Citations

Abstract Over the last 30 years, axillary surgery in patients with breast cancer has undergone a consistent patient-centered, evidence-based de-escalation of surgical intervention, including considerable practice changes over the last decade. As surgical approaches change, the role of breast imaging radiologists and axillary imaging must also evolve. Axillary imaging remains variable across radiology practices, with implementation of new protocols occurring at various speeds. Breast radiologists must be aware of recent trials and remain agile in adopting or responding to changing treatment paradigms. Breakthrough studies, such as the SOUND (Sentinel Node Vs Observation After Axillary Ultra-souND) trial, must be vetted and evaluated by individual practices before adoption. Breast radiologists should play a key role in multidisciplinary collaboration with colleagues involved in breast cancer care to assist with strategic planning and appropriate resource utilization.

e21573 Background: In melanoma, biomarkers such as lactate dehydrogenase (LDH), circulating tumor DNA (ctDNA), and the neutrophil-lymphocyte ratio (NLR) have been linked to disease progression. This study aims to compare survival outcomes in melanoma patients based on high versus low levels of these biomarkers, assessing their impact on survival within their respective groups. By evaluating these biomarkers, we hope to identify potential prognostic indicators that could guide treatment decisions and improve personalized care in melanoma management. Methods: We conducted a retrospective survival analysis of 43 melanoma patients, excluding 16 due to incomplete data at Dignity Health Cancer Institute in Phoenix, Arizona. Kaplan-Meier survival analysis was used to compare survival between groups with high vs low levels of biomarkers. Patients were stratified by median values for LDH, NLR, and the presence of detectable ctDNA. Patients included in the analysis were treated systemically with pembrolizumab, encorafenib/binimetinib, nivolumab, or ipilimumab/nivolumab. Survival curves were generated, and statistical significance was assessed using log-rank tests. Data was sourced from our electronic medical record and Signatera™ assay to obtain the primary endpoints. Specimens were standardized in accordance with Natera’s™ specifications. All analyses were executed in GraphPad Prism software. Results: When stratifying by ctDNA, 18 patients had undetectable ctDNA, while 9 had detectable ctDNA with an average level of 1330 (SD = 2067). The median survival for the high ctDNA group was 220 days, whereas the low ctDNA group had significantly longer survival, with only two deaths observed (p = 0.006) within the time period. For LDH, using a cutoff of 204 (IQR = 90.5), patients with high LDH had a median survival of 220 days, while those with low LDH had a significantly longer survival (p = 0.004). When comparing NLR with a cutoff at 2.94 (IQR = 3.7), no significant difference in survival was found between high and low NLR groups (p = 0.72). Conclusions: Our findings show that patients with higher levels of ctDNA and LDH have significantly shorter survival compared to those with low levels of these biomarkers. While NLR did not show a significant survival difference, the study suggests that higher ctDNA and LDH could be important markers for identifying patients at greater risk of poor outcomes. These results underscore the potential value of monitoring these biomarkers to assess disease progression and survival in melanoma patients. Further studies with larger cohorts are needed to validate these findings and refine melanoma prognostic models.

Abstract Breast image-guided procedures play a critical role in the diagnosis and management of breast cancer, serving as the gold standard for tissue sampling and preoperative localization. These minimally invasive procedures carry a very low risk of complications, with postprocedural infections occurring in fewer than 0.2% of cases. However, given the high volume of breast interventions performed annually, the potential impact of infections remains significant. Despite this, published guidelines addressing procedural cleanliness techniques in breast imaging are sparse and often provide conflicting recommendations, leading to variability in clinical practice and resource utilization. The lack of clear and specific guidance creates challenges for radiologists navigating institutional policies and best practice implementation. This review synthesizes existing standards and guidelines, evaluating the supporting evidence to propose an evidence-based best practice approach for maintaining clean techniques in breast image-guided procedures. By standardizing cleanliness protocols, we aim to enhance patient care, optimize procedural success, and promote consistency across breast imaging practices.