Chang, Isabela

Abstract We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group retrospective database of 2243 patients with stages I to IV disease diagnosed from 1992 to 2021 at 38 international institutions. A total of 779 patients had stage IA disease with median age of 35 years (range, 3-89) and median follow-up of 6.1 years. The 6-year progression-free survival (PFS) and overall survival were 86.3% and 97.7%, respectively. Outcomes were analyzed for the 2 groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n = 99) had a 6-year PFS of 65.5% vs 90.5% for those who received radiotherapy (RT) (n = 53). Patients with unresected disease (n = 627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n = 31), 89.6% for RT alone (n = 325), 76.8% for ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone (n = 40), and 94.3% for ABVD plus RT (n = 130). A total of 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests the following: (1) RT improves the PFS in patients with completely resected disease; (2) rituximab or ABVD alone does not appear to achieve a durable response; and (3) chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.

830 Background: Immune checkpoint inhibitors (ICIs) are standard therapy for MSI-H GI cancers. Lynch syndrome, caused by germline mutations in mismatch repair (MMR) genes, leads to MSI-H tumors and robust ICI responses, but its effect on irAEs remains poorly defined. Clarifying this risk may inform treatment selection and toxicity monitoring. Methods: We retrospectively reviewed MSI-H or MMR-deficient (dMMR) GI cancer patients (pts) treated with ICIs across Mayo Clinic (AZ, MN, FL) from January 2017 to June 2025. Eligible pts were identified using Mayo Data Explorer. Demographics, treatment, and irAEs (graded per CTCAE v5.0) were collected. Lynch status was determined by germline testing when available. Logistic regression estimated odds ratios (ORs) for any grade and grade ≥3 irAEs, adjusting for age, cancer type, prior chemotherapy, and treatment regimen. Results: A total of 209 pts with dMMR/MSI-H GI cancer were included: 61 with Lynch syndrome and 148 without. Lynch pts were younger (median 58 vs 76 years, p < 0.001) and more likely to have received prior chemotherapy (62% vs 43%, p = 0.009). Colorectal cancer was the predominant cancer type (74%), but Lynch pts had proportionally more non-colorectal GI cancers (15% vs 2.7%, p = 0.007). Overall, 29% of pts experienced an irAE, with rates significantly higher in Lynch vs non-Lynch pts (43% vs 24%, p = 0.005). The most frequent irAEs were gastrointestinal, endocrine, and dermatologic, followed by hepatic and pulmonary events. Grade ≥3 irAEs occurred in 16% overall, with no significant difference between groups (p = 0.124). In adjusted models, Lynch syndrome was independently associated with a higher risk of any grade irAE (OR 2.14, 95% CI 1.09 - 4.19, p = 0.026), while risk of severe irAEs was not increased (OR 1.55, 95% CI 0.64 - 3.59, p = 0.316). Lynch syndrome pts were more likely to have combination therapy (17% vs 6.8%, p = 0.029). However, there were no differences observed in any grade irAE between monotherapy and combination immunotherapy (OR 1.36, 95% CI 0.49 - 3.54, p = 0.535). Conclusions: Lynch syndrome is associated with a higher prevalence of any-grade irAEs among dMMR/MSI-H GI cancer pts treated with ICIs, though severe events were not increased. Incorporating Lynch status into immunotherapy planning may improve risk stratification and guide regimen selection.

