Tran, Nguyen H.

e16167 Background: Guidelines recommend systemic therapy for uHCC ineligible for locoregional therapy. Until the approval of tremelimumab + durvalumab for uHCC, in Oct 2022, 1L systemic therapies in the US included multikinase inhibitors and atezolizumab (A) + bevacizumab (B). It is crucial to understand factors driving real-world treatment decisions and outcomes in uHCC. Methods: Data were collected from electronic medical records from US Mayo Clinic sites. Pts with uHCC who initiated a 1L systemic therapy between Jun 2020–Oct 2022 (A + B was the only approved 1L immunotherapy (IO)-based regimen) with ≥2 follow-up visits, were included. Index was the date of first 1L systemic therapy. Pts were assessed by risk of post-index gastrointestinal (GI) bleeding (Child-Pugh class B or C, pre-index GI bleeding, uncontrolled hypertension [HTN] [≥2 anti-HTN drugs or ≥2 vital entries of SBP > 140 mmHg or DBP > 90 mmHg]), or significant varices and band ligation). Treatment patterns, overall survival (OS), and post-index GI bleeding were assessed. Results: A total of 186 pts met the inclusion criteria. Most common etiologies of liver disease were MASH (42.7%) and hepatitis C virus (40.2%). Pre-index GI bleeding was reported in 29.0% of pts, of which 46.3% occurred within 6 months (mo) pre-index; 62.4% of pts had EGD, of which 72.4% had varices. There were 128 (68.8%) pts with GI bleeding risk and 58 (31.2%) pts without GI bleeding risk. The most common 1L systemic therapies for pts with GI bleeding risk were A + B (72.7%) and A only (9.4%), while for pts without GI bleeding risk, A + B (29.3%), nivolumab + ipilimumab (13.8%), and B + chemotherapy (12.1%) were the most common. Median OS and OS rates at 12, 18, and 24 mo were lower, and post-index GI bleeding rate was higher in pts with vs without GI bleeding risk (Table). For pts treated with A + B, median OS and OS rates at 12, 18, and 24 mo were lower in pts with vs without GI bleeding risk (Table). Conclusions: In this network, prior to the approval of other 1L IO-based regimens for uHCC, many pts received A + B, despite risk of post-index GI bleeding. Median OS with A + B was shorter in pts with vs without GI bleeding risk. Data highlight the complexity of uHCC and the unmet need for guidance on characteristics-driven treatment decisions. © 2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Gastrointestinal Cancers Symposium. All rights reserved. Table. Full cohort A + B cohort All ptsN=186 GI bleeding risk N=128 No GI bleeding risk N=58 All pts N=110 GI bleeding risk N=93 No GI bleeding risk N=17 Median follow-up, mo 20.6 20.9 20.4 21.3 21.6 20.3 Median OS, mo 14.4 11.4 40.3 13.9 12.8 Not reached OS rates, % 12 mo 55.2 48.9 68.9 55.2 52.3 70.6 18 mo 45.3 38.1 61.1 44.1 41.6 57.8 24 mo 39.4 31.8 56.8 37.1 34.6 51.3 Post-index GI bleed, % 17.2 23.4 3.4 17.3 19.4 5.9

4085 Background: Cholangiocarcinoma (CC) is a rare disease with an increasing incidence among younger adults, which is poorly understood. Genomic profiling of tumors is both prognostic and predictive of benefit for targeted therapies. We investigated if there are clinical and molecular differences between younger vs older patients with CC. Methods: We collected TEMPUS genetic data via retrospective chart review from tumors in young vs old patients seen at our institution, defined as ≤50 vs > 50 years of age at time of diagnosis. We included patients diagnosed with CC between January 2008 and July 2024 with available clinical follow up and TEMPUS genetic sequencing data. We collected mutation data on the following actionable genes: FGFR2, IDH1/2, BRCA1, BRCA2, BRAF, ATM, ERBB2/3, and KRAS. Patient characteristics and gene expression variables were compared using Chi-square, Fisher’s exact and Wilcoxon rank-sum tests. Kaplan-Meier, log rank tests and a multivariable Cox model were used for survival analysis. This study was IRB exempt. Results: We included 410 patients, 84 in the young group with median age at diagnosis of 40.8 years, and 326 in the old group with median age 68.5 years. 