4211 Background: Celiac plexus radiosurgery is a novel non-invasive palliative treatment for pancreatic cancer pain that was recently added to NCCN guidelines. In the pivotal phase 2 trial (NCT03323489; Lancet Oncol 2024;25:1070-79), pain response was 53% (95% CI 42-64%). Prespecified exploratory analysis identified age and BMI as predictors; however, no clinically actionable patient selection tool was developed. We sought to identify additional predictors and create a practical risk stratification score. Methods: Post-hoc analysis of 90 evaluable patients from the phase 2 trial. Pain response was defined per protocol (≥2-point reduction in average pain from baseline to three weeks, on Brief Pain Inventory–Short Form). Candidate baseline predictors were examined by univariate and multivariate logistic regression. Only variables remaining significant in multivariate analysis were included in the final score to ensure independence and avoid overfitting. Internal validation used bootstrap resampling (500 iterations with replacement) to calculate optimism-corrected AUC. Analysis performed using Stata IC/16.1. Results: Univariate analysis identified 4 significant predictors: neurotoxic chemotherapy exposure (OR 5.33, 95% CI 2.13-13.4, p<0.001), baseline pain intensity (OR 1.73, p=0.003), age (OR 1.06, p=0.014), and therapy line (OR 0.65, p=0.04). On multivariate analysis, only neurotoxic exposure (OR 5.1, p=0.009) and baseline pain (OR 1.8, p=0.003) remained independently significant predictors. Age and therapy line lost significance due to collinearity. Dose-response analysis confirmed pain threshold optimization: >5 (61.5% response), >6 (65.8%), >7 (83.3%), >8 (85.7%), with >6 providing optimal discrimination. We created the SPIN (Severe Pain + Intact Nerves) score (0-2 points): baseline Pain >6 (+1), No prior Neurotoxic chemotherapy (+1). Response rates by score: 0 points: 32% (n=31); 1 point: 53% (n=40); 2 points: 89% (n=19). The 2-variable model achieved an apparent AUC=0.716. Following bootstrapping, the optimism-corrected AUC was=0.714. Conclusions: The simple score allows identification of distinct patient subgroups with markedly different probabilities of pain response following celiac plexus radiosurgery. This suggests the intervention should be considered earlier in the disease course, before exposure to neurotoxic agents. External validation is needed prior to clinical implementation. Financial support: Gateway for Cancer Research, The Israel Cancer Association. Clinical trial information: NCT03323489 .

Background:Retroperitoneal pain syndrome seen in pancreatic cancer is a major clinical challenge. Celiac plexus radiosurgery, a new palliative technique for retroperitoneal pain syndrome, decreased pain levels in a phase II study. Here Health-Related Quality of Life (HRQOL) outcomes are reported. Methods:Evaluable patients, who were enrolled between January 2018 and December 2021, in an international single-arm Phase II ethics-approved study (NCT03323489), were included. The pre-specified secondary endpoint-change in HRQOL from baseline to 3- and 6-weeks post-treatment, was measured by the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) version 4 questionnaire. Mean change was deemed clinically significant (CS) if the lower bound of the 95% confidence interval was above the predefined minimal clinically important difference (MCID) for that outcome. Findings:Of 90 evaluable patients, 51 (57%) and 44 (49%) had HRQOL FACT-Hep scores available at 3- and 6-weeks, compared to baseline. The majority of patients had pancreatic cancer (90%) and mean daily intravenous morphine equivalent consumption was 35.9 mg (SD 67.6).The mean increase of FACT-Hep total score from baseline was 9.3 points at 3-weeks (p = 0.0017) and 19.6 points at 6-weeks (p < 0.0001, 95% CI 13-26.3), representing a statistically significant (SS) 22% improvement from baseline, with CS demonstrated at 6-weeks. A sensitivity analysis, imputing no change from baseline in patients with missing data, demonstrated similar results. On multivariable analysis, lower baseline opioid use and baseline FACT-Hep scores were associated with an increased change in FACT-Hep from baseline to 3-weeks. Interpretation:Celiac plexus radiosurgery was associated with a SS improvement in HRQOL amongst patients with retroperitoneal pain at 3-weeks, and a SS and CS improvement at 6-weeks post intervention. Funding:This study received major financial support provided by Gateway for Cancer Research (G-17-100), additional support was provided from the Israel Cancer Association (20170128 and 20181272).

