Assessment of quality of life in pediatric cancer patients ... · Assessment of quality of life in pediatric cancer patients at diagnosis and during therapy ... sex and diagnosis

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Turkish Journal of Cancer Vol.31/ No. 4/2001

Assessment of quality of life in pediatric cancer patients at diagnosis and during therapy

NİLGÜN YARIŞ1, MELEK NUR YAVUZ2, A. AYDIN YAVUZ2,

AYŞENUR ÖKTEN1

Departments of 1Pediatric Oncology and 2Radiation Oncology Karadeniz Technical University Faculty of Medicine,

Trabzon-Turkey

The aim of this study was to assess the quality of life (QoL) of patients with cancer at diagnosis and during the therapy and to obtain effects of sex, age, diagnosis, stage of disease and treatment on QoL. Thirty (16 male, 14 female) newly diagnosed patients with cancer were evaluated at diagnosis and three months after initiation of the treatment. The performance status of children were obtained according to Lansky play-performance scale. The Health Utilities Index-2 (HUI-2) health status classification system was used for the assessment of health related quality of life (HRQL). The global and single attribute utility scores and Lansky scores were evaluated according to age, sex and diagnosis of patients, stage of disease, treatment modality and response to treatment. The mean performance score and global utility scores of patients at diagnosis were significantly worse than those at third months of therapy (p=0.01 and p=0.04, respectively). Almost all of our patients (96.7%) suffered from a deficit of one or more attribute. Additionally, it is important to note that emotional deficit is reported in 96% of patients and pain was also an important problem for most of the patients. The type of cancer did not seem to have important effect on HRQL except brain tumor. The stage of disease had considerable importance on performance and HRQL scores. Treatment modality had also an impact on performance status and HRQL. Surgical intervention, intensive chemotherapy and hospitalization had negative effects on QoL. We did not find any effect of radiotherapy on QoL. Good responder to the treatment has better HRQL. In conclusion, we obtained that children with cancer had significant deficit in almost all domains of life. The health related quality of life was better at third months of therapy than that at diagnosis, despite the negative effect of treatment on QoL. This suggested that cancer itself is a more important factor affecting the QoL compared with its treatment. [Turk J Cancer 2001;31(4):139-149] Key words: Childhood, cancer, quality of life

QoL in PEDIATRIC CANCER PATIENTS 140

Treatment of childhood malignancy has shown significant progression over the past 30 years. The prognostic outlook of cancer patients altered the cure rate and life expectancy is increased (1,2). In this regard, prevention of discomfort and side effects has gained considerable importance (3). Attentions have been focused on quality of life (QoL) of children who have cancer and those who have survived cancer. National Cancer Institute recommended that the health related quality of life (HRQL) assessment should be a part of clinical trials (4). HRQL measures aim to examine the impact of a particular disease or treatment on the patient. Cancer patients are most likely to have disabilities that alter QoL, because cancer has impact on nearly every domain of life, and cancer itself and its treatment can cause considerable toxicity and complications. Assessment of HRQL at relevant points in time including diagnosis, active treatment, end of the therapy, relapse and follow-up period during the remission is important for optimizing the QoL of the cancer patients (3,5,6). The aim of this study was to assess the QoL of our patients with cancer at diagnosis and during the therapy. We also wished to obtain effects of sex, age, diagnosis, stage of disease and treatment on QoL.

