Growth Hormone Pathway as a Prognostic and Therapeutic Biomarker in Patients With Unresectable Hepatocellular Carcinoma Treated With Radiation Therapy.

Purpose: Radiation therapy (RT) has emerged as an effective local therapy option for patients with unresectable hepatocellular carcinoma (HCC) and is associated with improved overall survival (OS). However, some patients still have poor outcomes after RT, and biomarkers are needed to stratify prognostic groups. High circulating growth hormone (GH) levels promote HCC proliferation and survival and are associated with aggressive disease. In this study, we evaluated whether pretreatment GH levels are associated with OS and progression-free survival (PFS) in patients who underwent RT for unresectable HCC. Methods and Materials: Patients undergoing RT for HCC during 2017-2023 were identified from a prospectively maintained database. Patients without GH levels measured within 8 weeks of RT were excluded. OS and PFS were compared between patients with high and low GH levels. Results: Thirty-four patients were included. Median age was 67 years, and 73.5% were men. Of the patients, 26.5% had high GH levels. Median follow-up was 10 (IQR, 4-25) months. The median PFS for the GH-low group was 7.9 months versus 3.9 months in the GH-high group ( Conclusions: In this hypothesis-generating exploratory analysis, high pretreatment GH levels were associated with worse survival outcomes in patients with unresectable HCC undergoing RT. Despite the retrospective design and limited cohort size, these findings provide biologically and clinically relevant preliminary evidence supporting GH as a potential prognostic biomarker. Validation in larger, prospective, multi-institutional cohorts is warranted, and any therapeutic implications related to targeting the GH/GH receptor axis should be considered exploratory.