2674 - A Translational Finite Element-Based Biomarker Framework for the Quantitative Assessment of Chronic Radiation-Induced Rectal Injury
Presenter(s)
J. Zhang1, Y. Deng1, X. Jin1, X. Ma2, F. Xia1, and Z. Zhang3; 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 2Fudan University Shanghai Cancer Center, Shanghai, China, 3Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Shanghai Clinical Research Center for Radiation Oncology; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
Purpose/Objective(s): Chronic radiation-induced rectal injury (RRI) remains a clinically meaningful toxicity after pelvic radiotherapy. Current CTCAE-based grading is symptom-driven, subjective, and often discordant with underlying tissue injury, limiting objective phenotyping and prospective biomarker development. We sought to establish a quantitative framework that can be translated to a patient-side assessment. We hypothesized that chronic radiation injury induces reproducible alterations in rectal wall biomechanics that can be quantified using finite element (FE)–based inverse modeling.
Materials/Methods: Male Sprague–Dawley rats received single-fraction pelvic irradiation (0, 12, 20, or 28 Gy) and were evaluated 3–4 months post-irradiation to model graded chronic RRI. Injury severity was independently validated using general condition monitoring, pelvic MRI, gross pathology, and histopathologic scoring. We developed an in vivo rectal balloon distension manometry platform to acquire pressure–volume curves during controlled inflation. Rectal wall mechanics were modeled using a three-parameter Yeoh constitutive model. FE-based inverse modeling identified material parameters (c10, c20, c30) by minimizing error between simulated and measured pressure–volume curves. Associations between FE-derived parameters and histopathologic scores were assessed and compared with conventional manometric metrics (absolute pressure P and pressure change ?P).
Results: Across MRI, gross pathology, and histopathology, chronic RRI demonstrated clear dose-dependent progression. Twenty-six pressure–volume datasets were successfully fitted with strong agreement between FE simulations and experimental measurements. FE-derived biomarkers showed robust correlations with histopathologic severity, including c10 (r = 0.7223, P < 0.0001) and MAX (c10, c20) (r = 0.7334, P < 0.0001). These associations substantially exceeded those observed using conventional manometric metrics (P and ?P), supporting improved sensitivity for quantifying structural injury.
Conclusion: We present a translational pipeline linking clinically feasible inputs—rectal balloon distension testing and pelvic imaging—to mechanistically interpretable rectal wall material biomarkers via FE-based inverse modeling. Compared with CTCAE-relevant functional measures, FE-derived parameters more accurately reflected histopathologic injury severity. With further validation, this framework may support routine post-radiotherapy surveillance, enable earlier detection of subclinical injury, and potentially enable risk-adaptive management strategies in pelvic radiotherapy.