Citations

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.

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.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

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 Background: Financial toxicity can have devastating long-term effects for cancer patients (pts) and their family members which may impact their access to care, adherence and, ultimately, outcomes. Identifying those at greatest risk is key to mitigating costs and distress to pts. Here we report results from a screening questionnaire on financial risks among Southeast Asian (SE-A) pts. Methods: This retrospective review included pts on the cancer patient registry at Mayo Clinic (Arizona, Florida, Minnesota, Wisconsin, and Iowa) who had completed a clinical visit in an oncology-related department (hematology, medical oncology, radiation oncology, etc) within the past 270 days prior to 6/4/24. Pts completed an electronic social determinant of health questionnaire of which financial risks and transportation needs are the focus of this study: 1) how hard is it for you to pay for the very basics like food, housing, medical care, and heating? 2) in the past 12 months, has lack of transportation kept you from medical appointments or from getting medications. Our primary endpoints include the association between financial risks, active bad debts (defined as having &gt;$5000 owed for high active bad debt, $0-$5000 for some active bad debt), pre-appointment review (PAR) flag status and transportation needs. Descriptive statistics and Chi-square were used to analyze factors associated with financial risks. Results: We identified 81, 731 pts who completed the questionnaire, among whom 387 were SE-A. Compared to non-SE-A and White, 6.5% have some active bad debt vs 3.3% and 3.6% (p&lt;0.001), and 1.0% had high active bad debt vs 0.8% and 0.7% (p&lt;.001); 58.4% had low financial risk vs 60% and 66% (p&lt;0.001) and 2.3% with high risk vs 1.5% and 1.6% (p&lt;0.001), 4.1% declined to answer and 29.7% were unknown. Bad debt was associated with PAR flag (P &lt;0.001) and financial risk (P&lt;0.001). For transportation among SE-A, 2.3% had unmet transportation needs, 1.8% declined/unable to answer, while 17.8% were unknown. Those with transportation needs were associated with active debt and financial risk (p&lt;0.001). Conclusion: In this cohort, we identified SE-A with highest rates of active debt and higher financial risks compared to Non-SE-A and White. A large percentage of patients declined to answer or are unknown. Future pilot questionnaire is in development to identify pts concerns for medical costs, financial strain and the receptivity to be connected to resources/referrals to address them. Citation Format: Nguyen H. Tran, Jordan Mason, Wendy Hanson, Kimberly Steinbert, Minji Lee, Robert McWilliams. Financial risks in southeast asian patients with cancer [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 7094.

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.

628 Background: Biliary tract cancers (BTC) are aggressive malignancies with poor survival outcomes and limited treatment options. This study compared the epidemiological and molecular differences of advanced BTC patients through a global collaboration involving the Mayo Clinic and National Cancer Center Hospital East. Methods: We included patients with advanced BTC who underwent comprehensive tumor molecular profiling who received at least 30 days of systemic therapy. Patients were grouped based on specific alterations. Overall survival (OS) was calculated from the start of first-line therapy until death and compared among subgroups using Cox regression models. Results: 332 (36%) out of 932 patients had at least one actionable mutation : somatic BRCA1/2 mutations N=106, FGFR2 fusions N=61, HER2 amplifications N=65, KRAS G12C/D mutations N=46, IDH1 mutations N=38, and TMB >10 mut/Mb N=16. BRCA1/2 -mutated BTC were more commonly found in older Asian males with intrahepatic tumors and often presented with peritoneal and liver metastases upon initial diagnosis. FGFR2 fusions were more prevalent in younger White females with intrahepatic tumors, while HER2 amplifications were mainly seen in Asian females with gallbladder tumors. KRAS mutations were primarily observed in Asian males, and IDH1 mutations were common in White males with intrahepatic tumors, frequently presenting with liver metastasis. Survival outcomes varied significantly based on the alteration type: patients with FGFR2 fusions had the longest median OS (mOS) at 23.3 months (mo) (95%CI 18.4-34.9), followed by those with IDH1 mutations (19.3 mo; 95% CI 17.4-NE) and TMB >10 mut/Mb (17.8 mo; 95% CI 13.6-NE). BRCA mutations had a mOS of 16 mo (95% CI 14.6-19.8), while HER2 amplifications and KRAS mutations had mOS of 15.5 (95% CI 11.9-20.2) and 11.6 mo (95% CI 10.0-20.9), respectively. Conclusions: These findings underscore the heterogeneity in clinical and genomic characteristics among BTC patients, highlighting the importance of tailored therapeutic approaches. Baseline patient characteristics stratified by mutation status. KRAS G12C/D (N=46) BRCA 1/2 (N=106) IDH1 (N=38) HER2 amplification(N=65) FGFR2 fusion(N=61) TMB>10 mut/Mb(N=16) P-value Median Age, year 67 68 64 66 52 73 <0.001 Female, n (%) 19 (41) 34 (32) 18(47) 34 (52) 45(74) 6 (38) <0.001 Race, n (%) <0.001 Asian 31 (67) 97 (92) 13 (34) 51 (79) 10 (16) 6 (38) White 14 (30) 8 (8) 24 (63) 13 (20) 48 (79) 10 (63) Primary tumor location, n (%) <0.001 Intrahepatic 28 (68) 45 (45) 33 (100) 19 (31) 54(95) 10 (67) Extrahepatic 9 (22) 27(27) 0 (0) 10 (16) 2 (4) 4 (27) Gallbladder 4 (10) 28 (28) 0 (0) 32 (53) 1 (2) 1 (7) Sites of Metastasis at diagnosis, n (%) Abdominal Wall / Peritoneal 9 (24) 15 (19) 4(13) 7 (12) 6 (10) 4 (27) 0.309 Bone 33 (92) 70 (90) 26 (87) 2 (3) 9(15) 0 (0) 0.212 Liver 20 (49) 52 (61) 28 (82) 45 (73) 45 (76) 6 (38) 0.001 Lung 26 (70) 65 (82) 22 (69) 36 (58) 27(45) 11 (69) 0.006

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.