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is commonly seen in immunocompromised patients. Telomere biology disorder (TBD), which is a genetic disorder marked by mutations in telomere-maintenance genes, leading to shortened telomere, accelerated aging, and multi-systems effects including the pulmonary and immune systems. Idiopathic pulmonary fibrosis (IPF) is the most common pulmonary manifestation in TBD. Opportunistic infections, such as PJP, occurring de novo are rare in TBD, presenting unique diagnostic and therapeutic challenges. Case Presentation We present a female in her seventies with chronic dry cough and exertional dyspnea referred for evaluation of interstitial lung disease (ILD). Her family history revealed early-onset pulmonary fibrosis in her mother and sister. A year before the presentation, she developed acute hypoxic respiratory failure with bilateral pulmonary infiltrates. Bronchoalveolar lavage confirmed PJP despite no established immunosuppression. She received Bactrim and prednisone without clinical improvement. High-resolution chest CT revealed progressive infiltrates and fibrotic lung disease. Surgical lung biopsy showed organizing pneumonia, diffuse alveolar damage, and fibrosis, consistent with probable usual interstitial pneumonia (UIP). Ultimately, she developed rapidly progressive ILD. Further evaluation ruled out autoimmune and connective tissue disease. Telomere studies confirmed TBD, with her lymphocyte and granulocyte telomere lengths between the 1st and 10th percentiles. (figure1) Genetic testing is underway for familial pulmonary fibrosis. Discussion This case illustrates a rare presentation of PJP de novo in a patient with TBD, highlighting opportunistic infections risk in those patients without immunosuppression and before transplantation. TBD results in quantitative and qualitative T-cell immunodeficiency, reducing CD4+ T-cell count, predisposing to opportunistic infections, including PJP. TBD patients often experience a rapidly progressive course of ILD due to inherited telomere dysfunction causing limited regenerative capacity of Alveolar epithelial type 2 cells (AEC2s) exacerbated by environmental or age-related factors such as oxidative stress or smoking. Management requires a multidisciplinary approach with early genetic testing, antifibrotic therapies, and prophylactic treatments to prevent infections. This case underscores the importance of considering TBD in patients with opportunistic infections like PJP in the absence of traditional immunosuppressive risk factor and in patients with premature or progressive pulmonary fibrosis. Conclusion Telomere biology disorder can present with rapidly progressive ILD with atypical infections like PJP while on immunosuppression. To the best of our knowledge de novo PJP pneumonia in patient with TBD is unreported in the literature. High clinical suspicion, quantitative CD4 evaluation and consideration of PJP prophylaxis prevent an otherwise fatal outcome. Figure1:

Abstract Introduction Lung involvement is common in ANCA-associated vasculitis (AAV), presenting in various forms: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis and diffuse alveolar hemorrhage (DAH), interstitial lung disease (ILD), and asthma.1 Radiologic manifestations are diverse, often complicating diagnosis based on imaging alone. Typical patterns include lung nodules, cavitation, pulmonary hemorrhage, and peripheral consolidation; however, cystic-like lesions are rarely seen.2 We present a case of AAV with bilateral cystic-like lung lesions. Case presentation A 54-year-old male with childhood asthma initially presented to an outside hospital due to progressive exertional dyspnea for 6 years and dysphonia for 1 year. Initial computer tomography (CT) revealed pulmonary cysts (Figure 1), and a CT-guided biopsy of a right upper lobe cystic lesion revealed intra-alveolar hemorrhage, though pathology was non-diagnostic. He received a diagnosis of congenital cystic lung disease and prescribed Trelegy and fluticasone inhalers. He was instructed to take oral prednisone with taper whenever dyspnea recurs for presumed asthma exacerbation. His exertional dyspnea indeed respond to prednisone but not to inhalers, and it would recur a few weeks later, and his dysphonia persisted. He came to our facility for second opinion given being told lung transplantation is the only ultimate treatment in his case. Additional history revealed chronic ear infection, bilateral rupturesd tympanic membrane, chronic rhinosinusitis, and recurrent nasolacrimal duct infection. He had been on oral prednisone for 4 weeks and remained on 10mg daily. Physical exam noted inspiratory wheezing. Further workups were notable for normal eospinophils, normal renal function, positive C-ANCA and PR3, normal pulmonary function test. High-resolution CT deomnstrated numerous areas of parenchymal lucency with circumferential surrounding groundglass opacity (GGO). At this point, the diagnosis of PR3-AAV is made. Patient is subsequently referred to rheumatology for further management. Discussion The diagnosis of AAV relies on clinical, serologic, radiologic, and pathologic data. The atypical presentation may delay diagnosis, especially in cases limited to ear, nose, and throat involvement and the radiological findings are of low specificity.3 While cystic lesions in AAV-related interstitial pneumonia are documented4, this case lacked a defined cyst wall. The central lucency may present partially destroyed lung parenchyma due to GPA-related necrosis (emphysema or pneumatocele) with surrounding areas of blood products deposited from prior peri-lesional hemorrhage. Clinicians should consider a broad differentials when encounter a cystic-like lesion with thorough history-taking being essential.