Patients and Methods

Thirty (16 male, 14 female) newly diagnosed patients with cancer were evaluated at diagnosis and three months after initiation of the treatment. The mean age of patients was 9.7 ± 4.6 (range: 2-16) years. The diagnosis of patients were non-Hodgkin's lymphoma in nine, Hodgkin's disease in four, brain tumor in six, neuroblastoma in three, germ cell tumor in three, soft tissue and bone sarcoma in five. The stage of disease was stage I in one patient, stage II in eight patients, stage III in eight patients and stage IV in seven patients (brain tumors were not staged). The performance status of children was obtained according to Lansky play-performance scale (Table 1), which is appropriate for use with children aged 1 to 16 years, inpatients and outpatients, in active treatment and long term follow-up (7). The Health Utilities Index-2 (HUI-2) health status classification system described by Feeny et al. (8) was used for the assessment of the HRQL (Table 2). Health utility index is one of the multiattribute health status classification system used for assessment of HRQL. It was developed specifically for childhood cancer and focuses on functional capacity rather than performance. It comprised seven attributes: sensation, mobility, emotion, cognition, self-care, pain and fertility. Three to five levels of functioning are defined for each attribute. Comprehensive health states are described as a specific combination of seven attribute levels. Mathematically there are 24.000 unique combinations of levels of the seven attributes; therefore the system are capable of representing 24.000 unique health states. In this study the fertility domain was omitted because we performed the study in on-therapy patients not in cancer survivors. Global utility scores provide measures of overall HRQL, on a scale anchored by dead: 0.00 and perfect health: 1.00. Single attribute utility scores are defined on a scale from 0.00 for the lowest level of the attribute to 1.00 for normal level (unimpaired level). Single attribute utility scores reflect the

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morbidity burden within a particular attribute. The HUI-2 questionnaire was practiced by interviews with parents, as recommended. The parents responded to the questions regarding their child’s functioning on each of the attributes and regarding any impairments that were results of child’s illness or treatment.

Table 1 Play Performance Scale for children

100 fully active, normal

90 minor restrictions in physically strenuous activity

80 active, but tires more quickly

70 both greater restriction of, and less time spent in, active play

60 up and around but minimal active play, keeps busy with

quieter activities

50 gets dressed, but lies around much of the day; no active play;

able to participate in quiet play and activities

40 mostly in bed; participates in quiet activities

30 in bed; needs assistance even for quiet play

20 often sleeping; play entirely limited to very passive activities

10 no play; does not get out of bed

0 unresponsive

Lansky score and HUI-2 scores were assessed at admission and at the end of third months of therapy. The global and single attribute utility scores, and Lansky scores were evaluated according to age, sex and diagnosis of patients, stage of disease and treatment modality. The effect of surgical intervention (except biopsy) on QoL was evaluated at diagnosis and at third months of treatment. Fifteen patients had been operated at diagnosis and surgical intervention was performed within the first three months of the therapy in three patients. Effects of radiotherapy and chemotherapy were also investigated three months after initiation of the treatment. Thirteen patients had received radiotherapy within three months. To analyze the effect of chemotherapy on QoL, the patients were evaluated by grouping them according to receiving intensive or non-intensive chemotherapy. Chemotherapy regimen was described as intensive when it contained more toxic drugs such as cisplatin, ifosfamide and high dose methotrexate and when hospitalization was necessary for administration of the chemotherapy. The chemotherapy protocols that could be administered outpatient such as COPP, ABVD, VAC, EVAC protocols were accepted as non-intensive. Twenty-three patients received intensive protocols and seven received non-intensive protocols. The effects of duration and frequency of hospitalization on QoL were also evaluated. Ten out of 23 patients


who received intensive protocol stayed in hospital less than five day for each course, whereas 13 patients stayed more than five day. The time between courses was three to four weeks in 16 patients, approximately six weeks in 7 patients. Before second evaluation of HUI-2 scores re-staging was done. Complete response was defined as totally disappearance of tumor mass and tumoral involvement and disease related symptoms, and normalization of abnormal tests. When tumor masses or organ involvement had a decrease of at least 50%, along with the disappearance of disease related symptoms, it was considered as a partial response. A decrease less than 50% or an increase not more than 25% in tumor size or organ involvement was considered as a stable disease. The effects of response on QOL were evaluated. Response was defined as complete in 11 patients, partial in five patients, stable disease in three patients and progressive disease in one patient. Nominal data were compared by using Fisher's exact test or χ2 test depending on the number of cases. The mean Lansky scores, global and single attribute scores were compared by using Student's t-test. The effects of sex, age, diagnosis of patients, stage of disease and treatment were evaluated by using Kruskal-Wallis test or Mann Whitney–U test depending on number of the group.

