Josephine Ståhl Kornerup

A thesis submitted November 30, 2015 for the degree of Doctor of Philosophy and defended January 20, 2016.

The PhD School of Science
Faculty of Science
Niels Bohr Institute, X-ray and Neutron Science, University of Copenhagen

Per Munck af Rosenschöld
Thomas Björk-Eriksson
Patrik Brodin
Annika Loft


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Paediatric photon and proton radiotherapy treatment planning based on advanced imaging

The overall cure-rates for young cancer patients are continuously increasing and about 80% of the children diagnosed with cancer today will survive for more than five years. However, the cancer treatment, usually a combination of surgery, radiotherapy and chemotherapy, is aggressive. Apart from affecting the cancer cells, the treatment regimen often leads to undesired damage in healthy tissue and these treatment-induced side effects may impair the function of vital organs. The severity of the injury can range from potentially lethal to being rather easily managed with regular follow-up and medication, and may have a considerable impact on the quality of life of the childhood cancer survivor. The major challenge in modern paediatric cancer therapy is therefore to reduce the incidence of treatment-related toxicities, while maintaining or improving the high cure-rates.

In this thesis, we study radiotherapy treatment planning in combination with the nuclear medicine imaging technique positron emission tomography (PET). Specifically, we investigate the potential impact on the radiotherapy treatment plans of modern radiotherapy modalities for paediatric and adolescent cancer patients, when adding the diagnostic information from PET.

In PET imaging, the patient is administered a radioactive isotope intravenously, which adds to the diagnostic radiation dose burden of the patient. The application of PET for paediatric patients may therefore be regarded as controversial, considering the long expected overall survival of the patients and due to the increased risk of secondary cancers following the increased radiation dose. In this context, radiation oncology experts must critically assess whether the use of PET is of benefit to the patients. The low number of paediatric cancer patients and the considerable variation in risk factors affecting their survival makes systematic analysis of PET imaging on outcome data difficult. In this work, we attempt to evaluate how our use of PET imaging has affected the paediatric patients and their treatment, by estimating the increased risk of secondary cancer and simulating the radiotherapy treatment plans.

We found that PET scanning can be added to the diagnostic scans used for radiotherapy treatment planning, with only a small increase of the diagnostic radiation dose and thus without considerably affecting the life expectancy of young cancer patients. We also found that for a cohort of paediatric patients with various types of cancer diagnoses, adding PET to the radiotherapy treatment planning does not result in any general increase or decrease of target volume extent. Overall, adding PET does not affect the radiotherapy dose distribution to healthy organs or the capability of delivering adequate dose to the target volumes. For the studied group of patients, our results indicate that including PET in radiotherapy treatment planning and target volume delineation, will not systematically increase or decrease the longterm risks associated with radiotherapy.

We investigated the theoretical radiotherapy treatment plans for young patients with head and neck cancer, had their plans been generated without PET imaging. The results show that plans generated for target volumes delineated without PET may result in inadequate target coverage of target volumes delineated with PET. Thus, if target volumes delineated with PET more accurately encompass cancer cells and tumour growth, omitting PET from target volume delineation and radiotherapy treatment planning may lead to severe under dosage of malignant tissue. This could potentially compromise the treatment results.

For the same group of patients, we found that although radiotherapy with protons instead of photons may provide several benefits in terms of reduced irradiated volumes of healthy tissue and lower doses to organs near the tumour, these benefits cannot be taken for granted. If proton therapy requires slightly larger safety margins between tumour and radiation field in order to ensure proper target volume dose coverage and the same clinical accuracy as photon radiotherapy, the normal tissue dose-sparing benefits of proton radiotherapy may to some extent be lost.

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