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e14545 Background: Next generation sequencing (NGS) identifies genomic alterations in DNA obtained from tissue biopsies and/or blood [circulating tumor (ct)DNA]. We anticipate a lower rate of copy number loss (CNL) in ctDNA compared to tissue, as lower ctDNA tumor fraction may limit the ability to detect a deletion. However, we observed several instances of a CNL in ctDNA that was not identified in a tissue specimen, prompting this systematic evaluation of an institutional dataset. We focused on BRCA1/2 pathogenic variants (PVs) given their therapeutic implications and coverage across testing platforms. Methods: Using an IRB-approved protocol, we evaluated an institutional repository of NGS results performed across the Mayo Clinic Enterprise. We focused on patients (pts) who had both tissue and blood NGS testing performed. We further narrowed this cohort to those with a BRCA1/2 PVs, somatic and/or germline, as determined by testing performed at Guardant Health, Tempus, or Foundation Medicine. We abstracted information about each variant, including type of alteration classification and functional impact. Demographic information, cancer characteristics, and germline testing information was collected. Fisher’s exact test was used to compare alteration frequencies in ctDNA vs tissue using GraphPad Prism v 10.1. Results: From Dec 2015-Sept 2024, we identified 158 unique pts with BRCA1/2 PV who had NGS results for both tissue and ctDNA. The median age at first reporting BRCA1/2 variant was 67 years (range: 29-98 years). 48% of pts were female, and the most common cancer type sites were lung (23%), colorectal (20%), and pancreaticobiliary (20%). We identified 198 unique pathogenic genomic alterations; 71 in BRCA1 & 127 in BRCA2 . Most common alteration was an SNV or indel (127/198), followed by CNL (n = 63), splice site variants (n = 5), fusions (n = 2), and rearrangements (n = 1). Of the 126 SNV or indels, 50 (39.7%) were identified in both ctDNA and tissue, 40 (31.7%) were detected in blood only, 36 (28.6%) identified only in tissue (p < 0.0001). Amongst the 63 CNL, only 3 (4.8%) were identified in both ctDNA and tissue; 41(65.1%) were only identified in ctDNA, and 19 (30.2%) in tissue only (p < 0.0001). In the 19 tissue-only CNL tests, 12/19 noted one or more additional pathogenic SNV/Indel in BRCA1/2. In the 41 ctDNA-only CNL tests, 1/41 noted one or more additional pathogenic SNV/Indel in BRCA 1/2 . Germline testing was available in 41/63 pts with copy number loss. 3/41 deletions were identified in germline (2 in ctDNA, 1 in tissue). Conclusions: We observed a low degree of concordance in CNL between tissue and ctDNA for BRCA1/2 . CNL detection in ctDNA that could not be confirmed in germline or with a second alteration warrants further attention. In particular, clinicians should be cautioned when interpreting ctDNA reports noting BRCA1/2 CNL without clarity if this represents biallelic loss or a synchronous loss of function.

