Health related quality of life and swallowing problems in oesophageal cancer

Sammanfattning: Poor overall survival, swallowing problems and severe side-effects from multi-modality treatment characterize the situation of patients with oesophageal and gastro oesophageal junction carcinoma (GOJ). With the poor prognosis and abundance of symptoms in this disease it is particularly important to consider health-related quality of life (HRQoL) as an important outcome in clinical decision-making. Several trials have addressed outcomes regarding oncological therapies and surgery, though patient-reported outcomes (PRO) are to a large extent lacking in trials on oesophageal cancer patients. This thesis addresses and aims to shed light on PRO and HRQoL with a special reference to swallowing problems (dysphagia) during and after neoadjuvant treatment and after surgery in oesophageal and GOJ carcinoma. Also, an aim is to report HRQoL collected one year after diagnosis in a Swedish population-based register. The current main curative intent treatment regime used for oesophageal cancer is multimodal, including neoadjuvant oncological treatment and surgery. Due to a scarcity of research it is still unknown whether the addition of radiotherapy to neoadjuvant chemotherapy affects HRQoL and swallowing problems. In Sweden and Norway, a multi-centre randomised controlled trial compared neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) prior to surgery, acronymed NeoRes, and PRO using HRQoL instruments was and endpoint in the trial. At diagnosis, the vast majority of the patients were in the palliative stage. Thus, adding knowledge of HRQoL outcomes in these settings is also very important. Paper I describes HRQoL outcomes collected in a nationwide Swedish population-based register twelve months after diagnosis. The outcomes were compared with a Swedish reference population and suggests that at one year after diagnosis of oesophageal cancer, subjects suffer with regard to most of the HRQoL aspects measured compared to the reference population, and particularly in the case of a palliative treatment intent. In addition, high levels of anxiety were reported in all subgroups and problems with swallowing were increased among those who received a palliative diagnosis and in those who were treated with definitive chemoradiotherapy. This study is important in order to increase knowledge of HRQoL outcomes in an unselected, a nation-wide population-based cohort. Paper II, addresses patients treated with neoadjuvant therapy, at the Karolinska University Hospital. These patients were assessed regarding dysphagia prior to any treatment, after the first cycle of chemotherapy and after completion of neoadjuvant therapy, prior to surgery. Patients reported dysphagia relief as already after the first cycle of chemotherapy, and after completed neoadjuvant therapy. This study is important for clinical decision-making at diagnosis of oesophageal cancer, suggesting that stents or gastrostomies may not be needed during neoadjuvant treatment, before surgery. Paper III addresses patient-reported dysphagia in the NeoRes trial. The data were collected before any treatment and after the conclusion of neoadjuvant therapy. In addition, we investigated whether dysphagia was correlated to histological response. This study confirmed the results of paper II, with an improved ability to eat solid food in both groups, although radiotherapy may also add side-effects that contribute to swallowing-problems. However, no correlation was detected between dysphagia response and histological response. Paper IV investigated the HRQoL outcome in the NeoRes trial, measured prior to treatment, after ended neoadjuvant treatment and one, three and five years after surgery. In comparisons between groups, differences were reported by patients regarding odynophagia after the termination of neoadjuvant therapy and coughing at three-year follow-up, both these symptoms was worse in patients treated with nCRT, compared to those receiving nCT. In addition, changes within groups in comparison with baseline were analysed. One finding is that regarding oesophageal-specific symptoms patients reported improvement to some extent. Conversely, functions and known treatment-related side-effects worsened after neoadjuvant therapy in both groups. In cnclusion, patients reported significantly more severe symptoms and decreased functions after the termination of neoadjuvant treatment, and at three- and five-years follow-up, when radiotherapy was added.