91.5% of patients were white. There was no difference in BMI between groups, however the older group had higher rates of hypertension (15.5% vs 57.7%), hyperlipidemia (6.0% vs 49.7%), cardiovascular disease (1.2% vs 20.6%), and type 2 diabetes (6.0% vs 21.5%), (all p < 0.01). Primary sclerosing cholangitis was more common in the young group (26.2% vs 4.3%, p < 0.01). ECOG status of 0 at first treatment was seen in 65.3% of young vs 52.5% of old patients (p = 0.02). FGFR2 alterations were more common in the young group (17.9% vs 8.0%, p < 0.01), while ATM mutations were more common in old vs young (5.5% vs 0%, p = 0.03). There was no age difference seen for the other genetic alterations. Mean tumor mutational burden was higher in the old group (4.1 vs 3.8 mut/mb, p = 0.01). MSI-high was found in 2% of cases with no difference between groups. There was no significant difference in overall survival between age groups. There was a numeric difference in overall survival in stage IV patients, though not statistically significant (17.8 months vs. 16.3 months, p = 0.08). In a multivariable Cox analysis, female sex, earlier stage at diagnosis and clinical trial enrollment were associated with favorable prognostics. Conclusions: Our data highlight relatively low rates of comorbidities associated with metabolic dysfunction in younger adults with CC, suggesting alternative factors are likely to explain the increasing incidence of early-onset disease. FGRFR2 is a more common pathogenic alteration among the young and could inform targeted therapies. Younger patients with CC may not have improved survival outcomes compared to their older counterparts. This underscores the aggressive nature of CC and the need for more effective therapies to improve outcomes.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have become the first-line treatment of unresectable hepatocellular carcinoma (HCC). The prognostic value of immune-related adverse events (irAEs) in these patients remains controversial. We aimed to investigate the association between irAEs and clinical outcomes in patients with HCC treated with ICIs. METHODS: We searched the PubMed, Scopus, Web of Science, and Central Register of Controlled Trials databases for articles published from inception to June 2024, using keywords including ICI, HCC, and irAEs. Statistical analysis was performed with a random effects model. RESULTS: Of 3,028 studies, 24 (4,127 patients) met the criteria for inclusion. Atezolizumab plus bevacizumab was the most common treatment regimen (n = 10 studies). IrAEs were associated with an increased objective response rate (pooled relative ratio: 1.73; 95% confidence interval [CI]: 1.36–2.21, I 2 = 41%), a higher disease control rate (pooled relative ratio: 1.45; 95% CI: 1.21–1.74, I 2 = 74%), and longer progression-free survival (pooled hazard ratio [HR]: 0.66; 95% CI: 0.52–0.84, I 2 = 71%). There was a trend toward longer overall survival for patients with irAEs compared with those without (pooled HR: 0.84; 95% CI: 0.63–1.12, I 2 = 73%). Subgroup analysis indicated a survival benefit for patients with grade 1–2 irAEs (pooled HR: 0.50; 95% CI: 0.36–0.67, I 2 = 0%) and for those with endocrine irAEs (pooled HR: 0.63; 95% CI: 0.48–0.83, I 2 = 12%). DISCUSSION: The development of irAEs is associated with favorable clinical outcomes in HCC, including improved progression-free survival and higher objective response rate. Overall survival benefit was noted in patients with mild irAEs but not those with severe irAEs.

