Barman, Hannah

e13156 Background: Breast Cancer (BC) patients are classified as HER2-positive (IHC3+ or IHC2+/ISH+) or HER2-negative (IHC0, IHC1+ and 2+/ISH-). Within the HER2-negative category, patients who meet HER2-low (IHC1+ or IHC2+/ISH-) criteria can benefit from HER2 targeted therapy like trastuzumab deruxtecan. Patients who meet IHC0 criteria with incomplete and faint membrane staining in >0 but ≤10% of tumor cells — defined as “HER2 Ultra-low”, may also benefit from HER2 targeted therapy. This study aimed to assess the prevalence of “HER2 Ultra-Low” expression based on re-scored HER2 IHC biopsy slides. Methods: This study utilized EHR data from all three US Mayo Clinic campuses. A total of 300 patients with advanced BC (stages III-IV), and clinically documented HER2 IHC0 status between Jan 2017 and Jan 2023, were identified. One biopsy slide per patient (IHC assay: VENTANA Pathway anti-HER2/neu (4B5) rabbit monoclonal primary antibody) was digitized and scanned at 40x magnification. Two Mayo Clinic pathologists independently scored and reported HER2 status according to 2023 ASCO-CAP guidelines and included tumor stain percentage for each slide. Patients were considered “HER2 Ultra-Low” if their slide was scored as IHC0 with >0% but ≤10% staining. Cohen’s κ was used to quantify agreement between pathologists. Results: The re-scored patients (n=300) had a mean age of 57.8 years (SD=13.5), with ~97% having IHC0 documentation within 30 days of the reviewed biopsy slide. A total of 285 (95%) patients remained classified as IHC0 by at least one pathologist. Of these, 60% (n=171) were determined as “HER2 Ultra-low” by at least one pathologist. The rate of “HER2 Ultra-Low” per pathologist ranged from 43% (n=121) to 45% (n=104). The overall inter-pathologist concordance was 57%; patients with no observable HER2 IHC staining accounted for majority of the concordant patients (Table). Conclusions: About 3 in 5 advanced BC patients originally classified as HER2 IHC0 met the “HER2 Ultra-Low” criteria by at least one pathologist, implying that significant number of additional patients may benefit from HER2 targeted therapy. The relatively low concordance between HER2 expert pathologists in identifying lower levels of HER2 expression suggests the need for increased precision enabled by digital tools, leveraging AI, training for community practice pathologists, and continuing to follow best practice recommendations in determining HER2 IHC status. [Table: see text]

PURPOSE Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their use is associated with immune-related adverse events (irAEs). Estimating the prevalence and patient impact of these irAEs in the real-world data setting is critical for characterizing the benefit/risk profile of ICI therapies beyond the clinical trial population. Diagnosis codes, such as International Classification of Diseases codes, do not comprehensively illustrate a patient's care journey and offer no insight into drug-irAE causality. This study aims to capture the relationship between ICIs and irAEs more accurately by using augmented curation (AC), a natural language processing–based innovation, on unstructured data in electronic health records. METHODS In a cohort of 9,290 patients treated with ICIs at Mayo Clinic from 2005 to 2021, we compared the prevalence of irAEs using diagnosis codes and AC models, which classify drug-irAE pairs in clinical notes with implied textual causality. Four illustrative irAEs with high patient impact—myocarditis, encephalitis, pneumonitis, and severe cutaneous adverse reactions, abbreviated as MEPS—were analyzed using corticosteroid administration and ICI discontinuation as proxies of severity. RESULTS For MEPS, only 70% (n = 118) of patients found by AC were also identified by diagnosis codes. Using AC models, patients with MEPS received corticosteroids for their respective irAE 82% of the time and permanently discontinued the ICI because of the irAE 35.9% (n = 115) of the time. CONCLUSION Overall, AC models enabled more accurate identification and assessment of patient impact of ICI-induced irAEs not found using diagnosis codes, demonstrating a novel and more efficient strategy to assess real-world clinical outcomes in patients treated with ICIs.

