Chiriboga, Guido

Anal squamous cell carcinoma (ASCC) is a rare malignancy of the lower gastrointestinal tract, with distant metastases typically involving the liver and lungs. Metastasis to the kidneys is uncommon, and only one prior case has been reported in the literature. Herein, we report a rare presentation of a patient with biopsy-confirmed metastatic ASCC presenting as bilateral renal lesions. We then provide a review of the literature for rare metastatic presentations of ASCC, highlighting all the cases described in the literature. Clinicians should maintain a high index of suspicion for unusual metastatic sites, perform targeted imaging and biopsy when indicated, and consider systemic therapies to optimize outcomes in rare metastatic presentations.

Abstract Purpose Cenobamate is approved for treating focal epilepsy and has potential for treating tumor‐related epilepsy (TRE) based on potential anti‐tumor effects, though there is little data on efficacy and safety in this patient population. Methods This was a retrospective, multi‐center study of patients with TRE who were prescribed cenobamate as adjunctive treatment between January 2020 and November 2024 at Mayo Clinic in Florida, Minnesota, and Arizona. Drug efficacy was assessed, and factors that were predictive of response to treatment were analyzed. Results A total of 17 patients were included, with 12 being drug resistant. The median seizure frequency for the entire group before starting cenobamate treatment was 12 (IQR = 4–64) per month, and after treatment at last follow‐up was 3 (IQR = 1–15) per month, with an overall 56.3% reduction. Four patients (23.5%) were seizure‐free, and 7 (41.1%) patients were responders (at least 50% seizure reduction). No adverse events were reported for patients on concurrent chemotherapy. Responders had significantly fewer seizures per month compared to non‐responders (5.72 ± 10.29 vs. 27.33 ± 30.17; p = .030). No clinical factors were predictive of responsiveness (or lack thereof) to cenobamate. Conclusions This study demonstrates that adjunctive therapy with cenobamate treatment for TRE is a feasible and potentially effective option. Clinical history, including drug resistance, did not predict drug efficacy. No adverse effects were reported in those treated with chemotherapy. Further studies are needed to validate treatment response and safety.

Background: Leprosy, caused by Mycobacterium leprae, presents on a spectrum ranging from tuberculoid to lepromatous disease. Borderline lepromatous leprosy represents an unstable immunological state that predisposes patients to immune-mediated reactions, including erythema nodosum leprosum (ENL), a severe inflammatory complication. Case Presentation: We report a case of a 62-year-old female with borderline lepromatous leprosy who presented with recurrent facial cellulitis and later developed disseminated ENL. She was initially diagnosed following a series of facial infections and confirmatory skin biopsy. Months later, she developed systemic inflammatory lesions consistent with ENL, requiring hospitalization. She was treated with high-dose corticosteroids for ENL and methotrexate to treat type 1 reaction and continued multidrug therapy (MDT) with minocycline, rifampin, and clarithromycin for leprosy, which led to significant clinical improvement. Conclusion: This case highlights the diagnostic challenges of leprosy in the United States and the importance of recognizing ENL as a severe immunologic complication requiring prompt intervention. A multidisciplinary approach is essential for optimal patient outcomes.

e16330 Background: Sarcomatoid hepatocellular carcinoma (SHC) is a rare and aggressive variant of hepatocellular carcinoma (HCC), accounting for less than 2% of all primary liver cancers. Characterized by the presence of both epithelial and mesenchymal components, SHC demonstrates a high degree of cellular plasticity, often associated with epithelial-mesenchymal transition. This phenotypic heterogeneity contributes to its aggressive clinical behavior, including rapid tumor progression, early metastasis, and poor response to conventional therapies. As a result, patients diagnosed with SHC typically have a median survival of less than 12 months, significantly lower than that observed in patients with conventional HCC. Methods: We conducted a retrospective study at the Mayo Clinic Comprehensive Cancer Center, focusing on patients diagnosed with SHC between April 2017 and December 2023. The data collected included demographics, performance status, underlying risk factors, alpha-fetoprotein (AFP) levels, next generation sequencing (NGS) testing, and the treatment received. Results: A total of ten patients with confirmed diagnoses of SHC were included, with median age at the time of diagnosis 63.5 years (37-77), predimonantly male (9 out of 10), and identifying white (8 out of 10). Alcoholic cirrhosis was identified as an underlying risk factor in three patients, NASH cirrhosis in two, and HCV in two patients. The majority (6 out of 10) of the patients had localized disease, with 4 patients having denovo metastatic disease with abdominal lymph node involvement. Five patients had NGS testing (Tempus, Guardant 360, and ProvsSeq523), with resultant pathogenic variants including TP53 in 3 patients, NTRK3 fusion, IDH2, EGFR, TERT, MLH1, ARIS1A, and PALB2. Four patients were treated with combined Yitrrium-90 and systemic therapy. Three patient started systemic therapy, and two patients underwent surgical resection. Systemic Therapy used included combined Atezolizumab/ Bevacizuamab, Pembrolizumab/ Lenvatinib, Gemcitabine/ Docetaxel, Gemcitabine/ Cisplatin, Cabozantinib, and pembrolizumab monotherapy. The median overall survival for this group was 11.5 months; 95% confidence interval (CI): 4.66-40.1 months. Seventy percent experienced progression, with a median progression-free survival after first line of treatment of 2.5 months; 95% CI: 1-15.3 months. Conclusions: Sarcomatoid HCC remains aggressive and difficult to treat cancer with limited overall survival. Immunotherapy based regimens have limited efficacy for this HCC variant.

