Centre Alexis Vautrin, Department of Medical Oncology, Nancy, France
Nancy-University, Paul Verlaine Metz University, Paris Descartes University, EA 4360 Apemac, Nancy, France
INSERM, CIC-EC CIE6, Nancy, France
Quality of Life in oncology platform, Canceropole Grand-Est, Nancy, France
University hospital Jean Minjoz, Department of Radiation Oncology, Besançon, France
Medical and Pharmaceutical University, Department of Biostatistics, Besançon, France
Centre Alexis Vautrin, Department of Radiation Oncology, Nancy, France
Clinique Saint-Vincent, Medical Oncology, Besançon, France
Centre Alexis Vautrin, Department of Surgery, Nancy, France
Abstract
Background
The aim of this study was to compare the responsiveness of the European Organization for Research and Treatment (EORTC) quality of life questionnaires (QLQ-C30, QLQ-CR38) and the Functional Assessment of Cancer Therapy-colorectal version 4 questionnaire (FACT-C).
Method
This prospective study included 127 patients with colorectal cancer: 71 undergoing chemotherapy and 56 radiation therapy. Responsiveness statistics included the Standardized Response Mean (SRM) and the Effect Size (ES). The patient's overall assessment of his/her change in state of health status was the reference criterion to evaluate the responsiveness of the QoL questionnaires.
Results
34 patients perceived their health as stable and 17 as improved between the first and the fourth courses of chemotherapy. 21 patients perceived their health as stable and 22 as improved between before and the last week of radiotherapy.
The responsiveness of the 3 questionnaires differed according to treatments. The EORTC QLQ-C30 questionnaire was more responsive in patients receiving chemotherapy, particulary functional scales (SRM > 0.55). The QLQ-CR38 and the FACT-C questionnaires provided little clinically relevant information during chemotherapy or radiotherapy.
Conclusion
The EORTC QLQ-C30 questionnaire appears to be more responsive in patients receiving chemotherapy.
Introduction
Colorectal cancer (CRC) is common in Western societies. The management of locally advanced rectal cancer includes preoperative chemoradiotherapy and surgery. Surgery followed by adjuvant or palliative chemotherapy is the standard of care of localized or advanced stages of CRC. These treatments may affect the patient's quality of life (QoL) and may be responsible for late side-effects or sequelae. QoL assessment is essential to better inform clinical decisions by providing insights into the patient's experiences of disease and treatment
Many questionnaires assess the QoL of patients with CRC. The more frequently used are
Responsiveness, or "sensitivity to change", an essential property of measuring instrument, is defined as the ability to detect a clinically meaningful change
Both instruments (QLQ-C30 followed by QLQ-CR38 and FACT-C) have subscales measuring physical, emotional, functional, and social aspects; the EORTC QLQ-C30 has additional subscales and single items assessing cognitive function, symptoms, and the financial impact of the disease. The QLQ-CR38 is mainly centered on surgery consequences and has some items about radiotherapy side-effects
This study was therefore designed to compare the responsiveness of the EORTC QLQ-C30, QLQ-CR38 and FACT-C questionnaires, based on the course of QoL during different treatments for CCR.
Patients and methods
This is a prospective longitudinal study carried out in four French hospitals (Alexis Vautrin Cancer Centre, Nancy and Oscar Lambret Cancer Centre, Lille; Nancy and Besançon university hospitals) between April 2003 and February 2007. The institutional review board had approved the study.
Patients
Patients who had histologically proven colorectal adenocarcinoma, an age above 18 years, able to read, speak and write French, no psychological condition that might potentially hamper compliance with QoL assessment, and life expectancy greater than 3 months were eligible.
Patients were not eligible if participating in another QoL survey, in case of cognitive impairment, or previous or concomitant other cancer. Written informed consent and permission from an ethics committee were obtained.
Two different groups of patients were recruited:
- before starting adjuvant or palliative chemotherapy (all fluoropyrimidine based regimens) (chemotherapy group),
- before starting preoperative radiotherapy for rectal cancer (radiotherapy group): Preoperative radiotherapy delivered 45 grays in 25 fractions (five weeks) with or without concomitant fluoropyrimidine.
Measures and data collection procedure
Patients' characteristics and clinical data were collected at baseline. QoL assessment was performed using three questionnaires: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C version 4.0), the EORTC QLQ-C30 version 3.0 and the EORTC QLQ-CR38. The EORTC colorectal questionnaire (QLQ-CR38) was developed to be used in conjunction with the QLQ-C30. The FACT-C combines the FACT-G with a CRC subscale (CCS). The 3 questionnaires FACT-C, QLQ-C30 and QLQ-CR38 were administrated together. The order in which these questionnaires were administrated to patients was randomized by center from a pre-established table of random number to avoid any systematic order.
