Treatment results of intensity-modulated radiotherapy for head and neck cancer

Intensity-modulated radiotherapy (IMRT) combined with concomitant chemosensitisation is the standard treatment of locally advanced head and neck squamous cell carcinoma. Despite providing improved disease control rates compared with radiotherapy alone, it is associated with substantial toxicity that can impair patients’ quality of life. With a decreased incidence of smoking- and alcohol-related carcinomas of the head and neck and an increased incidence of human papillomavirus-associated oropharyngeal carcinomas, more and more patients will survive the disease, thus having to cope with the long-term toxicities related to treatments. This stresses the importance of understanding the mechanisms behind radiotherapy-related toxicities and focusing on improving patients’ quality of life. Aims of the study The first study of this thesis focused on assessing the local control and survival and patterns of relapse following definitive concurrent chemo-IMRT for head and neck squamous cell carcinoma. The second study aimed at assessing the quality of life of patients treated with definitive IMRT for head and neck carcinoma during the first 12 months after initiation of the treatments, using the generic 15D instrument. The third study focused on evaluation of the salivary gland function of head and neck cancer patients treated with IMRT during and after the treatments with diffusion-weighted magnetic resonance imaging. Materials and methods The studies included in this thesis consisted of a total of 167 patients treated with IMRT for head and neck cancer at Helsinki University Hospital between 2000-2013. Study I was a retrospective analysis including 83 patients, Studies II-III were prospective analyses including 64 and 20 patients, respectively. Clinical and tumour-related factors were collected from hospital registries. Health-related quality of life (HRQoL) in Study II was assessed with the generic 15D instrument before and at 3, 6, and 12 months after the initiation of the radiotherapy course. In Study III, salivary gland function was assessed with diffusion-weighted magnetic resonance imaging and salivary gland scintigraphy prior to and at a mean of six months after completing the treatment. Results Definitive IMRT combined with concomitant weekly cisplatin resulted in excellent disease-control and survival rates. In Study I, the 2-year local control, overall survival, and disease-specific survival rates were 84%, 82%, and 89%, respectively. The corresponding 5-year Kaplan-Meier estimates were 79%, 69%, and 76%. In Study II, a significant decrease in overall HRQoL was seen during the first 3 months after the treatment onset. At 6 and 12 months, gradual recovery was seen. Dimensions reflecting mental well-being showed gradual improvement throughout the follow-up but remained decreased compared with the general population. The mean HRQoL was lower among patients with pharyngeal carcinoma compared with other primary sites. In Study III, apparent diffusion coefficient (ADC) measured with diffusion-weighted MRI increased as a function of RT dose absorbed by the salivary glands. A moderate statistical correlation between ADC-values of non-stimulated salivary glands and ejection fraction measured with salivary gland scintigraphy was found. Conclusions Definitive IMRT with concomitant weekly cisplatin provides excellent locoregional disease control in the treatment of patients with locoregionally advanced HNSCC. Health-related quality of life declined during the first 3 months after the treatment onset but gradually improved during the 12-month follow-up. The 15D instrument is feasible for evaluation of health-related quality of life of head and neck cancer patients treated with IMRT and seems to detect differences among different patient groups. Changes in ADC at 6 months after the treatment correlates with the RT dose absorbed by the major salivary glands as well as ejection fraction measured with salivary gland scintigraphy. Diffusion-weighted magnetic resonance imaging is a promising tool for detection of RT-induced salivary gland damage.