|Year : 2015 | Volume
| Issue : 4 | Page : 580-585
Quality of life measures in glioma patients with different grades: A preliminary study
P Mahalakshmi1, AJ Vanisree2
1 Department of Neuropsychiatric, MBI-Lab, China Medical University Hospital, Taichung, Taiwan; Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India
2 Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India
|Date of Web Publication||10-Mar-2016|
A J Vanisree
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
BACKGROUND: Plethora of information exists in the literature on pathology of the glioma while prevailing research data on quality-of-life (QOL) of glioma patients marks dearth thus demanding more studies. AIMS: In this study, we examined the QOL of different grades of glioma patients among the Chennai population in India. MATERIALS AND METHODS: A total of 162 patients with different grades of glioma enrolled from August 2007 to February 2011, at their first contact to Department of Neurology and Neurosurgery, Government General Hospital, Chennai, India were included and their QOL was assessed by European Organization for Research and Treatment of Cancer Core QOL questionnaire (EORTC QLQc-30), EORTC brain cancer module (QLQ BN-20). RESULTS AND CONCLUSION: Both low and high grade glioma (LGG and HGG) patients had poor mean scores in social functioning (87.0), physical functioning (82.0) and emotional functioning (75.2) and role functioning (58.9). The mean scores on cognitive functioning (61.9) and global QOL (60.3) were better. Age, Karnofsky performance status, World Health Organization grades showed significant associations with all functional scales. The percentage values were higher for symptoms of fatigue (76.9%), pain (71.5%), financial difficulties (77.6%) and appetite loss (38.46%) in both LGG and HGG. Similarly, with respect to QLQ-BN20 domains, HGG patients showed more symptoms than low grade with a significant correlation in communication deficit problems (P = 0.02), headache (P = 0.04), seizures (P < 0.01), hair loss (P < 0.05) than the other symptoms. This initial assessment suggests that an increasing burden of symptoms exists, with poor QOL and survival, which has become a major concern in different grades of glioma patients.
Keywords: Brain tumor, different grades of glioma, glioma, health related quality-of-life, outcomes, quality-of-life
|How to cite this article:|
Mahalakshmi P, Vanisree A J. Quality of life measures in glioma patients with different grades: A preliminary study. Indian J Cancer 2015;52:580-5
| » Introduction|| |
Gliomas (astrocytomas, oligodendrogliomas and ependymomas) are the most common types of brain tumors among central nervous tumors. Together, they make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors., A recent report on the cancer registry survey conducted by Indian Council for Medical Research on glioma incidence in India revealed 5.8% in Mumbai, 6.7% in Bangalore, 3.5% in Chennai, 5.6% in Dibrugarh and 28.2% in Trivandrum among males and 6.3% in Mumbai, 5.6% in Bangalore, 7.5% in Chennai, 0% in Dibrugarh and 21.8% in Trivandrum among females. Due to an increasing burden of symptoms, poor quality-of-life (QOL) and survival has become the major concern along with the therapeutic efficacy in different grades of glioma.
Each grade of glioma has their individual impact on survival. The median survival of glioblastoma multiforme (GBM) (World Health Organization [WHO] Grade IV) is only 12-15 months, 2-5 years for patients with anaplastic glioma (WHO Grade III) and 4-10 years for patients with low-grade glioma (LGG), (including WHO Grades I and II). Burden of symptoms for each grade of glioma differs and studies evaluating new therapeutic protocols for the individual grades of glioma patients mainly consider mean survival and progression-free survival as a primary response measures. It is also increasingly important to assess the effects of present therapies on disease burden and health-related quality-of-life (HRQOL).
