Quality of Life after Surgery for Lower Grade Gliomas

Abstract

Background:

Few large studies have investigated quality of life (QOL) for adults diagnosed with lower grade glioma (LGG).

Methods:

QOL was assessed for 320 adults with LGG (World Health Organization grade 2/3) enrolled in the International Low Grade Glioma Registry using the Medical Outcomes Study 36-Item Short Form (SF-36) health survey. Data on symptoms were also collected. QOL outcomes were examined by treatment group and also compared to those from a population-based case/control study of meningioma (the Meningioma Consortium), in which 1722 meningioma cases diagnosed among residents of Connecticut, Massachusetts, California, Texas, and North Carolina from May 1, 2006 through March 14, 2013 were enrolled and frequency matched to 1622 controls by age, sex and geography.

Results:

The LGG sample average age is 45 years at time of interview and 53.1% male. Almost 55% of patients had received radiation and chemotherapy (primarily temozolomide); 32.4% had received neither treatment. Almost 2/3 LGG subjects report difficulty with speaking, memory, or thinking and over 1/3 report personality change or difficulty driving. After controlling for age and other co-morbidities, individuals diagnosed with LGG report levels of physical, emotional, and mental health functioning below those reported in a meningioma as well as a general healthy population.

Conclusions:

Despite being relatively young, persons with LGG report significantly reduced QOL compared to persons with non-malignant brain tumors and to a control population, highlighting the need to better acknowledge and manage these symptoms for this group of patients diagnosed in the prime of life.

Precis

Despite their relatively young age, persons with lower grade glioma (LGG) report a high symptom burden and significantly reduced quality of life (QOL) compared to persons with non-malignant brain tumors and healthy controls. These findings emphasize the need to better recognize the symptoms that LGG patients experience and develop accessible rehabilitative interventions for symptom management and QOL maintenance.

Introduction

Lower grade gliomas (LGGs) are malignant primary brain tumors, with astrocytomas and oligodendrogliomas being the most common types. These constitute approximately 5.3% of all adult brain tumors^1,2. LGGs are characteristically slow growing, with extended survival compared to other malignant brain tumors, and typically present in the second through fourth decades of life in otherwise healthy individuals³. While less aggressive than their high-grade counterparts, these tumors are associated with neurologic and systemic symptoms and diminished quality of life (QOL)^4–20. These negative effects are attributed to both natural disease progression as well as treatment^21–26, which typically consists of maximal safe surgical resection followed at some point by radiation, chemotherapy, or a combination of the two. Despite the clinical significance of maintaining levels of functioning and QOL in a relatively young patient population, few studies have investigated these outcomes exclusively for individuals diagnosed with LGG, with most focusing on higher grade tumors or including LGG as a small subset. Using data from the International Low Grade Glioma Registry²⁷, a focused research effort to better understand risk factors as well as outcomes associated with this diagnosis, this study examines patient-reported symptoms and QOL for a relatively large sample size of persons with LGG overall, by various sub-factors, as well as compared to healthy controls and individuals diagnosed with meningioma, a generally non-malignant primary brain tumor. The objective of this analysis is to better define the symptoms that this young group of persons experience, and to help guide rehabilitative treatments and supportive care for this population.

Methods

The International Low Grade Glioma (LGG) Registry

Eligible participants are aged 21–79 years at enrollment who have undergone surgery, including resection or biopsy only, at time of diagnosis. There are no restrictions with respect to sex, gender, race, date of diagnosis, or treatment. All patients presenting with a histologically confirmed intra-cranial supra-tentorial (Topography codes C71.0–71.4) low grade (WHO 2007 version Grade II) glioma (Morphology codes: mixed glioma (ICD-0 9382), oligodendroglioma (ICD-0 9450) or astrocytoma (ICD-0 9400, 9410, 9420) or WHO 2016 version LGG (i.e. diffuse astrocytoma (ICD-0 9400,9411) and oligodendroglioma (ICD-0 9450)) will be included and then uniformly defined by molecular subtype using the 2016 World Health Organization guidelines classification of glioma. Persons with a previous history of a brain tumor of unknown diagnosis prior to the LGG diagnosis are excluded. Recruitment (which is ongoing) into the Registry occurs via a variety of methods including 1) direct contact within clinical settings, 2) via social media outreach, and 3) via the support of national and international brain tumor patient organizations. Participants with LGG may enroll into the Registry at any time in the disease trajectory.

The Meningioma Consortium

Eligible individuals include all persons diagnosed with a histologically confirmed intracranial meningioma among residents of the states of Connecticut, Massachusetts, and North Carolina, as well as the Alameda, San Francisco, Contra Costa, Marin, San Mateo, and Santa Clara counties of California, and the Brazoria, Fort Bend, Harris, Montgomery, Chambers, Galveston, Liberty, and Waller counties of Texas from May 1, 2006, to February 26, 2010. Cases were identified through the Rapid Case Ascertainment systems and state cancer registries of the respective sites, and patients were between the ages of 20 and 79 years at time of diagnosis. The majority of cases were interviewed within one year from time of surgery, with a mean time between surgery and interview of 0.93 years (median, 0.59 years). Control individuals were selected via random-digit dialing and were matched to cases by a 5-year age interval, sex, and state of residence. Study patients with a history of meningioma and/or a brain lesion of unknown outcome were excluded.

