J Cancer Surviv DOI 10.1007/s11764-015-0427-1
Chemotherapy-induced peripheral neuropathy, physical activity and health-related quality of life among colorectal cancer survivors from the PROFILES registry Floortje Mols & Antoinetta J. M. Beijers & Gerard Vreugdenhil & Anna Verhulst & Goof Schep & Olga Husson
Received: 22 August 2014 / Accepted: 12 January 2015 # Springer Science+Business Media New York 2015
Abstract Purpose To gain insight into the association of physical activity (PA), chemotherapy-induced peripheral neuropathy (CIPN) and health-related quality of life among colorectal cancer survivors, up to 11 years after diagnosis. Methods Data of the second data wave of a Dutch prospective population-based survey among colorectal cancer survivors diagnosed between 2000 and 2009 as registered by the Eindhoven Cancer Registry was used. Eighty-three percent (n=1648) of patients filled out the EORTC QLQ-C30 and the EORTC QLQ-CIPN20 of which 506 patients (31 %) were treated with chemotherapy.
F. Mols (*) : O. Husson CoRPS-Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, PO Box 90153, 5000 LE, Tilburg, The Netherlands e-mail:
[email protected] F. Mols Comprehensive Cancer Centre The Netherlands, Eindhoven Cancer Registry, Eindhoven, The Netherlands A. J. M. Beijers : G. Vreugdenhil Department of Internal Medicine, Maxima Medical Centre, Veldhoven, The Netherlands G. Vreugdenhil Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands A. Verhulst Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands G. Schep Department of Sports Medicine, Maxima Medical Center, Veldhoven, The Netherlands
Results Treatment with chemotherapy was associated with a higher percentage of patients reporting CIPN symptoms regardless of PA. Furthermore, not meeting the Dutch PA guideline of 150 min of moderate to vigorous PA a week was associated with more CIPN among patients treated with chemotherapy. Also patients not treated with chemotherapy reported CIPN-like symptoms, especially when not meeting the PA guideline. Statistically significant and clinically relevant worse scores on almost all EORTC QLQ-C30 subscales were reported by those not meeting the PA guideline compared to those who did meet the guideline, regardless of CIPN symptoms. However, these differences were more pronounced in the group with many CIPN symptoms (e.g. upper 30 %). Implications for Cancer Survivors Alertness among health care professionals and patients for the importance of PA is warranted, as meeting the PA guideline was associated with less CIPN-like symptoms and a higher health-related quality of life regardless of treatment with chemotherapy. Keywords Cancer . Chemotherapy . Chemotherapy-induced peripheral neuropathy . Physical activity . Health-related quality of life
Introduction Due to the increasing prevalence of colorectal cancer, which is currently the third most common cause of cancer among men and women [1], more patients are living with the side effects of this condition and its treatment. Especially the development of chemotherapy-induced peripheral neuropathy (CIPN) is of major concern. In particular, since the indications for chemotherapy are broadened and relatively new chemotherapeutic
J Cancer Surviv
agents, with CIPN as the major dose-limiting side effect, are in use [2] while there is currently no well-accepted method to prevent or treat CIPN [3]. The prevalence of CIPN varies considerably between studies (e.g. 10–79 %) [2, 4–6]. In general, CIPN can occur due to treatment with certain chemotherapeutic agents like taxanes (e.g. paclitaxel, docetaxel), vinca alkaloids (e.g. vincristine, vinblastine), thalidomide, bortezomib and platinum derivatives (e.g. cisplatin, oxaliplatin) [7–10]. Oxaliplatin is often the cause of CIPN among colorectal cancer patients. These agents can cause structural damage to the peripheral nerves, which can result in abnormal somatosensory processing of the peripheral and/or central nervous system [11]. This subsequent CIPN can affect both small and large fibre sensory axons. Damage to small fibres causes burning pain, cutaneous hyperesthesias, and loss of pain and temperature senses while involvement of large fibres causes loss of vibration sense, loss of proprioception, loss of reflexes, slowed nerve conduction and subsequent muscle weakness [10]. Usually, CIPN begins with paresthesias (sensations of burning, numbness, tingling, itching or prickling) and dysesthesias (an abnormal unpleasant sense of touch) in the toes and fingers after which they can spread to both the lower and upper extremities [12]. Given the nature of CIPN symptoms, one could argue that CIPN is likely to have a negative influence on the ability to engage in regular physical activity. Regular physical activity plays an important role in colorectal cancer prevention [13, 14], recurrence [15] and mortality [16, 15]. Also, physical activity is associated with a better health-related quality of life and less pain, fatigue, insomnia and mental distress among colorectal cancer survivors [17–21]. Whether CIPN actually is negatively associated with the ability to engage in regular physical activity is yet unknown as the literature on the association between CIPN and physical activity is scarce. One could also argue that physically active patients develop less CIPN to begin with, or that physical activity could reduce CIPN symptoms. For instance, a study among lymphoma patients showed that exercise reduced restrictions from side effects such as CIPN [22], and a study among ovarian cancer survivors showed that being physically active (e.g. meeting the physical activity guideline) was inversely associated with CIPN [23]. A recently proposed conceptual model states that exercise may result in fewer neuropathic symptoms by increasing mitochondrial energy production and blood flow to the peripheral nervous system [24]. Our aim was to gain insight into the association of physical activity with CIPN among a population-based sample of colorectal cancer survivors up to 11 years after diagnosis. Also, since both the presence of CIPN and a lack of physical activity are negatively associated with health-related quality of life [17–21, 25], we will assess the association of CIPN with health-related quality of life for those meeting and not meeting
the Dutch physical activity guideline of 150 min of moderate to vigorous physical activity per week.