QOL measurement scales and outcome concerns have become increasingly important to assess the outcomes of research programs in recent years and to assess whether new therapeutic and technological strategies are justified in terms of efficacy, cost and net QOL benefit. Furthermore, QOL is a multidimensional construct, with many more domains than physical well-being. Recently, European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30), EORTC brain cancer module (EORTC QLQ-BN20) is being widely used to maximize the coverage of QOL issues and to fulfill demands of the reliability, validity, responsiveness and sensitivity of measurements and ascertain health and meaningful life-style in a primary brain tumor population.,,,, Emotional (EF), physical (PF), cognitive (CF) and social functioning (SF) as well as spiritual well-being in distinct areas is influenced by a person's beliefs, experience, expectations and perceptions. Patients report deterioration in their physical and intellectual ability, emotional state, personal relationships and career development so that they require integrated intervention strategies, including a suitable therapeutic approach and/or behavioral therapy. Difficulty in understanding the potential etiologies for the symptoms, better research models are needed to understand the possible factors, which can contribute to decreased QOL and symptom burden in order to develop treatment targeted interventions to improve patient's QOL. The present study investigates the potential impact of risk factors that affects QOL and survival of different grades of glioma patients among Chennai populations in southern part of India.
| » Materials and Methods|| |
Study design and participants
The study group comprised of 162 patients with different grades of glioma enrolled from August 2007 to February 2011, at their first contact to Department of Neurology and Neurosurgery, Government General Hospital, Chennai, India was included. Socio-demographic variables and medical variables of the recruited patients are presented in [Table 1]. QOL was assessed using two standard questionnaires (EORTC QLQ-C30 and QLQ-BN20 questionnaire). In addition, there was a study with specific questionnaire to collect data on the socio-demographic status of the study subjects. A baseline assessment was scheduled after referral by the general physician and before the diagnosis was made by the consultant in neuromedicine. At the time of the baseline interview, patients did not undergone surgery. All brain tumor patients were informed at a return appointment when the clinical tests were complete. Follow-up assessments were scheduled for those with a confirmed diagnosis of brain tumor 3 months later. Patients were eligible for enrolment in the study if they met the following criteria: Inclusion criteria include patients who were diagnosed with brain tumor, were over 18 years of age, were conscious and able to sign the consent form. Exclusion criteria includes suspect of brain tumor patients before the confirmation, those who had severe cognitive problems resulting in obvious difficult in communicating, those who had other disease such as diabetes, neurodegeneration, and heart related problems. Patients received written information about the study both in their mother language (Tamil) and in English. Telephonic interview was conducted offering further information about the study and enquiring whether they were willing to participate. In the written and the oral information, it was clearly stated that participation was voluntary and that confidentiality was assured.
Patients QOL were measured with the EORTC QLQ-C30. It is a 30-item questionnaire and consists of five functional scales (physical, role, cognitive, emotional and social), three symptoms scales (fatigue (FA), pain (PA) and nausea and vomiting (NV)) and a global health related QOL The remaining single items (six items) assess additional symptoms commonly reported by cancer patients including: Dyspnea (DY), lack of appetite, sleep problem, constipation as well as the perceived financial difficulties (FI) of the disease and treatment. The items on PF have dichotomous responses (yes or no). The sections on symptoms, anxiety, depression and limitations have a 4-point response choices ranging from 1 (not at all) to 4 (very much). The global questions on general health and QOL are a 7-point visual analog scale ranging from 1 (very poor) to 7 (excellent). Apart from the PF, all items employ 1-week time frame. Similar studies were performed for EORTC QLQ-BN20 questionnaire, which is 20-item questionnaire. The QLQ-BN20 consists of 20 questions; seven single item symptom scales (headaches, seizures, drowsiness, hair loss, itchy skin, leg weakness and bladder control), along with four multi-item scales (future uncertainty, visual disorder, motor dysfunction and communication deficit). Raw scores for the QLQ-BN20 items were computed and subsequently transformed linearly to a 0-100 scale.
