Clinical study
Life after surgical resection of a low-grade glioma: A prospective cross-sectional study evaluating health-related quality of life

https://doi.org/10.1016/j.jocn.2021.03.038Get rights and content

Highlights

  • Low grade glioma patients report limitations in HRQoL for>120 months after surgery.

  • Cognitive, emotional, and social functioning are most impacted.

  • Patients also experience significant fatigue and insomnia.

  • These functional impairments and symptoms are strongly associated with global HRQoL.

  • Interventions targeting these domains and symptoms may improve HRQoL for LGG patients.

Abstract

Health related quality of life (HRQoL) has become an important consideration in LGG patients. We report the largest prospective, longitudinal, cross-sectional cohort study of HRQoL in LGG patients, aiming to identify actionable determinants of HRQoL. Post-operative LGG adults at a large tertiary center underwent HRQoL assessment using the EORTC QLQ-C30 questionnaire administered at follow-up visits and by mail. Scores at 12 month intervals were compared with those from a normative reference population. Spearman’s Rho was used to evaluate correlation of subdomain and symptom scores with global HRQoL and change over time. There were 167 participants and 366 questionnaires analysed. Patients reported reduced global HRQoL at nearly every 12 month interval with significant impairments at 12, 72, 108, and 120+ months postoperative. They also reported a significant impairment in each functional subdomain at 12 months, which persisted to varying degrees over 120 months, as did significant fatigue and insomnia. Role, emotional, and social subdomains, as well as fatigue, were significantly associated with global HRQoL at the first 12 month interval. Overall, there was no significant correlation between time from surgery and global HRQoL or the subdomain functional or symptom sections of the QLQ-C30. LGG patients report considerable, sustained impairments in HRQoL after surgery, particularly in cognitive, emotional, and social function, as well as suffering significant fatigue and insomnia. These are strongly associated with global HRQoL and thus can be considered determinants of global HRQoL that with intervention, may improve HRQoL for our LGG patients.

This is the largest prospective longitudinal study of HRQoL in postoperative LGG patients yet reported and is ongoing. It identifies several determinants of impaired HRQoL with available management options and interventions that have the potential to significantly improve HRQoL in these patients.

Introduction

Advances in surgical techniques and adjuvant therapy options, have led to dramatic improvements in brain tumor patient care over the past two decades. Consequently, with extended survival and reduction of gross neurological morbidity, measures of treatment success have shifted to more patient-centred metrics, including health-related quality of life (HRQoL).[1], [2] HRQoL is a complex, self-assessed, multidimensional concept encompassing the physical, emotional, role, social and cognitive components of quality of life associated with illness and its treatment.

Low-grade gliomas (LGG) are a heterogenous group of almost universally fatal primary central nervous system neoplasms classified by the World Health Organisation (WHO) as tumour grades I or II.3 They are uncommon, with an incidence of 1/100,000 people per year 4, but due to young age at diagnosis (median 37 years)5 and association with neurological deficit, LGG cause disproportionate levels of morbidity.5

Maximal safe surgical resection is the mainstay of initial treatment.[6], [7], [8], [9] Aggressive surgical resection and adjuvant radiation and chemotherapy have modestly improved survival of this fatal disease, resulting in challenges not previously encountered.[10], [11], [12], [13] Improvements in quantity of survival must be accompanied by improvements in quality of survival. HRQoL is thus a key quality metric for care of patients with LGG.

Depending on tumor location, patients with LGG may experience cognitive, psychiatric, somatic, and other symptoms, including neurological deficit and epilepsy.[14], [15], [16] Patients also suffer from nonspecific symptoms, including headaches, fatigue, anxiety, and sleep disturbance.[17], [18] Additionally, surgical resection and subsequent radio- and chemotherapy may also have effects on HRQoL. Therefore, both tumor and treatment may affect HRQoL. Despite this, the long-term HRQoL of LGG patients is an understudied, and at times an under-recognized, challenge for this population.

Previous studies are limited by small populations, use of a range of non-comparable HRQoL instruments, inadequate evaluation of longitudinal change and lack of comparison with a normative population or consideration of clinically meaningful difference (CMD).[7], [19], [20] Our recent study that specifically investigated these parameters in meningioma patients demonstrated significantly impaired HRQoL for years postoperative relative to a normative population.21 A LGG population study investigating longitudinal HRQoL changes at multiple time points with reference to a normative population represents a knowledge gap.

Here, we report a single-center prospective longitudinal evaluation of HRQoL in a cross-sectional cohort of postoperative LGG patients. The main aim of the study was to identify factors contributing to impaired HRQoL that could be modified to improve HRQoL for our patients. Therefore, less attention was given to nonmodifiable predictors that do not lend themselves to interventions to improve HRQoL. Thus, attention was given to factors for which interventions may be available, such as fatigue, sleep disturbance, social function, emotional disturbance, and cognitive dysfunction.

Section snippets

Patients and methods

The Melbourne Health Human Research Ethics Committee approved this study in 2013 (study number 2013.246). The study is a prospective longitudinal study, with a cross-sectional cohort design. The study included adults (age > 18 years) who had undergone biopsy or resection of an intracranial LGG and were in routine follow-up at the Royal Melbourne Hospital Neuro-Oncology and Neurosurgery Outpatient and Private clinics over 5 years. This includes patients treated at two large tertiary institutions

Results

We consented 167 post-operative patients for participation and a total of 366 questionnaires were included for analysis. There were 64 patients who completed the questionnaires once, 51 patients who completed them twice, 25 patients who completed them three times and 27 patients who completed them four or more times, generally at 6 monthly intervals. The median time from surgery to completion of each questionnaire for the 167 patients was 25, 38, 50 and 60 months for the first, second, third,

Discussion

Treating clinicians are well versed in the risks and benefits of LGG management, however, discussions around expected HRQoL changes after surgery are difficult and seldom occur between practitioner and patient. Despite the relatively prolonged survival of many LGG patients, few studies have investigated HRQoL in large cohorts. In particular, longitudinal change in HRQoL after time from diagnosis is understudied with many studies only comparing two arbitrary timepoints in different patient

Limitations

In addition to the questionnaire limitations, our study is susceptible to selection and reporting bias inherent in the design, as for other survey based HRQoL studies. The study included only patients attending the clinic for follow up, thus potentially selecting against those with severe impairments, and underestimating the magnitude of HRQoL impairment. In cases where a patient had not been captured (largely due to administrative error), questionnaire mail-outs were used. The study design may

Conclusion

We present the largest prospective longitudinal series of long-term HRQoL outcomes following surgical resection of a LGG. We found that LGG patients report sustained clinically significant impairments in global HRQoL, particularly in perceived cognitive, emotional, role and social functioning, and fatigue and insomnia. Role functioning, social functioning, and fatigue were highly correlated with global HRQoL outcomes at 12 month interval assessments, and strategies targeting these domains from

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