Abstract Background: Recombinant activated factor VIIa (rFVIIa, NovoSeven®) is an FDA-approved medication for managing bleeding in patients with hemophilia A or B with inhibitors and for those with congenital factor VII deficiency. Its use has expanded off-label in the perioperative context to manage unexpected bleeding complications. However, there is still a gap in real-world data regarding institutional practices, dosing, and outcomes associated with rFVIIa. Methods: With IRB approval, we identified patients who received rFVIIa in the perioperative period between 2020 to 2024 at Mayo Clinic. A detailed chart review was conducted to gather demographic data, comorbid conditions, bleeding disorders, timing, and dosing of perioperative rFVIIa (pre-, intra-, and postoperative), along with postoperative outcomes. We focused on thrombotic and bleeding events, hospital readmissions, and return to the operating room (OR). Descriptive statistics were used for patient characteristics, rFVIIa dosing patterns, and postoperative complications. Type of surgical interventions were stratified based on UCLA perioperative risk stratifications, with a risk score of 5 equating to very high risk surgery and a score of 1 equating to very low risk surgery. Results: Of the 55 patients included, the median age at surgery was 42.3 years (SD 27.4), and 69% were male. The majority were non-Hispanic white (91%). The most common bleeding diatheses were Factor VII deficiency (54.6%), Factor VIII inhibitor (12.7%), and Glanzmann thrombasthenia (7.3%). Less frequent conditions included Hemophilia A (3.6%) and Hemophilia A with inhibitors (3.6%). Among patients with Factor VII deficiency, mild deficiency accounted for 65.9% of cases, followed by severe (19.5%) and moderate (14.6%) forms. Adjunctive medications to control bleeding included emicizumab, FEIBA, and rituximab. Mean estimated blood loss was 136 mL (SD 211 mL), and mean length of stay was 5.7 days (SD 6.4). Surgical risk strongly correlated with perioperative outcomes: blood loss increased from 19 mL in very low-risk surgeries to 352 mL in very high-risk surgeries, while mean length of stay increased from 4.5 days (risk 1) to 19 days (risk 4) and 11 days (risk 5). Actual rFVIIa dosing ranged from 7.2 to 7211.5 mcg/kg per dose, with a median of 67.4 mcg/kg and a mean of 852.8 mcg/kg, reflecting variability in clinical practice. When stratified by surgical risk, the highest median doses were observed in very low- and low-risk surgeries (84.4 and 86.8 mcg/kg, respectively), while very high-risk surgeries had the lowest median dose (30.0 mcg/kg). In the postoperative period, thrombotic events did not occur in the first 90 days but were documented in 1.8% of patients between 90 and 365 days and in 1.8% after 365 days. Bleeding complications were frequent and demonstrated predominance in the immediate post-op period. Within the first 30 days after surgery, 18.2% of patients experienced bleeding complications, with 3.6% classified as major and 14.5% classified as minor, based on ISTH criteria. Between 30 and 90 days, bleeding complications occurred in 9.1% of patients (3.6% major and 5.5% minor), between 90 and 365 days, bleeding was observed in 10.9% of patients, all of which were minor, and beyond one year, bleeding complications were documented in 23.6% of patients, with 3.6% major and 21.8% minor. Readmissions were also common and followed a similar time distribution. In the first 30 days, 7.3% of patients had readmissions related to the prior surgery, and 3.6% had unrelated readmissions. Between 30 and 90 days, 3.6% of readmissions were related and 3.6% were unrelated. Between 90 and 365 days, 3.6% were related and 14.5% were unrelated to the initial procedure. Returns to the OR occurred in 1.8% of patients between 30 and 90 days and in 1.8% between 90 and 365 days. Conclusions: In conclusion, perioperative rFVIIa was most frequently used for Factor VII deficiency but was also administered to patients with Factor VIII inhibitor and Glanzmann's thrombasthenia, as well as several rare congenital and acquired bleeding disorders. Postoperative thrombotic events were rare, while ISTH-defined bleeding complications and readmissions were common. Most bleeding complications were minor, but their frequency was highest in the early postoperative period and again beyond one year. High-risk surgeries were associated with greater blood loss, prolonged hospitalization, and a higher burden of postoperative complications.