According to the type of treatment, different timings of QoL measurements were used:
- Patients treated by adjuvant or palliative chemotherapy were asked to complete all questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38 and FACT-C) before the first, the third and the fourth courses of chemotherapy administered at 2 weeks interval.
- Patients treated by preoperative radiotherapy for rectal cancer were asked to fill the three questionnaires before the first fraction and during the last week of radiotherapy.
The developers of the EORTC QLQ-C30 provide information on what a clinically important difference is for this questionnaire. They have suggested that in groups, the mean change scores was about 5 to 10 in the means scores for those who reported a "little" change, about 10 to 20 for those who reported "moderate" change, and more than 20 for those who reported a large change
The change in health status was assessed between baseline and before the fourth course for patients receiving chemotherapy, and between baseline and the last week of radiotherapy for patients treated with radiation therapy. The patient's overall assessment of his/her change in state of health was the reference criterion to evaluate the responsiveness of the questionnaires. The question was worded: "Compared to the situation before your treatment, how would you evaluate your state of health?" It was recorded according to seven levels of answers: the first 3 answers (much worse, moderately worse and slightly worse) were considered to reflect a clinically significant deterioration, the fourth answer (no change) was considered to reflect stability and the last 3 answers (slightly better, moderately better and much better) were considered to reflect a clinically significant improvement
Statistical analysis
Statistical analysis was conducted using a pre-specified plan. Completed questionnaires were scored according to the developers' instructions. Transformed FACT-C subscores were determined by converting the original values linearly to a range of 0 (worst QoL) to 100 (best QoL) to facilitate readability of the tables. QoL scores (quantitative variables in each scales) were expressed as mean and standard deviation. The Wilcoxon test was used to test differences between values of the two measurements in each group. Statistical significance for analyses was considered to be at p < 0.05.
Test-retest reliability was assessed between the third and the fourth courses of chemotherapy at two weeks interval in patients who reported no change in their state of health. To assess reliability, a sample of 30 patients with stable health between the 2 testing times was considered as sufficient because it can be approximated by the standard normal distribution. The Intra-class correlation coefficient (ICC) was computed from a one-way analysis of variance (ANOVA). ICC is the ratio of the variance of interest to the sum of the variance of interest plus error
Responsiveness statistics included the Standardized Response Mean (SRM) and the Effect Size (ES). It is based on the comparison of signal (mean change in clinically changed patients) to noise (SD of change in stable patients). The SRM is calculated as the mean change in scores between baseline and follow-up divided by the standard deviation (SD) of this change
Data were analysed using Statistical Analysis System software version 9.0 (Cary, North Carolina, USA, 2004) for Windows.
Results
Sociodemographic and clinical data
Between April 2003 and February 2007, 127 patients were enrolled in the study: 71 patients in the chemotherapy group and 56 patients in the radiotherapy group. Sociodemographic characteristics of the study population and medical data are presented in Table
Sociodemographic and clinical patient characteristics
Chemotherapy Group
Radiotherapy Group
p
Total
N
71
56
127
Age (years)
60
66
0.001
64
Median
Gender (%)
Men
38 (53)
43 (77)
0.007
81 (64)
Women
33 (47)
13 (23)
46 (36)
Marital status (%)
Single
3 (4)
4 (7)
7 (6)
Married
53 (69)
44 (80)
0.52
97 (76)
Widower
7 (6)
5 (4)
12 (9)
Divorced
8 (21)
3 (9)
11 (6)
Localisation (%)
Colon
55 (76)
1 (2)
< .0001
56 (44)
Rectum
16 (24)
55 (98)
71 (56)
Disease status (%)
Non metastatic
30 (42)
50 (89)
80 (63)
Metastatic
40 (56)
5 (9)
< .0001
45 (35)
Unknown
1 (2)
1 (2)
2 (2)
Between the first and the fourth courses of chemotherapy, 56 (78.9%) patients answered the question on the perceived change in health: five patients perceived their health as worsened, 34 as stable and 17 as improved.
Between the starting and the last week of radiotherapy, 48 (85.7%) patients answered the question on the change in their health: ten patients perceived their health as worsened, 21 as stable and 22 as improved.