Scoring of the responses to the QLQ-C30 (version 3.0) was carried out as previously described. The raw scores for each domain and single item were transformed to give a value between 0 and 100. For the five functional scales and the global health status/QOL scale, item responses were recorded so that a higher score represented a better level of functioning. For the symptom-oriented scales and items, a higher score corresponded to a severe level of symptoms. Differences of at least 10 points (on a 0-100 scale) were classified as clinically meaningful changes in the mean value of a HRQOL parameter. Differences between or within subgroups at baseline with respect to each patient characteristic variable were assessed for all QOL subscales or items using the Mann Whitney U-test or Kruskal-Wallis test. Spearman's rank correlation was used to investigate the relationships between the age, Karnofsky performance status (KPS), WHO grade and QLQ-C30, QLQ-BN20 subscales and items. A P < 0.05 was considered statistically significant. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software package, version 16.0 (SPSS Inc., Chicago, IL, USA).
| » Results|| |
A total of 186 brain tumor patients (excluding the pathologically confirmed non-cancer patients after surgery) were enrolled between August 2007 and February 2011, of whom 162 (87%) were pathologically confirmed glioma patients in Chennai population. Of these 186 patients, 162 were respondents and for 24 patients data was not available due to administrative errors or inability to complete the questionnaire due to profound neurological deficits. Baseline demographic data of 162 patients were represented in [Table 1]. The patients were in the age group between 18-72 years. There were 64 females (39.5%) and 98 males (60.4%). KPS ranged from 50 to 100. The distribution of KPS scores were as follows (score: [n: (%)]: <50: 22 [13.5%], 50: 26 (16.04%), 60: 11 (6.7%), 70: 32 (19.7%), 80: 51 [31.4%], 90: 15 [9.25%], 100: 5 [3.08%)]. Age seemed to present a considerable effect on the KPS scores. Older patients tended to have lower KPS scores; in fact, age had a greater effect on KPS than did any of the other variables were considered.
Majority of the patients had educational qualifications up to higher secondary level, 46 patients were at the primary level (up to 8th standard) and 52 patients were illiterate. Off 162 respondents, 98 (60.4%) patients filled the questionnaire themselves, whereas 64 (39.5%) patients required assistance due to illiteracy and some patients required assistance due to neurological deficits, motor weakness and other had cognitive (not severe) impairment. Twelve patients required assistance due to other causes. The scores in these patients were given by patients themselves, but were filled in the questionnaire by the care givers. Questionnaire was mainly filled in local language Tamil (n = 142, 87.6%) or in English (n = 20, 12.3%). Majority of the patients (n = 96, 59.25%) belonged to the lower socio-economic status while only 66 (40.7%) patients had monthly income of more than Rs. 3000/month.
Association of QLQ-C30 (functional scales) with variables such as age, sex, location, KPS, WHO grades were investigated. The proportions of all glioma patients with different scores at baseline prior to surgery in the functioning and symptom domains were depicted in [Table 2] and [Table 3]. Both HGG and LGG patients had mean scores in SF (87.0), PF (82.0) and EF (75.2) and RF (58.9). The mean scores on CF (61.9) and global QOL (60.3) were better. The percentage values were higher for symptoms of FA (76.9%), PA (71.5%), FI (77.6%) and appetite loss (AP) (38.46%), whereas other symptoms like DY, diarrhea and constipation their scores were found be lesser than 40% of all patients. [Table 4] shows mean QLQ-BN 20 scores of baseline patients including both histological subtypes of HGG and LGG irrespective of other data of the patients. Symptom domain scores and communication deficit scores were poor in HGG.
|Table 2: Association between QLQ--C30 (functional scales) with variables|
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|Table 4: Comparisons between high grade and low grade gliomas with BN--20 domains (symptom scales)|
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Age of patients in this study was divided into two groups; less than 50 and more than 50, discrimination for QOL widely being adopted in earlier QOL studies. A significant variation was found when functional scales such as PF (P < 0.05), EF (P < 0.04), SF (P < 0.01) and global QOL (P < 0.05) were analyzed. No significant difference was found in case of CF, RF within these groups. Similarly, in symptom scales, FA and PA were found to be significant than other symptoms (NV, DY, AP, FI). Older patients were observed to present more symptoms such as nausea, PA, FA and appetite than younger patients. With respect to sex and tumor location there was no significant difference when compared with both QLQ-C30 domains of both functional and symptom scale. Secondary and higher educational status did not significantly influence global QOL score (secondary vs. higher secondary).
