Combined RBE and OER optimization in proton therapy with FLUKA based on EF5-PET

Helge Henjum; Tordis Johnsen Dahle; Andrea Mairani; Sara Pilskog; Camilla Stokkevåg; Camilla Grindeland Boer; Kathrine Røe Redalen; Heikki Minn; Eirik Malinen; Kristian Smeland Ytre-Hauge

doi:10.1002/acm2.14014

Combined RBE and OER optimization in proton therapy with FLUKA based on EF5-PET

J Appl Clin Med Phys. 2023 Sep;24(9):e14014. doi: 10.1002/acm2.14014. Epub 2023 May 10.

Authors

Helge Henjum¹, Tordis Johnsen Dahle^{1

2}, Andrea Mairani^{3

4}, Sara Pilskog^{1

2}, Camilla Stokkevåg^{1

2}, Camilla Grindeland Boer², Kathrine Røe Redalen⁵, Heikki Minn^{6

7}, Eirik Malinen^{8

9}, Kristian Smeland Ytre-Hauge¹

Affiliations

¹ Department of Physics and Technology, University of Bergen, Bergen, Norway.
² Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
³ Centro Nazionale di Adroterapia Oncologica (CNAO Foundation), Pavia, Italy.
⁴ Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.
⁵ Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
⁶ Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
⁷ Turku PET Centre, University of Turku, Turku, Finland.
⁸ Department of Physics, University of Oslo, Oslo, Norway.
⁹ Department of Medical Physics, Oslo University Hospital, Oslo, Norway.

Abstract

Introduction: Tumor hypoxia is associated with poor treatment outcome. Hypoxic regions are more radioresistant than well-oxygenated regions, as quantified by the oxygen enhancement ratio (OER). In optimization of proton therapy, including OER in addition to the relative biological effectiveness (RBE) could therefore be used to adapt to patient-specific radioresistance governed by intrinsic radiosensitivity and hypoxia.

Methods: A combined RBE and OER weighted dose (ROWD) calculation method was implemented in a FLUKA Monte Carlo (MC) based treatment planning tool. The method is based on the linear quadratic model, with α and β parameters as a function of the OER, and therefore a function of the linear energy transfer (LET) and partial oxygen pressure (pO₂ ). Proton therapy plans for two head and neck cancer (HNC) patients were optimized with pO₂ estimated from [¹⁸ F]-EF5 positron emission tomography (PET) images. For the ROWD calculations, an RBE of 1.1 (RBE_1.1,OER ) and two variable RBE models, Rørvik (ROR) and McNamara (MCN), were used, alongside a reference plan without incorporation of OER (RBE_1.1 ).

Results: For the HNC patients, treatment plans in line with the prescription dose and with acceptable target ROWD could be generated with the established tool. The physical dose was the main factor modulated in the ROWD. The impact of incorporating OER during optimization of HNC patients was demonstrated by the substantial difference found between ROWD and physical dose in the hypoxic tumor region. The largest physical dose differences between the ROWD optimized plans and the reference plan was 12.2 Gy.

Conclusion: The FLUKA MC based tool was able to optimize proton treatment plans taking the tumor pO₂ distribution from hypoxia PET images into account. Independent of RBE-model, both elevated LET and physical dose were found in the hypoxic regions, which shows the potential to increase the tumor control compared to a conventional optimization approach.

Keywords: hypoxia; oxygen enhancement ratio; proton therapy; relative biological effectiveness.

MeSH terms

Head and Neck Neoplasms* / radiotherapy
Humans
Hypoxia / etiology
Oxygen
Positron-Emission Tomography
Proton Therapy* / methods
Radiotherapy Planning, Computer-Assisted / methods
Relative Biological Effectiveness

Substances

Oxygen

Abstract

MeSH terms

Substances

Grants and funding