Introduction and outline 15 CHAPTER 1 Outline of the thesis In chapter 1 the typical features of LRRC are explained in comparison with locally advanced primary rectal cancer. The importance of achieving resection with clear margins is highlighted. Treatment options are discussed and the concept of total neoadjuvant treatment is introduced. In chapter 2 the concept of induction chemotherapy is investigated by comparing a cohort of LRRCpatientswhohave received inductionchemotherapybefore reirradiation to a cohort which only received preoperative reirradiation before surgery for their local recurrence. In chapter 3 the impact of introducing this treatment with induction chemotherapy in LRRC on clear resection margin rate and pathological response is further analysed. Lateral sidewall recurrences are notoriously difficult to treat due to their possible fixation to the muscular sidewall, iliac vessels and neuroplexus. Preliminary data on the effect of induction chemotherapy on resectability and downstaging in these cases are presented in chapter 4. Chapter 5 evaluates the impact of having hadmetastases in the past or havingmetastases at the time of LRRCdiagnosis, in comparison to LRRC patients who never hadmetastases. If response to neoadjuvant treatment becomes a treatment goal, evaluation of response is also necessary. In primary rectal cancer response evaluation has become important not only for surgical treatment planning, but also for selection of patients for organ preservation approach. The combination of endoscopy and MRI is a reliable to evaluate response in rectal cancer. The situation in LRRC is different as endoscopy is not always possible after prior abdominoperineal resection, and even if endoscopy would be possible, the bulk or complete local recurrence is not visible intraluminally. Imaging in LRRC becomes more important, but is hampered by postoperative changes and fibrosis. In chapter 6 mrTRG after induction chemotherapy and chemo(re)irradiation is correlated with final pathology. In chapter 7 the contribution of PET/CT in response evaluation after induction chemotherapy is analysed. Chapter 8 is the closing chapter with discussion of the findings and speculation on future perspectives. A short summary of all chapters is also provided in chapter 8.