Atormac
briv
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 1990  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
    Similar in PUBMED
 Related articles
    Article in PDF (1,717 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this Article
   Abstract
  Subjects and Methods
  Results
  Discussion
  Conclusions
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed544    
    Printed16    
    Emailed0    
    PDF Downloaded13    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents    
ORIGINAL ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 6  |  Page : 1613-1618

Health-related Quality of Life Assessment in Patients with Malignant Gliomas


1 Department of Neurology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey
2 Department of Neurosurgery, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey
3 Department of Neurosurgery, Kırıkkale Yuksek Ihtisas Research and Training Hospital, Kirikkale, Turkey
4 Department of Neurosurgery, Baskent University, Medical Faculty, Istanbul, Turkey
5 Department of Neurosurgery, Sakarya University Training and Research Hospital, Sakarya, Turkey

Date of Submission07-Apr-2021
Date of Decision13-Jul-2021
Date of Acceptance02-Aug-2021
Date of Web Publication23-Dec-2021

Correspondence Address:
Dr. Rahsan Kemerdere
Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Fatih, Istanbul
Turkey
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.333476

Rights and Permissions

  Abstract 


Background: High-grade gliomas have limited time of survival despite aggressive treatment. Patients experience a decline in their physical and mental capacities, affecting their quality of life (QoL), and require proper therapeutic strategies.
Objective: To assess the QoL of malignant glioma patients before and after the treatment in a longitudinal study of six months.
Methods and Material: Forty-nine patients who were pathologically diagnosed with glioblastoma and anaplastic glioma according to WHO 2016 were included in this prospective study. The assessment of quality of life was done using the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QoL) questionnaire core-30 prior to surgery, 1 and 5 months after the operation.
Results: The decline in Karnofsky scores of the patients was statistically significant. Among the symptom scales, fatigue was more prominent after surgery while pain was noticeable during chemotherapy which was correlated with increased age. The mean overall QoL scores showed a clinically significant decline during the postoperative period. The functional scores demonstrated a significant decline in between all periods. Sex was significantly correlated with preoperative emotional and physical functioning. The patients with right-sided lesions had higher mean scores for social and cognitive functioning.
Conclusions: Low KPS, older age, and female gender may affect cancer symptoms and physical and social activities in malignant glioma patients. Cognitive functions as well as social and occupational roles gradually decline during the first six months of treatments. Overall QoL of high-grade glioma patients deteriorates especially after radiotherapy and during the first months of chemotherapy.


Keywords: EORTC, glioma, high grade, quality of life
Key Message: Regarding the fact that QoL of patients with high-grade glioma starts to break down during the first half of survival, physical therapy and psychological support may be encouraged to increase the independence of patients and help to manage emotional collapse.


How to cite this article:
Taskiran E, Kemerdere R, Akgun MY, Cetintas SC, Alizada O, Kacira T, Tanriverdi T. Health-related Quality of Life Assessment in Patients with Malignant Gliomas. Neurol India 2021;69:1613-8

How to cite this URL:
Taskiran E, Kemerdere R, Akgun MY, Cetintas SC, Alizada O, Kacira T, Tanriverdi T. Health-related Quality of Life Assessment in Patients with Malignant Gliomas. Neurol India [serial online] 2021 [cited 2022 Jan 26];69:1613-8. Available from: https://www.neurologyindia.com/text.asp?2021/69/6/1613/333476




High-grade gliomas constitute more than 40% of primary brain tumors.[1] Glioblastoma (GBM), which stands for about half of these malignant tumors, is a fatal disease with a limited time of survival despite aggressive treatment.[2] Long-term survival denoting >36 months is only seen in 2%–5% of the patients;[3] three-year survival is seen in 16% of the patients receiving Stupp protocol.[4] However, nonsurgical treatment modalities such as immunotherapy, which are promising to increase lifespan up to 14 years, are imminent.[5] In fact, longer survival has a sense in the presence of well-being and an active life. Quality of life (QoL) is a complex phenomenon involving both psychological and physical elements and affects a person's socialness.[6] Due to its rapidly progressive nature, patients with malignant glioma experience decline in their physical and mental capacities and cognitive states, which affects QoL and requires proper therapeutic strategies.[7] Therefore, it is more challenging to study QoL in patients with diffuse gliomas than other tumor types. There are scarce studies evaluating the influence of chemotherapy and radiotherapy on health-related QoL (HRQoL) during the disease process.[8] Nevertheless, the research on the overall HRQoL of patients with malignant glioma is evolving.[7],[9],[10]

The aim of the present study was to assess the QoL of malignant glioma patients before and after the treatment in a longitudinal study of 6 months. We used the EORTC QoL questionnaire core-30 (QLQ-C30) to demonstrate the functioning, global health status, and symptoms experienced by the patients.