Abstract Background & Objectives Cholangiocarcinoma is a rare and aggressive biliary tract cancer. Although surgery offers the best chance for long-term survival, most patients are not surgical candidates at diagnosis. Radiation therapy (RT) is often used for local tumor control, but data on optimal RT technique and integration with systemic therapies are limited. This study evaluated overall survival (OS) and progression-free survival (PFS) in patients treated with RT and assessed potential prognostic factors. Methods This retrospective review included patients with cholangiocarcinoma treated with RT between 2015 and 2025. Survival was estimated using the Kaplan-Meier method, and log-rank tests compared outcomes by disease stage, lymph node involvement, RT technique (fractionated RT vs stereotactic body RT [SBRT]), immunotherapy use (durvalumab), and time from diagnosis to RT. Results Thirty-eight patients met inclusion criteria. The cohort was 55% female and 45% male, with a median age of 66 years. Median OS for the cohort was 23.0 months from diagnosis, and median PFS was 11.0 months. Disease stage and lymph node involvement were not statistically significant. Patients treated with durvalumab had median OS and PFS that were not reached, compared with 22.0 months (p = 0.41) and 8.0 months (p = 0.33) in those without immunotherapy. Patients treated with SBRT had a median PFS of 29.0 months versus 8.0 months for fractionated RT (p = 0.23), and median OS was not reached in the SBRT group versus 23.0 months for fractionated RT (p = 0.11). Longer time from diagnosis to RT showed a trend toward improved OS (p = 0.07). Conclusion RT for cholangiocarcinoma was associated with a median overall survival of nearly two years. Although limited by sample size, observed trends suggest potential survival benefits with SBRT and durvalumab. The association between longer time to RT and improved survival likely reflects selection bias. Larger studies are needed to further define optimal RT technique and integration of immunotherapy in cholangiocarcinoma management.

714 Background: Celiac plexus radiosurgery demonstrates impressive short-term pain control (3-6 weeks) in pancreatic cancer patients with minimal side effects, leading to NCCN guideline inclusion. In the trial, irradiation of the adjacent tumor was left to physician's discretion, but did not impact short-term pain outcomes (the primary endpoint). In this analysis we 1) report long-term efficacy, and 2) test the hypothesis that concurrent tumor irradiation affects durability. Methods: Single-arm study of 125 patients across five countries with baseline pain ≥5/10 and pancreatic cancer or celiac axis invasion. Subjects lacking pain scores at both 3- and 6-weeks post treatment were excluded. Pain measured via Brief Pain Inventory (weeks 0-6), then Numeric Rating Scale. Linear mixed-effects models with both linear & quadratic time terms analysed pain trajectories. Sensitivity analyses for missing data included multiple imputation, 'last observation carried forward', and worst-case scenarios. Prescription dose was tested as a moderator variable in the mixed-effect model. Results: A total of 107 patients analyzed (median age 64, 54% female, 92% pancreatic cancer, 86% metastatic). Median baseline pain was 6/10 (SD 1.7). Of the 82 cases in which the adjacent tumour was included within target volume, it was prescribed a median dose of 15Gy. Patients alive at 12/26/39 weeks: 79/33/24; pain outcome available for: 52/25/16. Median survival was 18 weeks. Peak effectiveness was at 18.5 weeks (95% CI: 15.7-20.7) with 3.4-point reduction (60% improvement, p<0.001), followed by gradual waning. Multiple imputation suggested sustained efficacy through 39 weeks. Higher prescription doses to adjacent tumor were associated with improved palliative durability (dose×time² interaction: p=0.046). Conclusions: Celiac plexus radiosurgery provides clinically meaningful pain reduction for at least four months. A post-hoc hypothesis generating analysis revealed concurrent tumor irradiation enhanced durability with a dose-response relationship. These exploratory, potentially practise changing findings warrant validation in a randomized trial. Financial support: Gateway for Cancer Research , Israel Cancer Association . Clinical trial information: NCT03323489 .