548 Background: TNBC is associated with higher risk of recurrence and poorer survival rates than other breast cancer subtypes. For node-positive TNBC or tumors larger than 0.5 cm, chemotherapy is generally recommended. For stage I TNBC, the benefit from chemotherapy, the optimal regimen, and whether to administer it in the neoadjuvant versus adjuvant setting remain controversial. Here, we report the treatment patterns and clinical outcomes of patients with stage I TNBC treated at Mayo Clinic. Methods: Using the Mayo Clinic Tumor Registry data, we identified patients with stage I TNBC treated between 2010 and 2021. We used the pathologic tumor (T) category for patients treated with upfront surgery and the clinical T category for patients receiving neoadjuvant chemotherapy. We used the Kaplan-Meier method and log-rank test to compare recurrence-free survival (RFS) according to treatment groups, measured from the day of surgery. RFS was reported at a median follow-up of 3.9, 6.2, and 7.3 years for patients who received chemotherapy neoadjuvantly, adjuvantly, and surgery alone with no chemotherapy, respectively. Results: A total of 602 patients with Stage I TNBC were included, with a median age of 62 years. 290 (48%) underwent upfront surgery followed by adjuvant chemotherapy (pT1a: 2%, pT1b: 25%, pT1c: 74%), 127 (21%) received neoadjuvant chemotherapy followed by surgery (cT1a: 2%, cT1b: 11%, cT1c: 87%), and 185 (31%) underwent primary surgery without any chemotherapy (pT1mi/T1a: 33%, pT1b: 32%, pT1c: 35%). Most patients treated with neoadjuvant therapy received anthracycline/cyclophosphamide + taxane (70%), while most patients treated in the adjuvant setting received a non-anthracycline containing regimen (60%). The 5-year RFS was 96% (95% CI: 93-100%) for patients who received chemotherapy neoadjuvantly, 95% (95% CI: 92-98%) for those who received chemotherapy adjuvantly, and 85% (95% CI: 80-91%) for those treated with surgery alone and no chemotherapy ( P < 0.0001). 71 (56%) of the 127 patients who received neoadjuvant therapy achieved a pCR, with only 1 RFS event (at 14 months) in that group, compared to 4 RFS events among those not achieving pCR (at 12, 20, 28 and 75 months, respectively). Among patients not receiving chemotherapy (either adjuvantly or neoadjuvantly), the 5-year RFS rates were 94% for pT1mi/T1a, 92% for pT1b and 72% for pT1c (T1mi/a/b vs T1c, P = 0.009). Conclusions: In this large cohort of stage I TNBC, patients who received chemotherapy (adjuvantly or neoadjuvantly) had better 5-year RFS compared with those treated with locoregional therapy only. Among patients receiving chemotherapy, 5-year RFS was nearly identical regardless of whether chemotherapy was administered before or after surgery. Interestingly, patients undergoing upfront surgery were more likely to receive an anthracycline-sparing chemotherapy regimen.

Background : Metastatic lung carcinoids (MLCs) represent a rare subset of lung cancers with distinct histologic subtypes. Survival outcomes and prognostic factors have not been well-studied in the real-world setting. This study investigates the impact of various treatments, including chemotherapy, hormonal therapy, and no treatment, on the overall survival (OS) of patients with typical and atypical MLC. Methods: Patients with MLC between 2010 and 2020 were included from the National Cancer Database based on histologic codes ICD-O-3 8240/3 and 8249/3. Kaplan–Meier curves and multivariate Cox proportional hazard regression were used to compare OS and evaluate prognostic factors. Results: The median age at diagnosis was 68 and 69 years for atypical and typical MLC, respectively. The 3-year OS for the atypical MLC cohort was 22.11%, and for typical MLC was 41.94% ( P < 0.001). In the atypical MLC cohort, chemotherapy showed a nonsignificant benefit in OS (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.73–1.05; P = 0.21), whereas hormonal therapy was associated with significantly improved OS (HR, 0.72; 95% CI, 0.52–0.98; P =0.04). However, in the typical MLC cohort, chemotherapy was associated with adverse OS (HR, 2.15; 95% CI, 1.85–2.49; P < 0.0001), and hormonal treatment showed better, albeit nonsignificant OS (HR, 0.84; 95% CI, 0.67–1.05; P = 0.13). Conclusion: There is a notable difference in survival outcomes between typical and atypical MLC based on the treatment strategies. While hormonal therapy shows improvement in the OS, the effectiveness of chemotherapy varies depending on the histologic subtype. These findings emphasize the necessity for personalized therapeutic approaches based on the specific characteristics of MLC, ultimately contributing to improved patient outcomes in this challenging oncologic group. Further research is warranted to validate and expand upon these observations.

