Research in radiotherapy and particle therapy

Radiotherapy is a modality to treat cancer with ionizing radiation. Particle therapy uses charged particles to reduce the radiation dose given to healthy tissue: it will be available in Norway from 2024. Haukeland University Hospital has ongoing research on biological response to radiotherapy and development and testing of new treatment strategies for improving future cancer therapy.

Radiotherapy is an important modality for treating cancer, either alone or in combination with other modalities such as surgery, chemotherapy and immunotherapy. It works by damaging the DNA of cancer cells directly or indirectly, causing the cancer cells to die or stop them from dividing. Radiotherapy can also influence our immune system, but the mechanisms behind this interaction are largely unknown.

We are developing improved strategies for combating cancer with radiotherapy and particle therapy.

Ionizing radiation inevitably also kills healthy tissue surrounding the tumor. Healthy tissue has an increased repair capacity compared to tumorous tissue that we exploit in radiotherapy by treatment delivery in fractions over several weeks. Precision is crucial in external beam radiotherapy. This is because we focus radiation into the tumor by sending beams through the body from several directions. Image-guidance ensures that the radiation actually hits the tumor. Increased precision spares the surrounding healthy tissue, and enables treatment with higher doses and fewer fractions without an unacceptable risk of adverse effects.

The biological response to radiation can vary a lot from tumor to tumor and within a single tumor. For instance, parts of the tumor with reduced access to oxygen can be resistant to radiation (oxygen is a mediator for indirect damage on DNA). Tissue and blood samples as well as functional imaging (e.g. MR and PET) can provide valuable information about the tumor biology, enabling us to deliver a more personalized radiation treatment.

Particle therapy differs from conventional radiotherapy with photons by interacting in a more delimited area in the patient, thus damaging DNA more efficiently. Particle therapy gives less radiation to the surrounding healthy tissue, thereby reducing the risk of adverse effects such as organ damage or secondary cancers. However, we need more knowledge on the biological effects of particle therapy and on how to better clinically exploit the improved precision and biological effect.

About the initiative

The project Establishing a framework for interdisciplinary clinical particle therapy research at Haukeland University Hospital was established in 2018 with generous support from Trond Mohn Foundation, Norwegian Cancer Society, Helse Vest RHF, Haukeland University Hospital (HUH) and the University of Bergen (UoB).

The motivation behind this project was to join the forces and competence of clinicians and researchers to improve cancer care, in the context of the introduction of particle therapy in Bergen from 2024. It was our belief that high quality clinical research in radiotherapy and particle therapy would demand a framework with well-functioning interdisciplinary teams of researchers and clinical staff, scientific support to aid implementation of advanced methods and clinical translation, high quality data as well as international collaboration. These values have therefore been prioritized in both budget and activities in addition to carrying out the outlined research. Currently more than ten researchers in addition to clinical staff are daily involved in the project. Furthermore, a key role of this project has been supporting and collaborating with the other ongoing research projects in particle therapy in Bergen (i.e. at HUH, the UoB and Western Norway University of Applied Science (HVL)).

The long-term aim of the common research activities is to develop and implement technology, models and strategies to offer improved treatment with modern photon and particle therapy. This will allow for increased tumor control and/or reduced probability of normal tissue complications.

Specifically, we will:

Perform comparative planning studies of photon and particle therapy along with predictive risk models for selected tumor sites to be used for defining clinical protocols.
Develop and improve biological dose-response models for pelvic irradiation and establish constraints for normal tissue complications for photon, proton and carbon ion therapy.
Expand the spectrum of suitable indications for particle therapy delivery by developing technology and strategies for image-guidance and adaptive therapy.
Develop models to predict for patient-specific internal organ motion in the pelvis and head and neck for use in optimization of particle therapy delivery.
Improve planning of particle therapy by quantitative use of functional imaging to re-distribute dose and LET within the tumor to maximize tumour control.

WP1: Clinical data collection and comparative planning

In WP1 we have ongoing studies collecting clinical and image data, respectively, for head and neck and lung cancer patients. We are also performing comparative planning of photon and proton therapy for children, head and neck, prostate and lung cancer patients.

WP2: Integration of functional imaging in particle therapy planning

In WP2, we have explored two different methods for quantifying hypoxia from functional images and using this information in shaping the target dose distribution with proton and photon radiotherapy.

WP3: Organ motion modelling

In WP3, we are developing a statistical motion model for pelvic organs and furthermore we are investigating the impact of interplay on dose delivery in treatment of lung cancer with scanning beam particles.

WP4: Image guidance and adaptation in particle therapy

In WP4 we have an ongoing study with an adaptive protocol for lung cancer. In addition, we are investigating methods and technology to reduce uncertainties related to estimation of proton stopping power for proton dose calculation and range uncertainties in collaboration with the University of Bergen and Western Norway University of Applied Science.

WP5: Dose-response modelling

In WP5 we have explored the impact of the variable relative biological effectiveness (RBE) of proton therapy in children and head and neck cancer patients.

WP6: Clinical integration and research infrastructure

In WP6 we have developed various tools to aid the ongoing research activities.

Visiting address
Department of Oncology and medical physics
Parkbygget
Haukelandsveien 22
Haukeland University Hospital
N–5021 Bergen/Norway

Project leader

Liv Bolstad Hysing

Email: liv.bolstad.hysing@helse-bergen.no

Phone: +47 55 97 77 74

Project group:

Liv Bolstad Hysing (project leader), Sara Pilskog, Camilla Stokkevåg, Marianne Brydøy

Steering group:

Olav Mella (project responsible), Anfinn Mehus, Ása Karlsdottir, Helga Gripsgaard

Scientific support group (interal):