of 458, invasive cancer [n = 4] and DCIS [n = 6]). Calcification distribution (OR = 23.80, p = .041), calcification morphology (OR = 10.84, p = .005), increased calcifications (OR = 29.40, p = .001), and having a concurrent newly diagnosed breast cancer or high-risk lesion (OR = 10.24, p = .001) were associated with malignancy. Cancer yields did not significantly differ between grouped punctate calcifications vs. calcifications with other features (1.2% [2 of 162] vs. 2.7% [8 of 296], p = .506). The cancer yield was 1.6% (7 of 437) in women without newly diagnosed breast cancer or high-risk lesions. CONCLUSION: The cancer yield of probably benign calcifications assessed by digital magnification view was below the 2% threshold for grouped punctate calcifications and for women without newly diagnosed breast cancer or high-risk lesions. Calcification distribution, morphology, increase in calcifications, and the presence of newly diagnosed breast cancer/high-risk lesion were associated with malignancy. KEY POINTS: • Among 458 probably benign calcifications assessed by digital magnification view, the overall cancer yield was 2.2% (10 of 458). • The cancer yield was below the 2% threshold for grouped punctate calcifications (1.2%, 2 of 162) and in women without newly diagnosed breast cancer or high-risk lesions (1.6%, 7 of 437). • Calcification distribution, morphology, increase in calcifications, and the presence of newly diagnosed breast cancer/high-risk lesion were associated with malignancy (all p < .05).

Application of Artificial Intelligence Computer-Assisted Diagnosis Originally Developed for Thyroid Nodules to Breast Lesions on Ultrasound.

As thyroid and breast cancer have several US findings in common, we applied an artificial intelligence computer-assisted diagnosis (AI-CAD) software originally developed for thyroid nodules to breast lesions on ultrasound (US) and evaluated its diagnostic performance. From January 2017 to December 2017, 1042 breast lesions (mean size 20.2 ± 11.8 mm) of 1001 patients (mean age 45.9 ± 12.9 years) who underwent US-guided core-needle biopsy were included. An AI-CAD software that was previously trained and validated with thyroid nodules using the convolutional neural network was applied to breast nodules. There were 665 benign breast lesions (63.0%) and 391 breast cancers (37.0%). The area under the receiver operating characteristic curve (AUROC) of AI-CAD to differentiate breast lesions was 0.678 (95% confidence interval: 0.649, 0.707). After fine-tuning AI-CAD with 1084 separate breast lesions, the diagnostic performance of AI-CAD markedly improved (AUC 0.841). This was significantly higher than that of radiologists when the cutoff category was BI-RADS 4a (AUC 0.621, P < 0.001), but lower when the cutoff category was BI-RADS 4b (AUC 0.908, P < 0.001). When applied to breast lesions, the diagnostic performance of an AI-CAD software that had been developed for differentiating malignant and benign thyroid nodules was not bad. However, an organ-specific approach guarantees better diagnostic performance despite the similar US features of thyroid and breast malignancies.

Outcomes Following Negative Screening MRI Results in Korean Women with a Personal History of Breast Cancer: Implications for the Next MRI Interval.