INTRODUCTION:The prognostic impact of positive bile duct margins (R1) after resection of perihilar cholangiocarcinoma (PHC) remains unclear, and evidence on the role of adjuvant radiation (RT) is limited. METHODS:We retrospectively reviewed 110 patients who underwent curative-intent resection for PHC from 1997 to 2018. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify risk factors of OS and DFS. RESULTS:R1 margins were present in 50 patients (45.5 %). Median OS and DFS for the cohort were 47.5 and 30.2 months. OS and DFS did not differ by margin status. On multivariable analysis, lymph node metastasis independently predicted worse OS (HR 3.81; p < 0.001) and DFS (HR 3.32; p = 0.001), while larger tumor size predicted recurrence (HR 3.12; p = 0.001). Adjuvant chemotherapy was associated with improved OS (HR 0.45; p = 0.049). Among R1 patients, adjuvant RT was associated with longer DFS (68.6 vs 17.8 months; p = 0.049) but not OS. CONCLUSIONS:R1 resection was not associated with inferior survival in this cohort. Lymph node metastasis was the strongest prognostic factor. Adjuvant RT was associated with improved DFS in the R1 patients, supporting its use for local control and warranting prospective validation.

BACKGROUND:Sexual dysfunction is a significant toxicity of pelvic radiation therapy (RT) for female rectal cancer patients and may be more common with intensity-modulated techniques compared to three-dimensional conformal radiation therapy (3D-CRT). However, limited research has evaluated dose sparing of female sexual organs at risk (OARs), particularly erectile tissues that are critical for sexual function. PURPOSE:This feasibility study aimed to demonstrate the practicality of contouring and sparing female sexual OARs in rectal cancer RT by generating sexual organ-sparing volumetric modulated arc therapy (SO-VMAT) plans from a small 3D-CRT cohort and comparing dose distributions to guide future planning. METHODS:Nine female patients with low rectal adenocarcinoma treated with concurrent chemoradiation using 3D-CRT were retrospectively analyzed. Sexual OARs (bulboclitoris, external genitalia, and vagina) were contoured and incorporated into replanned SO-VMAT plans. Institutional dose-volume constraints were applied for standard OARs and planning target volumes (PTVs). SO-VMAT and 3D-CRT plans were normalized to equal PTV coverage, and dose-volume metrics were compared using Wilcoxon signed-rank tests. RESULTS:Contouring and sparing of female sexual OARs was feasible in all cases. Compared to 3D-CRT, SO-VMAT reduced radiation doses to sexual OARs. For the bulboclitoris, SO-VMAT lowered V3000cGy and V4000cGy (both p = 0.02). For the external genitalia, SO-VMAT reduced maximum and mean dose (both p = 0.02) as well as V1000cGy (p = 0.004) and V2000cGy (p = 0.01). Vaginal sparing was observed at V4000cGy (p = 0.03). SO-VMAT provided significant bladder sparing, whereas bowel and femoral head doses remained comparable. Target coverage remained equivalent between techniques. CONCLUSION:This study demonstrates that female sexual OARs can be systematically contoured and effectively spared during rectal cancer RT using SO-VMAT. Compared with 3D-CRT, SO-VMAT achieved meaningful dose reductions while maintaining target coverage. These preliminary findings support multi-institutional studies with patient-reported outcomes to validate clinical relevance and guide integration of female sexual OARs into treatment planning.

Background and purpose:Predicting hepatocellular carcinoma (HCC) response to Stereotactic Body Radiation Therapy (SBRT) can be challenging. Here, we assessed the value of a radiomics-based machine learning (ML) approach for predicting HCC response to SBRT, using pre-treatment and early post-treatment magnetic resonance imaging (MRI). Materials and Methods:This retrospective single-center study included 87 patients (M 67, mean age 65.3 ± 9.1y) with HCC treated with SBRT who underwent gadoxetate MRI both pre- and early post-treatment (around 9.5 weeks). Tumor radiomics features were extracted on pre- and post-SBRT MRIs on pre- and post-contrast T1-weighted imaging (T1WI) [pre-contrast, arterial phase (AP), portal venous phase (PVP), transitional phase and hepatobiliary phase]. Long term response was assessed using modified RECIST criteria. Different ML models were developed based on 1st and 2nd order radiomics features to predict long-term objective response (partial and complete response) versus no response (stable and progressive disease). The cohort was randomly divided into training/validation (70 %) and testing 30 %. Results:A total of 87 tumors were assessed (mean size 2.7 ± 1.6 cm). Objective long-term response was observed in 43 (49.4 %) patients. The best predictive outcomes were achieved using models combining pre- and early post-treatment radiomics, with top performing model combining pre-treatment T1WI-pre-contrast, pre-treatment T1WI-AP and post-treatment T1WI-PVP, achieving an AUC of 0.85 [95 % CI: 0.67---1], sensitivity of 0.7 and specificity of 1. Conclusions:Our initial findings show promising results for ML radiomics in predicting long-term response of HCC to SBRT, which may have implications for management decisions.