ABSTRACT Metabolic-associated steatohepatitis-driven hepatocellular carcinoma (MASH-HCC) incidence is rapidly rising worldwide. Lipid metabolic reprogramming is a hallmark of solid tumors to satisfy cancer high metabolic demand. However, it may confer sensitivity to ferroptosis, a cell death mode driven by iron-dependent lipid peroxidation. In this report, we describe the lipid metabolic landscape in MASH-HCC and characterize long chain acyl-CoA synthetases (ACSLs), a family of enzymes involved in synthesis of cellular lipids. Bulk RNA-sequencing, single-cell RNA-sequencing, spatial transcriptomics and immunohistochemistry analyses of human MASH-HCC were integrated to identify differentially expressed lipid metabolism genes. Ferroptosis in vitro was assessed in human HCC cell lines. A characterization of ACSLs was also conducted at the single-cell level in a diet-induced experimental murine model of MASH-HCC. Our analysis revealed that in human MASH-HCC, ACSLs exhibit a heterogeneous expression, with ACSL4 notably enriched in tumor tissues, contrasting with ACSL5 upregulation in non-cancerous MASH. We identified a unique lipid metabolic gene signature of MASH-HCC, which included genes associated with ferroptosis vulnerability. In vitro , ACSL4 upregulation was associated with increased ferroptosis sensitivity in human HCC cell lines. Lastly, single-cell RNA-sequencing revealed elevated ACSL4 expression in immune cells in a murine MASH-HCC model, suggesting a role of ACSL4 in shaping the tumor immune microenvironment. Overall, this report offers new insights into lipid metabolic landscape and ferroptosis sensitivity for novel MASH-HCC treatments. GRAPHICAL ABSTRACT

634 Background: CAT is the second leading cause of cancer-related death, yet the genetic underpinnings of VTE risk in BTC remain underexplored. The evaluation of CAT risk is based on Khorana score (KS), which is limited to clinical parameters. Incorporation of a genomic signature in CAT risk assessment may allow for individualized risk assessment. Methods: We collected data from consecutive patients (pts) with BTC treated at Mayo Clinic Hospitals (Phoenix, Rochester, Jacksonville) between 1998-2024. Genomic profiling was conducted on FFPEs and blood samples through next-generation sequencing (NGS) (NextSeq, Tempus xT CDx, FoundationOne CDx). Association between CAT and clinic-pathologic features (age, gender, race, ethnicity, BMI, tumor site (TS), surgery, stage, radiotherapy, systemic therapy, history of thromboembolism (hVTE)) were assessed with multivariate Cox regression (p<0.05). A separate Cox regression adjusting for age, hVTE, radiotherapy, systemic therapy, metastatic disease stratified for TS was used for gene associations. Benjamini–Hochberg method was applied (q<0.1) based on previous publications. Median overall survival (mOS) was calculated from the date of diagnosis to the date of death or last follow-up. Results: 740 adult pts were included, median age 62 years (IQR: 56-71), male/female (51%/49%), median BMI 26.6 (IQR: 22.8-31.1) with intrahepatic (496, 67%) and extrahepatic BTC (173, 23%), gallbladder cancer (71, 10%). 244 (33%) had metastatic disease. 216 (29%) experienced CAT. For those with CAT, 31 (14%) scored 1, 9 (4%) scored 2 and 1 (<1%) scored 3 on KS. mOS was 33 months (mos) (95% CI 28.9-38.4) vs. 55 mos (95% CI 25.1-39.1) (p=0.2) for pts with and without CAT, respectively. hVTE was associated with CAT (HR 3.14, 95% CI 1.98-4.98, p<0.001) along with systemic therapy (HR 1.19, 95% CI 1.11-2.89, p<0.01) and metastatic disease (HR 1.65, 95% CI 1.11-2.44, p<0.01). 305 pts (41%) underwent NGS. The most common altered genes were TP53 (126, 41%), KRAS (64, 21%), CDKN2A (63, 21%). The most common altered currently targetable genes were FGFR2 (43, 14%), IDH1 (30, 10%) and HER2/ERBB2 (16, 5%). MYC (4, 1%) (HR 11.60, 95% CI 3.04-44.25, p<0.001, q=0.058) and HER2/ERBB2 (HR 2.45, 95% CI 1.26-4.77, p=0.008, q=0.087) alterations were significantly associated with an increased risk of CAT. MYC alterations were all copy number gains (100%). The most frequent HER2/ERBB2 alterations were copy number gains (10, 62%). FGFR2 fusions (31, 10%) were linked to a lower CAT risk (HR 0.46, 95%CI 0.22-0.93, p=0.032, q=0.075) with FGFR2-BICC1 being the most frequent (5,16%). Conclusions: MYC and HER2/ERBB2 alterations are novel predictive biomarkers for an increased risk of CAT in BTC, while FGFR2 fusions confer lower risk. The knowledge of mutational status lends insight into guidance for anticoagulant prophylaxis management for this subgroup and integration with KS.