KPS scores were categorized as two groups; less than 80 and greater than 80 and functional as well as symptom scales were compared within these two groups. A significant variation was found with almost all of the function scales more specifically in PF (P = 0.01), EF (P = 0.05), CF (P = 0.001), RF (P < 0.001) and QOL (P < 0.001). Similarly, in symptoms scales, FA (P < 0.001), PA (P < 0.01), AP (P < 0.001) were significant. Patients with less than 80 showed poor functional scales and more PA than >80 KPS patients. Tumor types are an important patient related factor that influences the baseline global scores. HGG (Grades III and Grade IV) versus LGG (Grades I and II) was worse with global health status/QOL (P = 0.04), PF (P < 0.001), EF (P = 0.05), SF (P < 0.001) similarly, for symptom scales, FA (P < 0.001), NV (P = 0.05), PA (P = 0.05)and FI (P = 0.02) showed significance among the grades.
In the study population of the two groups, HGG patients showed more symptoms than LGG patients with a significant correlation in communication deficit problems (P = 0.02), headache (P = 0.04), seizures (P < 0.01), hair loss (P < 0.05) than the other symptoms (future uncertainty, visual disorder, motor dysfunction, drowsiness, itchy skin) [Table 4].
| » Discussion|| |
Studying QOL, especially in patients with life-threatening diseases such as cancer is becoming increasingly important. It is argued that such understanding may help to deliver effective and efficient health-care. In general, QOL issues in brain tumor patients are varied from two broad perspectives:First, in clinical decision-making for individual patients including decisions to treat patients with curative or palliative intent and secondly, in the evaluation of new treatment modalities in group of patients. Yet the question remains like what are the factors that determine the quality of survival for brain tumor patients? It is important to assess these factors prospectively in order to identify not only the existence of physical signs or symptoms, but also the factors that predispose to them at a much earlier stage. The use of the EORTC QLQ-C30 and EORTC QLQ-BN20, simple questionnaires provide useful information to interpret the results with an added advantage of being ranked best  among the assessment models for measuring QOL in patients-with cancer.
In this study, the median values were lower for PF, EF and SF. Thus, the patients reported more difficulties in these domains than RF and CF. These domains are significantly related to the age factors. Mostly middle aged patients and old aged patients were found to be affected most significantly in these domains. Score for global QOL and other domains were relatively low before starting the therapy as also supported by a report Budrukkar et al., suggesting that the surgical intervention, diagnosis of a neoplasm, fear and future uncertainty could be the factors responsible for low scores. SF, psychological function and EF support networks also play a critical role in patients diagnosed with malignant glioma., Emotional distress mental problems have a stronger impact on QOL in low grade of glioma than physical ones. The median values were higher for symptoms of FA, PA and financial impact, which means that the patients suffered more problems with these symptoms than other. The current observation of most of the old age people (above the age of 60) being suffered from FA and PA was in consistent with the previous reports showing the existence of similar symptoms mostly in the middle aged.,
There was no significant difference with variables such as sex, tumor location when compared with QLQ-C30 scales. Some studies have reported even the tumor location can be a factor for predicting QOL of glioma patients for example cross total resection of supratentorial glioblastomas and anaplastic astrocytomas is feasible and is directly associated with longer and better survival when compared with subtotal resection. A study also observed the best survival rates occurred in patients who had at least three of the following features: <40 years of age, high KPS, frontal tumors and total resection. Still others have reported that tumor laterality had no effect on KPS, cognitive outcome, HRQOL. However, there exist uncertain relationship between tumor location and QOL which could be due to tumor laterality itself is not a sufficiently sensitive variable for analysis of QOL or could be the usage of different modules. In order to ascertain this, the study demands a larger number of patients and more effective scales to know these effects on QOL of different grades of glioma patients.