Abstract Background: Ovarian cancer is the sixth leading cause of cancer deaths among women in the United States. South Asians in the USA, including Asian Indians and Pakistani Americans (AIPA), are a rapidly growing yet under-researched group. This study aims to analyze the clinical features, survival rates, treatment, and outcomes of ovarian cancer among AIPA women in the United States. Methods: Adult women diagnosed with ovarian cancer between 2000 and 2023 within the Surveillance, Epidemiology, and End Results (SEER) registry were identified utilizing ICD codes. The analysis focused on comparing clinical characteristics and outcomes between AIPA and Non-Hispanic White (NHW)women and excluded all women of other races/ethnicities or unknown race/ethnicity. Baseline characteristics, including age at diagnosis, disease stage, and treatment, were compared between AIPA and NHW women utilizing a chi-squared test for categorical variables and a t-test for continuous variables. The 5-year overall survival (OS) was estimated for each race/ethnicity by the Kaplan-Meier method, and the OS was further compared between AIPA and NHW in a cox-proportional hazard regression analysis adjusting for age at diagnosis, grade, histology, TNM stage, surgical debulking, completeness of debulking surgery, and receipt of chemotherapy. Similar comparisons of baseline characteristics and OS were also performed in the subset of women with high-grade serous ovarian cancer (HGSOC). Result: A total of 86, 485 women met the inclusion criteria, of which 1, 179 were AIPA and 85, 306 were NHW. AIPA had a significantly younger median age at diagnosis compared to NHW women in the overall population (57 vs. 65 years, p&lt;0.001) and among 448 AIPA and 29, 677 NHW women with HGSOC (58 vs. 65 years, p&lt;0.001). Approximately two-thirds of women in both groups presented with Stage III or IV ovarian cancer at diagnosis and had a serous subtype of ovarian cancer. Similarly, after the exclusion of unknown grade, high-grade tumors accounted for more than two-thirds (75 vs. 72%) of the ovarian cancer cases in both groups. AIPA were more likely to undergo debulking surgery (85 vs. 80%, p&lt;0.001) and receive chemotherapy (77 vs. 72%, p&lt;0.001) compared to NHW women. The unadjusted 5-year OS for AIPA and NHW women were 56% vs. 43% in the overall population, and 53% vs. 41% among women with HGSOC, respectively. In multivariate analysis of the entire study population, AIPA women had a significantly better OS than NHW women (HR: 0.86, 95%CI: 0.79 - 0.94, p&lt;0.001). Among women with HGSOC, a similar trend of better OS was noted in multivariate analysis among AIPA women compared to NHW (HR: 0.88, 95%CI: 0.77 - 1.01, p=0.07), although this did not reach statistical significance. Conclusion: The younger age at diagnosis, along with a generally better prognosis, among AIPA women compared to NHW women, suggests a possible enrichment of DNA-repair gene alterations among AIPA women. Citation Format: Aditi Karki, Sumeet Kumar Yadav, Muhammad Rafiqul Islam, Raja Pramanik, Ramila Shilpakar Dangol, Zeba Aziz, Sandhya Pruthi, Maryam Shahi, Jamie N. Bakkum-Gamez, Scott H. Kaufmann, Fergus J. Couch, Siddhartha Yadav. Clinical characteristics and survival outcomes of ovarian cancer among South Asian women in United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7118.

Background: Cerebral venous sinus thrombosis (CVT) is a rare cause of stroke, constituting 0.5–3% of all strokes with an extremely varied spectrum of presentation, predisposing factors, neuroimaging findings, and eventual outcomes. A high index of suspicion is needed because timely diagnosis can significantly alter the natural course of the disease, reduce acute complications, and improve long-term outcomes. Due to its myriad causative factors, protean presentation, and association with several systemic diseases, CVT is encountered not only by neurologists but also by emergency care practitioners, internists, hematologists, obstetricians, and pediatricians. Discussion: Anticoagulation remains the mainstay of treatment for CVT. Heparin and warfarin previously had been the anticoagulation of choice. Recently there has been an increased interest in utilizing direct-acting oral anticoagulants in the treatment of CVT given comparable safety and efficacy with ease of utilization. However recent clinical guidelines given by multiple societies including the American Stroke guidelines and European guidelines do not include these agents so far in their treatment recommendations. Ongoing multicentric clinical trials are currently reviewing the role of these agents in both short-term as well as long-term. Our review of the literature supports the safety and reinforces the efficacy of DOAC in the treatment of CVT. Additionally, patient satisfaction has been shown to be better with the use of DOAC. In conclusion, DOAC continues to have a valid role in the management of CVT.

