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Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.

Head and neck cancer (HNC) is a group of malignant tumours located in the mucosa of the upper aero-digestive tract. The location of the tumour, close to several critical organs, can often result in great suffering for the patient both due to the tumour itself but also the treatment can be associated with side effects impairing quality of life. The prognosis in HNC varies greatly by primary tumour site and tumour stage at presentation, but as a group approximately two thirds of patients will still be alive 5 years after diagnosis. The predominant pattern of failure is local recurrence, and this thesis addresses this problem with a focus on 1) how to treat recurrent head and neck cancer with re-irradiation, and 2) achieving improved local control at first diagnosis by dose-escalated radiotherapy. In Paper I we investigated the overlapping volumes in re-irradiation for HNC. We found that that there is a lack of consensus regarding the definition of re-irradiation in HNC and in this study, we used a more strict definition than in previously published material and propose that future studies on re-irradiation should do the same, making it possible to compare results from different studies. We also found that severe acute side effects were more common in patients who received a cumulative dose of ≥100 Gy in the overlapping volume. In Paper II we investigated the association between cumulative doses to organs at risk and serious late side effects in re-irradiation for HNC. We found an association between the dose to the carotid arteries and the risk of developing carotid blowout syndrome, and similarly, between the dose to bone and osteoradionecrosis. Our results support the existing proposed dose constraint for the carotid arteries of a cumulative dose of 120 Gy. In Paper III we investigated two different modalities of achieving radiation dose escalation of the primary tumour in oropharyngeal cancer, simultaneous integrated boost (SIB) and brachytherapy boost. In our anal