Radiotherapy in advanced head and neck cancer

Abstract: 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 analyses we found no differences in survival or serious side effects comparing the two different boost modalities, suggesting that the two treatment options are equal in these respects. In Paper IV we investigated a cohort of 215 patients who had received dose-escalated radiotherapy for oropharyngeal cancer and a matched cohort of 215 patients who had received standard dose radiotherapy to compare survival outcome and serious side effects. We found no predictive factors to guide selection patients for dose-escalated radiotherapy. However, the remarkably good overall survival in the dose-escalated cohort, despite an overrepresentation of advanced T-stage tumours, encourages further attempts to identify such factors. We also found that osteoradionecrosis and dysphagia were more common after treatment with dose-escalated radiotherapy compared to standard dose radiotherapy.