  Subjects and Methods Top


Participants

In total, 56 patients who were scheduled for surgery with the initial diagnosis of high-grade glioma according to preoperative cranial magnetic resonance images (MRI) at our clinic from September 2017 to October 2020 were selected to complete the survey. Among these, 49 of the patients who were pathologically diagnosed as glioblastoma WHO Grade IV and anaplastic glioma WHO Grade III were enrolled in the study. Only the patients with newly diagnosed disease who had no other type of cancer or severe comorbidities decreasing the QoL were included. The exclusion criteria comprised previous psychiatric or cognitive disorders and any prior history of radiotherapy or chemotherapy. The Karnofsky Performance Scores (KPS), neurological examination, and presence of seizures were noted at the time of admission. KPS <50 were not included. No one was excluded due to deterioration during the study period. The extent of resection was based on postoperative MRI (Total resection indicating no contrast-enhanced lesion and subtotal was resection of <90% of the tumor). All patients received radiotherapy and chemotherapy starting one month after the operation according to the Stupp protocol.[4] Thus, the first postoperative follow-up (one month after surgery) was before the initiation of adjuvant therapies. The assessment of QoL was done using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) prior to surgery as well as 1 and 6 months after the operation. The questionnaires were filled by the patients or their caregivers in case of neurological deficits or cognitive impairments. The patients or their caregivers have given informed consent for the research. Our study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki, and ethical approval was obtained from the ethics review board of our Medical Faculty.

The EORTC core quality of life questionnaire (QLQ-C30) version 3.0

The questionnaire consists of 30 items that aggregate into 15 scales. The first 28 items have four-point scales that are coded with the same response categories: “Not at all,” “A little,” “Quite a bit,” and “Very much.” The last two items include seven-point scales assessing overall health and QoL rating between 1 and 7.

The scales represent different aspects of QoL in cancer patients. It integrates five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status/QoL scale (overall QoL), various single items evaluating common additional symptoms experienced by cancer patients (dyspnea, loss of appetite, insomnia, constipation, and diarrhea), and financial effect of the disease. First, raw scores of each item were calculated and then converted to a value on a 0–100 scale. The lower the score, the worse the HRQoL for the global health status and functional scales and the better for the symptom scale. Mean differences of at least 10 points were accepted as clinically significant according to the previous studies.[11]

Statistical analysis

Statistical analysis was performed using SPSS version 20.0 package (SPSS Inc., Chicago, IL, USA). Nonparametric tests were used for significance as normal distribution was not assumed. Mann–Whitney U-test and Kruskal–Wallis test were used to assess differences between the subgroups of EORTC items at baseline with respect to each characteristic variable. Wilcoxon signed-rank test was used to compare preoperative and postoperative follow-up scores. Spearman correlations were used to assess correlations between the scores of items and KPS/age. P < 0.05 was deemed to indicate statistical significance.


  Results Top


Demographic data of the patients are outlined in [Table 1]. The mean age of the patients was 55.30 ± 15.79 years of age (range: 14–86). Three patients died because of the disease; the sixth-month follow-up of these patients was recorded as missing data.
Table 1: Demographic data of the patients and tumors

Click here to view


Seventeen patients had epilepsy as the presenting symptom (34.7%). Postoperative Engel scores were Class 1 in 35 patients (71.4%), Class 2 in 12 (24.5%), and Class 3 in two patients (4.1%). Presence of epilepsy showed significant difference only in physical functioning before surgery (P = 0.048). Contrariwise, postoperative scale scores did not show a statistically significant difference with the Engel scores.