BACKGROUND:Multilayer in-stent restenosis (ISR) remains a clinical challenge. Intravascular brachytherapy (IVBT) offers a "metal-free" treatment modality for multilayer drug-eluting stent (DES)-ISR; however, long-term outcome data on IVBT safety and efficacy are lacking. AIMS:We sought to compare 3-year clinical outcomes between patients treated with IVBT and those treated with a non-IVBT strategy. METHODS:Patients treated for multilayer DES-ISR (≥2 layers) at Mount Sinai Hospital (2012-2019) were included for analysis. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, target lesion revascularisation and myocardial infarction, at 3-year follow-up. RESULTS:A total of 647 patients (mean age 66.6±9.9 years, 25.5% female) were included: 453 patients (70%) were treated with IVBT and 194 patients (30%) with a non-IVBT strategy. Baseline characteristics were similar, except for IVBT-treated patients having a higher incidence of prior coronary artery bypass grafting. The IVBT group had a lower mean SYNTAX score (11.9±10.7 vs 14.2±11.3; p=0.028) and were significantly less likely to receive a DES (0.4% vs 25.8%; p<0.001). At 3-year follow-up, the incidence of MACE was lower in the IVBT-treated group compared to the non-IVBT group (propensity score-adjusted analysis: 39.5% vs 47.8%; hazard ratio 0.73, 95% confidence interval: 0.53-0.99; p=0.044). There were no significant differences between the incidence of the individual components of MACE in each group. CONCLUSIONS:Multilayer DES-ISR is associated with a high rate of adverse outcomes at 3-year follow-up. Treatment with IVBT was associated with a lower rate of MACE compared to treatment with a non-IVBT strategy at long-term follow-up.

Purpose: While immunotherapy has been established as the standard of care for patients with Barcelona Clinic for Liver Cancer class C hepatocellular carcinoma (HCC), outcomes for patients with portal vein thrombus (PVT) remain poor. This study evaluates the benefit of radiation therapy (RT) in addition to immunotherapy for patients with advanced PVT. Methods and Materials: A retrospective chart screen was performed to identify patients with HCC with PVT treated with definitive RT with concurrent (defined as within 6 weeks) immunotherapy. Kaplan-Meier survival analysis was performed to assess progression-free survival (PFS) and overall survival (OS). Cox proportional hazard modeling was employed for each covariate using R software version 4.3.3. Results: Sixty-two patients met the inclusion criteria from 2016 to 2023. The median follow-up was 18.9 months. Most patients were male (85.8%), with a median age of 64, and 61% had Child-Turcotte-Pugh (CTP) A liver function. Treatments included stereotactic body RT (61%) or fractionated RT (39%) with immunotherapy (74% single-agent). Portal vein tumor thrombosis classifications were Vp3 (47%) and Vp4 (45%). Median overall PFS was 3.70 months, and OS was 7.7 months. Patients with CTP A had better outcomes (PFS 5.3 months, OS 10.2 months; PFS hazard ratio 2.13, OS hazard ratio 3.08, P < .05). There was no significant difference in PFS or OS for patients who received single-agent immunotherapy with radiation versus multiagent immunotherapy (atezolizumab-bevacizumab) with radiation. Multivariate analysis identified no other significant predictors. Conclusions: The addition of radiation to immunotherapy may improve outcomes for patients with advanced PVT with HCC who have inferior outcomes with immunotherapy alone. Particularly for patients with CTP A liver function who would be eligible for clinical trials, the addition of radiation may improve OS beyond reported outcomes. Prospective studies are needed to verify these results.