Generally, patients with KPS <70 are excluded by many investigations; however, in the present study KPS <70 has been included for QOL assessment with the only exclusion of patients who will not be able to complete performance. In the current study, patients with <70 QOL were filled either by them or also by their care givers. QOL is a very important consideration in the overall management of these patients. As KPS score >70 have the best prognosis, whereas patients with a KPS scores <40 have a significantly reduced overall survival time. Patients with KPS 80-100 presented with better functioning and global health status/QOL and fewer FA, PA, insomnia and AP symptoms than those with KPS <80. It is noteworthy that 69.2% of patients had KPS of 80-100 while no difference was shown in any scale or item of QLQ-C30 among these KPS subgroups (KPS 80, 90 and 100; data not shown). Correlation analysis showed that KPS was more strongly related to PF but more weakly related to global health status/QOL. Patients with a brain tumor were chosen for chemotherapy on the basis of good performance status (KPS ≥ 60), which could be a prognostic factor for good QOL after treatment.
In this study, most of the patients were of HGG and they showed a significant difference with PF, EF, CF and SF. Both high and LGG had more burden on patient's SF and EF than other functioning. A report states that the LGG population had lower reported emotional well-being scores compared with a normal population. The reason for the lower emotional well-being scores compared to a normal population may be related to the diagnosis of cancer, which has been shown to lead to emotional distress. Further, in LGG the tumor itself is the most important factor responsible for reduction of QOL score. In those patients who have a relatively poor baseline QOL score, the score was improved after chemotherapeutic intervention and was maintained for a substantial period until the time of further progression. A significant correlation was obtained with Global QOL with social well-being, in this study as most of these patients were illiterate and hence lack of interactions about their disease with doctors. Further, lack of affordability for therapy and surgery, poor interactions with others, emotional disturbances, depression cumulatively contribute to the strong relationship of QOL and FA.
QOL in brain tumor patients is complex and multidimensional in nature with symptoms having interrelationships with each other as well as patient, tumor and treatment factors. The major concern for glioma patients with symptoms were FA, sleep, PA, seizures, mood and cognitive function., In brain specific BN20 domains, results suggest that most of patients of tumor suffer with headache, seizures and more hair loss. A significant association instead of difference was found with headache, hair loss, seizures in HGG patients than in LGG. A significant correlation was obtained between FA and age factor and no significance with other clinical factors. Further research is required not only to define this symptom burden in a better way, but also to examine individual symptoms within specific populations. It is important for clinicians to realize and manage symptoms specific for each patients with glioma.
Symptom scales like FA, uncertainty about the future, motor difficulties, drowsiness, communication difficulties and headache were more common in high grades of glioma, which is in line with the other reports. Four symptoms (PA, AP, FI and NV) were reported more frequently in HGG patients. We also found even the hair loss was found to be predominant in HGG suggest the possible severity of glioma progression or the treatment effects. The symptoms and realms of QOL can be interrelated and because an individual patient is subject to different environmental and demographic factors, so the study of QOL can become quite complex.
Despite several limitations such as insufficient data, lack of statistical power, this study could highlight poor emotional, PF and PA in LGG. In addition to the poor emotional, physical SF, Global QOL, FA, PA hair loss was prominent in HGG. The limitations of this study could be met with refinement of analyses and data in future studies that could provide better care to the seriously affected glioma patients in Chennai population. The addition of QOL information to therapeutic strategies will be beneficial to both patients and physicians to make tailored and truly informed decisions about therapy and an improved QOL could in turn increase the overall survival of the patients.
| » Acknowledgment|| |
The study was supported by grants from the University Grants commission (UGC), India. We strongly acknowledge Dr. R. Arunkumar, Chief Neurosurgeon, Department of Neurology and neurosurgery, Government General Hospital, Madras Medical College, Chennai, India for his constant support throughout the study.
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[Table 1], [Table 2], [Table 3], [Table 4]