Test-retest reliability
The test-retest reliability of the questionnaires was studied among 34 patients receiving chemotherapy who perceived their health as stable (Table
Test-retest reliability (ICC) of the QLQ-C30, QLQ-CR38 and FACT-C for patients with stable colorectal cancer undergoing chemotherapy (data obtained between the third and the fourth treatment)
n
ICCa
95% CIb
EORTC QLQ-C30:
Physical function
34
0.87
0.76-0.93
Role function
33
0.80
0.64-0.90
Emotional function
34
0.73
0.52-0.85
Cognitive function
34
0.79
0.62-0.89
Social function
34
0.84
0.71-0.92
Global QoL/GHS
34
0.33
-0.01-0.59
Fatigue
34
0.82
0.67-0.90
Pain
34
0.74
0.54-0.86
Nausea and vomiting
34
0.43
0.11-0.67
Dyspnoea
34
0.63
0.37-0.79
Sleep disturbance
34
0.76
0.58-0.87
Appetite loss
34
0.74
0.54-0.86
Diarrhoea
34
0.33
-0.003-0.60
Constipation
34
0.54
0.25-0.74
Financial impact
34
0.75
0.56-0.87
EORTC QLQ-CR38:
Body image
32
0.71
0.49-0.85
Future perspective
32
0.76
0.56-0.87
Sexual functioning
31
0.82
0.66-0.91
Sexual enjoyment
11
NA
NA
Radiation-induced effects micturition
32
0.67
0.43-0.82
Chemotherapy side effects
32
0.70
0.47-0.84
General gastrointestinal symptoms
32
0.65
0.39-0.81
Defecation problems
26
NA
NA
Stoma-related problems
6
NA
NA
Sexual dysfunction of men
14
NA
NA
Sexual dysfunction of women
3
NA
NA
Weight loss
32
0.36
0.02-0.63
FACT-C:
Physical Well-Being
34
0.76
0.57-0.87
Social/Family Well-Being
33
0.51
0.23-0.73
Emotional Well-Being
34
0.79
0.62-0.89
Functional Well-Being
34
0.73
0.52-0.85
Colorectal Cancer Specific
34
0.77
0.59-0.90
FACT-C total score
34
0.75
0.55-0.87
Trial Outcome Index-Colorectal
34
0.82
0.66-0.90
a Intraclass correlation coefficient; b confidence interval; NA: Not Applicable (n < 30)
Description of the QoL scores and responsiveness of the questionnaires
- Chemotherapy group
Because only 5 patients perceived their health as worsened, the responsiveness has been studied only in patients with improvement of their health. Between the first and the fourth courses of chemotherapy, 17 patients perceived their health as improved: 12 patients were slightly better, 3 moderately better and only 2 patients were much better. All patients except two had previous surgery for resection of the primary tumor before chemotherapy. Seven patients received adjuvant chemotherapy and 10 patients were treated for metastatic disease. In these patients with improved health status, no difference in changes of scores between baseline and before the fourth course of chemotherapy has been found between patients with adjuvant treatment versus those treated for metastatic disease (data not shown).
Description of scores (Table
Mean scores before the first course of chemotherapy, changes of scores between the first and the fourth courses of responsiveness statistics in patients who perceived improved health (n = 17)
n
Score before 1stchemother.Mean (SD a)
Difference
Mean
(SD a)
Pb
SRMc (CI 95%)
ESd (CI 95%)
EORTC QLQ-C30:
Functional scalese :
Physical function
16
67.8 (30.2)
+14.9 (22.5)
0.02
0.64 (0.19;1.08)
0.48 (0.14;0.86)
Role function
16
55.9 (39.1)
+21.9 (16.7)
0.03
0.60 (0.08;1.13)
0.56 (0.10;1.07)
Emotional function
17
