Nutritional interventions as a means to reduce chemotherapy-induced toxicity in paediatric cancer patients

Abstract

Every year about 600 children are diagnosed with cancer in the Netherlands. The different forms of cancer can be divided into three main subtypes: haematological, solid or neurological tumours. Different treatment modalities are available, including surgical resection of the tumour, radiotherapy, immunotherapy and/or chemotherapy. Unfortunately, treatment itself can lead to short- or long-term side effects, which can last for a long time or even throughout the entire life. Prevention of these unwanted effects caused by therapy is preferable, so patients will suffer less from intense treatment trajectories. In this thesis, the way by which nutritional interventions can potentially lower the side effects, mainly of chemotherapy. Nutritional interventions encompass temporary changes in diet, e.g. fasting or dietary restriction, where caloric intake is lowered entirely or partially. Research in the aging field has shown that nutritional interventions can slow down aging through activation of the ‘survival’ response. This response leads to changes in metabolism where energy (derived from nutrition) is spent less on growth and proliferation, but invested in maintenance processes, such as DNA damage repair, stress signalling and antioxidant systems. Side effects of chemotherapy to the healthy tissues are (partially) caused by damage to the DNA. The damage to the DNA and subsequent development of side effects, could potentially be prevented or better repaired through activation of the ‘survival’ response. The thesis begins with a general introduction, followed by chapter 2 which describes the most commonly used chemotherapies and its most common side effects. Chapter 3 includes an overview of nutritional interventions that can be used alongside cancer treatment schedules, how to implement these interventions alongside treatment schedules and literature describing the results of clinical trials looking at the effects of nutritional interventions alongside cancer treatment in adult patients. In chapter 4 the effects of a culture medium mimicking nutritional interventions are described. Non-transformed cells appeared protected from the damaging effects of multiple chemotherapies. Chapters 5 and 6 describe the results of studies in young wildtype mice that have fasted before being treated with chemotherapy or radiotherapy. These mice appear to be protected against multiple side effects of anti-cancer treatment, including decreased appetite, body weight loss and, specifically for cisplatin, damage to the kidneys and liver. In chapter 7 and 8 study protocols of clinical trials are given for implementation of fasting in Wilms tumour patients and adult kidney donors, respectively. Both studies take place in a surgical setting, where one of the patient’s kidneys is resected. Aim of the studies is to assess the feasibility and potential enhanced recovery due to fasting. The thesis concludes with a general discussion.