Results The mean Lansky performance score of patients at diagnosis were significantly worse than those at third months of therapy (p=0.01) (Table 3). Age, sex and diagnosis of patients had no effects on performance score of patients. The patients who had early stage disease had significantly better performance status than those with advanced stage disease at admission and at third month (p=0,0001 and p=0.0001, respectively). Patients who were operated at diagnosis had worse Lansky score than the others (p=0.04). Patients who had complete or partial response had better performance score than poor responder at third months of therapy (p=0.04). The mean global utility score of 30 patients at third months of therapy were significantly better than that at diagnosis (p=0.04). The mean single attribute utility scores for mobility, emotion, self-care and pain at diagnosis were significantly lower than those at three months of therapy (Table 3). Twenty-three different health states were reported describing the health status of the 30 patients at diagnosis, whereas 15 health states were reported at third months of treatment. Only one of the patients had no deficit on any of the five attributes at diagnosis and at third months of therapy. Twenty-nine of children identified as having deficit, most (67%) had a deficit in three or more attributes at presentation whereas half (50%) had three or more deficit at third month. In table 4 frequencies of the number of attributes affected are reported. When single attribute utility scores were evaluated it was obtained that the sensation and cognition deficit were reported in very few patients at diagnosis and at third months of therapy. Emotional deficit and pain were obtained in the majority of the patients (Table 5).

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Table 2 The Multiattribute Health Status Classification System

Attribute

Level Description Sensation 1 Ability to see, hear, and speak normally for age 2 Requires equipment to see or hear or speak 3 Sees, hears, or speaks with limitations even with

equipment 4 Blind, deaf, or mute

Mobility 1 Ability to walk, bend, lift; jumps, or runs normally for age 2 Walks, bends, lifts, jumps, or runs with some limitations but

does not require help 3 Requires mechanical equipment (such as canes, crutches,

braces, or wheelchair) to walk or get around independently 4 Requires the help of another person to walk or get around

and mechanical equipment as well

5 Unable to control or use arms and legs Emotion 1 Generally happy and free from worry 2 Occasionally fretful, angry, irritable, anxious, depressed, or

suffering night terrors 3 Often fretful, angry, irritable, anxious, depressed, or

suffering night terrors 4 Almost always fretful, angry, irritable, anxious, depressed

5 Extremely fretful, angry, irritable, anxious, depressed, usually required hospitalization or psychiatric institutional care

Cognition 1 Learns and remembers school work normally for age 2 Learns and remembers school work more slowly than

classmates as judged by parents and/or teachers 3 Learns and remembers school work very slowly and

usually requires special educational assistance

4 Unable to learn and remember Self-care 1 Eats, bathes, dresses, and uses the toilet normally for age 2 Eats, bathes, dresses, and uses the toilet independently

but with difficulty 3 Requires mechanical equipment to eat, bathe, dress, or

use the toilet independently

4 Requires the help of another person to eat, bathe, dress, or use the toilet

Pain 1 Free pain and discomfort 2 Occasional pain. Discomfort relieved by nonprescription

drugs or self-control activity without disruption of normal activities

3 Frequent pain. Discomfort relieved by oral medicines with occasional disruption of normal activities

4 Frequent pain; frequent disruption of normal activities. Discomfort requires prescription narcotics for relief

5 Severe pain. Pain not relieved by drugs and constantly disrupts of normal activities

Fertility 1 Ability to have children with a fertile spouse 2 Difficulty in having children with a fertile spouse 3 Unable to have children with a fertile spouse


Table 3 HUI-2 and Lansky Performance Scores of patients*

Attributes diagnosis 3rd month p Sensation 1.00 ± 0 0.98 ± 0.012 0.18 Mobility 0.77 ± 0.23 0.86 ± 0.21 0.02 Emotion 0.68 ± 0.18 0.70 ± 0.15 0.0001 Cognition 0.98 ± 0.07 0.97 ± 0.08 0.24 Self-care 0.71 ± 0.31 0.84 ± 0.21 0.005 Pain 0.72 ± 0.12 0.78 ± 0.10 0.03 Global 0.81 ± 0.12 0.85 ± 0.11 0.04 Lansky 59 ± 23 68 ± 18 0.01