Bleeding diathesis is an uncommon side effect of ibrutinib use and is seen in less than 5% of the population. We describe a case of an elderly woman with ibrutinib-induced spontaneous major extradural haematoma presenting as acute compressive myelopathy. She is a known case of splenic marginal zone lymphoma with multiple extramedullary relapses and presented to the emergency department with acute-onset low backache, followed by urinary retention. MRI revealed extradural haemorrhage. After possible evaluation, she was diagnosed with ibrutinib-induced extradural haematoma.

Key Clinical MessageStone heart syndrome has a complex interaction with digoxin toxicity, where, theoretically, the administration of intravenous calcium can worsen a patient's condition. Research on this subject is conflicting, so it is imperative to approach it cautiously.

Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion. Further, transfusion carries many risk factors that must be balanced with benefits. Therefore, transfusion practice in ICU patients has constantly evolved, and we endeavor to present a contemporary review of transfusion practices in this population guided by clinical trials and expert guidelines.

e13036 Background: In January 2023, the FDA approved elacestrant for ESR1-mutated, ER+/HER2- MBC based on a companion diagnostic cell free (cf)DNA test (Guardant Health). In this study, we analyze the trends of liquid biopsy utilization at Mayo Clinic (MC) over a 3 year period to understand the impact of this drug approval on testing patterns and identify emergent alterations in patients (pts) with MBC. Methods: We extracted clinically performed Guardant 360 and Guardant 360 CDx ordered at MC sites in Rochester (MN), Florida (FL), Arizona (AZ), and across 9 additional Mayo Clinic Health System (MCHS) sites. Pts with MBC were identified using the EMR and analyzing visit diagnosis codes and staging information. Shifts in testing patterns were analyzed over a 3 year period from January 1, 2021 - December 31, 2023. Data was collected on the number of tests, serial testing, frequency of pathogenic mutations, and emergent mutations in ESR1 and PIK3CA. Chi-square test was used to compare the categorical values. Results: Between 2021-2023, 2,741 pts with MBC were seen across all sites. A total of 408 cfDNA tests were performed in 370 unique patients with MBC. Most pts (90%) had 1 test performed. The proportion of pts with MBC tested was 85/1350 (6.3%) in 2021, 77/1495 (5.2%) in 2022, and 208/1558 (13.4%) in 2023. The increased proportion of pts tested in 2023 was statistically significant compared to prior years (p<0.0001), while no difference was observed between 2021 and 2022 (p 0.19). Testing patterns varied by site, with FL ordering the highest number of tests, followed by MN and AZ. Of the 34 providers practicing during the entire period seeing more than 10 MBC pts, the number of providers ordering Guardant testing increased from 15/34 (2021) and 14/34 (2022) to 20/34 (2023), though not statistically significant (p 0.15). Of the 41% with EMR-documented staging available, testing was highest in the ER+/HER2- (81.3%) subtype, followed by TNBC (13.6%) and then HER2+ (5.2%). The most commonly identified mutations identified in the first testing were PIK3CA (41.1%), TP53 (40.5%), ESR1 (30.5%), and ATM (13.2%). D538G (8.0%), Y537N (4.4%), and Y537S (3.5%) were frequent emergent mutations seen in ESR1. Conclusions: We observed an increase in cfDNA testing at the start of 2023 which aligns with the FDA approval of elacestrant. We observed variation by site and individual providers that warrants further exploration to improve cfDNA testing in MBC pts at Mayo Clinic.

e23537 Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults > 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.