69.6 (16.1)
+16.2 (16.7)
0.003
0.84 (0.28;1.54)
1.00 (0.35;1.68)
Cognitive function
17
77.5 (20.4)
+10.8 (16.6)
0.02
0.64 (0.16;1.29)
0.52 (0.14;1.09)
Social function
17
62.7 (34.1)
+13.7 (38.3)
0.16
0.35 (-0.17;0.88)
0.40 (-0.20;0.89)
Global QoL/GHS
17
54.9 (20)
+14.2 (14.7)
0.001
0.96 (0.38;1.67)
0.71 (-0.23;1.44)
Symptom scalesf :
Fatigue
16
42.8 (27.9)
-16.3 (25.8)
0.02
- 0.63 (-1.07;-0.19)
- 0.58 (-1.13;-0.15)
Pain
17
28.4 (31)
-17.6 (37.5)
0.07
- 0.47 (-0.90;-0.09)
- 0.56 (-1.07;-0.05)
Nausea and vomiting
16
12.7 (22.5)
-6.2 (21.8)
0.27
- 0.28 (-0.69;0.28)
- 0.27 (-0.66;0.25)
Single itemsf :
Dyspnoea
16
21.6 (26.2)
-8.3 (25.8)
0.22
- 0.32 (-1.05;0.65)
- 0.31 (-0.89;0.17)
Sleep disturbance
16
45.1 (31)
-12.5 (38.2)
0.21
- 0.32 (-0.86;0.19)
- 0.40 (-0.98;0.38)
Appetite loss
16
29.4 (30.9)
-12.5 (26.9)
0.08
- 0.46 (-0.93;0.01)
- 0.40 (-0.87;0.08)
Diarrhoea
17
19.6 (23.7)
+3.9 (33.1)
0.63
0.11 (-0.38;0.64)
0.16 (-0.41;1.17)
Constipation
17
17.6 (29.1)
-5.9 (27.0)
0.38
- 0.21 (-0.75;0.31)
- 0.20 (-0.67;0.31)
Financial impact
17
5.9 (17.6)
+3.9 (11.1)
0.16
0.35 (0.11;0.57)
0.22 (-0.05;0.49)
EORTC QLQ-CR38:
Functional scalese:
Body image
16
81.7 (28)
+3.8 (14.2)
0.30
0.27 (-0.33;0.69)
0.13 (-0.13;0.37)
Future perspective
16
45.1 (28.7)
+22.9 (31.5)
0.01
0.70 (0.27;1.27)
0.79 (0.27;1.38)
Sexual functioning
14
20.2 (20.9)
+5.9 (16.8)
0.21
0.37 (-0.28;0.86)
0.28 (-0.15;0.83)
Sexual enjoyment
7
54.2 (43.4)
+9.5 (41.8)
0.57
0.23 (-0.56;1.28)
0.21 (-0.73;0.91)
Symptom scalesf :
Radiation-induced effects micturition
16
23.5 (15.2)
+4.8 (15.7)
0.23
0.30 (-0.23;0.91)
0.32 (-0.23;0.89)
Chemotherapy side effects
16
18.6 (19.5)
+4.2 (18.4)
0.38
0.23 (-0.30;1.1)
0.21 (-0.77;0.92)
General Gastrointestinal symptoms
16
23.0 (12)
-7.0 (14.3)
0.07
-0.49 (-1.38;0.11)
- 0.58 (-1.45;0.17)
Defecation problems
13
15.4 (11.5)
-1.8 (8.2)
0.43
-0.22 (-1.10;0.41)
- 0.16 (-0.65;0.32)
Stoma-related problems
4
31.0 (21.5)
-1.2 (13.7)
0.87
-0.10 (-1.15;1.02)
- 0.05 (-1.96;2.43)
Sexual dysfunction of men
8
43.8 (41.7)
-2.1 (35.0)
0.87
-0.06 (-1.43;0.82)
- 0.04 (0.84;0.64)
Sexual dysfunction of women
2
8.3 (11.8)
-8.3 (11.8)
0.50
-0.70 (-1.44;-0.31)
-0.70 (-1.44;-0.31)
Weight loss
16
25.5 (34.4)
-22.9 (33.8)
0.02
-0.67 (-1.01;-0.35)
- 0.66 (-1.01;-0.36)
FACT-Ce:
Physical Well-Being
17
78.0 (15.3)
+5.3 (15.8)
0.18
0.34 (-0.20;0.85)
0.34 (-0.17;0.87)
Social/Family Well-Being
17
74.3 (21.1)
+3.2 (18.3)
0.48
0.17 (0.47;0.59)
0.15 (-0.39;0.48)
Emotional Well-Being
17
74.3 (19.6)
+3.3 (13.7)
0.34
0.24 (-0.32;0.64)
0.16 (-0.16;0.48)
Functional Well-Being
17
50.8 (17.1)
+10.0 (13.2)
0.007
0.75 (0.20;1.27)
0.58 (0.19;0.93)
Colorectal Cancer Specific
16
69.6 (10.6)
+3.9 (12.9)
0.25
0.30 (-0.26;0.88)
0.36 (-0.27;0.98)
FACT-C total score
17
69.5 (8.6)
+1.6 (9.0)
0.49
0.19 (-0.36;0.71)
0.18 (-0.35;0.81)
Trial Outcome Index-Colorectal
17
66.4 (10.6)
+4.7 (13.0)
0.152
0.36 (-0.20;0.96)
0.44 (-0.29;0.99)
a Standard Deviation. b Wilcoxon test for the difference. c Standardized Response Mean. d Effect Size
e Higher score indicates a higher level of functioning or better quality of life. f Higher score indicates more symptoms/problems. Bold indicate p values < 0.05.