BACKGROUND:Accurate delineation of organs at risk (OARs) is crucial yet time-consuming in the radiotherapy treatment planning workflow. Modern artificial intelligence (AI) technologies had made automation of OAR contouring feasible. This report details a single institution's experience in evaluating two commercial auto-contouring software tools and making well-informed decisions about their clinical adoption. METHODS:A cohort of 36 patients previously treated at our institution were selected for the software performance assessment. Fifty-eight OAR structures from seven disease sites were automatically segmented with each tool. Five radiation oncologists with different specialties qualitatively scored the automatic OAR contours' clinical usability by a 4-level scale (0-3), termed as quality score (QS), representing from "0: not usable" to "3: directly usable for a clinic." Additionally, quantitative comparison with clinically approved contours using Dice similarity coefficient (DSC) and the 95% Hausdorff distance (HD95) was performed in complement to QS from physicians. RESULT:Software A achieved an average QS of 2.17 ± 0.69, comparable to Software B's average QS of 2.17 ± 0.72. Software B performed better with more OARs (42 vs. 37) that required minor or no modification than Software A. Major modifications were needed for 13 out of 58 automated contours from both tools. Both DSC and HD95 scores for the two tools were comparable to each other, with DSC: 0.67 ± 0.23 versus 0.66 ± 0.21 and HD95: 13.07 ± 15.84 versus 15.55 ± 18.45 for Software A and Software B, respectively. Correlation coefficients between the physician score and the quantitative metrics suggested that the contouring results from Software A aligned more closely with the physician's evaluations. CONCLUSION:Based on our study, either software tool could produce clinically acceptable contours for about 65% of the OAR structures. However, further refinement is necessary for several challenging OARs to improve model performance.

External beam radiation therapy is becoming an increasingly useful tool in the management of hepatocellular carcinoma at all clinical stages. The data supporting its use is now maturing, with randomised trials showing excellent results in early, intermediate, advanced, and palliative stages. This review details the current best evidence available and makes a compelling case that external beam radiation therapy should be included in clinical guidelines. Doing so will benefit patients with an effective, low cost, and globally available treatment that can dramatically improve outcomes.

524 Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver strongly associated with liver cirrhosis and the etiologies producing cirrhosis. As such, racial and ethnic factors might affect incidence rates of HCC resulting in disparities. While disparities have been reported, the effect of gender within certain populations, particularly Hispanic and non-Hispanic White ancestry, have not been fully explored. This study looks at the changing incidence rates of HCC in the US amongst different populations with a particular focus on the impact of gender on incidence. Methods: Incidence rates of HCC between 2000 and 2021 among different sexes within racial and ethnic groups in the United States were analyzed utilizing delay-adjusted data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Annual percent change (APC) was calculated by using Joinpoint Regression software. Results: Overall, HCC incidence rates since 2014 to 2021 show a slight decrease (APC, -0.06). While Hispanic men HCC incidence rates declined from 2012 to 2021 (APC, -0.44), Hispanic women incidence have had a steady increase since 2000 (APC, +2.52). Non-Hispanic Black men (APC, -3.07) rates vastly declined from 2015 to 2021 while non-Hispanic black women interestingly experienced a slight decrease in incidence from 2013 to 2021 (APC, -0.34). Non-Hispanic White men experienced stagnant rates of HCC since 2014 (APC, -0.05) while non-hispanic white women (APC, +3.59) showed increasing trends in HCC incidence since 2003. For comparison, non-Hispanic Asian/Pacific Islander men (APC, -2.19) and women (APC, -2.36), which both experienced a decline since 2007. This analysis was repeated without significant change. Further corroborations are necessary to validate these findings. Conclusions: These findings show that while the incidence rates of HCC overall have decreased, this benefit appears to be largely driven in male populations. In contrast, in women, and particularly Hispanic and Non-Hispanic White women, incidence rates have been increasing. This phenomenon likely reflects the changes in etiologies of cirrhosis and HCC. Surveillance strategies and screening might need to be optimized to reflect these trends.