5 Background: Metastatic anal squamous cell carcinoma is rare and associated with a poor prognosis. There is limited evidence on the impact of local interventions on survival outcomes in patients with metastatic disease. We aimed to evaluate the survival of patients with liver-only metastatic anal cancer following definitive local management of liver lesions. Methods: This is a single-institution retrospective cohort study of patients with liver-limited metastatic anal cancer who underwent curative-intent local therapy. Clinical characteristics were collected and analyzed. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS). Prognostic factors associated with DFS and OS were assessed using Cox-proportional hazards models. Results: Twenty-five patients were included, median age was 59 years, and 92% were female. None of the patients had known HIV infection, 92% had HPV-positive disease and 76% had metachronous liver metastases following locoregional disease. All patients received chemoradiation for the primary lesion Unilobar hepatic involvement was present in 76% of the patients, with 56% having a single metastatic lesion. Pre-intervention systemic therapy was provided to 52% of the patients, including 8 who received carboplatin and paclitaxel, with a median duration of 3 months and ORR of 69%. Definitive treatment of metastatic disease included surgical resection (60%), non-surgical interventions (20%), and multimodal therapy (20%). All patients had viable tumor in the pathological specimen. With a median follow-up of 22 months, median DFS was 7.3 months, and median OS was 51.3 months. An ECOG performance status of 2, poorly differentiated histology, and extrahepatic recurrence were identified as significant prognostic factors in the univariate analysis, but not in the multivariate analysis. Conclusions: Our results demonstrate potential for long-term survival in liver-limited metastatic anal squamous cell carcinoma amenable to local therapeutic intervention combined with systemic therapy. These findings warrant further prospective study of local therapy in oligometastatic anal cancer. Characteristics N=25 (%) Median number of liver metastases (range), lesions- 1- 2-3- >3 1 (1-20)14 (56)8 (32)3 (12) Median maximal diameter of liver metastases (range), cm 3 (0.9-11.9) Best response of liver metastases to chemotherapy (N=13)- Complete response- Partial response- Stable disease- Progressive disease 2 (15)7 (54)3 (23)1 (8) Surgical procedure (N=20)- Right/left hemi-hepatectomy- Segmentectomy- Wedge resection 4 (20)14 (70)2 (10) Non-surgical procedure (N=10)- Local ablation- Radiotherapy- Other 5 (50)3 (30)2 (20) Hepatic surgical margins (N=20)- Positive margins- Close margins (<1mm)- Negative margins 02 (10)18 (90) Recurrent disease- Yeso Intrahepatico Extrahepatic- No 20 (80)14 (70)6 (30)5 (20)

566 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for unresectable hepatocellular carcinoma (HCC). Conflicting data exist regarding the prognostic value of immune-related adverse events (irAEs) in these patients. We aimed to explore potential the association between irAEs and prognosis in HCC patients treated with ICIs. Methods: We searched PubMed, Scopus, Web of Science, and CENTRAL databases for articles published from inception to June 2024 using keywords including ICI, HCC, and irAEs. Two reviewers independently screened studies for eligibility and relevant data. A random effects model was used for statistical analysis, and subgroup analysis was performed by the grade of irAEs. Results: Of 3,028 studies, 25 (n=4,116 patients) met criteria for inclusion. Atezolizumab plus bevacizumab was the most common treatment regimen (n=10 studies). About half (49.5%) of patients experienced irAEs. irAEs were associated with increased objective response rate (ORR) (pooled OR: 1.72; 95% CI: 1.36 – 2.19, I 2 =39%), higher complete response rate (pooled OR: 1.45; 95% CI: 1.21-1.74, I 2 =74%), and longer progression-free survival (PFS) (pooled HR: 0.66; 95% CI: 0.52-0.84, I 2 =71%). Although irAEs were associated with longer overall survival, this difference was not statistically significant (pooled HR: 0.83; 95% CI: 0.62 – 1.11, I 2 =73%). Subgroup analysis showed a survival benefit for patients with grade 1-2 irAEs (pooled HR: 0.50; 95% CI: 0.36-0.67, I 2 =0%) but not for those with grade 3-4 irAEs (pooled HR: 0.95; 95% CI: 0.24-3.72, I 2 =84%). Conclusions: The development of irAEs is associated with a favorable prognosis in HCC, including improved PFS and higher ORR. A survival benefit was noted in patients with mild irAEs, but not in those with severe irAEs. Future studies are needed to determine if a differential survival benefit relates to the continuation vs. discontinuation of ICI therapy.