The differences between the results of EORTC scores in three different follow-up periods were evaluated [Table 2]. Although the mean overall QoL scores increased between the preoperative and postoperative first-month follow-up (PO1), only 14 patients (28.6%) showed clinically significant improvement (>10 points), which was not statistically significant. On the other hand, deterioration between the first and sixth months after surgery had statistical significance [Figure 1]b. The scores of physical functioning (PF) demonstrated a gradual statistically significant decline in most patients especially one month after surgery [Figure 1]c. The scores of emotional functioning (EF) decreased significantly in between all follow-ups specifically between the two postoperative periods [Figure 1]d. The differences in the scores of role functioning (RF), cognitive functioning (CF), and social functioning (SF) were all clinically significant in a negative way among preoperative and postoperative records, particularly after surgery [Figure 2]. The scores of financial functioning (FF) increased significantly in 14 patients (28.6%) at the PO1 in comparison with the preoperative results.
Figure 1: Mean KPS (a), overall QoL (b), physical (c), and emotional functioning (d) scores between preoperative (1), postoperative 1 month (2), and 6 months (3). Only the significant P levels are presented.

Click here to view
Figure 2: Mean role (a), social (b), cognitive functioning (c), and financial (d) scores between preoperative (1), postoperative 1 month (2), and 6 months (3). Only the significant P levels are presented.

Click here to view
Table 2: Clinically important changes in EORTC scores of patients

Click here to view


According to the correlational analysis, age of the patients was weakly correlated with postoperative overall QoL at six months (r = −0.368, P = 0.012), preoperative and postoperative PF at six months (r = −0.300, P = 0.036; r = −0.368, P = 0.012, respectively), postoperative CF at one month (r = −0.292, P = 0.042), and preoperative SF (r = −0.308, P = 0.042). It was moderately correlated with postoperative RF at one and six months (r = −0.408, P = 0.004; r = −0.414, P = 0.004, respectively). Among the symptom scales, age was correlated weakly with postoperative pain at one and six months (r = 0.359, P = 0.011; r = 0.333, P = 0.024, respectively), postoperative fatigue and insomnia at one month (r = 0.299, P = 0.037; r = 0.288, P = 0.045, respectively), postoperative dyspnea at six months (r = 0.288, P = 0.045). Consistent with these findings, age was negatively correlated with the functional scores but positively correlated with the symptom scores.

Sex was significantly associated with merely the preoperative EF (P = 0.05) and preoperative PF (P = 0.001). Males had higher mean scores in both scales (mean = 78.39 and 90.12, respectively) [Figure 3].
Figure 3: Scores of emotional functioning related to sex.

Click here to view


The mean KPS scores before and after surgery (at the first and sixth months) were 83.06 (range: 50–100), 73.06 (range: 30–90), and 63.47 (range: 40–90), respectively. The decline in KPS of the patients was significant statistically (P < 0.0001) [Figure 1]a. The correlation analyses showed that preoperative KPS scores were weakly correlated only with SF (r = 0.316, P = 0.027). There was statistically significant correlation between KPS scores and global health status, PF, SF, and financial scores at PO1 (r = 0.466, P = 0.001; r = 0.466, P = 0.001; r = 0.336, P = 0.018; r = -0.283, P = 0.049, respectively). FF demonstrated a weak negative correlation while the others showed moderate positive correlations to KPS scores. There was statistically significant, but weak correlations, between KPS scores and global health status/QoL, PF scores at postoperative six-month (PO6) (r = 0.327, P = 0.027; r = 0.327, P = 0.027, respectively).

73.5% of the lesions (n = 36) were resected totally while two of the patients (4.1%) underwent biopsy. No statistically significant difference was found when we compared the excision rate (total vs. subtotal-biopsy) with the postoperative scores.

We compared the side of lesion with the pre- and postoperative scores. We found statistically significant difference in SF (P = 0.017) at PO1 in CF at preoperative and postoperative six-month (P = 0.007 and 0.006). The patients with right-sided lesions had higher mean scores (51.78) for SF than left-sided ones (30.15). The preoperative cognitive mean score was 84.52 for right-sided lesions whereas 61.90 for left-sided ones. On the contrary, cognitive mean scores at PO6 were 53.33 and 23.81 for the right and left sides, respectively.

We categorized the locations of tumors into lobar (n = 41) and deep (n = 8) to evaluate the scores according to the localization. Statistically significant results were achieved for RF and CF at PO1 (P = 0.042 and 0.019, respectively) for pain and fatigue scores at PO1 (P = 0.020 and 0.011, respectively) and insomnia at PO6 (P = 0.038). The patients with tumors localized in deep areas (insular and thalamic) had worse mean scores for RF, CF, pain, fatigue, and insomnia at signified periods compared to lobar tumors.