*Data was given as mean ± standard deviation

Table 4 Frequencies of Attributes Affected

Number of attributes

affected Number and % of

patients at diagnosis Number and % of

patients at 3rd month 0 1 (0.03) 1 (0.03) 1 2 (0.07) 3 (0.10) 2 7 (0.23) 11 (0.37) 3 5 (0.17) 3 (0.10) 4 13 (0.43) 10 (0.34) 5 2 (0.07) 1 (0.03) 6 0 1 (0.03)

Sex and age had no effects on the global HUI-2 score and any of the six attributes utility score. When six diagnostic groups were evaluated, the global utility score at admission was found significantly related with diagnosis (p=0.04). Single attribute score for motility at diagnosis and for cognition at third months of treatment were significantly related with diagnosis (p=0.04 and p=0.02, respectively). When the diagnostic groups were compared two by two, patients with brain tumor had significantly worse global utility scores and motility scores than Hodgkin's and non-Hodgkin's lymphoma at diagnosis and cognition scores at third months of therapy (for Hodgkin's lymphoma p=0.01, p=0.02 and p=0.04, respectively; for non-Hodgkin's lymphoma p=0.01, p=0.02 and p=0.02, respectively). The patients with early stage disease (Stage I-II) had significantly better global utility score (p=0.001) and single attribute utility scores for mobility (p=0.02), for emotion (p=0.009), self-care (p=0.001) and pain (p=0.005) than those with advanced disease (Stage III-IV) at diagnosis. Early stage disease had better global utility score, motility score and self care score three months after initiation of the treatment (p=0.01, p=0.01 and p=0.03, respectively).

Table 5 Health status of patients at diagnosis (1) and at third months (2)

Attribute frequency (%) Attribute

level Sens. 1 Sens. 2 Mob. 1 Mob. 2 Emot. 1 Emot. 2 Cog. 1 Cog. 2 S-C. 1 S-C. 2 Pain 1 Pain 2 1

30 (100)* 29 (96.7) 11 (36.7) 17 (56.7) 3 (10.0) 1 (3.3) 28 (93.3) 27 (90.0) 13 (43.3) 16 (53.3) 2 (6.7) 4 (13.3)

2

0 1 (3.3) 11 (36.7) 9 (30.0) 11 (36.7) 17 (56.7) 2 (6.7) 2 (6.7) 9 (30.0) 11 (36.7) 14 (46.7) 21 (70.0)

3

0 0 2 (6.7) 1 (3.3) 13 (43.3) 8 (26.7.) 0 1 (3.3) - 1 (3.3) 14 (46.7) 5 (16.7)

4

0 0 5 (16.7) 2 (6.7) 3 (10.0) 4 (13.3) 0 0 8 (26.7) 2 (6.7) 0 0

5

- - 1 (3.3) 1 (3.3) 0 0 - - - - 0 0

Total deficit (level 2-4/5)

0 1 (3.3) 19 (63.3) 13 (43.3) 27 (90.0) 29 (96.7) 2 (6.7) 3 (10.0) 17 (56.7) 14 (46.7) 28 (93.3) 26 (86.7)

*Number of patients (%) Sens.: Sensation, Mob.: Mobility, Emot.: Emotion, Cog.: Cognition, S-C.: Self-care


The patients who were operated at diagnosis had significantly worse single attribute utility scores for motility, emotion, self-care and global utility scores (p=0.01, p=0.002, p=0.04, and p=0.007, respectively). There were no associations between radiotherapy and global and any of the single attribute utility scores. The parents of patients who were treated with intensive protocols reported significantly worse levels of global, emotional and self-care utility scores than those treated with non-intensive protocols (p=0.04, p=0.008 and p=0.03, respectively). The duration and frequency of hospitalization were significantly related with the global, emotional and self care utility score (for duration of hospitalization p=0.02, p=0.009 and p=0.04, respectively; for frequency of the hospitalization p=0.003, p=0.001 and p=0.005, respectively). Patients who had complete or partial response had better global utility score (p=0.007) and single attribute utility score for sensation (p=0.008), emotion (p0.004), self-care (p=0.02), pain (p=0.003) than those who had stable or progressive disease.