Abstract To assess breast imaging fellowship program directors’ perspectives of the outcomes of the first-ever virtual interview season. A 19-question survey was constructed by members of the Fellowship Match Committee of the Society of Breast Imaging and distributed via email to 103 program directors. An initial email with a link to the survey was distributed on May 17, 2023, with 2 reminder emails sent on May 31, 2023, and June 20, 2023. The survey was closed on June 26, 2023. Results were compiled, and a descriptive statistical analysis was performed using Excel. There were 36 total responses yielding a response rate of 35% (36/103). The majority of programs, 61% (22/36), did not fill positions with any internal candidates. Overall, 72% answered that the perception of their fellow’s performance was equal to or higher than those in prior years. Despite the effects of the pandemic on clinical exposure for this cohort, 73% of programs stated that the fellow’s foundational knowledge was equivalent or better. Remarkably, 81% of respondents stated that procedural skills were equivalent or better, and 78% stated that communication skills were equivalent or better. This is the first study to investigate the outcomes of the unexpected pivot to virtual interviews. Despite the lack of preparation for this operational shift, it does not appear to have negatively impacted the program directors’ impressions of their matched fellows.

INTRODUCTION Atrial fibrillation (AFib) is a recognized complication in patients with chronic lymphocytic leukemia (CLL) treated with Bruton tyrosine kinase inhibitors (BTKis). Early detection and management of AFib are critical due to its association with increased morbidity and mortality. Traditional detection methods, such as intermittent EKGs and wearable devices, often capture only brief snapshots of cardiac activity, potentially missing episodes. Recent advances in artificial intelligence (AI) have enabled the development of algorithms that analyze electrocardiograms (EKGs) to predict AFib risk. These algorithms can potentially identify patients with undetected AFib and assess risk at a single point, reducing the need for continuous monitoring. This study evaluates the utility of an AI-enabled EKG algorithm in predicting AFib in patients with CLL treated with ibrutinib and acalabrutinib. METHODS Patients with CLL treated with ibrutinib and acalabrutinib were identified from a single-center database. Patients with CLL who received BTKi therapy at Mayo Clinic between 2015 and 2024 with available EKGs in the EMR were included. Patients were excluded if they received BTKi for non-CLL indications or if patients with CLL had documented AFib without accompanying EKGs in their medical records. An AI-enabled EKG algorithm developed by Attia et al. (Lancet, 2019) was used to estimate AFib probability (AFibAI). EKGs were categorized into pre-treatment, during treatment, and post-treatment phases. Mean values of all EKGs within each phase were used for analysis to reduce heterogeneity. Paired t-test was used for continuous variables and ROC analysis was used to evaluate diagnostic performance. A p-value of <0.05 was used for statistical analysis. RESULTS The analysis included 383 individual CLL patients (74% male, median age71; ace/ethnicity not available), of which 79 were treated with acalabrutinib and 304 with ibrutinib, with a total of 5844 EKGs analyzed. The AFibAI was significantly higher in EKGs with documented AFib compared to other EKGs, mostly normal sinus rhythm (0.5710 vs. 0.1857, p <0.001). Pre-treatment AFibAI was higher in patients who ultimately developed AFib after starting BTKi treatment compared to those who did not. Mean AFibAI at baseline was 0.2176 for those who developed AFib and 0.0986 for those who did not (p <0.001; difference between means: -0.1191 +/- 0.02005, 95% CI: 0.-0.1585 - 0.0796). Differences of baseline AFibAI were similar when stratified by BTKi. Trends in AFibAI scores indicated a significant increase during and after BTKi treatment in patients who developed AFib, with mean score of 0.2176 at baseline to 0.4064 post-treatment (p<0.001). In patients who did not develop Afib during BTKi therapy, there was minimal increase of AFibAI scores from 0.1041 at baseline to 0.1620 post-treatment (p = 0.0002). The ROC analysis showed an area under the curve of 0.7280 (SE = 0.03911, 95% CI: 0.6514 to 0.8047, p <0.001), indicating fair discriminatory ability. The sensitivity at the optimal threshold (0.1202) was 65.45% and the specificity was 74.59%, with a Youden's Index of 0.4004. To achieve a sensitivity of ≥90% for detecting patients who ultimately develop AFib, a threshold of 0.2368 was established (specificity of 41.82%). DISCUSSION Our study demonstrates the efficacy of an AI-enabled EKG algorithm in estimating atrial fibrillation risk among CLL patients treated with BTKis. We demonstrated that baseline AFibAI was notably higher in patients who ultimately developed AFib, suggesting that it could potentially identify patients at elevated risk before the onset of AFib. Early identification would allow for closer monitoring and timely intervention, potentially mitigating complications. Pending validation with an external cohort, the 90% sensitivity threshold could help identify the patients at highest risk, where other treatment options could be considered. The trend across different treatment phases revealed a significant increase in scores during treatment, indicating that AFibAI is responsive to changes induced by BTKi therapy and suggest its utility for patient monitoring. Practical questions remain about its impact on clinical decision-making and management. Future prospective studies should confirm the validity of identifying high-risk patients and its role in both treatment decisions and patient outcomes.