592 Background: Deficient mismatch repair/microsatellite instability (MSI-H) in biliary tract cancers (BTC) is rare, estimated to be 1-5%. MSI-H across solid tumors has shown unprecedented durable response to immune checkpoint inhibitors (ICI) regardless of anatomic location. Here we describe the clinical outcomes of unresectable BTC patients with MSI-H treated with ICIs and their conversion to surgery. Methods: We conducted a multicenter, retrospective analysis of patients (pts) with advanced BTC who had been identified with MSI-H by molecular analysis performed between 2017 and 2024 at Mayo Clinic and University Hospitals Seidman Cancer Center. The outcomes of interest were overall survival (OS), defined as time from initiation of first-line systemic treatment to death; Time-to-treatment failure (TTF), defined as time from initiation of treatment to cessation due to any cause; and response. All analyses were done descriptively. Results: We identified 22 MSI-H pts with BTC, 19 with cholangiocarcinoma and 3 with gallbladder cancer. Median age at diagnosis was 61 (range 26-86), 20 (90.9%) were Caucasian, 9 (40.9%) were male gender, and 5 (22.7%) had etiology as Lynch syndrome. Twelve (54.5%) pts had metastatic disease at diagnosis. Twenty pts (90.9%) received first line systemic therapy, of whom 11 (55%) continued onto second line. Among the 20 pts that received first line therapy, median TTF was 7.6 months (95% CI: 4.8-14.3), objective response was observed in 7 (35%) pts, and disease control was observed in 15 pts (75%). Among the 11 pts that continued onto second line systemic treatment, objective response was observed in 4 pts (36%) and disease control was observed in 6 pts (55%). Among the 20 pts that received first line therapy, 19 (95%) ever received ICI +/- chemotherapy as a part of their treatment plan. Two-year OS for pts who ever received ICI was 63% (95% CI: 41%-96%). In total, 4 pts (20%) were restaged to resectable following treatment with an ICI, underwent resection, and currently have no evidence of disease. Conclusions: Administration of ICI during treatment plan in pts with MSI-H confirmed durable response and even downstage pts to resectable stage for curative intent. Testing for MSI-H should be performed upfront to guide treatment decision.

537 Background: A+B is the preferred first-line (1L) standard of care for uHCC, with emerging RW evidence supporting its use in a broad patient (pt) cohort. We evaluated pt characteristics, clinical and treatment outcomes in pts treated at five U.S. institutions: Mayo Clinic, Houston Methodist, Moffitt Cancer Center, Mays Cancer Center, and University of Arizona. Methods: This is a retrospective study of uHCC pts who initiated A+B after January 1, 2019. De-identified pt data were extracted by treating oncologists. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed using Kaplan-Meier methods for all pts and for a “trial-like” subgroup with characteristics similar to those in the IMbrave150 trial (ECOG performance status [PS] 0-1, Child-Pugh [CP] class A, albumin-bilirubin [ALBI] grade 1-2). HCC-related hospitalizations were evaluated within 1 year of A+B initiation. Results: A total of 300 eligible pts were treated with 1L A+B (median age 68 years, 79% male, 79% White, 82% BCLC C, 44% viral etiology,12% ECOG PS >1). Liver function was CP A in 73% (36% A5, 31% A6, 6% not reported), CP B in 26% pts (15% B7, 7% B8, 5% B9), and CP C in 2 (<1%) pts. Compared with CP A, more CP B pts had characteristics of compromised liver function (CP A vs B: cirrhosis: 61% vs 91%; ascites: 7% vs 46%; encephalopathy: 4% vs 17%; esophageal varices: 14% vs 32%), bile duct invasion (2% vs 11%), and ECOG PS>1 (8% vs 22%), all Ps<0.001. Over a median follow-up of 8.7 mos, 244 (81%) pts discontinued A+B, primarily due to disease progression. Toxicity-related treatment discontinuation and hospitalizations due to treatment-related adverse events (TRAE) were similar between the two groups (Table). Median OS (mOS) was 14.4 mos (95% CI: 12.3, 18.2) and