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Journal of Cancer Research and Therapeutics, Vol. 6, No. 1, January-March, 2010, pp. 22-26 Original Article Magnitude of fatigue in cancer patients receiving radiotherapy and its short term effect on quality of life Janaki M. G., Amrit R. Kadam1 , Mukesh S., Nirmala S., Arul Ponni, Ramesh B. S., Rajeev A. G. Department of Radiation Oncology, M. S. Ramaiah Medical College, Code Number: cr10006 DOI: 10.4103/0973-1482.63566 Abstract Background : Fatigue is one of the most common, ongoing symptoms reported by patients undergoing radiotherapy and has profound effects on the quality of life. Aims : This study attempts to identify the magnitude of fatigue and its implication on the quality of life during radiotherapy. Methods and Materials : A prospective study was conducted from March 2004 to September 2005, on 90 patients with histologically proven cancer, receiving radiotherapy. Pretreatment and weekly assessment of fatigue and QOL was done during radiation treatment using Brief Fatigue Inventory Scale and EORTC QLQ C30 respectively and repeated one month after completion of radiotherapy. All the scores were measured in the 0 to 100 scale. Statistical Methods Used : Trimean, SPSS 11.0 and Sysstat 8.0 were used for statistical analysis. Results : Fatigue was present in 87.8% of patients initially and increased gradually over the course of radiotherapy and peaked in the last week. However at follow up it was nearing the pretreatment level. There was significant reduction in the functional scores ( P < 0.001) of QOL (physical, role and emotional function), which returned to pretreatment level at follow up. In the seventh week impairment of cognitive function (P=0.059) was noted. Significant reduction of social function (P < 0.001) at second week and global health status (P < 0.001) at fifth week was noted while financial difficulty was seen from second week onwards. Conclusion : Fatigue is transiently increased by radiotherapy before reaching pretreatment level after few weeks of completion of radiotherapy. QOL is also affected by fatigue which follows the same pattern.Keywords: Cancer, fatigue, quality of life, radiotherapy Introduction Early cancer detection and improved treatments have resulted in increased survival rates over the last few decades. [1] However, declining quality of life (QOL) and increased fatigue remains a major concern in cancer patients. [2],[3] Cancer-related fatigue is defined by the National Comprehensive Cancer Network (NCCN) as "a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning, can be described in terms of perceived energy, mental capacity, and psychological status". [4] Persistent fatigue is recognized as one of the most common, ongoing symptoms reported by patients following cancer treatment namely radiation and chemotherapy. It is known to have profound effects on the quality of life. [5] Fatigue can be the initial manifestation of cancer and may be present before any treatment is initiated and gets aggravated during radiotherapy and chemotherapy. [6] Radiation therapy forms an integral part of management of a cancer patient. Generally about 80% of cancer patients require radiation at some point of time either in the form of radical, adjuvant or palliative intent. The radiation treatment is delivered over a period of several weeks in which invariably normal tissues are also irradiated. These result in side effects impairing the nutrition, general condition of the patient and add up to the fatigue already present. [5] Fatigue prevalence increases over the course of radiotherapy. [7] Unlike simple tiredness or situational fatigue, it is more debilitating and severe; less likely to be relieved by simple rest; and may lead to withdrawal from meaningful and enjoyable activities and may even lead to discontinuation of treatment. [8] Despite all these, there are only few studies that have quantified the impact of fatigue on overall quality of life (QOL) in cancer patients. The aim of this study is to evaluate the magnitude of fatigue in cancer patients receiving radiotherapy and its relative impact on different QOL domains/subscales. Methods and Methods The study was carried out from March 2004 to September 2005, on patients with histologically proven cancer receiving radiotherapy in our department. Age more than fifteen years and KPS of 70 or more were the inclusion criteria. Patients who received chemotherapy in the previous six months were excluded from the study. Patients with post-op (53.3%), radical (21.1%), palliative (24.4%) and pre-op (1.1%) intent where taken into the study. Radiation dose varied from 3000cGy to 7000cGy in 10 to 35 fractions depending on the site and intent of treatment. Ninety patients fulfilled these criteria and were included in the study. The patients' characteristics are shown in [Table - 1]. Fatigue and quality of life were assessed using Brief Fatigue Inventory Scale and EORTC QOL C30 questionnaire respectively. All the patients were asked to fill the questionnaires, once before start of treatment, then every week during the course of treatment and one month post treatment. Patients, who did not know to read and write, were explained about the questionnaire in their mother tongue and response was noted by the person interviewing. For the scoring of Fatigue in the brief fatigue inventory scale, the average score was taken from Q1, Q2 and Q3. The score ranged from 0 - 10, where 0 represented "no fatigue" and 10 denoted "as bad as you can imagine". The quality of life was scored using EORTC QOL C30 scoring manual version 3.0. According to the parameter studied different formulae were used for calculating.