Introduction: Telomere biology disorders (TBD) are multisystemic accelerated aging syndromes due to abnormal telomere length (TL) shortening and increased cancer risk. Pediatric-onset TBD is characterized by severely shortened TL and specific associations with germline pathogenic variants mainly in DKC1, TINF2, PARN genes and characteristic clinical features [bone marrow failure (BMF), abnormal nail/skin/oral mucosa]. Adult-onset TBD is genetically distinct (predominantly, TERT, TERC, and RTEL1 mutations) with varied organ involvement [interstitial lung disease (ILD), BMF, cirrhosis, or bone disease] and heterogenous outcomes. In our previous study of predominantly adult patients with short telomeres, multiple organ involvement (Mangaonkar A et al. Blood Cancer J 2021) predicted poor overall survival (OS). We sought to validate these findings in a larger, well annotated adult cohort of TBD patients. Methods: Patients with suspected TBD underwent comprehensive clinical and molecular evaluation through our TBD-dedicated clinic after regulatory approval. TL was assessed through clinical flow cytometry fluorescence in-situ hybridization (FlowFISH).Clinical and laboratory features, including pulmonary imaging, lung volumes/function testing, hepatic imaging (MR elastography/fibroscan) and bone density assessments were retrospectively abstracted. Germline and somatic genetic testing was performed on peripheral blood through targeted panels for known TBD and myeloid genes respectively. Cox proportional hazard model was used to identify significant variables that also retained independent prognostic impact. Results: Overall, 122 patients met criteria for TBD as defined by lymphocyte TL (LTL) <=10th percentile and/or a presence of a germline-TBD variant; 34 patients LTL <1st percentile, 84 1st and the 10th percentile (27 with TBD-germline variants) and 4 with only TBD-germline variants. Median age at diagnosis was 56 (18-77) years, with 72 (59%) males. Clinical features included presence of ILD (n=81, 66%), BMF (n=39, 32%), cirrhosis/hepatic fibrosis (n=19, 38%), bone disease osteopenia/osteoporosis/fractures, n=53, 70%), MDS/AML (n=11, 9%), non-hematological cancer (n=38, 31%), and head and neck cancer (n=2). Germline pathogenic variants were detected in 22 (18%), most frequently in TERT (n=10), RTEL1 (n=7) and TERC (n=2), while variants of uncertain significance (VUS) were seen in 35 (29%) patients, especially in TERT (n=20), TERC/RTEL1(n=6), NAF1 (n=4). Somatic variants in hematopoietic cells were detected in 37 (30%) patients with frequent alterations seen in DNA damage response and repair (PPM1D/TP53, n=11), and splicing component (U2AF1/SF3B1/ZRSR2, n=9) genes. At last follow-up [median of 3 (0-18) years], there were 26 (21%) deaths (most commonly, progressive ILD-18, cancer of lung/breast/pancreas-3, transplant-related complications-2). After censoring patients at the time of any transplantation (lung transplant-26, liver transplant-5, bone marrow transplant-8), the Kaplan-Meier estimate of median OS was not reached. Univariate survival analysis found adverse OS predicted by older age at diagnosis (P=0.006), presence of ILD (P=0.0002), hepatic fibrosis/cirrhosis (P=0.02), and somatic DNA repair variants (P=0.03). Multivariate model analysis found that only presence of ILD retained independent prognostic impact (HR=2, P=0.02). Among radiographic ILD subtypes, UIP was the most common (51%), followed by NSIP (10%), and others (6%), with median FEV1 of 2L (range: 0.5-4.6), FVC 2.4L (0.7-6.2), and TLC 4L (1.9-7.4). TBD-ILD patients were older (P<0.0001) with a male preponderance (P=0.03), 52 (64%) with multi-organ involvement, and had a less severe hematological phenotype [lower incidence of BMF (P<0.0001) and fetal hemoglobin elevation (P=0.01)], more frequent bone disease (P=0.0009), relatively longer telomeres in lymphocytes (P=0.04), and no particular association with any germline or somatic genetic alterations. Conclusions: Presence of ILD is an independent and significant predictor of adverse survival in adult TBD. Within adult TBD, patients with ILD represent a unique clinical subtype without any obvious genetic or pathologic correlates. Focusing on definitive therapeutic measures in this subgroup of adult TBD has the best chance to alter natural history and improve outcomes.

