Reducing toxicity in proton therapy through biological optimization

Bioproton aims to bring proton therapy treatment planning forward with the ambition to reduce the risk of treatment related toxicity for cancer patients.

Proton therapy has been established internationally as an important radiotherapy modality and two facilities are planned to open in Norway within four years. The main benefit of protons is the superior dose distribution compared to conventional radiotherapy: A high radiation dose can be delivered to the tumor while minimal dose is deposited distal to the tumor volume since the proton beam stops in the tumor. However, proton therapy has an increased biological effect compared to photon therapy, i.e. protons produce more damage than photons for the same physical dose. A simplistic dose scaling factor, RBE (relative biological effectiveness), of 1.1 is today used clinically, although in vitro, in vivo and recent clinical data show that the RBE effect can be significantly higher and therefore lead to unforeseen toxicity.

Our objective is to reduce the risk of toxicity in cancer patients through development, validation and application of a novel biological optimization system for proton therapy, including the different RBE dependencies in the treatment planning process.

Clinical use of biological optimization is hindered by uncertainties regarding translation of preclinical results to the clinic, but recent in vivo and clinical data on the proton RBE opens the way to bring RBE modelling forward. We therefore aim to reach our objectives through: i) Using recent clinical and in vivo data to improve and validate in vitro based RBE models for proton therapy. Since recent data demonstrate particularly strong clinical evidence for enhanced RBE in normal brain tissue, we will also focus especially on validating RBE models for application in the treatment of brain tumors. ii) Develop a complete Monte Carlo based computational system for biological optimization, and iii) Apply biological optimization in silico to quantify the potential reduction in risk of toxicity, and identify patient groups eligible for clinical trials with biological optimization.

Project leader

Kristian Smeland Ytre-Hauge University of Bergen.

Project partners

Camilla H. Stokkevåg – Haukeland University Hospital
Armin Lühr – TU Dortmund University
Rune Sylvarnes – University Hospital of North Norway
Andrea Mairani – Heidelberg ion-beam therapy center
Ilker Meric – Western Norway University of Applied Sciences
Eirik Malinen – University of Oslo
Marianne Brydøy – Haukeland University Hospital
Eivind Rørvik – Oslo University Hospital
Kathrine R. Redalen – Norwegian University of Science and Technology

Project period: 2021 – 2025.
Financed by the Research Council of Norway.