Background Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain. Methods This multicentre, single-arm, phase 2 study was done at eight hospitals in five countries (Israel, Poland, Canada, the USA, and Portugal). Eligible patients aged 18 years or older with an average pain level of 5-10 on the Brief Pain Inventory short form (BPI-SF), an Eastern Cooperative Oncology Group performance status score of 0-2, and either pancreatic cancer or other tumours involving the celiac axis, received a single fraction of 25 Gy of external- beam photons to the celiac plexus. The primary endpoint was complete or partial pain response based on a reduction of the BPI-SF average pain score of 2 points or more from baseline to 3 weeks after treatment. All evaluable patients with stable pain scores were included in response assessment. The trial is registered with ClinicalTrials.gov, NCT03323489, and is complete. Findings Between Jan 3, 2018, and Dec 28, 2021, 125 patients were treated, 90 of whom were evaluable. Patients were followed up until death. Median age was 655 years (IQR 583-718), 50 (56%) were female and 40 (44%) were male, 83 (92%) had pancreatic cancer, and 77 (86%) had metastatic disease. Median baseline BPI-SF average pain score was 6 (IQR 5-7). Of the 90 evaluable patients at 3 weeks, 48 (53%; 95% CI 42-64) had at least a partial pain response. The most common grade 3-4 adverse events, irrespective of attribution, were abdominal pain (35 [28%] of 125) and fatigue (23 [18%]). 11 serious adverse events of grade 3 or worse were recorded. Two grade 3 serious adverse events were probably attributed to treatment by the local investigators (abdominal pain [n=1] and nausea [n=1]), and nine were possibly attributed to treatment (seven were grade 3: blood bilirubin increased [n=1], duodenal haemorrhage [n=2], abdominal pain [n=2], and progressive disease [n=2]; and two were grade 5: gastrointestinal bleed from suspected varices 24 days after treatment [n=1] and progressive disease [advanced pancreatic cancer] 89 days after treatment [n=1]). Interpretation Celiac plexus radiosurgery could potentially be a non-invasive palliative option for patients with retroperitoneal pain syndrome. Further investigation by means of a randomised comparison with conventional celiac block or neurolysis is warranted. Funding Gateway for Cancer Research and the Israel Cancer Association.

Purpose/Objective(s) The use of atezolizumab and bevacizumab for advanced hepatocellular carcinoma (HCC) is a recently established standard of care. Addition of locoregional therapies (LRT) such as external beam radiotherapy (RT), radioembolization (Y90), transarterial chemoembolization (TACE), and/or radiofrequency ablation (RFA) may hold promise for further improving outcomes, but the safety of these approaches with atezolizumab/bevacizumab has not been established. This study assessed the safety of upfront LRT in conjunction with this immunotherapy regimen in HCC. Materials/Methods We reviewed all patients initiating atezolizumab with or without bevacizumab (IO) for HCC from July 2020 to January 2022 at a single institution. Patients receiving LRT (RT, Y90, TACE, and/or RFA) within 30 days of IO initiation (LRT+IO) were identified alongside a comparison arm of all patients initiating IO alone. Bevacizumab was typically held until after LRT. Treatment-related toxicities were recorded according to CTCAE definitions from the date of treatment initiation until discontinuation of IO or last follow up. Baseline, 1 month, and 3-month Child-Pugh (CP) score, ALBI score, transaminases, and total bilirubin were additionally recorded and analyzed using a repeated-measure mixed effects model. Results 50 HCC patients initiating atezolizumab were identified, 49 (98%) of these in combination with bevacizumab. Median follow up was 6.5 months (range 1.2-20), median age was 64 (34-79). 37 (74%) patients had BCLC stage C disease and 12 (34%) BCLC stage B. The majority of patients (86%) had CP class A liver function. Baseline characteristics were balanced between arms on univariate analysis (p>0.05). Of 27 (54%) patients in the LRT+IO arm, 9 received RT alone, 4 received RT combined with Y90 or TACE, 10 received Y90 alone, 3 received TACE alone, and 1 received RFA. The majority of the LRT+IO arm (63%) received LRT after the first infusion of atezolizumab. Grade 3 toxicities were observed in 2 (7.4%) patients in the LRT+IO arm, compared to 2 (8.6%) patients in the IO-only arm (p=0.87); grade 2 toxicity incidence was 63% in the LRT+IO arm versus 43% in the IO-only arm (p=0.17). The receipt of LRT+IO was associated with transient increase in CP and ALBI scores at 1 month relative to IO alone (median score increase 1 and 0.34, respectively, p<0.01); this association did not persist at 3 months. There was no treatment-related liver failure or grade 4/5 toxicity reported in either arm. LRT+IO was not associated with increased ALT, AST, or total bilirubin at 1 or 3 months. Conclusion In this single institution retrospective cohort study, upfront locoregional therapy with atezolizumab and bevacizumab for HCC was not associated with a significantly greater incidence of grade 2/3 toxicity or clinically significant liver dysfunction relative to the initiation of atezolizumab and bevacizumab alone. Further studies are needed to verify the safety of combination therapy and to assess clinical benefit.