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Measurement of health-related quality of life (QOL) over time often yields results that may be difficult to understand. Patients may change their internal standards of QOL as a result of adaptation to deteriorating health, a phenomenon referred to as response shift.To examine changes in internal standards of fatigue, global health/QOL, and physical function in patients with inoperable lung cancer at 3 months (n = 115) and 6 months (n = 89) after a baseline measurement close to diagnosis. Significant changes were expected to occur only in patients who reported improvement or deterioration in fatigue and global health/QOL.Fatigue, global health/QOL, and physical function were assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30, version 3.0). At follow-up, this questionnaire was administered conventionally and as a retrospective baseline assessment (thentest). Subjective transition questions were used to form mutually exclusive patient subgroups (i.e., deterioration, stable, or improvement).With respect to fatigue, significant changes occurred in patients reporting deterioration at 3 months follow-up and in patients reporting improvement after 6 months, but not in patients reporting improvement after 3 months or deterioration after 6 months. Significant changes in global health/QOL were found in patients reporting improvement at both 3 and 6 months follow-up and unexpectedly in stable patients after 3 months. No significant changes were found in patients reporting deteriorated global health/QOL at 3 and 6 months. Unexpectedly, changes occurred at both 3 and 6 months in patients reporting improved physical function.Given these mixed findings, it cannot be concluded that changes in internal standards occurred. These severely ill patients reported high levels of symptoms at baseline and may in part have adapted to their symptoms before study entry.