Statistical analysis The data collected was tabulated using Microsoft Excel work sheet and the data was analyzed using SPSS 11.0 and Sysstat 8.0. Trimean was calculated for all the parameters of QOL. The trimean is a good measure of central tendency. It is computed by adding the 25 th percentile plus twice the 50 th percentile plus the 75 th percentile and dividing by four. The trimean is almost as resistant to extreme scores as the median and is less subject to sampling fluctuations than the arithmetic mean in extremely skewed distributions. The significance was obtained by Wilcoxon Signed rank test between first week and one month post treatment. 'P' values for the difference of percentage was computed using on-line Java - Script tests on difference in two proportions estimates from a single population, based on a set of random paired observations for all the study parameters. Results Ninety patients participated in the study. The fatigue distribution among the patients is shown in [Table - 2] and [Figure - 1]. Majority of patients during the start of treatment had mild (52/90, 57.8%) and moderate (24/90, 26.7%) degree of fatigue. Severe degree of fatigue was noted in 3.3% (3/90); however 12.2% (11/90) had no fatigue at the start of treatment. During the course of treatment, the severity of fatigue increased. The number of patients reporting severe fatigue increased from 3.3% to 12% and moderate fatigue from 26.7% to 56%. However there was no statistically significant difference (P>0.05). At follow up it was seen that fatigue scores were nearing the pretreatment levels. (P>0.05). The distribution of various parameters of quality of life is shown in the [Table - 3]. There was significant reduction in the physical activity at the end of fourth week after the start of treatment (93.2% to 85%, P< 0.001). But there was no significant difference between the scores at the start of treatment and follow up score. There was significant reduction in role function at the end of fourth week (87.25% to 79%, P< 0.001) which improved at follow up (P=0.3626). There was also reduction in emotional function at the end of fourth week of treatment (85.25% to 83.25%, P< 0.001). It improved at follow up (83.25% to 95.75%, P< 0.001) There was no change in the cognitive function during first six weeks. In the seventh week impairment of cognitive function (95.75% to 83.50% P=0.059) was noted. The social function was significantly reduced during the second week of treatment (P< 0.001). However at follow up it was same as that during start of treatment. (P=0.918). The global health status was significantly reduced at the end of fifth week (P< 0.001) but it improved at follow up. (P=0.406). Patients had significant financial difficulty at second week of treatment, remained so during the course of treatment and at follow up (P< 0.022). Discussion The term Fatigue has roots in several disciplines. To the physiologist, fatigue is considered a decrease in the capacity to perform work; a pathologist may view it as an indicator of a neuromuscular or metabolic disorder, and to the psychologist a symptom of depression associated with decreased motivation to engage in the mental and physical activities. [9] Fatigue in oncology is unique. Unlike acute fatigue, in which tiredness comes on quickly, lasts a short time, and is relieved by rest, cancer fatigue is prolonged, debilitating, that is persistent or recurring. [10] Various definitions of cancer related fatigue have been given till date, like the National Comprehensive Cancer Network, [4] International Classification of Disease 10th revision (ICD-10), [10] Medical Subject Headings, [11] Marcello et al,[12] suggesting that its definition as well as understanding is very difficult. Fatigue can be either regarded as a symptom of the underlying disease (both upon presentation and in the course of relapses) or as a side effect of treatments, or as a sign of a concomitant condition. [12] In relation to the kind of therapy instituted and the type of tumor, fatigue has very specific phenomena and differs not only from fatigue in healthy people, but also from fatigue in people suffering from other diseases. [13] Fatigue is one of the most common QOL-related symptoms in cancer today. [14] For patients and oncologists, improving the QOL of cancer patients requires a heightened awareness of fatigue, a better understanding of its impact, improved communication and familiarity with interventions that can reduce its debilitating effects. [15] Almost every patient suffers from fatigue during cancer treatment and in the scientific literature reported prevalence rates of fatigue are up to 99%. [16] Following completion of therapy, cross-sectional studies involving cancer patients with different stages of disease, indicate that over 75% of patients have significant ongoing symptoms of fatigue. [17] Application of the diagnostic criteria for cancer-related fatigue (CRF) indicates that between 14 and 30% of patients have ongoing CRF with associated disability when surveyed 1-5 years after completion of treatment, [18] well in excess of the rates in the general population. [19] Research shows that chronic fatigue is associated with problems and limitations in different areas of life. Severe fatigue leads not only to physical restrictions but also to serious impairment in QOL, social activities and the ability to go to work. [16],[20] Gregory et al from the fatigue coalition group reported that fatigue prevented patients from leading a normal life and conducting their daily routine. The patients with low physical performance levels were more depressed, anxious and socially insecure. In addition, pain or depression was more likely to occur in patients experiencing fatigue on a daily basis than those experiencing it less frequently. The mental/emotional effects of fatigue reported in ≥30% of patients. Most patients reported a need to push themselves to do things (77%), decreased motivation or interest (62%) and feelings of sadness, frustration, or irritability (53%) during their experiences with fatigue. In addition, fatigue affected typical cognitive tasks, such as concentrating (38%), remembering things (35%), and keeping dates straight (34%) The social/behavioral activities were more difficult in ≥30% of patients when experiencing fatigue. [21] Results of this study, also shows the same effect of fatigue on QOL. However, the study is limited by the fact that, fatigue was assessed in all cancer patients, regardless of primary site and type of the treatment. Fatigue during Radiotherapy is unique as the treatment is protracted over many weeks and the patient needs to travel all the way everyday to receive the treatment. It is also associated with significant acute radiation accompaniments which alter the patient's nutrition, blood parameters leading to aggravation of the baseline fatigue. We have observed that the fatigue starts increasing from second week onwards and this coincides with the beginning of radiation reactions which settles at around four weeks after completion of radiation. Barbara et al., have shown that the fatigue increased during second week of radiation and decreased subsequently, probable explanation being the patient's ability to adapt to the treatment. [22] These authors have also observed that the radiotherapy free week ends were associated with a lesser fatigue. However we did not observe this in our study. The quality of life parameters assessed such as the role function (routine work), emotional (irritability, tension and worry) and social function (social activities) showed a significant reduction during radiation but returned to normal at the end of one month of completion of radiotherapy. However the cognitive function (comprehension, memory) was affected only during the last week of radiation. Our interesting observation was that the financial difficulty was significant from the second week onwards and persisted at follow up also. This probably reflects the socioeconomic status of our patients and those from any developing country in general. Observations like these and from various other trials will probably help the healthcare givers in the developing countries to formulate and plan more cost effective treatment strategies and supportive care program. Fatigue, like pain is a subjective symptom and hence varies from patient to patient and from time to time for any given patient, making it very difficult to assess its impact on quality of life. There are various questionnaires which are used to assess fatigue. Brief fatigue inventory scale is one among them. It has nine items on a ten point scale ranging from zero to ten. BFI is simple to use, easy to understand and is highly consistent. EORTC QLQ-C30 can be a useful instrument for the early detection of patients' impaired cognitive function and psychological morbidity. [23] The EORTC QLQ-C30 (version 3.0) is a 30-item cancer-specific core questionnaire that addresses various domains of QOL. It contains five function subscales (physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning), three symptom subscales (fatigue, pain and nausea/vomiting), two single items assessing global health and 'overall' QOL and a number of single items addressing various symptoms and perceived financial impact. [24] Cancer related fatigue is present in majority of the patients at the start of treatment. Several clinical factors have been identified as causative elements in fatigue: pain, emotional distress, sleep disturbance, anemia, nutrition, activity level, and other co morbidities. These factors must be addressed in mitigating cancer-related fatigue. [25] It has been shown that exercise; including walking and aerobic exercise and resistance training, have beneficial effects on some symptoms related to cancer, including fatigue, distress, anxiety, and depressive symptoms. A recent systematic review indicates a trend toward improved physical functioning with exercise programs. An exercise prescription should take into account the patient's history and any physical constraints that may impact exercise safety and compliance. [21] There also is strong evidence that psychosocial interventions, including support groups, stress management, education, and behavioral intervention, are effective in treating fatigue in patients with cancer. [26] In our set of patients, it is our observation that explaining the details of treatment, associated treatment related morbidity before the beginning of radiation to the patient and the relatives takes care of the fatigue to a large extent. Weekly reassurance is also very important especially when they develop mucositis, radiation enteritis and other associated problems. Timely recognition and treatment of acute radiation accompaniments, nutritional support and maintenance of hemoglobin to some extent takes care of fatigue during radiation. We have excluded patients who received chemotherapy in the previous six months as chemotherapy per se causes varying degrees of fatigue. So our study examines fatigue that is solely contributed by radiotherapy. Further studies should be conducted to assess the fatigue with respect to primary site, volume of irradiation and other altered fractionation regimes. It becomes more imperative to study fatigue and QOL during concurrent chemo radiation as it is the standard care in most of the cancers. This might give better insight into the magnitude and management of fatigue in cancer patients undergoing more intensive treatment. Conclusion Radiotherapy causes transient increase in the fatigue which accumulates over weeks and reaches to the pretreatment level at one month after completion of treatment. The physical, role, cognitive and social functions also are reduced during treatment and returns to baseline at one month follow up. Further studies should be conducted to assess the fatigue with respect to primary site. This might give better insight into the magnitude and management of fatigue in cancer patients undergoing radiation. References
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