Background There are limited data on outcomes following screening breast MRI in women with a personal history of breast cancer (PHBC). Purpose To investigate outcomes and factors associated with subsequent cancers following a negative screening MRI study in women with a PHBC. Materials and Methods Consecutive women with a PHBC and a negative prevalence screening breast MRI result between August 2014 and December 2016 were retrospectively identified. Inclusion criteria were prevalence screening MRI performed as part of routine surveillance protocol (1-3 years after treatment) and follow-up data for at least 12 months. The incidence and characteristics of subsequent cancers were reviewed. Logistic regression analysis was used to investigate associations between clinical-pathologic characteristics and subsequent cancers. Performance metrics were compared among screening MRI, mammography, and US. Results A total of 993 women (mean age ± standard deviation, 53 years ± 10) were evaluated. Ten second in-breast cancers (ie, ipsilateral or contralateral) occurred at a median interval of 31.8 months (range, 13.3-44.8 months) after MRI, of which eight (80%) were ductal carcinoma in situ (DCIS) or node-negative T1 cancers. Only one node-negative T1mi (tumor ≤1 mm) second in-breast cancer visible on a mammogram was detected within 24 months of MRI. Of second in-breast cancers, 40% (four of 10) were detected only at subsequent screening MRI, which was performed a median of 30.5 months after negative prevalence screening MRI. Ten local-regional recurrences occurred at a median interval of 16.9 months (range, 6-35 months). Previous treatment for DCIS was associated with second in-breast cancers (odds ratio, 3.73; 95% CI: 1.04, 13.38; P = .04). In 1048 women who underwent prevalence screening MRI (including all Breast Imaging Reporting and Data System categories), MRI showed a lower abnormal interpretation rate and higher specificity than mammography or US (P < .001 for all). Conclusion After a negative screening MRI result, 90% of subsequent cancers were detected at intervals longer than 24 months and there was a low second in-breast cancer rate (1%). © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Chang in this issue.

Implications of US radiomics signature for predicting malignancy in thyroid nodules with indeterminate cytology.

OBJECTIVES: The purpose of this study was to evaluate the role of the radiomics score using US images to predict malignancy in AUS/FLUS and FN/SFN nodules. METHODS: One hundred fifty-five indeterminate thyroid nodules in 154 patients who received initial US-guided FNA for diagnostic purposes were included in this retrospective study. A representative US image of each tumor was acquired, and square ROIs covering the whole nodule were drawn using the Paint program of Windows 7. Texture features were extracted by in-house texture analysis algorithms implemented in MATLAB 2019b. The LASSO logistic regression model was used to choose the most useful predictive features, and ten-fold cross-validation was performed. Two prediction models were constructed using multivariable logistic regression analysis: one based on clinical variables, and the other based on clinical variables with the radiomics score. Predictability of the two models was assessed with the AUC of the ROC curves. RESULTS: Clinical characteristics did not significantly differ between malignant and benign nodules, except for mean nodule size. Among 730 candidate texture features generated from a single US image, 15 features were selected. Radiomics signatures were constructed with a radiomics score, using selected features. In multivariable logistic regression analysis, higher radiomics score was associated with malignancy (OR = 10.923; p < 0.001). The AUC of the malignancy prediction model composed of clinical variables with the radiomics score was significantly higher than the model composed of clinical variables alone (0.839 vs 0.583). CONCLUSIONS: Quantitative US radiomics features can help predict malignancy in thyroid nodules with indeterminate cytology.

Comparison of diagnostic performance of the ACR and Kwak TIRADS applying the ACR TIRADS' size thresholds for FNA.

OBJECTIVE: To investigate the diagnostic performances and unnecessary fine-needle aspiration (FNA) rates of two point-scale based TIRADS and compare them with a modified version using the ACR TIRADS' size thresholds. METHODS: Our Institutional Review Board approved this retrospective study and waived the requirement for informed consent. A total of 2106 thyroid nodules 10 mm or larger in size in 2084 patients with definitive cytopathologic findings were included. Ultrasonography categories were assigned according to each guideline. We applied the ACR TIRADS' size thresholds for FNA to the Kwak TIRADS and defined it as the modified Kwak TIRADS (mKwak TIRADS). Diagnostic performances and unnecessary FNA rates were evaluated for both the original and modified guidelines. RESULTS: Of the original guidelines, the ACR TIRADS had higher specificity, accuracy, and area under the receiver operating characteristic curve (AUC) (63.1%, 68.9%, and 0.748, respectively). When the size threshold of the ACR TIRADS was applied to the Kwak TIRADS, the resultant mKwak TIRADS had higher specificity, accuracy, and AUC (64.7%, 70.3%, and 0.765, respectively) than the ACR TIRADS. The mKwak TIRADS also had a lower unnecessary FNA rate than the ACR TIRADS (54.8% and 56.4%, respectively). The false-negative rate of the Kwak TIRADS was the lowest (1.9%) among all TIRADS. CONCLUSION: The modified Kwak TIRADS incorporating the size thresholds of the ACR TIRADS showed higher diagnostic performance and a lower unnecessary FNA rate than the original point-scale based TIRADS. KEY POINTS: • Of the original guidelines, the ACR TIRADS had the highest specificity, accuracy, and area under the receiver operating characteristic curve (AUC) (63.1%, 68.9%, and 0.748, respectively). • When the size threshold of the ACR TIRADS was applied to the Kwak TIRADS, the resultant modified version of Kwak TIRADS had higher specificity, accuracy, and AUC (64.7%, 70.3%, and 0.765, respectively) than the ACR TIRADS. • The false-negative rate of the Kwak TIRADS was the lowest (1.9%) among all TIRADS.