Discussion Social, environmental, political, economical factors and health status affect individual’s quality of life. The health status is defined as the complete physical, mental and social well being and not merely the absence of disease or infinity (9). Health related quality of life measures assess the effect of a disease on health status. Cancer has an important effect on physical, mental and social domain of health. Accurate HRQL information could make a major contribution to improving the management and optimizing QoL of children with cancer (6,10). Despite its importance, there are currently little studies about the impact of cancer and its treatment on quality of life of pediatric cancer patients (3,5,10). There has been an increase in the use of HRQL evaluation in clinical research on adult cancer patients (12). Studies on adult cancer patients provided information about the HRQL in different patient groups, in different therapeutic regimens and about the prognostic effect of HRQL (13-15). HRQL research in pediatric oncology has only just begun using comprehensive, disease-specific instruments (5,11,16,17). Lansky (6), described a play performance scale for assessing functional performance capacity of children with cancer, similar to Karnofsky scale of adulthood. Bradlyn et al. (18) used Quality of Well Being scale as a measure of HRQL for children with cancer. Goodwin et al. (19) reported on the development and validation of Pediatric Oncology Quality of Life Scale for assessing the QoL of children with cancer. In 1992 Feeny et al. (8) described HUI-2 system, which was a multi-attribute health status classification system specific for childhood cancer. The multidimensional HUI-2 health status classification system uses seven attributes to assess seven domain of health status. Therefore the system is designed to assess the extent of deficits in health status for each attribute to inhibit or prohibit normal functioning. Although it is recommended that the HRQL assessment should be performed repeatedly (on admission, during the active treatment, at the end of therapy and during long-term follow-up) on and off-therapy patients (5,6,16,17), it has generally been used for assessing long term QoL in survivors of childhood cancer (20-22). Apajasalo et al. (23) reported that the perceived

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HRQL of adolescent and adults surviving malignancies in childhood is at least as good as that of normal population. Similarly, it was reported that bone cancer survivors was not necessarily at risk of developing long term emotional or social problems and are not precluded from leading active and independent lives (24). In contrast, high risk ALL survivors have lower cognitive and emotional score compared with healthy population (25). Billson et al. (26) used six attributes by excluding fertility like us to assess 48 children with cancer, completed their treatment and obtained 67% of patients having a deficit in one or more domain and neuroaxial tumors had lower scores. Although survival rates reach up to 80-90% in Hodgkin's disease, decrease especially in cognition, emotion and pain scores were reported in Hodgkin's disease survivors (27). It was shown that brain tumor survivors suffer a greater burden of morbidity than standard risk ALL patient (28). There were few studies measuring the HRQL on-therapy patients. Feeny et. al. (8) compared patients on- and off-therapy for high risk ALL, Wilms tumor and neuroblastoma. They obtained patients on-therapy suffered a greater burden of morbidity than those who were off-therapy. Assessment of HUI weekly in patients with ALL who were on maintenance therapy has shown a decline in HUI scores during the corticosteroid treatment (29). We measured HRQL at diagnosis and at third months of therapy. Almost all of our patients (96.7%) had suffered from a deficit of one or more attribute. Additionally, it is important to note that emotional deficit is reported in as high as 96% of patients, pain was also an important problem for most of the patients. We found that performance and HRQL was worse on admission and got better with treatment. The type of cancer did not seem to have important effect on HRQL except brain tumor. The stage of disease has considerable importance on performance and HRQL scores. Treatment modality also had an impact on performance status and HRQL. The surgical intervention, intensive chemotherapy and hospitalization have negative effect on QoL. We did not find any effect of radiotherapy on QoL possibly because of the very short time between the radiotherapy and measurement to obtain the effect of radiotherapy. As one would expect, good responder to the treatment has better HRQL. In summary, we showed that the multi-attribute health status classification system provides a useful tool for evaluating the HRQL during active treatment. We obtained that children with cancer had significant deficit in almost all domains of life. The HRQL was better at third months of therapy than that at diagnosis, despite the negative effect of treatment on QoL. This suggested that cancer itself is a more important factor affecting the QoL compared to its treatment.

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