Between the first and the fourth courses of chemotherapy, patients reported a "moderate" change for 5 functional scales (difference of scores greater than 10 points) and they reported a large change for the role function scale (difference of scores greater than 20 points). All these scales had a statistically significant (p < 0.05) except for the "social function" scale.
Patients also reported a "moderate" change of fatigue, pain, insomnia and appetite loss with a decrease of these symptoms (difference of scores greater than 10 points). But only the "fatigue" domain had a statistically significant (Δ = -16.3 (SD = 25.8), p = 0.02).
Considering the QLQ-CR38 scores, a statistically significant difference of the scores was only observed for the future perspective single item and the weight loss scale which showed "very much" change with a difference scores greater than 20 points (Δfuture perspective = +22.9 (SD = 31.5), p = 0.01 and Δweight loss = -22.9 (SD = 33.8), p = 0.02).
For the FACT-C scales, the only statistically significant difference of the scores was observed for the Functional Well-Being subscale (Δ = +10.0 (SD = 13.2), p = 0.007).
Responsiveness (Table
The indicators of responsiveness (SRM and ES) have been calculated for patients with improved health. The physical, role, emotional and cognitive function and the fatigue scale of the QLQ-C30 appeared to be responsive with values of the indicators (SRM and ES) greater than 0.5 reflecting moderate ability to detect an effect of chemotherapy treatment. The SRM for the global QoL/GHS score reflected moderate ability to detect treatment effect (SRM = 0.96). The indicators of responsiveness for the future perspective, weight loss and sexual dysfunction in women subscales of the QLQ-CR38 questionnaire reflected moderate ability to detect an effect of chemotherapy on change of clinical state (absolute values of SRM and ES between 0.51 and 0.79).
The changes in clinical state evaluated by the total score of the FACT-C questionnaire were not significant (SRM and ES < 0.20). Only a moderate ability of the Functional Well-Being scale to detect an effect of treatment was observed (SRM and ES between 0.58 and 0.75).
- Radiotherapy group
Between before radiotherapy and the last week of treatment, ten patients perceived their health as worsened, 21 as stable and 22 as improved. Among 22 patients with improvement, 16 patients were slightly better, 4 moderately better and only 2 patients were much better.
Description of scores (Table
Mean scores before the radiotherapy, change of scores between before and the last week of radiotherapy and responsiveness statistics in patients who perceived improved health (n = 22)
n
Score before radiotherapy Mean (SDa)
Difference Mean (SDa)
Pb
SRMc (CI 95%)
ESd (CI 95%)
EORTC QLQ-C30:
Functional scalese :
Physical function
22
83.9 (18.4)
-6.5 (16.4)
0.08
- 0.39 (-0.78;0.02)
- 0.35 (-0.85;0.21)
Role function
21
74.6 (27.2)
-6.3 (28.1)
0.07
- 0.22 (-0.74;0.22)
-0.23 (-0.78;0.21)
Emotional function
22
79.2 (17.8)
+3.8 (14.2)
0.23
0.26 (-0.19;0.67)