Combining radiomics with ultrasound-based risk stratification systems for thyroid nodules: an approach for improving performance.

OBJECTIVES: To develop a radiomics score using ultrasound images to predict thyroid malignancy and to investigate its potential as a complementary tool to improve the performance of risk stratification systems. METHODS: We retrospectively included consecutive patients who underwent fine-needle aspiration (FNA) for thyroid nodules that were cytopathologically diagnosed as benign or malignant. Nodules were randomly assigned to a training and test set (8:2 ratio). A radiomics score was developed from the training set, and cutoff values based on the maximum Youden index (Rad_maxY) and for 5%, 10%, and 20% predicted malignancy risk (Rad_5%, Rad_10%, Rad_20%, respectively) were applied to the test set. The performances of the American College of Radiology (ACR) and the American Thyroid Association (ATA) guidelines were compared with the combined performances of the guidelines and radiomics score with interpretations from expert and nonexpert readers. RESULTS: A total of 1624 thyroid nodules from 1609 patients (mean age, 50.1 years [range, 18-90 years]) were included. The radiomics score yielded an AUC of 0.85 (95% CI: 0.83, 0.87) in the training set and 0.75 (95% CI: 0.69, 0.81) in the test set (Rad_maxY). When the radiomics score was combined with the ACR or ATA guidelines (Rad_5%), all readers showed increased specificity, accuracy, and PPV and decreased unnecessary FNA rates (all p < .05), with no difference in sensitivity (p > .05). CONCLUSION: Radiomics help predict thyroid malignancy and improve specificity, accuracy, PPV, and unnecessary FNA rate while maintaining the sensitivity of the ACR and ATA guidelines for both expert and nonexpert readers. KEY POINTS: • The radiomics score yielded an AUC of 0.85 and 0.75 in the training and test set, respectively. • For all readers, combining a 5% predicted malignancy risk cutoff for the radiomics score with the ACR and ATA guidelines significantly increased specificity, accuracy, and PPV and decreased unnecessary FNA rates, with no decrease in sensitivity. • Radiomics can help predict malignancy in thyroid nodules in combination with risk stratification systems, by improving specificity, accuracy, and PPV and unnecessary FNA rates while maintaining sensitivity for both expert and nonexpert readers.

Safety of Inactivated Influenza Vaccine in Cancer Patients Receiving Immune Checkpoint Inhibitors.

BACKGROUND: Cancer patients are at a higher risk for developing influenza (flu)- related complications. It is unclear if the flu vaccine exacerbates immune events in patients treated with immune checkpoint inhibitors (ICIs). METHODS: We conducted an institutional review board-IRB-approved retrospective review of advanced cancer patients on ICIs who received the flu vaccine during three 3 consecutive seasons: 2014-2015, 2015-2016, and 2016-2017. The primary outcome assessed was any "new onset" immune-related adverse event (IRAE). A subset analysis of vaccinated patients newly treated with anti-programmed cell death protein 1 (PD-1) agents (nivolumab or pembrolizumab) was conducted to assess overall IRAE rates for comparison with published clinical trials. RESULTS: During the three 3 seasons, 370 patients met criteria for ICI and vaccination within ~ twoapproximately 2 months (65 days). The most common underlying cancers were lung (46%) and melanoma (19%); 61% of patients received an anti-PD-1 agent only. In the entire cohort, 20% experienced an IRAE (any grade); incidence of grade 3 or 4 toxicity was 8%. No grade 5 events occurred. In the subset of 170 patients newly treated with anti-PD-1 agents, the overall IRAE rate was 18% and, grade 3/4 events occurred in 7.6%. Influenza was diagnosed in 2 patients. CONCLUSIONS: No increase in incidence or severity of IRAEs was detected in patients on ICIs who received the inactivated influenza vaccine within ~ approximately 2 months of ICI. For newly treated patients on anti-PDI-1 agents, IRAE rates were comparable to those from published clinical trials and did not vary with order of administration. Routine seasonal flu vaccination is encouraged in patients on ICIs.