556 Background: Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) is a rare and complex liver cancer with features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), making its management challenging. This study aims to analyze the clinical characteristics, genomic profiles, and treatment outcomes of cHCC-CCA patients in a real-world setting. Methods: We conducted a retrospective analysis of cHCC-CCA patients across three first-line treatment groups: chemotherapy alone(Gemcitabine/Cisplatin, FOLFOX), HCC-directed therapies (atezolizumab/bevacizumab, lenvatinib, nivolumab, durvalumab, sorafenib), and chemoimmunotherapy (Gemcitabine/Cisplatin combined with immunotherapy). This international study, involving Mayo Clinic and the National Cancer Center East (Japan), assessed overall survival (OS) using Kaplan-Meier and Cox regression models. Results: A total of 68 patients were included, with a mean age of 66 years; 74% were male and 66% were White Non-Hispanics. Cirrhosis was present in 74% of patients at diagnosis, and Hepatitis B and C were common etiologies in 57%. Prior primary resection and regional therapies (Transarterial chemoembolization (TACE), Transarterial radioembolization (TARE)) were recorded in 39% and 50% of patients, respectively. Advanced/metastatic disease was present in 52% of the cohort. The distribution of first-line treatments was as follows: 47% received chemotherapy alone, 39% received HCC-directed therapy, and 14% received chemoimmunotherapy. Genomic alterations were detected in 44% patients, with TP53 (28%), ARID1A (25%), and TERT (22%) being the most frequent. The HCC-directed therapy group demonstrated the best overall response rate (52%) and had a median OS of 15.8 months (mo), compared to 11.8 mo for chemotherapy and 4.7 mo for chemoimmunotherapy (p=0.8). Patients who received regional treatments had a longer median OS of 15.8 mo compared to those who did not (10.2 mo) (p=0.4). Conclusions: HCC-directed therapy showed a trend towards better survival outcomes compared to other treatments, though not statistically significant. A considerable proportion of patients had genomic alterations, which may have influenced survival outcomes. Ongoing research with larger cohorts is underway to further elucidate the impact of genomic variations on treatment efficacy and refine therapeutic strategies for this challenging malignancy. Baseline characteristics of patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA). Total(N=68) Mean age at diagnosis, years (SD) 66(6.4) Gender, n (%) Male 50 (74%) Ethnicity, n (%) White, Non-Hispanic 45 (66%) Cirrhosis at diagnosis, n (%) 50 (74%) Etiology of Liver disease, n (%) Viral (Hepatitis B and C) 39 (57%) History of Primary resection, n (%) 27 (39%) Regional treatment, n (%) 34 (50%) Afp, n (%) < 200 23 (64%) ca19_9, n (%) < 50 27 (82%)

732 Background: Ampullary carcinoma (AC) is a rare malignancy arising from the ampulla of Vater which has a more favorable prognosis compared to other pancreatic malignancies. Current guidelines favor surgical resection followed by adjuvant therapy for average risk patients (pts), however the type of regimen as well as other perioperative treatment modalities are still being explored. The objective of this retrospective study aims to provide insight into the management of locoregional disease. Methods: Pathology records from Mayo Clinic (AZ, FL, MN) denoting AC between 2010 to 2024 were searched using Mayo Data Explorer and selected for retrospective review. Pt demographics, treatment courses, and next generation sequencing (NGS) data were collected. Statistical analysis was conducted using SAS version 9.04. Results: A total of 137 pts (62% male, n = 85) were identified with median age 66 years old. Histologic subtypes were 54% pancreatobiliary (44/81), 40% intestinal (32/81), 6% mixed (5/81), with 56 pts unknown. Stages at diagnosis were 81% resectable (111/137), 11% locally advanced (15/137), and 8% metastatic (11/137). Nearly all (93%, n = 103/111) pts with localized disease had resection with a 97% R0 resection rate (100/103). Majority (68%, n = 75/111) of resectable pts had perioperative chemotherapy with 5-FU or gemcitabine-based regimens (24%, n = 18/75 neoadjuvant vs. 76%, n = 57/75 adjuvant). Perioperative chemoradiation was given in 17% (19/111) of pts. At median follow up of 30.5 months, recurrence rates were 40% (41/103), primarily to the liver (18/41). Median recurrence free survival (RFS) was 29.3 months (95% CI 24.7 – NE). Median overall survival (OS) has not been reached. The 5-year RFS and OS rates were 0.37 (95% CI 0.25 - 0.55) and 0.69 (95% CI 0.58 - 0.82), respectively. Univariate analysis showed no difference in OS with the addition of neoadjuvant or adjuvant chemotherapy or chemoradiation. Somatic NGS testing showed pathogenic mutations in 90% of pts (63/70): 57% KRAS (36/63; 44% G12D, 19% G12V, 8% G12C, 8% G12D, 19% others); 13% homologous recombination (HR) (8/63); 6% ERRB2 /Her2 amplification (4/63), and 5% mismatch repair (MMR) (3/63). Conclusions: AC has a favorable prognosis in resectable pts. However, high recurrence rates indicate the need for better systemic therapies and improved selection of pts who would benefit from these treatments. Future research should focus on refining perioperative strategies to enhance outcomes and reduce recurrence.