0.21 (-0.15;0.57)
Cognitive function
22
94.7 (7.9)
-4.5 (15.6)
0.19
- 0.29 (-0.67;0.17)
- 0.57 (-0.55;0.21)
Social function
22
78.8 (24.2)
-5.3 (22.0)
0.27
- 0.24 (-0.69;0.21)
- 0.21 (-0.78;0.16)
Global QoL/GHS
22
54.9 (22.7)
+5.7 (26.4)
0.32
0.21 (-0.32;0.53)
0.25 (-0.24;0.75)
Symptom scalesf :
Fatigue
22
38.9 (25.1)
+2.0 (28.4)
0.74
0.07 (-0.37;0.56)
0.08 (-0.37;0.70)
Pain
22
23.5 (23.9)
+8.3 (27.6)
0.17
0.30 (-0.16;0.84)
0.34 (-0.16;1.04)
Nausea and vomiting
22
2.3 (7.8)
+3.0 (12.2)
0.26
0.24 (-0.21;0.70)
0.38 (-0.75;1.33)
Single itemsf :
Dyspnoea
21
11.1 (16.1)
0.0 (14.9)
1.00
0.0 (-0.52;0.44)
0.0 (-0.41;0.38)
Sleep disturbance
22
28.8 (34.6)
-7.6 (35.5)
0.33
- 0.21 (-0.62;0.30)
- 0.21 (-0.64;0.30)
Appetite loss
21
20.6 (28.8)
+4.8 (35.4)
0.54
0.13 (-0.31;0.66)
0.16 (-0.32;0.91)
Diarrhoea
22
28.8 (31.4)
-1.5 (33.3)
0.83
- 0.04 (-0.56;0.39)
- 0.04 (-0.48;0.56)
Constipation
22
15.2 (24.6)
+12.1 (24.2)
0.03
0.50 (0.06;0.97)
0.49 (0.06;1.20)
Financial impact
21
10.6 (26.0)
+5.7 (26.4)
0.33
0.22 (0.17;0.31)
0.06 (-0.15;0.24)
EORTC QLQ-CR38:
Functional scalese :
Body image
20
90.9 (16.3)
-3.3 (14.5)
0.32
- 0.23 (-0.7;0.27)
- 0.20 (-0.81;0.50)
Future perspective
21
56.1 (26.0)
+4.8 (21.8)
0.33
0.21 (-0.23;0.72)
0.18 (-0.21;0.57)
Sexual functioning
20
16.7 (27.9)
-5.8 (21.8)
0.24
- 0.26 (-0.76;0.19)
- 0.20 (-0.54;0.17)
Sexual enjoyment
10
33.3 (49.4)
-26.7 (30.6)
0.02
- 0.87 (-1.79;-0.45)
- 0.53 (-1.03;-0.15)
Symptom scalesf :
Radiation-induced effects micturition
21
21.7 (22.6)
+19.3 (21.9)
0.0006
0.88 (0.42;1.44)
0.85 (0.36;1.50)
Chemotherapy side effects
21
15.2 (23.6)
+5.3 (13.0)
0.08
0.40 (-0.11;0.89)
0.22 (-0.15;0.55)
General Gastrointestinal symptoms
21
26.7 (14.9)
-0.4 (11.9)
0.88
- 0.03 (-0.50;0.46)
0.02 (-0.38;0.36)
Defecation problems
19
37.6 (21.6)
-1.5 (14.8)
0.66
- 0.10 (-0.59;0.41)
- 0.07 (-0.42;0.27)
Stoma-related problems
1
9.5 (00.0)
+23.8 (-)
-
-
-
Sexual dysfunction of men
9
35.9 (44.5)
+7.4 (20.6)
0.31
0.35 (-0.28;1.09)
0.16 (-0.09;0.65)
Sexual dysfunction of women
2
16.7 (23.6)
+16.7 (0.0)
1.00
0
0.70 (0.65;1.10)
Weight loss
21
28.8 (34.6)
+1.6 (38.7)
0.85
0.04 (-0.40;0.55)
0.04 (-0.43;0.67)
FACT-Ce :
Physical Well-Being
19
81.4 (16.4)
-5.0 (14.3)
0.15
- 0.34 (-0.77;0.17)
- 0.30 (-0.94;0.10)
Social/Family Well-Being
19
71.3 (25.7)
-7.4 (16.2)
0.06
- 0.45 (-0.96;0.09)
- 0.28 (-0.63;0.03)
Emotional Well-Being
19
77.5 (17.6)
0 (12.7)
1.00
0.0 (-0.78;0.31)
0.0 (-0.34;0.37)
Functional Well-Being
18
50.1 (20.0)
-2.5 (17.1)
0.55
- 0.14 (-0.71;0.40)
- 0.12 (-0.56;0.35)
Colorectal Cancer Specific
19
67.7 (11.5)
-3.2 (12.3)
0.27
- 0.26 (-0.64;0.24)
- 0.28 (-0.80;0.18)
FACT-C total score
19
69.1 (11.4)
-3.0 (8.5)
0.14
- 0.35 (-0.96;0.19)
- 0.26 (-0.64;0.15)
Trial Outcome Index-Colorectal
19
65.7 (13.7)
-2.6 (10.2)
0.29
- 0.25 (-0.78;0.31)
- 0.18 (-0.60;0.20)
a Standard Deviation. b Wilcoxon test of the change. c Standardized Response Mean. d Effect Size.
e Higher score indicates a higher level of functioning or better quality of life. f Higher score indicates more symptoms/problems. Bold indicate p values < 0.05.
