2276 - Impact of Post-SABR Lymphopenia on Outcomes of SABR Combined with ICI or TKI in Extrahepatic Metastatic Hepatocellular Carcinoma
Presenter(s)
E. Yang1, J. I. Yu2, H. C. Park2, M. J. Goh3, B. G. Song3, W. Kang3, D. H. Sinn3, G. Y. Gwak3, Y. H. Paik3, J. H. Lee3, M. S. Choi3, J. Y. Hong4, M. Kwon5, J. E. Shin5, and N. Kim2; 11Department of Radiation Oncology, Ewha Women's University Mokdong Hospital, Ewha Women's University School of Medicine, Seoul, Korea, Republic Of, 2Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South), 3Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South), 4Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South), 5Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South)
Purpose/Objective(s):
Stereotactic ablative body radiotherapy (SABR) combined with immune checkpoint inhibitors (ICI) is increasingly adopted for extrahepatic metastatic hepatocellular carcinoma (emHCC), yet the impact of post-SABR lymphopenia (PSL) on ICI efficacy remains unclear. We evaluated the impact of PSL on outcomes in patients with emHCC receiving ICI versus tyrosine kinase inhibitors (TKI).Materials/Methods:
This single-center retrospective study included 150 patients with emHCC who received metastasis-directed SABR with ICI (n=56) or TKI (n=94) within 30 days (January 2010–June 2025). The most common SABR site was spine (n=74, 49.4%), non-spine bone (n=46, 30.7%), and lung (n=15, 10.0%). Median biologically effective dose (a/ß=10) was 72 Gy. PSL was defined as absolute lymphocyte count (ALC) <1,000/µL at 1-month post-SABR. Primary outcomes were local control (LC), progression-free survival (PFS), and overall survival (OS) by Kaplan-Meier. Cox models assessed PSL-drug interactions; logistic regression identified PSL predictors.Results:
PSL occurred in 75 patients (50.0%): 35.7% in ICI and 58.5% in TKI. Among patients without PSL (n=75), ICI showed superior PFS and OS versus TKI (median PFS 10.7 vs 5.4 months, p=0.036; median OS 34.4 vs 18.4 months, p=0.018), with a marginal LC difference (p=0.050). Among patients with PSL (n=75), no significant differences were observed (all p>0.05). PSL-drug interactions were significant for LC (p=0.009) and PFS (p=0.015), persisting after multivariable adjustment (LC p=0.011; PFS p=0.049). Notably, baseline lymphopenia had no such effect, supporting a PSL-induced mechanism. Larger planning target volume (PTV) and lower baseline ALC independently predicted PSL.Conclusion:
PSL selectively impaired ICI but not TKI efficacy in patients with emHCC receiving SABR. As larger PTV and lower baseline ALC predicted PSL, minimizing irradiated volume may preserve immune competence and ICI efficacy. Prospective validation is needed to optimize drug selection with SABR.| Interaction Term | Univariable analysis | Multivariable analysis† | ||
| HR (95% CI) | p | HR (95% CI) | p | |
| Baseline lymphopenia × ICI | ||||
| Local control | 0.96 (0.22–4.17) | 0.957 | 0.83 (0.19–3.67) | 0.801 |
| Progression-free survival | 1.38 (0.61–3.16) | 0.444 | 1.27 (0.55–2.95) | 0.575 |
| Overall survival | 1.02 (0.29–3.62) | 0.970 | 1.11 (0.31–3.99) | 0.873 |
| Post-SABR lymphopenia × ICI | ||||
| Local control | 6.19 (1.59–24.03) | 0.006 | 5.52 (1.41–21.60) | 0.011 |
| Progression-free survival | 2.54 (1.20–5.35) | 0.016 | 2.20 (1.02–4.74) | 0.045 |
| Overall survival | 2.49 (0.77–8.07) | 0.126 | 2.49 (0.75–8.25) | 0.133 |