Introduction
The incidence of non-Hodgkin’s lymphoma (NHL) increases with age, and currently, the mean age at diagnosis is 66 years [
1]. Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive NHL. Due to aging of the population, clinicians will increasingly be confronted with elderly patients diagnosed with DLBCL.
Standard treatment for patients with DLBCL consists of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Not only in younger but also in elderly patients, this treatment schedule improves complete remission rates and survival [
2‐
9]. However, in daily practice, elderly patients frequently do not receive standard immunochemotherapy treatment [
4,
7,
9‐
12]. Reasons for suboptimal treatment are comorbidity and poor performance status, but also high age alone is adduced as an argument to refrain from standard treatment [
4,
7,
10‐
12].
Little is known about the influence of patient characteristics on treatment decision-making by clinicians. In a recent survey among hematologists, we observed that comorbidities, cognitive disorders, and functional status are frequently taken into consideration in treatment decision-making [
13]. In the second part of this survey, case vignettes of DLBCL patients with varying age and extent of comorbidity were presented to the respondents. By means of case vignettes, more information is gathered about decision-making in the daily clinical practice. Here, we present the results of the second part of this survey.
Discussion
The aim of the present study was to gain more insight into treatment decision-making by hematologists in DLBCL patients of varying age, comorbidity, and social support by use of case vignettes.
We observed that almost all respondents would treat DLBCL patients without a relevant medical history with curative intent. In the eldest patient category, intentional dose reductions are frequent. This is in line with the results of previous reports [
11,
13]. In a recent study among DLBCL patients older than 75 years, dose reductions occurred in 31 % of patients at start of treatment with R-CHOP and age was the most important reason in 27 % of cases [
4]. However, in 68 % of patients, there was no clear argumentation.
Furthermore, we found that treatment decision-making is to a large extent influenced by the presence of comorbidity. In case of serious comorbidity, respondents frequently applied dose reductions in advance or refrained from treatment with curative intent. This is in line with the results of the first part of this survey in the same respondents and was also observed is previous studies [
5,
9,
13,
16,
17]. In elderly patients, comorbidity is common and a prevalence of up to 87 % in patients aged older than 80 years is described [
10]. Comorbidity is associated with lower survival in elderly NHL patients [
9,
11,
16‐
21]. The impaired outcome in patients with comorbidity can not only be the result of the direct impact of comorbidity on outcome but can also be the consequence of less intensive treatment schedules or less treatment tolerability [
16,
22].
In addition, the results of this study showed that cognitive impairment has an important influence on treatment decisions. In case of mild cognitive impairment, most patients would be treated with curative intent; however, there was a marked decrease in this percentage in case of dementia. This was most pronounced for the eldest patients above 80 years of age. It has been shown that dementia is associated with an increased mortality rate in NHL patients [
9,
23].
Lastly, we observed that depression, especially when not treated adequately, appeared to affect the treatment regime of DLBCL patients. The prevalence of depression in DLBCL patients is high [
24]. Moreover, a study among cancer survivors observed increased all-cause mortality in patients with depressive symptoms even after adjustment for major clinical predictors [
25]. This might be explained by lower treatment compliance in depressed patients or by a higher incidence of depression in patients with poor performance status [
26]. Expected low treatment adherence or worse coping strategies may be reasons for clinicians to treat patients with a depression with adapted chemotherapy schedules.
Interestingly, respondents working in university hospitals seem to treat elderly patients less often with full-dose chemotherapy. This might be the consequence of a referral bias, and possibly these respondents have less experience in treating elderly DLBCL patients.
Respondents declared that comorbidity and cognitive impairment in DLBCL patients largely influence treatment decision-making. In daily clinical practice, the extent of comorbidity and cognitive impairment in a patient is in general judged by the physician without performing a systematic assessment, among others because the latter is time-consuming. Clinical judgment by a physician is however less reliable in detecting geriatric problems compared to a systematic evaluation by comprehensive geriatric assessment (CGA) [
27‐
31]. However, no large prospective randomized controlled trials have been performed investigating the role of CGA in the treatment of elderly DLBCL patients, and therefore, it is not clear how the results of CGA might influence treatment decision-making.
The strengths of our study are that more information is provided about factors that influence treatment decision-making by clinicians, an important topic in cancer treatment. Furthermore, by presenting case vignettes, various situations that resemble daily clinical practice could be studied. Moreover, hematologists of university, tertiary medical teaching hospitals, and general hospitals participated in the study, making the results generalizable. Possible limitations of our study might be that, even though the response rate was reasonable, especially hematologists with a particular interest in this subject responded. In addition, it cannot be entirely excluded that in clinical practice other treatment decisions are made than that the decisions that were indicated in the cases by respondents. At last, an initial treatment decision is not fixed and it is possible that treatment is for example intensified if treatment tolerability appears to be good.
In conclusion, patients without a relevant medical history are in general treated with curative intent irrespective of age. However, in the presence of mild cognitive impairment, dementia, comorbidity, or depression dose reductions in advance are frequently applied or patients are not treated with curative intent. This is most prominent in the eldest patient category.