HyperSightTM-CBCT based monitoring of sarcopenia during definitive radiotherapy of prostate cancer: a longitudinal feasibility study

Clinical Snapshot

Key Findings

• P Value: p = 0.021 for CSA decline in NF/MHF cohort

• Effect Size: NF/MHF cohort: -153.0 mm² decline (FF-LF)

• Primary Outcome: Cross-sectional muscle area decline during radiotherapy

• Nnt Or Sensitivity: CSA loss >5% associated with acute GU toxicity (OR 4.90, 95% CI not specified)

• Confidence Interval: Not specified for primary outcome

Clinical Application

Requires HyperSight™ CBCT technology and trained personnel for muscle assessment Limited immediate applicability due to novel technology requirements; may inform future TGA-approved imaging protocols for sarcopenia monitoring in Australian cancer centres Prostate cancer patients receiving definitive radiotherapy, particularly those on longer fractionation schedules

Abstract

BACKGROUND: Sarcopenia and treatment-related muscle loss are associated with increased toxicity and reduced resilience in cancer patients. HyperSight™ cone-beam CT (CBCT) provides improved soft-tissue contrast compared with conventional CBCT and may enable reliable longitudinal skeletal-muscle monitoring during image-guided radiotherapy (IGRT). This study evaluated the feasibility of HyperSight™ CBCT-based muscle assessment in prostate cancer patients and explored the clinical relevance of intratreatment muscle decline. METHODS: Eighty-eight patients with non-metastatic prostate cancer were treated on an Ethos® system with HyperSight™ CBCT. Patients received ultrahypofractionated (UHF) or normo-/moderately hypofractionated (NF/MHF) radiotherapy; 28% received androgen-deprivation therapy. Cross-sectional muscle area (CSA) and radiodensity (HU) were assessed on planning CT (PCT) and serial CBCTs (first, second, last fraction [FF, SF, LF]); HU values were z-standardized to subcutaneous fat (zHU). Agreement between PCT and CBCT was evaluated using concordance correlation coefficients (CCC), regression, and Bland-Altman analysis. Longitudinal changes were analyzed using mixed-effects models, and associations with acute genitourinary/gastrointestinal (GU/GI) toxicity (RTOG ≥ 2) using regression models. RESULTS: HyperSight™ CBCT showed excellent agreement with PCT for CSA (CCC = 0.981). The NF/MHF cohort showed a significant longitudinal CSA decline (FF-LF: -153.0 mm², p = 0.021), whereas no significant within-cohort change was observed in UHF. Muscle density (zHU) decreased significantly in both cohorts (NF/MHF: p < 0.001; UHF: p = 0.0017). Weight loss and age were independently associated with zHU change, while no independent predictors of CSA decline were identified. In the NF/MHF cohort, CSA loss > 5% was associated with acute GU toxicity in univariate analysis (OR 4.90, p = 0.033; Fisher's exact p = 0.014), but not after adjustment for age, weight loss, ECOG performance status, and ADT; no associations were found for GI toxicity or in the UHF cohort. CONCLUSIONS: HyperSight™ CBCT enables quantitative skeletal-muscle assessment during prostate radiotherapy and detects intratreatment reductions in muscle density, which may represent an early imaging marker of muscle decline. Muscle loss showed an exploratory association with acute GU toxicity in NF/MHF patients in univariate analysis, but not after adjustment. These findings support the feasibility of CBCT-based muscle monitoring and warrant further evaluation in larger cohorts. CLINICAL TRIAL NUMBER: Not applicable.

References

1. 1.Siefert, V., Bettenhausen, J. V., Bicu, A. S., Schmidt, R., Willam, M., Eckl, M., Stieler, F., Ehmann, M., Buergy, D., Fleckenstein, J., Beuthien-Baumann, B., Schlemmer, H. P., Froelich, M. F., Schoenberg, S. O., Giordano, F. A., Boda-Heggemann, J., & Dreher, C. (2026). HyperSightTM-CBCT based monitoring of sarcopenia during definitive radiotherapy of prostate cancer: a longitudinal feasibility study. Radiation Oncology, Article 99920-x. https://doi.org/10.1038/s41598-025-99920-x