To boost or not to boost : Improving quality of life after rectal cancer

For most patients with rectal cancer, treatment consists of surgical resection of the rectum, which is preceded by (chemo)radiotherapy depending on the disease stage. This treatment can have a negative effect on the quality of life of patients on the short and long term. Rectum-sparing techniques, i.e. a local excision or a non-operative approach with active surveillance strategy in patients with a complete response to (chemo)radiotherapy, may have better effects of patients’ quality of life. The first part of this thesis describes the effects of the operative treatment for rectal cancer on patient-reported outcomes such as functioning, symptoms and work ability during the first two years after diagnosis. The impact of different radiotherapy schedules (short course versus chemoradiation) and surgical procedures (with or without permanent stoma) are evaluated. Also, the difference in quality of life between older and younger patients with rectal cancer is investigated including the effect of postoperative complications on functioning domains. Furthermore, preferences of patients and volunteers (without rectal cancer) for different treatment scenarios for rectal cancer are discussed. The second part of this thesis focuses on the role of radiotherapy in rectal cancer treatment. The chapters mainly focus on how this treatment can be optimised to render more rectal cancer patients eligible for rectum-sparing treatment options. Also, a model was developed and validated with the aim to predict (near)complete tumour response preoperatively based on MRI scans before and after chemoradiation. In one of the chapters, the results of a randomised controlled trial are evaluated in which the effect of an additional radiation dose (a boost) to the tumour prior to chemoradiotherapy on complete tumour response is investigated in comparison with standard chemoradiation. Lastly, the trial was evaluated regarding the study design, i.e. trials within cohorts-design, including patient recruitment and generalisability. The most important conclusions of this thesis are that quality of life and workability are substantially deteriorated during and shortly after treatment. And although they improve, many domains and symptoms are still worse than in the general population at two years after diagnosis. A boost prior to chemoradiation does not increase the chance of a complete tumour response in the setting of planned surgery. Innovations in radiotherapy treatment, novel boost approaches and better patient selection are warranted