Quality of life research: adding an important dimension to the evaluation of therapeutic outcomes

Patients facing a cancer diagnosis and difficult treatment regimen are forced to deal with concerns about their own mortality and the effect on loved ones, job, and financial issues, as well as possible depression and concern about dealing with the physical effects of therapy on their health [1]. Fortunately, survival for patients with diffuse large B-cell lymphoma (DLBCL) has improved as a result of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy, originally administered with a cycle duration of 21 days, and further enhanced by a reduction of cycle length to 14 days (dose-dense therapy) and by the addition of the monoclonal anti-CD20 antibody rituximab [2,3]. However, concern has been raised about additional toxicities with this regimen [4,5]. The study reported in this issue of Leukemia & Lymphoma by Tholstrup et al. on ‘Quality of life in patients with diffuse large B-cell lymphoma treated with dose-dense chemotherapy is only affected temporarily’ [6] provides another dimension in evaluation of this therapy, finding that it has only short-term effects on quality of life, thus giving newly diagnosed patients a measure of hope and additional incentive to complete this regimen because it shows that their global health status, physical, and role functions will return to baseline levels within 3 months after completion of therapy.

R-CHOP (CHOP with rituximab) therapy has been quantitatively evaluated from a number of perspectives. Randomized clinical trials beginning in 2002 consistently demonstrated a survival advantage, leading to evidence-based recommendations that previously untreated patients with DLBCL who are candidates for curative intent with combination therapy should receive rituximab [7]. Economic analyses have demonstrated that the addition of rituximab is cost-effective [8]. However, the measurement of quality of life outcomes is more varied and subjective.

Quality of life, or more specifically health related quality of life (HRQoL), has been studied from multiple perspectives. It is important that the questions selected to assess it have been validated to reflect a specific conceptual model [9]. In general, however, it is agreed that these questionnaires should cover physical, social, and psychological/emotional functioning and well-being, as well as some symptoms [10]. Other characteristics of a good measure are its reliablility (i.e. repeated uses under similar circumstances will provide similar results), sensitivity (i.e. able to discriminate between patients with different treatments or in different groups), and responsiveness (i.e. able to demonstrate changes over time) [10]. Finally, the measure should be clinically meaningful such that differences between groups or over time can be interpreted as being clinically significant. Tholstrup et al. [6] selected the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) including 30 questions, version 3 [11], abbreviated as the EORTC-QLQ30, which is one of the most widely used measures of overall quality of life in studies of patients with cancer on clinical trials. However, while other valid instruments exist, they may not be comparable, and thus it is necessary to compare studies using the same instrument [12].

Because the EORTC-QLQ30 has been used in other populations, it was possible to compare the cancer patients' scores to those for an age- and gender-matched Norwegian general population. This is important, because patients without cancer may also experience lower quality of life due to other chronic conditions and the effects of aging; thus, this comparison allows the cancer patients' outcomes to be placed in perspective. Prior to therapy, the patients with lymphoma scored significantly lower than the reference population for a number of measures, including overall global health status and functional scales, and also had greater fatigue and appetite loss. During treatment these conditions worsened; however, by 3 months after treatment they had generally returned to baseline levels. Diarrhea was one symptom not elevated at baseline that increased during treatment and had not returned to baseline levels at 3 months.

While this study took the lead in assessing the effect of this therapy on quality of life measures, it should be seen as a first step, since the sample size was quite small and the therapy received by the patients was not homogeneous (e.g. not all received rituximab). In addition, four of the 30 clinically eligible patients originally included in the study did not have data from at least two time points, and another four did not complete all four questionnaires administered at different time points before and after therapy (including one who died from an acute myocardial infarction which was thought likely related to treatment toxicity). Thus, there may have been selection bias associated with those who were able to continue in the study long enough to complete the questionnaires at each time point. In addition, the time-frame of follow-up was short, just 3 months after therapy, and thus the study cannot provide information on long-term effects of this therapy. Furthermore, the results could not be stratified by age group. Thus, larger studies are needed to confirm these findings and identify subgroups of treated patients who may have greater problems. Nevertheless, the type of information being provided should be helpful to cancer patients and their physicians in gaining confidence that the immediate effects of dose-dense therapy can be tolerated and are relatively short-lived.

Potential conflict of interest: A disclosure form provided by the author is available with the full text of this article at www.informahealthcare.com/lal .