median rwPFS was 6.8 mos (95% CI: 5.8, 8.4). In the trial-like subgroup (n=194), mOS was 19.5 mos (95%CI: 14.6, 24.7) and median rwPFS was 8.8 mos (95% CI: 7.6, 12.1). In the CP B subgroup, mOS was 5.6 mos (95% CI: 4.6, 11.3) and median rwPFS was 3.1 mos (95% CI: 2.4, 5.8). Conclusions: This study demonstrates the RW outcomes of 1L A+B in a diverse pt cohort. Results from the “trial-like” pts further confirm the reproducible efficacy of A+B in clinical practice. Although pts with CP-B had higher hospitalization rates due to disease progression or symptoms, consistent with their underlying liver complications, they had similar rates of toxicity-related treatment discontinuation and TRAE-related hospitalizations compared to CP-A. Further characterization of safety for A+B in CP B pts within a prospective, controlled trial is warranted. N (%) CP A (n=219) CP B (n=79) Treatment discontinuation* 167 (76) 75 (95) Atezolizumab-related toxicity 20 (12) 13 (17) Bevacizumab-related toxicity 26 (16) 16 (21) Hospitalization* 87 (40) 58 (73) Symptom-related 42 (48) 35 (60) Progression 8 (9) 11 (19) TRAE 7 (8) 6 (10) *P-value comparing CP A vs CP B <0.001.

536 Background: The prognosis of advanced BTC remains poor. Although targeted agents have expanded late-line options, many patients (pts) become ineligible for these therapies after progressing on first-line treatment. Herein, we examined the real-world impact of targeted therapy on survival in advanced BTC. Methods: In this international collaborative study between the Mayo Clinic (US) and the National Cancer Center East (Japan), we included pts with advanced BTC with comprehensive tumor molecular profiling who had received at least 30 days of systemic therapy. Pts were categorized into 3 groups: 1) non-actionable, 2) pts with alterations who received matched targeted therapy at any point during their treatment (matched group), and 3) those with mutations who did not receive matched therapy (unmatched group). OS was calculated from the start date of first-line therapy until death and compared among three subgroups using Cox regression models. Results: Of 932 pts, 366 (39.3%) had an actionable alteration, and 135 of these received matched therapy. 566 (61.7%) did not have an actionable alteration (Table). The most common alterations were somatic BRCA1/2 (N=106, 11.4%), HER2 amplification (N=65, 7%), FGFR2 fusion (N=61, 6.5%), KRAS G12C/D (N=46, 4.9%), and IDH1 (N=38, 4.1%). 78.7% of FGFR2 fusions were found in Caucasian pts, whereas BRCA1/2 (97.5%), HER2 (78.5%), and KRAS G12C/D (67.4%) alterations were more prevalent in Asian pts. The median OS was significantly longer in the matched group (21.4 months; 95% CI 18.4-27.9) compared to the unmatched group (14.6 months; 95% CI 12.8-17.6) and the non-actionable group (17.2 months; 95% CI 15.5-19.0). The 36-month OS rate was 33% in the matched group vs. 7% in the unmatched group (p < 0.0001). After adjusting for age, gender, prior surgical resection, primary tumor location, and country of origin, matched targeted therapy remained a strong independent predictor for improved OS (HR 0.61; 95% CI 0.48-0.79). Conclusions: These real-world findings suggest that matched targeted therapies significantly improve survival in advanced BTC, underscoring the need to incorporate them earlier in the treatment course and address barriers to treatment access. The regional prevalence of actionable alterations should also be considered when developing new targeted therapies. Patient baseline characteristics stratified by actionable alterations and targeted therapy. Non-actionable(N=566) Unmatched group(N=231) Matched group(N=135) Site, n (%) Japan 409 (72%) 166 (72%) 50 (37%) US 157 (28%) 65 (28%) 85 (63%) Age at Dx > 65, n (%) 324 (57%) 122 (53%) 54 (40%) Female, n (%) 235 (42%) 92 (40%) 77 (57%) Primary tumor location (category), n (%) Intrahepatic 217 (43%) 115 (55%) 99 (76%) Extrahepatic 150 (30%) 39 (19%) 17 (13%) Gallbladder 142 (28%) 54 (26%) 14 (11%) Prior surgical resection, n (%) 220 (42%) 74 (34%) 48 (37%)