Factors Predicting Breast Cancer Development in Women During Surveillance After Surgery for Atypical Ductal Hyperplasia of the Breast: Analysis of Clinical, Radiologic, and Histopathologic Features.

BACKGROUND: This study aimed to evaluate the risk of breast cancer development for women under surveillance after surgery for atypical ductal hyperplasia (ADH), as well as the clinical and pathologic factors associated with breast cancer development. METHODS: From November 2003 to December 2014, the study included 205 women (mean age, 47.1 ± 11.2 years; range 18-73 years) with a pathologic diagnosis of ADH at surgical excision who had preoperative mammography and ultrasonography (US) images and pathology slides available for review. The patients were classified into three groups according to the detection method as follows: negative group (with ADH occult on imaging), mammography group (with ADH detected on mammography), and US group (with ADH detected on US only). Clinical, radiologic, and histopathologic factors associated with breast cancer development after ADH surgery were evaluated. RESULTS: Breast cancer developed in 15 patients (7.3%) during surveillance after ADH surgery (follow-up period, 63.9 ± 40.8 months). Palpable lesions had significantly higher rates of breast cancer development after ADH surgery (26.7% vs 6.8%; P = 0.045). Breast cancer development after ADH surgery did not differ according to the detection method (P = 0.654). Palpability was significantly associated with breast cancer development during surveillance after ADH surgery (hazard ratio, 3.579; 95% confidence interval 1.048-12.220; P = 0.042). CONCLUSION: The breast cancer development rate for women under surveillance after ADH surgery was 7.3%. Palpability at the time of ADH diagnosis was significantly associated with breast cancer development.

Comparing recall rates following implementation of digital breast tomosynthesis to synthetic 2D images and digital mammography on women with breast-conserving surgery.

OBJECTIVES: To evaluate the recall rates of digital mammography (DM) and synthetic images after adding digital breast tomosynthesis (DBT) in patients with breast-conserving surgery. METHODS: From November 2015 to April 2017, 229 women with breast-conserving surgery due to breast cancer who underwent DBT after surgery were included (mean interval, 12.9 ± 1.4 months). All women underwent combo-mode DBT examinations including full-field DM, tomosynthesis, and reconstructed synthetic 2D images. Three board-certified breast radiologists reviewed the images sequentially: synthetic 2D+DBT and, 1 month later, DM and then DM+DBT. Recall rates and the abnormality type causing the recall were calculated and compared for each mammographic modality and breast density. RESULTS: Of the 229 patients included, 230 mammography images were reviewed. One patient (0.4%) developed locoregional recurrences during follow-up (mean duration, 25.8 ± 4.5 months). Recall rates for synthetic 2D+DBT were significantly lower than for DM alone (4.1% (2.6-6.2) vs. 11.6% (9.2-14.5), respectively; p < 0.001). Recall rates did not differ between synthetic 2D+DBT and DM+DBT (4.1% (2.6-6.2) vs. 2.9% (1.9-4.5), respectively; p = 0.234). Recall rates of synthetic 2D+DBT and DM+DBT were significantly lower than those of DM alone, regardless of mammographic breast density (all p < 0.05, respectively). CONCLUSION: Adding DBT to synthetic 2D images or DM shows significant reduction in recall rates compared with DM alone for women who undergo breast-conserving surgery for breast cancer, regardless of mammographic density. KEY POINTS: • Recall rates for synthetic 2D+DBT were significantly lower than those of DM alone (4.1% (2.6-6.2) vs. 11.6% (9.2-14.5), respectively; p < 0.001). • No significant differences were seen in recall rates between synthetic 2D+DBT and DM+DBT (4.1 (2.6-6.2) vs. 2.9 (1.9-4.5), respectively; p = 0.234). • Reader-averaged recall rates after adding DBT to synthetic 2D or DM were significantly lower than those of DM alone, regardless of mammographic breast density (all p < 0.05, respectively).