SummaryBackgroundAlpha‐1 antitrypsin deficiency (AATD) is caused by mutations in SERPINA1, which encodes alpha‐1 antitrypsin, a protease inhibitor (Pi). Individuals with AATD and the homozygous Pi*ZZ genotype have variable risk of progressive liver disease but the influence of comorbid lung disease is poorly understood.AimsTo characterise patients with AATD Pi*ZZ and liver disease (AATD‐LD‐Pi*ZZ) with or without lung disease and describe liver disease‐related clinical events longitudinally.MethodsThis was an observational cohort study of patients in the Mayo Clinic Healthcare System (January 2000–September 2021). Patients were identified using diagnosis codes and natural language processing. Fibrosis stage (F0–F4) was assessed using a hierarchical approach at baseline (90 days before or after the index date) and follow‐up. Clinical events associated with liver disease progression were assessed.ResultsAATD‐LD‐Pi*ZZ patients with lung disease had a longer median time from AATD diagnosis to liver disease diagnosis versus those without lung disease (2.2 vs. 0.2 years, respectively). Compared to those without lung disease, patients with lung disease had a longer time to liver disease‐related clinical events (8.5 years and not reached, respectively). AATD‐LD‐Pi*ZZ patients without lung disease were more likely to undergo liver transplantation compared with those with lung disease.ConclusionIn patients with AATD and lung disease, there is a delay in the diagnosis of comorbid liver disease. Our findings suggest that liver disease may progress more rapidly in patients without comorbid lung disease.

136 Background: Studies using International Classification of Diseases (ICD) codes have aimed to characterize the safety profile of cancer therapies in the Real-World Data setting, but this approach has limitations including an inability to illustrate patient journey and offer insights into drug-Adverse Event (AE) causality. Using data from a cohort of ~9000 patients treated with immune checkpoint inhibitors (ICI) at Mayo Clinic, we recently demonstrated the feasibility of applying Augmented Curation (AC), a natural language processing (NLP)-based innovation, on unstructured electronic health record (EHR) data to detect and characterize immune related AEs (irAEs). While the ability to identify and extract clinical details from EHRs has been previously demonstrated, our approach focuses on applying these techniques to identify implied textual causality of drug-event pairs. This study aims to build upon our prior findings and compare the accuracy, speed, and resource savings enabled by AC analysis versus manual review of patient notes. Methods: We compared the prevalence of adrenal insufficiency, colitis, and hypophysitis (A.C.H) among ICI patients at Mayo Clinic using ICD codes and AC which leverages SciBERT to perform scientific NLP tasks. AC models trained to identify drug-adverse event relationships were used to assess irAEs and subsequent treatments and demonstrated strong performance with F1 scores of 0.85. Manual curation of relevant clinical data, i.e. medications and adverse events, was employed to create a “gold standard” A.C.H. cohort. Time required for manual review compared to AC was documented for overall comparison. Corticosteroid/immunosuppressant use and ICI discontinuations were used as proxies of severity. Results: In our cohort, 540 unique patients experienced at least one of the A.C.H. irAEs. A.C.H patients were found to receive corticosteroids for their respective irAE 79% of the time and discontinued the ICI due to the irAE 7.7% of the time. 6.1% of Colitis patients were treated with a 2L immunosuppressant. Similar to the previous study, AC showed higher sensitivity, PPV and NPV compared to ICD codes alone within the A.C.H. cohort. Sentence extraction and entity classification using AC models on all 9,000-patients took ~10 minutes, whereas manual review of this cohort would take roughly 9 weeks (~10 minutes per patient). Conclusions: The results from this study reinforce that AC models are a valuable tool to comprehensively extract information and to impute relationships between entities, such as therapies and AEs. The AC models demonstrated better accuracy at a much greater speed compared to manual review of patient EHRs. Leveraging AC models provides the ability to manipulate unstructured clinical text married to structured EHR data at scale while minimizing need for manual curation.