2572 - The First Carbon Ion Radiotherapy Center in America: Relative Biological Effectiveness Modeling and Clinical Dose Prescription System

Purpose/Objective(s):

Our institution is installing a multi-ion radiotherapy center, offering protons and, for the first time in America, carbon ions.

The biological effects after exposure to carbon ions differ substantially from those of photons and protons. The relative biological effectiveness (RBE) models implemented in Asian and European centers are calibrated to reproduce in vitro clonogenic survival of a reference cell line exposed to carbon ions and have limited accuracy for other cell lines, ions other than carbon, and different biological endpoints. Consequently, these models are currently being integrated with, or replaced by, updated versions.

We have developed a unified, fully predictive RBE framework to compute radiation-induced effects across ion types and biological endpoints. This presentation introduces the framework, its benchmarking, and a strategy to build upon clinical experience from established carbon ion centers.

Materials/Methods:

The predictive RBE framework integrates Monte Carlo simulations, microdosimetry, and first-of-its-kind parameter-determination strategies based on measurable cellular characteristics and tissue histology. The model was benchmarked against published RBE data using in vitro clonogenic survival and in vivo rat myelopathy as endpoints.

Additionally, we implemented a strategy to reproduce the results of the Japanese clinical dose prescription system used in most carbon ion centers. Specifically, the clinical dose was computed as the product of the RBE-weighted dose and a clinical scaling factor. Our implementation was compared to the Japanese system for different scenarios in water phantoms and clinical plans.

Results: Based solely on photon in vitro data, the model successfully predicted the in vitro survival of multiple cell lines after irradiation with ions from protons to uranium. Additionally, for the first time, our model predicted normal tissue complication probability (NTCP) curves for radiation-induced myelopathy in rats exposed to ions from protons to oxygen under various fractionation schemes.

Using appropriate model parameters and clinical normalization, our framework provided RBE results equivalent to those obtained with the Japanese clinical dose prescription system for carbon ions.

Conclusion: The proposed framework advances the state of the art in RBE modeling by overcoming the limitations of current models and offering unique predictive capabilities across different ions and biological endpoints, while ensuring consistency with established clinical practice for both proton and carbon ions. In the latter case, this allows us to build upon the extensive Japanese clinical experience with carbon ions for dose prescriptions and constraints.

Future studies are planned to exploit the model’s predictive nature to estimate proton and carbon ion clinical outcomes for tumor control and NTCP based on photon data.