Since the publication of the study by Glimelius et al., palliative chemotherapy, when compared with the best supportive care alone, is usually considered to improve the QOL and survival of patients with metastatic pancreatic cancer and cancer of the bile ducts, respectively [1
]. In a consecutive trial reported by Burris et al., Gemcitabine monotherapy appeared to be superior to 5-FU in terms of the clinical benefit rate and survival and therefore established a new standard of care for advanced pancreatic cancer [2
]. A large number of trials evaluating Gemcitabine-based combinations produced negative results or only marginal improvement concerning survival, and the data on the improvement of QOL were controversial [7
Thus far, QOL assessment has focused on palliative 1st
-line treatment, but there is still a paucity of data on the degree of improvement in QOL that can be achieved by chemotherapy [14
]. In addition, there is a large uncertainty on the differences concerning the QOL aspects of patients in different treatment lines and on the QOL effects of adjuvant chemotherapy after surgery with curative intent.
Frequent, computer-assisted assessments of the EORTC-QLQ-C30 during adjuvant and palliative treatment in daily clinical practice, as presented in our analysis, may shed light on some of these questions.
Most importantly, and in accordance with other studies, our data indicate that patients under 1st
-line palliative chemotherapy experience a stabilisation of physical and psychosocial symptoms and global QOL, rather than a real measurable improvement. These data, which suggest QOL stabilisation, are in line with the results reported by Romanus et al., who treated patients with Gemcitabine or Gemcitabine/Bevacizumab [6
]. As in our analysis, these treatments resulted in a modest improvement in pain and mood and a slight slowing of functional deterioration but no significant improvement of global QOL. Furthermore, the most effective chemotherapy protocol, FOLFIRINOX, has also been shown to only slow the deterioration of QOL instead of significantly improving it, despite prolonging survival [4
In an exploratory analysis with limited statistical power, we attempted to correlate the chemotherapy response, defined as disease stabilisation on CT-scans at 6–8
weeks after the start of chemotherapy, with QOL data. Our data indicate the importance of achieving disease-stabilisation, at the least, as these patients also seem to accomplish significant gains in important aspects of QOL.
Only recently, based on a small phase III trial, palliative chemotherapy with 5-FU/Folinic Acid/Oxaliplatin (OFF) has become the standard of care in the 2nd
-line setting [12
]. The QOL data were not reported in this trial. A number of phase II studies have also reported a measurable effect of 2nd
-line chemotherapy [16
]. However, due to infrequent assessments and the associated low compliance, QOL data have rarely been reported. As in the 1st
-line palliative setting, the QOL trajectories shown by 2nd
-line palliative chemotherapy patients indicate a stabilisation, rather than an improvement, of physical and psychosocial symptoms and global QOL.
These results are of clinical importance because they indicate a comparable effect of palliative chemotherapy on many of the aspects of QOL under 1st- and 2nd-line palliative chemotherapy in terms of constant QOL data during treatment. When stabilisation, but not a significant improvement of QOL, is obtainable with palliative chemotherapy, treatment should be initiated as soon as possible, when the clinical symptom burden is still low.
The comparison of QOL outcomes during different chemotherapy lines, as presented here, suggests that most of the QOL aspects show a progressive deterioration during the course of the disease over the chemotherapy lines. Though 2nd- and 3rd-line palliative chemotherapy patients reported higher symptom burden than adjuvant and 1st-line palliative chemotherapy patients, only 1st- and 2nd-line palliative chemotherapy patients showed stable QOL trajectories in contrast to 3rd+-line patients, who reported considerable QOL deteriorations over time.
In that regard, the outcomes for patients receiving adjuvant chemotherapy are of great interest. In contrast to the palliative situation, our data indicate that during the course of adjuvant chemotherapy, most of the subscales of QOL show a continuous improvement, probably caused by the fading of postoperative health problems. According to our analysis, deleterious effects of adjuvant chemotherapy on QOL seem highly unlikely. This information is of immediate clinical relevance in cases where adjuvant chemotherapy is suggested to our patients.
Comparing different studies on QOL in patients with cancer of the pancreas or bile ducts has some limitations, especially when different instruments and questionnaires are used. In our opinion, one of the major problems of assessing QOL in these rapidly progressive cancers is the timing and frequency of the assessments. We have no knowledge about the optimal frequency, but when too much time elapses between two surveys, we cannot detect rapid but clinically important changes in QOL [8
The computer-assisted assessment of QOL data in daily clinical practice, as used in our analysis, offers important advantages over QOL assessments that have long time intervals, which are presented in most clinical studies. The computer-assisted assessments enabled us to evaluate QOL at many time points with short intervals, allowing a more robust estimate of longitudinal QOL changes during each treatment course. For patients with aggressive tumours, such as pancreatic cancer, usually with limited efficacy of palliative systemic treatments, QOL assessments are of even greater importance.
Certainly QOL has always to be seen as a multifactorial process and patients’ subjectively perceived QOL is influenced by a variety of factors. Patients experience positive and negative effects also due to their status, social and family support and individual coping strategies. Chemotherapy especially ameliorates the tumor associated symptoms but it is only one way to improve quality of life of patients with advanced cancer. A recent study, conducted by Temel et al., in patients with newly diagnosed metastatic non-small-cell lung cancer demonstrated impressively that early palliative care intervention in concert with standard oncology care improves QOL and median survival and reduces depressive symptoms, compared with patients receiving only standard treatment [26
]. Besides treatment possibilities, high socioeconomic status also has been found to influence overall cancer survival positively [27
] and social support was linked to cancer survival as well, although the results are divergent [29
]. Lately, Cavalli-Björkman et al. reported that colorectal cancer patients, who did not live in a joint household with their significant other, were irrespective of age and co-morbidity less likely to receive combination chemotherapy and had poorer survival [30
]. Social support in terms of rehabilitation programs in a setting of 12
weeks resulted in better QOL and improved physical functioning [31
], whereas a 6-day residential psychosocial course did not show any effects [32
]. Taken these findings together, it is obvious that a lot of research still has be done to identify influential factors on patients’ QOL, and how they relate to each other.
Our analysis has some limitations. As the number of patients included is relatively low, the statistical power is limited. Furthermore, some heterogeneity exists in the evaluated population, which concerns important clinical factors and the applied systemic treatments. Nevertheless, the patients included in this study represent our daily clinical practice.