Pattern-based vs. score-based guidelines using ultrasound features have different strengths in risk stratification of thyroid nodules.

OBJECTIVE: To evaluate and compare the diagnostic performances between recently published pattern-based and score-based TIRADS according to the experience level of the performer. METHODS: From July 2013 to January 2019, 8657 thyroid nodules in 8364 patients that had been cytopathologically diagnosed as benign or malignant were included (mean size, 22.0 mm ± 12.1). Thyroid nodules were categorized into US-based final assessment categories and US-FNA indications of five recently published TIRADS. Radiologists performing the US examinations were divided into the experienced vs. inexperienced group. Diagnostic performances and unnecessary biopsy rates were calculated and compared between the five TIRADS, also the experienced vs. inexperienced group. RESULTS: Of the 8657 thyroid nodules, 6706 (77.5%) were benign and 1951 (22.5%) were malignant. Diagnostic performances for US-based final assessment categories showed higher sensitivity and NPV for EU-TIRADS (92.7% and 96.5%), while Kwak-TIRADS had higher specificity, PPV, accuracy, and AUC (89.6%, 68.0%, 86.5%, and 0.878; all p < 0.05, respectively). Diagnostic performances for US-FNA indications showed higher sensitivity and NPV for KTA/KSThR TIRADS (98.5% and 97.0%), while Kwak-TIRADS had higher specificity, PPV, accuracy, and AUC (70.3%, 46.6%, 74.5%, and 0.797; all p < 0.05, respectively). Unnecessary biopsy rates were the lowest in Kwak-TIRADS for both US categories and US-FNA indications (32.0% and 53.4%, p < 0.001). Similar trends were seen in both the experienced and inexperienced group. CONCLUSION: The currently published score-based guidelines for thyroid nodules have significantly higher specificity, PPV, accuracy, and AUC and lower unnecessary biopsy rates, whereas pattern-based guidelines have higher sensitivity and NPV, regardless of the level of experience of the performer. KEY POINTS: • For US-based final assessment categories, EU-TIRADS had higher sensitivity and NPV, while Kwak-TIRADS had higher specificity, PPV, accuracy, and AUC. • For US-FNA indications, KTA/KSThR TIRADS had higher sensitivity and NPV, while Kwak-TIRADS had higher specificity, PPV, accuracy, and AUC. • Similar trends were seen in diagnostic performances for both experienced and inexperienced groups.

BI-RADS category 3, 4, and 5 lesions identified at preoperative breast MRI in patients with breast cancer: implications for management.

OBJECTIVES: To investigate outcomes and retrospectively evaluate characteristics of additional lesions initially assessed as BI-RADS category 3, 4, and 5 at preoperative MRI to determine appropriate follow-up management. METHODS: We retrospectively reviewed 429 lesions other than primary cancer initially assessed as BI-RADS category 3, 4, and 5 at preoperative MRI in 391 patients with breast cancer from March 2012 to December 2013. We investigated their malignancy rate and outcome according to BI-RADS category assessments. We also analyzed clinical and imaging characteristics of each lesion. Pathological results and imaging follow-up of at least 2 years were used as reference standards. RESULTS: Of 429 lesions in 391 patients (mean 48.1 years ± 9.4), the malignancy rate of BI-RADS 3, 4, and 5 lesions was 1.4% (3/213), 17.8% (38/214), and 50% (1/2), respectively. Of BI-RADS 3 lesions or BI-RADS 4 or 5 lesions that were followed up after benign-concordant biopsy (n = 114), two contralateral masses (2/306, 0.7%) were diagnosed as malignancy at 13.3 and 33.2 months after initial detection, within a median follow-up of 63.3 months. None of the NME or foci or lesions followed up after benign-concordant biopsy had a delayed diagnosis of malignancy. Of the 391 patients, 97.4% (381/391) received at least one type of adjuvant therapy. CONCLUSION: The incidence of delayed cancer diagnosis among additionally detected lesions other than primary cancer is very low and short-term follow-up is unnecessary. Contralateral masses which were not confirmed by biopsy may need annual follow-up. KEY POINTS: • 1.4% (3/213) of BI-RADS 3 lesions were malignant including 2 delayed diagnoses after 13.2 months and 33.2 months, and 17.8% (38/214) of BI-RADS 4 lesions and 50% (1/2) of BI-RADS 5 lesions were malignant. • The incidence of delayed diagnosis from additional MRI-detected lesions was very low (0.7%, 2/306) during follow-up, which were all T1N0 contralateral cancer. • Annual follow-up might be adequate for preoperative MRI-detected BI-RADS 3 lesions and BI-RADS 4 lesions followed up after benign-concordant biopsy.