Background: Follicular dendritic cell sarcoma (FDCS) is a rare low- to intermediate-grade sarcoma, typically presenting as a slowly growing, painless mass composed of spindle-shaped cells in a whorled pattern. First described in 1986, FDCS has since been identified in several hundred cases. FDCS originates from mesenchymal dendritic cells and is distinct from other histiocytic neoplasms. Its management aligns more with soft tissue sarcomas. Epidemiologically, FDCS is exceedingly rare, constituting less than 0.4% of soft tissue sarcomas. Methods: With IRB approval, we identified patients with biopsy-proven FDCS treated at Mayo Clinic. Chart review extracted clinical characteristics, laboratory testing, treatment data, and clinical outcomes, compiled into Excel. Data analysis was performed through RStudios. Descriptive statistics of patient characteristics, such as gender and stage of disease, were summarized in tables. We compared overall survival (OS) through Kaplan Meier curves, stratifying patients into cohorts based on topics of interest, such as differences in survival in nodal vs. extranodal disease or differences in survival among different chemotherapy regimens. Results: Forty patients met the inclusion criteria, of biopsy proved FCDS. Median age at diagnosis was 57.7 years (SD 14). Men comprised 45% of patients. Locations of malignancy were abdomen and pelvis (32.5%), thoracic and pulmonary regions (32.5%), lymph nodes and neck (20.0%), musculoskeletal (2.5%), and other locations (12.5%). Primary therapies included surgical resection (42.5%), systemic chemotherapy (32.5%), no treatment (10.0%), radiation (2.5%), with data missing for 12.5% of cases. Concurrent or preceding Castleman's Disease was seen in 7.5% (3/40) of patients; one case preceded FCDS, and two were concurrent. Of these patients with Castleman's Disease, one was resected and the other two were not. Two cases were unicentric, and one was multicentric. First-line systemic chemotherapy was most often gemcitabine and docetaxel, with 9/40 patients receiving this regimen. Ifosfamide and doxorubicin were utilized in 3/40 patients. 2/4 patients had received doxorubicin alone. 2/4 patients had received CHOP. The response rate for patients with gemcitabine and docetaxel was complete response for 2/9 (22%) patients, partial response for 2/9 (22%), stable disease for 2/9 (22%), progressive disease for 1/9 (11%), and missing for 2/9 (22%), giving an overall response rate of 67%. For ifosfamide and doxorubicin, one patient had partial response (33%), another had stable disease (33%), and the last patient's data was missing (33%), adding up to a 66% overall response rate. For CHOP, one patient had progressive disease, and the other had partial response. For doxorubicin, both patients had stable disease. At a median follow-up of 29.5 months (IQR 9.2-75.2 months), the median OS was 160.68 months for the group with both nodal and extranodal disease versus 39.95 months for the extranodal disease-only group. The median OS of the nodal disease alone was not reached, with an estimated 2-year OS of 75%. To evaluate the impact of various primary therapies on outcomes in patients with advanced disease, we conducted a survival analysis by therapy used (no treatment, radiation, surgical resection, and systemic chemotherapy). Patients receiving no treatment had a median survival time of 28.9 months, while those treated with radiation had a median survival time of 19.3 months. Patients undergoing surgical resection had an undetermined median survival time, but notably, 80% were alive at the end of the time period analyzed in this study with a median follow-up time of 60.7 months. Those receiving systemic chemotherapy had a median survival time of 30.7 months. Conclusions: This project is one of the largest known single-center studies dedicated to FDCS. We show that the incidence of preceding or concurrent Castleman's Disease is relatively low. Gemcitabine and docetaxel was the most utilized chemotherapy regimen, but there weren't enough data to conclude if this regimen had a better response rate compared to others. Surgical resection of advanced disease is associated with superior outcomes. When systemic therapy is needed, the median survival was lower.