Background. Study of myeloid neoplasms (MN) has been rapidly transformed by genome characterization. Gene mutations have been reported to influence disease phenotype and risk of disease progression, and the evaluation of mutational status can provide valuable insights to improve the decision-making process. In this international study, we evaluated the clinical impact of mutational screening in patients with CMML, which is characterized by significant clinical and genomic heterogeneity, including a substantial proportion of patients with poor outcomes and unmet needs. Currently, only limited molecular information has been incorporated into CMML classification and prognostication. Methods. We retrospectively collected 3182 CMML patients. We used MOSAIC, an AI-based framework for multimodal analysis in rare cancers (PMID: 38875514) to develop innovative, molecular-based tools for classification and prognostication. An independent validation of the results on 516 prospectively collected patients was performed. Results. Bayesian Networs and Hierarchical Dirichlet Processes were used to identify genomic associations and define a CMML molecular classification. We identified 11 clusters with distinct clinical and genomic features, including splicing machinery, signal transduction and tyrosine kinase pathways aberrations, and high-risk molecular signatures (i.e., AML-like and TP53 mutations). Up to 15% of patients showed clear genomic overlap with other MN. Importantly, extensive multi-color flow cytometry on T lymphocytes, NK and myeloid cells (BD FACSymphony A5 Cell Analyzer) revealed specific immunologic and inflammation signatures associated with molecular subgroups. We then integrated molecular and clinical information to build an international CMML Prognostic Scoring System (iCPSS). We assessed the performance of different statistical and AI-based methods; L1-penalized Cox Model resulted as the best performing method. Selected features included hematological parameters (WBC, Hb, PLT and marrow blasts), cytogenetic abnormalities, and mutations in 10 genes (ASXL1, DNMT3A, EZH2, NRAS, RUNX1, SETBP1, STAG2, TET2, TP53, U2AF1). By Bayesian thresholds optimization, we identified 5 risk classes (i.e., very-low, low, intermediate, high and very-high) with median overall survival (OS) ranging from 99 to 9 months (P<.001), and median leukemia-free survival (LFS) ranging from 210 to 18 months (P<.001). iCPSS provided better patient discrimination across all clinical endpoints compared to currently available prognostic tools, with a Concordance Index (CI) for OS of 0.75 versus 0.62-0.64, respectively. Notably, compared to available scoring systems, up to 40% of patients were reassigned to higher or lower risk classes by the iCPSS. External validation on an independent prospective cohort confirmed that the performance of iCPSS is superior to existing prognostic models (CI for OS 0.71 vs 0.54-0.61, respectively) To demonstrate the clinical utility of iCPSS, we focused on 753 patients who underwent allogeneic stem cell transplantation (HSCT). In multivariable analysis, iCPSS stratified the probability of OS post-HSCT (P<.001) and identified groups of patients with different probabilities of disease relapse, ranging from 9% to 62% (P<.001). We employed a clinical- and genomic-based decision support system (PMID: 38723212) to determine the optimal timing of HSCT. Preliminary analyses indicated that higher-risk patients according to iCPSS (i.e., intermediate, high, and very high) benefit from an immediate HSCT strategy. Lower-risk patients (i.e., very low and low) had life expectancy maximized with delayed HSCT. Modeling decision analysis using iCPSS compared to conventional scores, resulted in a change in transplantation policy for a significant proportion of patients (up to 25%). Conclusion. Molecular information significantly improves the classification of CMML patients, providing a basis for refining diagnostic boundaries with other MN and for a more rational inclusion of patients in clinical trials. The iCPSS demonstrated superior performance over currently available scoring systems and improved HSCT decision making process.