  Discussion Top


The new concept in diffuse glioma surgery has improved to provide good QoL besides increasing survival. Although this is predominantly true for low-grade gliomas, there is a recent trend for measuring HRQoL in glioblastoma patients.[10],[12] Nevertheless, the gap of knowledge remains. In this respect, we aimed to provide data about the well-being of high-grade glioma patients at three time periods: 1. Before surgery, 2. After surgery and before radiotherapy, 3. After radiotherapy and during chemotherapy. Main determinants of QoL in cancer patients are both symptoms of disease and side effects of treatment modalities. Our results in the first period show mainly the burden of disease itself. It reflects the effects of surgical treatment in the early follow-up, whereas it exhibits both the effects of radiotherapy and chemotherapy in the second follow-up (six months after surgery).

Symptom scales and additional cancer symptoms

It is reported that the symptoms frequently encountered during the treatment of glioblastoma such as nausea, vomiting, loss of appetite, and constipation increased over time after Stupp protocol, but overall QoL was not considerably affected during adjuvant therapies.[8] However, there are studies affirming that disease-related symptoms have a negative impact on HRQoL[13] as the symptoms were related to the overall QoL in our study. The main symptoms that bothered our patients were fatigue, loss of appetite, pain, and insomnia. Fatigue was more prominent after surgery, while pain was prominent during chemotherapy. Similarly, Solanki et al.[12] and Steinbach et al.[14] reported that fatigue and lack of good quality sleep were among the most common factors which affect social life and daily activities of long-term survivors of GBM. Our results also suggested that increased age was associated with worse scores of pain, fatigue, insomnia, and dyspnea following surgery.

Functional scales

Physical deterioration leading to depression devastates HROoL.[15] The main disabling issue after surgery was varying degrees of hemiparesis detected in 36% of our patients. Over 80% of the patients had normal activity before the operation. However, their ability to self-care decreased progressively over time after surgery and radiotherapy such that only 19.5% were capable of normal activity during chemotherapy. We observed a statistically significant decline in the mean KPSs of the patients both after surgery and radiotherapy and also during chemotherapy. However, weakly, preoperative KPSs were correlated only with SF. On the other hand, postoperative KPS scores were significantly related to physical and social activities after surgery. In a study by Piil et al.,[10] emotional condition recuperated over one-year survival time in high-grade glioma (HGG) patients reciprocally with decreased anxiety while physical activity sustained the early decline in functional capacity. This conclusion is important to decrease the dependency of GBM patients by a well-timed rehabilitation program and improve global QoL in their short survival.

The scores of role, cognitive, and SF gradually decreased between each follow-up. That is to say, the patients' involvement in social and occupational roles was unpleasantly affected during the first six months of treatment. In line with this, radiation-induced leukoencephalopathy was found to be responsible for cognitive impairment in about 25% of long-term survivors in radiological absence of active tumor.[16] As expected, postoperative social and cognitive scores were also influenced by the side of lesion in our patients. Right-sided lesions had significantly higher scores both in pre- and postoperative periods, showing the effect of the disease process on cognitive functions. Although there is uncertainty about the effect of tumor location on QoL,[10],[12] our patients with tumors in deep locations had worse scores of CF, RF, pain, and fatigue after surgery and insomnia during chemotherapy. Yet, it is unconfident to conclude with these results because of the small sample size and require further studies.

Gender is among the contributory factors affecting the level of QoL.[9] In the present study, males did better than females in preoperative EF and PF tests. The decline in EF was more conspicuous after surgery in men, whereas it was more prominent during adjuvant therapies in women [Figure 3]. The result of sex difference is in line with previous studies on brain tumors and many other chronic diseases as well.[17]

Global health status and financial effects

The deterioration in global health was prominent in most patients (56.5%) after radiotherapy and throughout chemotherapy. However, the patients performed better scores before starting radiotherapy as it was associated with increased KPS scores in the first month [Figure 4]. This outcome may be attributed to the side effects of radiotherapy and mass decreasing effect of surgery. Despite our results, overall QoL in most long-term survivors was reported to be preserved despite cognitive impairments and depressive symptoms.[14] Although financial problems had significant contribution to QoL in some long-term GBM survivors,[18] only 28% of our patients expressed significant difficulties one month after surgery. This was only correlated with decreased KPSs.
Figure 4: Correlation results of Global Health scores with Karnofsky performance.

Click here to view


The main limitations of the study were low patient number and lack of specific brain cancer modules, which can be met with improvement of data in forthcoming studies.