PURPOSE Nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Abstract Background: Sarcopenia is one of the early pathological features of cancer cachexia, yet the effect of sarcopenia on clinical outcomes in patients with advanced HCC is unclear. Our objective was to determine the effect of Sarcopenia on response to systemic therapy with advanced HCC. Methods: Patients with unresectable and advanced liver cancer were retrospectively evaluated between 2010 to 2019. Skeletal muscle area (SMA) was computed with a previously validated computed tomography (CT) body composition AI algorithm. The skeletal muscle index (SMI) was derived from the skeletal muscle area (SMA) (cm2) divided by patient height (m2) calculated from images at the level of L3 on pretreatment CT. Sarcopenia cutoffs for females was less than 39 cm2/m2 SMI or less than 50 cm2/m2 SMI for males. Patients’ demographics, systemic treatment response, toxicity, progression-free survival (PFS) and overall survival (OS) were compared between first-line therapy groups. Kaplan-Meier and Cox proportional hazards regression were used for survival analysis comparisons. Results: A total of 146 patients with advanced HCC were assessed from Mayo Clinic Arizona and Emory University. Seventy-six patients received immunotherapy as first-line treatment and seventy patients received TKI as first-line therapy. Sarcopenia at baseline was assessed in a total of 91 patients at first-line systemic treatment: n=48 with immunotherapy (IO) and n=43 with tyrosine kinase inhibitor (TKI). Sarcopenia was more prevalent in male patients (p=0.009), and in patients with low BMI (p=0.02). When comparing those with sarcopenia at baseline, higher response rate was observed in patients treated with IO without sarcopenia (47% versus 15%, p=0.019), this was not observed in TKI group. Interestingly, median PFS and OS was not significantly changed in patients with or without sarcopenia treated with IO or TKI on first-line therapy. Conclusions: Sarcopenia was associated with reduced response rate (RR) in patients treated with IO, but not in TKI groups. Both didn’t translate into deleterious effect in PFS and or OS. Further research with sufficient adjustments for confounding factors is warranted to better elucidate the prognostic value of sarcopenia in these patients. Citation Format: Gehan Botrus, Pedro Luiz Serrano Uson Junior, Heidi Kosiorek, Mehmet Akce, Isabela Chang, Zhubene Mesbah, Eric Yancey, Daniel Blezek, Jason Klug, Lana Khalil, Puneet Raman, Mohamad Sonbol, Mitesh Borad, Daniel Ahn, Tanios Bekaii-Saab. Prognostic impact of Sarcopenia on clinical outcomes in advanced hepatocellular carcinoma (HCC) treated with systemic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6274.

4130 Background: Circulating cell-free tumor DNA (ctDNA) genomic profiling is an emerging tool for pancreatic cancer. The impact of detected genomic alterations in tumor response to systemic treatments and outcomes is under investigation. Methods: Patients with advanced pancreatic cancer and ctDNA collected at time of initial diagnosis were retrospectively evaluated. Results of ctDNA analysis were correlated with patients’ demographics, systemic treatment response, progression-free survival (PFS) and overall survival (OS). Results: A total of 104 patients were included in the analysis. The mean age was 70.5 years (SD: 8.3), 50% were male, 37% with locally advanced disease and 63% with metastatic disease. Somatic alterations were detected in 84.6 % of the patients, no genetic alterations were detected in 15.4%, and were associated more with locally advanced pancreatic cancer as opposed to metastatic, p = 0.025. 60.6 % of the cohort had ≥ 2 genomic alterations detected. 28% were treated with FOLFIRINOX and 63% with gemcitabine plus nab-paclitaxel as first-line systemic treatment. Patients with any detectable genomic alterations when compared to patients with no detectable variant had worse median PFS (6.2 versus 15.3 months, p = 0.005) and patients with ≥ 2 detectable genomic alterations had worse median PFS (5.6 versus 11.0 months, p < 0.001) and worse median OS (11.5 versus 24.2 months, p = 0.001). KRAS was detected in 62.5% of the patients and was associated with PD to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (5.8 versus 13.0 months, p < 0.001) and worse median OS (11.5 versus 26.3 months, p = 0.002). TP53 was detected in 60% of patients and was associated with worse median PFS (5.9 versus 10.9 months, p = 0.02) and worse median OS (13.5 versus 24.2 months, p = 0.001). CCND2 was detected in 14% of the patients and was associated with worse median PFS (3.6 versus 8.2 months, p = 0.004). Conclusions: Our study showed that initial detection of ctDNA may identify different genomic alterations that help predict disease outcomes, confirmation of these findings in larger studies are warranted.