Guideline Implementation on Fine-Needle Aspiration for Thyroid Nodules: Focusing on Micronodules.

OBJECTIVE: We investigated patients who were referred to our institution after fine-needle aspiration (FNA) was performed at outside clinics to evaluate how many nodules satisfied the FNA indications of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and compare that to the number of thyroid nodules that satisfy the FNA indications of the American College of Radiology (ACR)-TIRADS and American Thyroid Association (ATA) guidelines. METHODS: Between January 2018 and December 2018, 2,628 patients were included in our study. The included patients were those referred for thyroid surgery after having a suspicious thyroid nodule. We retrospectively applied the three guidelines to each thyroid nodule and determined whether each nodule satisfied the FNA indications. We compared the proportion of nodules satisfying the FNA indications of each guideline using a generalized linear model and generalized estimating equation. RESULTS: The median size of the 2,628 thyroid nodules was 0.9 cm (range, 0.2 to 9.5 cm). We found that FNA was not indicated for 54.1%, 47.7%, and 19.1% of nodules and 87.3%, 99.0%, and 97.8% among them were micronodules (<1 cm) according to the ACR-TIRADS, ATA guideline, and K-TIRADS, respectively. The proportion of micronodules which satisfied the FNA indications was significantly higher for the K-TIRADS (65.1%) compared to the ACR TIRADS (12.1%) and ATA guideline (12.1%) (P<.001). CONCLUSION: Among patients referred for thyroid surgery to our institutions, about 35% of the micronodules underwent FNA despite not being appropriate for indications by the K-TIRADS. Systematic training for physicians as well as modifications to increase the sensitivity of the guideline may be needed to reduce the overdiagnosis of thyroid cancers, especially for micronodules.

Role of elastography for downgrading BI-RADS category 4a breast lesions according to risk factors.

BACKGROUND: Elastography has been introduced as an additional diagnostic tool to ultrasonography (US) which helps clinicians decide whether or not to perform biopsy on US-detected lesions. PURPOSE: To evaluate the role of strain elastography in downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4a breast lesions according to personal risk factors for breast cancer in asymptomatic women. MATERIAL AND METHODS: Strain elastography features of a total of 255 asymptomatic category 4a lesions were classified as soft and not soft (intermediate and hard). Malignancy was confirmed by surgery or biopsy, and benignity was confirmed by surgery or biopsy with no change on US for at least six months. Malignancy rates of lesions with soft and not soft elastography were calculated according to the presence of risk factors. RESULTS: Of 255 lesions, 25 (9.8%) were malignant and 230 (90.2%) were benign. Of 195 lesions in average-risk women, the malignancy rate of lesions with soft elastography was 1.5% (1/68), which was significantly lower than the 14.2% (18/127) of lesions with not soft elastography ( P = 0.004). Of 60 lesions in increased-risk women, the malignancy rate of lesions with soft elastography was 15.0% (3/20), which was not significantly different from the 7.5% (3/40) of lesions with not soft elastography ( P = 0.390). CONCLUSION: In average-risk women, category 4a lesions with soft elastography could be followed up with US because of a low malignancy rate of 1.5%.