e16265 Background: The pivotal TOPAZ-1 trial established durvalumab plus gemcitabine and cisplatin (GC) as a new first-line standard of care for advanced biliary tract cancer (ABTC). However, weekly administration of GC can lead to significant toxicity limiting its tolerability in clinical practice. Based on previous studies, we implemented biweekly regimen of GC on days 1 and 15 together with durvalumab on day 1 of each 28-day cycle to optimize the treatment delivery and improve tolerability. Here, we report the Mayo Clinic experience with biweekly GC with monthly durvalumab in patients with ABTC. Methods: At our three-site institution, we retrospectively identified patients with ABTC between January 2021 and August 2024, who received biweekly GC with monthly durvalumab. Patient demographics, tumor characteristics, treatment details - treatment related adverse events (trAEs) graded according to the NCTCAE V5.0 were collected. Outcomes included median progression-free survival (mPFS), median overall survival (mOS) and clinically assessed overall response rate (ORR) and disease control rate (DCR). Results: 57 patients were included in our analysis, median age was 68 years (range 35-90), and 57.9% were females. 91.2% of patients had ECOG performance status of 0-1. 71.9% had intrahepatic cholangiocarcinoma, 19.3% extrahepatic cholangiocarcinoma and 8.7% gallbladder carcinoma. 70.2% had metastatic disease, 21 % locally advanced unresectable disease and 8.7% recurrent metastatic disease. Patients were followed for a median of 9.1 months (2.3-28.5). 91.2% of the patients received biweekly GC plus monthly durvalumab while 8.8% switched from weekly to biweekly GC plus monthly durvalumab due to treatment toxicities. Median number of treatment cycles was 5. Maintenance regimens included durvalumab (19.3%), gemcitabine/durvalumab (8.8%) and GC/durvalumab (8.8%). Median duration of follow up was 9.1 months (range 2.3 – 28.5). ORR was 36.9% and DCR was 72% (complete response 5.3%, partial response 31.6% and stable disease 35.1%). mPFS was 7.2 months, while mOS was 16 months. Grade(G) 3 or 4 trAEs included abnormal liver function tests (15.7%), infections (11.5%), anemia (8.7%), thrombocytopenia (5.2%), peripheral neuropathy (1.7%), acute kidney injury (1.7%). Immune-related AEs were noted in 6 patients (10.5%) including colitis, gastritis, hepatitis, myocarditis and hypothyroidism. There was no patient with severe neutropenia or febrile neutropenia. Only 5 patients (8.8%) stopped treatment due to trAEs. Conclusions: Biweekly GC on days 1 and 15 plus durvalumab on day 1 of each 28-day cycle is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in the TOPAZ-1 trial indicating that a de-escalation strategy is feasible with improvement in patient centered outcomes.

10587 Background: The American Society of Clinical Oncology (ASCO) and NCCN recommend germline testing for patients (pts) with biliary tract cancers (BTC), particularly those diagnosed at a young age. Prior studies estimate that approximately 15% of pts with BTC harbor pathogenic germline alterations. Germline testing can identify hereditary cancer syndromes, guide targeted therapy, and inform family counseling. This study aimed to further characterize and describe the prevalence of pathogenic germline variants (PGVs) in patients with young-onset BTC (YO-BTC). Methods: We conducted a retrospective review of medical records for pts diagnosed with YO-BTC (ages 18–55) across all Mayo Clinic tri-sites from January 2014 to October 2024. Data collected included results from germline DNA sequencing, tumor genetic testing, demographics, history of other malignancies, and family history of cancer. The primary outcome was the identification of pathogenic germline mutations associated with cancer predisposition. Results: Among 239 pts with YO-BTC, the median age at diagnosis was 43 years (range 19–55), with 62% female and 65.2% identifying as white. Clinical germline testing (e.g., Invitae, Ambry, Myriad) was performed in 123 pts (51.5%), revealing PGVs in 15 pts (12.1%), variants of uncertain significance (VUS) in 30 pts (24.3%), and likely benign variants in 4 pts (3.2%). Among those with PGVs, DNA repair mutations were the most common findings (10/15), including ATM (4), CHEK2 (2), BRCA2 (2), BAP1 (1), and PALB2 (1). One pt had a Lynch syndrome-associated mutation (MSH6), and four had mutations in other cancer-related genes (MUTYH, HOXB13, RMRP, and PIK3CA). Tumor genomic profiling (via CARIS, TEMPUS, or FoundationOne) was performed in 9 pts with PGVs, detecting the variant in 4 (44%), while liquid biopsy (Guardant) identified the PGV in 4 of 6 cases (66.6%).The majority of PGV carriers had advanced BTC (14/15), with intrahepatic cholangiocarcinoma being the most prevalent (11/15), while 4 had extrahepatic cholangiocarcinoma. Additionally, most PGV carriers had a first- or second-degree relative with a prior history of malignancy (14/15), and 3 pts had a second malignancy. Of the 15 pts with PGVs, 4 had BTC associated with primary sclerosing cholangitis. Conclusions: In this large institutional series of YO-BTC, PGVs were identified in 12.1% of pts, demonstrating a significant yield from germline testing in this population. Notably, tissue and liquid biopsies demonstrated different detection rates for PGVs, underscoring the variability in PGVs reporting across platforms. Germline testing through CLIA-approved methods should remain the standard of care. DNA repair pathway mutations, particularly ATM, CHEK2, and BRCA2, were the most frequently identified PGVs, highlighting their role in the pathogenesis of YO-BTC and their potential to guide treatment decisions.