Exercise, concomitant to therapy, has a positive influence on therapy-induced side-effects in patients with haematological malignancies
Keywords: cancer, supportive care, sport-therapy, haematological malignancies, neuropathy
Exercise interventions as a supportive measure in cancer therapy are becoming more and more relevant. With cancer therapy becoming more complex and effective, higher survival rates as well as longer life-spans are being achieved. Consequently, patients’ quality of life is becoming increasingly important and the management of therapy-related side-effects therefore essential. An increasing amount of studies are demonstrating, that the previously propagated rest and immobility during cancer therapy is not only counterproductive but that exercise interventions hold enormous potential regarding the management of side-effects in supportive cancer care and should therefore be taken more seriously. Especially haemato-oncological patients have to cope with many debilitating side-effects due to the disease itself, the long and complex medical therapy as well as the associated immobility. The symptoms cause physiological, psychological and social restraints, leading to acute as well as lasting reductions in patients’ quality of life. Poor health and severe side-effects such as chemotherapy-induced peripheral neuropathy (CIPN) are highly relevant, as they can cause dose reductions, disruptions or discontinuation of medical therapy, consequently impacting the clinical outcome. Although the positive effects of exercise interventions are rather well documented in entities such as breast cancer, the amount of research in haematological patients, especially concomitant to therapy, is still relatively low. For instance only one previous randomized, controlled trial (RCT)1 has evaluated lymphoma patients. Furthermore, the potential role of exercise regarding CIPN has never been investigated previously, although it is highly prevalent in haemato-oncological patients. Previous studies on patients with neuropathies of similar pathophysiology as CIPN, showed improved parameters after balance exercises, whole body vibration or Tai Chi. This effect has not been investigated in oncological patients. The primary aim of this work was to improve patients quality of life, therefore investigating whether exercise interventions are feasible for patients with haemato-oncological malignancies, during all phases of therapy and whether it is furthermore possible to reduce immobility and attenuate or possibly even prevent debilitating side-effects such as reduced physical performance, muscle atrophy, loss of balance control, absent reflexes, pain or CIPN. This has been approached within a cumulative dissertation. Three studies form the main part of this thesis (the full text articles can be found in the appendix), while the introduction aims to give a better insight into the research issue and current state of the art. In a large randomized, controlled trial (RCT), the effects of exercise (endurance-, strength- and sensorimotor training) on quality of life and therapy-related side-effects were evaluated in lymphoma patients (N=61) undergoing therapy. Patients in the intervention group trained twice a week for 36 weeks, while the control group had no intervention. Intergroup comparisons revealed a significant improvement in quality of life, static and dynamic balance control, aerobic performance level, level of activity as well as CIPN related symptoms, in the intervention group. The exercise intervention, especially sensorimotor training, proved to be a feasible and promising method to support lymphoma patients during therapy. In order to assess the previous findings appropriately, two reviews were conducted/composed analyzing the various exercise interventions, especially regarding the side-effects of CIPN. To evaluate the efficacy, safety and feasibility of aerobic exercise interventions for patients with haematological malignancies, a meta-analysis was conducted. RCTs that investigated the effects of aerobic endurance training alone or in combination with resistance training in patients with haematological malignancies, were included. The search identified nine relevant RCTs. Analysis revealed that the above mentioned exercise interventions can improve quality of life, especially physical functioning, depression and fatigue. Currently, there is inconclusive evidence regarding anxiety, physical performance and adverse events. As the RCT within this work was the first to show beneficial effects of an exercise intervention on symptoms of CIPN and further references are lacking, a systematic review was conducted in order to better understand the effects and underlying mechanisms of various exercise interventions on sensory and motor symptoms of peripheral neuropathy (PNP) in general. The search revealed 18 exercise intervention studies on patients with PNP. Evidence and study quality is highest (11 studies) for diabetic neuropathy (DPN). In addition to the RCT within this work on CIPN, further 6 studies investigated patient groups with neuropathies of heterogeneous origin. Current data suggests that specific exercise interventions are feasible, safe and promising for patients with neuropathies. Analysis revealed that balance exercises target the relevant symptoms of PNP best in neuropathies with similar pathophysiology as CIPN. Studies focusing exclusively on strength, or a combination of endurance and strength, appear to have a lower impact. For primarily metabolic-induced neuropathies such as DPN, endurance training additionally has the potential to prevent the onset and reduce the progression of PNP. To summarize, it could be shown that sensorimotor training is a relevant exercise intervention for therapy of haemato-oncological patients. Additionally, effects on sensory as well as motor symptoms of CIPN could be achieved for the first time, opening a promising new field for research and exercise therapy, even enabling preliminary recommendations for the translation into practice. Nevertheless, further studies are necessary to enable researchers to better understand possible structures and underlying mechanisms with the intention to improve supportive care for cancer patients.