Methods Setting and participants Details of the data collection have been previously described [26]. However, since our cancer registry data is updated on a regular basis, some additional details of clinical characteristics were available for analysis in the present paper. In brief, data collection was performed within PROFILES which is a registry for the physical and psychosocial impact of cancer and its treatment [27]. PROFILES is linked directly to the population-based Eindhoven Cancer Registry (ECR), which compiles data of all individuals newly diagnosed with cancer in the south of The Netherlands [28]. Our prospective yearly survey was set up in December 2010. All individuals diagnosed with colorectal cancer between 2000 and 2009 as registered in the ECR were eligible for participation (except those already included in a 2009 PROFILES survey [29, 30] or another study (n=169)). Those with unverifiable addresses, with cognitive impairment, who died prior to the start of study or were terminally ill, and those with stage 0/carcinoma in situ, were excluded. The data presented in this paper are based upon the second data collection wave, which included a CIPN questionnaire. This is therefore a cross-sectional study. A certified medical ethics committee approved this study and all patients signed informed consent. Data collection Survivors were informed of the study via a letter from their (ex-) attending specialist. Non-respondents were sent a reminder. Socio-demographic and clinical characteristics Survivors’ socio-demographic and clinical information was available from the ECR. Comorbidity at time of the study was assessed with the adapted Self-administered Comorbidity Questionnaire [31]. Socio-economic status was determined by an indicator developed by Statistics Netherlands [32]. Questions on marital status, educational level, current occupation, height and weight (to calculate body mass index (BMI)) were added to the questionnaire. Health-related quality of life The EORTC QLQ-C30 (Version 3.0) was used to assess health-related quality of life [33]. It contains five functional scales, a global health status/QOL scale, three symptoms
J Cancer Surviv
scales and six single items. Each item is scored on a Likert scale ranging from (1) Not at all to (4) Very much, except for the global QOL scale, which ranges from (1) Very poor to (7) Excellent. Scores were transformed to a 0–100 scale [34]; a higher score on the functional scales and global QOL means better functioning and QOL, whereas a higher score on the symptom scales mean more complaints. Chemotherapy-induced peripheral neuropathy CIPN was assessed with the EORTC QLQ-CIPN20 [35] which contains three subscales assessing sensory, motor and autonomic symptoms. Each item is measured on a Likert scale ranging from (1) Not at all to (4) Very much. Scores were transformed to a 0–100 scale with higher scores representing more complaints. Physical activity Physical activity was assessed with questions derived from the validated European Prospective Investigation into Cancer (EPIC) Physical Activity Questionnaire [36]. Patients were asked how much time (average number of hours per week, in summer and winter separately) they spend on the following activities: walking, bicycling, gardening, housekeeping and sports. Additionally, six separate sports and the time they spend on this sport could be specified by the patient in an open question. To include an estimate of intensity, metabolic equivalent intensity values (MET value: 1 MET=4.184 kJ/kg body weight per hour) were assigned to each activity, according to the compendium of physical activities [37, 38]. Total physical activity was calculated by summing hours per week of all activities. The duration of moderate to vigorous physical activity (MVPA) was assessed as time (hrs/wk) spent on walking, bicycling, gardening and sports (≥3 MET), excluding housekeeping and light intensity sports (