  Conclusions Top


Our results suggested that low KPS, older age, and female gender may affect cancer symptoms, physical and social activities in malignant glioma patients. In addition, cognitive functions as well as social and occupational roles gradually decline during the first six months of treatment. Overall QoL of HGG patients deteriorates, especially after radiotherapy and during the first months of chemotherapy. Consequently, among the modifiable factors, physical therapy may be the main concern that should be encouraged to increase the independence of patients while psychological support may help to manage emotional breakdown.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Buckner JC, Brown PD, O'Neill BP, Meyer FB, Wetmore CJ, Uhm JH. Central nervous system tumors. Mayo Clin Proc 2007;82:1271–86.  Back to cited text no. 1
    
2.
American Association of Neurological Surgeons. Glioblastoma Multiforme. Available from: https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Glioblastoma-Multiforme. 2020. [Last accessed on 2021 Feb 05].  Back to cited text no. 2
    
3.
Krex D, Klink B, Hartmann C, Von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain 2007;130:2596–606.  Back to cited text no. 3
    
4.
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459–66.  Back to cited text no. 4
    
5.
Gesundheit B, Ben-David E, Posen Y, Ellis R, Wollmann G, Schneider EM, et al. Effective treatment of glioblastoma multiforme with oncolytic virotherapy: A case-series. Front Oncol 2020;10:702.  Back to cited text no. 5
    
6.
Aaronson NK. Quality of life: What is it? How should it be measured? Oncology (Williston Park) 1988;2:69–76.  Back to cited text no. 6
    
7.
Jakola AS, Gulati S, Weber C, Unsgård G, Solheim O. Postoperative deterioration in health related quality of life as predictor for survival in patients with glioblastoma: A prospective study. PLoS One 2011;6:e28592. doi: 10.1371/journal.pone. 0028592.  Back to cited text no. 7
    
8.
Taphoorn MJB, Stupp R, Coens C, Osoba D, Kortmann R, van den Bent MJ, et al. Health-related quality of life in patients with glioblastoma: A randomised controlled trial. Lancet Oncol 2005;6:937–44.  Back to cited text no. 8
    
9.
Cheng JX, Zhang X, Liu BL. Health-related quality of life in patients with high-grade glioma. Neuro Oncol 2009;11:41–50.  Back to cited text no. 9
    
10.
Piil K, Jakobsen J, Christensen KB, Juhler M, Jarden M. Health-related quality of life in patients with high-grade gliomas: A quantitative longitudinal study. J Neurooncol 2015;124:185–95.  Back to cited text no. 10
    
11.
Cocks K, King MT, Velikova G, Fayers PM, Brown JM. Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials. Eur J Cancer 2008;44:1793–8.  Back to cited text no. 11
    
12.
Solanki C, Sadana D, Arimappamagan A, Rao KV, Rajeswaran J, Subbakrishna DK, et al. Impairments in quality of life and cognitive functions in long-term survivors of glioblastoma. J Neurosci Rural Pract 2017;8:228–35.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Rooney AG, Carson A, Grant R. Depression in cerebral glioma patients: A systematic review of observational studies. J Natl Cancer Inst 2011;103:61–76.  Back to cited text no. 13
    
14.
Steinbach JP, Blaicher HP, Herrlinger U, Wick W, Nängele T, Meyermann R, et al. Surviving glioblastoma for more than 5 years: The patient's perspective. Neurology 2006;66:239–42.  Back to cited text no. 14
    
15.
Litofsky NS, Farace E, Anderson F, Meyers CA, Huang W, Laws ER, et al. Depression in patients with high-grade glioma: Results of the glioma outcomes project. Neurosurgery 2004;54:358–67.  Back to cited text no. 15
    
16.
Hottinger AF, Yoon H, Deangelis LM, Abrey LE. Neurological outcome of long-term glioblastoma survivors. J Neurooncol 2009;95:301–5.  Back to cited text no. 16
    
17.
Mainio A, Hakko H, Niemelä A, Koivukangas J, Räsänen P. Gender difference in relation to depression and quality of life among patients with a primary brain tumor. Eur Psychiatry 2006;21:194–9.  Back to cited text no. 17
    
18.
Flechl B, Ackerl M, Sax C, Dieckmann K, Crevenna R, Gaiger A, et al. Neurocognitive and sociodemographic functioning of glioblastoma long-term survivors. J Neurooncol 2012;109:331–9.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow