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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. [ABSTRACT FROM AUTHOR]