A "small" deterioration of physical (Δ = -6.5, SD = 16.4), role (Δ = -6.3, SD = 28.1), and social functioning (Δ = -5.3, SD = 22.0) of QLQ-C30 and a "moderate" increase of constipation (Δ = +12.1, SD = 24.2) was observed during the last week of radiotherapy as compared to baseline; these differences were statistically significant only for constipation (p = 0.03)
No statistically significant changes were observed in QLQ-CR38 scales except for radiation-induced effects micturition scale (Δ = +19.3 (SD = 21.9), p = 0.0006) and sexual enjoyment scale (Δ = -26.7 (SD = 30.6), p = 0.02). Indeed, patients reported a large decrease in sexual enjoyment scores. For the FACT-C scales, no statistically significant differences of the scores including the global score were observed.
Responsiveness (Table
The indicators of responsiveness (SRM and ES) have been calculated for patients who perceived their health as improved. The SRM for the global QoL/GHS score was 0.21, reflecting a minimal ability to detect an effect of radiotherapy treatment on clinical change, as well as the pain (SRM = 0.30) and constipation (SRM = 0.50) subscales or items.
Indicators of responsiveness for the various scores of the QLQ-CR38 questionnaire reflected a fair ability to detect a treatment effect on clinical change. Only indicators for radiation-induced effects on micturition and sexual enjoyment (absolute values greater than or equal to 0.71) reflected a good responsiveness.
Analysis of responsiveness in all domains and the global score of the FACT-C questionnaire proved a fair ability to detect a particularly treatment effect. (absolute values of SRM and ES indices between 0.14 and 0.45).
Discussion
Test-retest reliability and responsiveness are two essential properties of a measuring instrument. To be responsive, a questionnaire should be reproducible
In CRC patients, the reproducibility of the EORTC QLQ-C30 questionnaires is good or excellent except for nausea/vomiting subscale (which can be explained by changes in the symptom intensity and changes in antiemetic treatment) and surprisingly for QoL/GHS questionnaire. The reproducibility of QLQ-CR38 questionnaire was good or excellent. The FACT-C showed a good reproducibility except for the Social/Family Well-Being subscale (ICC < 0.60). The responsiveness of each of these 3 questionnaires, according to the patient's assessment of his/her change in their state of health, differs according to treatment types: the EORTC QLQ-C30 questionnaire, compared to the QLQ-CR38 and FACT-C, appears as the most appropriate instrument to measure and to detect an effect of chemotherapy on QoL changes. Indicators of responsiveness of the global QoL/GHS score reflect moderate ability (ES) or a good ability (SRM) to detect an effect of chemotherapy on change of health status. In our study, the QLQ-CR38 and the FACT-C questionnaires provided little clinically relevant information during chemotherapy or radiotherapy. Four of the 12 scores of the QLQ-CR38 are related to sexuality and many answers to questions on this topic were missing. These conclusions are similar whatever the indicator of responsiveness used: Standardized Response Mean and Effect Size, all results going in the same direction.
Sensitivity of these questionnaires to detect change compared to the patient's assessment significantly differs according to the type of treatment (chemotherapy or radiotherapy). The best correlation between QoL assessment by self-rating questionnaires and the patient's overall assessment of his/her change in state of health is observed in patients receiving chemotherapy but only with the QLQ-C30. Indeed, measurements of functional scales and global QoL scores of the QLQ-C30 questionnaire are the most sensitive except for social function scale.
Our results suggest a lack of sensitivity of these QoL questionnaires compared to the patient's overall assessment of his/her change in state of health. These results of responsiveness in patients receiving chemotherapy are confirmed by the evolution of the QoL scores between the first and the fourth course of chemotherapy. Indeed, a clinical relevant variation was observed for all functional scales by the QLQ-C30, with mean difference superior to 10 points in ten scales and superior to 5 points for all scales.
These results can be explained by items on chemotherapy side-effects such as fatigue. No significant score's variations appeared with the FACT-C questionnaire which could be because this scale summates individual items that may not be changing in the same direction. Only the Functional Well-Being subscale reflects a good ability to detect an effect of chemotherapy on change of health status in patients.
That is likely to explain that this questionnaire is less responsive than the EORTC QLQ-C30.
It should be noted that, as SRM is unrelated to sample size and unit of measure, it lends itself to comparison between different measures which have been tested on samples of different sizes.
Interpretation of the results of the course of QoL scores and their responsiveness for patients receiving chemotherapy was performed independently of the chemotherapy regimen and of the disease status.
The EORTC QLQ-C30 detect QoL impairments in dimensions that are not specifically related to the primary cancer
However, we did not observe these results for these 3 subscales in patients ongoing radiotherapy.
The FACT-G questionnaire seems particularly useful as it provides a global score making it easier to use in the context of therapeutic trials
These 3 questionnaires referred to QoL issues are structured differently. Indeed, the QLQ-CR38 contains more symptoms items. The FACT-C questionnaire investigates more functional domains like QLQ-C30. The two specific questionnaires (QLQ-CR38 and FACT-C) have been developed for measuring the same disease so they might be comparable. Nevertheless, only few items are similar (for example: questions about body image and stoma).
Recently an updated version of the QLQ-CR38, the QLQ-CR29, has been developed
A limitation of this study is that the responsiveness analysis relied only on patients who perceived their health as improved. We did not analyse the responsiveness in patients with a decline in health due to the low number of patients. The response-shift phenomenon can be a possible explanation for the large percentage of patients who reported an improvement in their health status, while only a small percentage of participants reported a decline in health status. Response-shift can be considered the result of an adaptive response to a changed health status, and as such is viewed as a positive phenomenon. Several studies showed that it is plausible that a change in health perception is not primarily introduced by an intervention (e.g. chemotherapy), but by coping with the disease itself
Another limitation is that the questionnaire scales are differently constructed, therefore, it was difficult to compare directly the responsiveness of these questionnaires. Indeed, while some QoL measures include single symptoms items, others include summated scales. For example "diarrhea" is measured by a single item in QLQ-C30 questionnaire. However, diarrhea is part of the "colorectal cancer specific" concerns in FACT-C. Nausea and pain are separate two-item symptom scales in QLQ-C30, while they are both included in the "physical well- being" scale of FACT-C.
We studied the responsiveness during treatment but long-term complications have not been examined. It could be considered a limitation of this study. A strength of the present study is, however, that it was performed in various clinical situations for CRC patients.
Conclusion
Implications for practice: The present results showed that the responsiveness of QoL questionnaires, an essential property, is different according to the type of treatment. We hypothesized that disease-specific scales tend to be more responsive than generic health status measures. Unfortunately, our results were not conclusive. We observed that EORTC QLQ-C30 functional subscales may be responsive to improvement in overall health state in patients undergoing chemotherapy and we confirm that QLQ-CR38 needs improvement. An updated version of the QLQ-CR38, the QLQ-CR29 is now available
This study on responsiveness of the questionnaires provides arguments for the choice of generic to assess QoL in patients with CRC.
Implications for future research: Further investigation of the responsiveness to change of the EORTC CR29 module is warranted.
Abbreviations
CRC: ColoRectal Cancer; EORTC: European Organization for Research and Treatment of Cancer; ES: Effect Size; FACT-C: Functional Assessment of Cancer Therapy-Colorectal; FACT-G: Functional Assessment of Cancer Therapy-General; GHS: Global Health Status; QLQ-CR38: Quality-of-Life ColoRectal module; QoL: Quality of Life; RE: Relative Efficiency; SRM: Standardized Response Mean; TOI-C: Trial Outcome Index of FACT-C.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
Conception and design: FG, TC, MM
Provision of study materials or patients: LU, JM, MCK, MM, LT, IL, PM, PR, TC
Collection and assembly of data: LU, CR, IL
Data analysis and interpretation: LU, CR, FG, TC
Manuscript writing: LU, CR, TC, FG
Final approval of manuscript: All authors contributed to the manuscript and have read and approved its final version.
Acknowledgements
We gratefully acknowledge C. Carnin, P. Bataillard, E. Petit and E Lesieu for assistance with patient interviews, Thomas Roederer at the center of clinical epidemiology, INSERM CIE 6 University hospital Nancy for statistical assistance. We thank the physicians G. Créhange, P. Maingon, G. Truc, J. Fraisse, J. Cuisenier, B. Chauffert, E. Désandes and J.M. Tortuyaux who helped to recruit patients. We also thank Sonya Eremenco, Evanston, Illinois, for permission to use the FACT-C, and the EORTC QoL Unit, Brussels, for permission to use the EORTC QLQ-C30 and QLQ-CR38 questionnaires. This study was supported by grants from the French Ministry of Health Clinical Research Hospital Program (PHRC 2004) and the cancéropole Grand-Est.