Both studies were approved by the Human Investigation Committees at the Yale University School of Medicine and Brigham and Women’s Hospital.

Questionnaire

Participants completed a questionnaire requesting information on demographics, treatment, as well as family and medical history. Health-related QOL was measured using the Medical Outcomes Study Short-Form 36 Health Survey (SF-36)²⁸. This instrument includes 8 individual scales for Physical Functioning, Role-Physical, Bodily Pain, Social Functioning, Mental Health, Role-Emotional, Vitality, and General Health perceptions. Each scale is scored from 0 to 100, with 100 representing the best score. The SF-36 also has 2 summary scales: the Physical Component Summary scale and the Mental Component Summary scale. The summary scales are standardized to a reference healthy population with a mean score of 50 and a standard deviation of 10.

Statistical Analysis

Statistical analyses were carried out using R version 4.2.1 and SAS version 9.4 and included descriptive statistics. Chi-square, Fisher’s exact tests, and ANOVA were used to determine whether demographics of the study population differed between LGG cases, meningioma cases, and controls. Generalized linear models were used to provide adjusted estimates of outcome risk. The effect of multiple comparisons was controlled for using a Bonferroni correction to make pairwise comparisons across the study groups. Estimates of SF-36 means were adjusted for the effects of age (continuous) and time since treatment (continuous). The SF-36 variables were coded according to the guidelines presented in Ware et al²⁸. In order to address the possible risk of confounding, we conducted a sensitivity analysis comparing SF-36 means in a sample where study groups were matched by 10-year age interval, sex, race, and education using R package MatchIt.

Results

Demographics statistics are presented in Table 1. A total of 320 persons with LGG were studied. The majority of LGG participants were male (53.1%), white (93.4%), and college educated (71.2%) with a mean age of 45 years. Regarding tumor type, approximately 47% of LGG cases were diagnosed with oligodendroglioma, 35% with astrocytoma, and 8.4% with mixed glioma. Tumors were evenly distributed between right and left hemispheres, with a small percentage of LGG participants reporting a bilateral lesion. Most LGG cases (54.7%) were treated with both radiation and chemotherapy (primarily temozolomide) after surgery and the average reported time since treatment was 5 years (SD=6.1). Compared to participants with meningioma and controls²⁹, LGG participants were significantly younger (p<0.01), more likely to be white (p<0.05), male (p<0.05), and college-educated (p<0.05), and less likely to report having a comorbid condition (p<0.05).

Table 1:

Population Summary Table

	LGG Group		Meningioma Group		Control Group
	(n = 320)		(n = 1722)		(n = 1622)
Characteristic	No.	%	No.	%	No.	%	P-Value
Age at interview/diagnosis, years
20–29	32	10	28	1.6	22	1.4
30–39	89	27.8	109	6.4	109	6.7
40–49	88	27.5	323	18.8	310	19.2
50–59	69	21.6	480	28.0	482	29.8
60–69	37	11.6	515	30.0	435	26.9
70+	5	1.6	261	15.2	257	15.9
Average Age	45		57.6		57.3		p < 0.01
SD	12.1		11.8		12
Sex
Male	170	53.1	476	27.6	454	28.0	p < 0.05
Female	150	46.9	1246	72.4	1168	72.0
Race
White	299	93.4	1433	83.2	1396	86.1	p < 0.05
Black	2	0.6	142	8.2	80	4.9
Asian	7	2.2	61	3.5	64	3.9
More than one race	11	3.4	29	1.7	24	1.5
Other/Unknown	1	0.3	57	3.3	58	3.6
Education
College Graduate	228	71.2	750	43.6	921	56.8	p < 0.05
Non-College Graduate	86	26.9	964	56.0	698	43.0
Unknown	6	1.9	8	0.4	3	0.2
Comorbidity *
One or More	21	6.6	378	21.9	383	23.6	p < 0.05
Tumor Type
Astrocytoma	112	35.0	--	--	--	--
Oligodendroglioma	151	47.2	--	--	--	--
Mixed Glioma	27	8.4	--	--	--	--
Other/Unknown	30	9.4
WHO Grade
Grade 2	233	72.8	--	--	--	--
Grade 3	59	18.4	--	--	--	--
Other/Unknown	28	8.8	--	--	--	--
Treatment
Radiation Only	12	3.8	183	10.6	--	--
Chemotherapy Only	28	8.8	1	0.06	--	--
Both	175	54.7	2	0.1	--	--
Neither	103	32.2	1516	88.0	--	--
Unknown	2	0.6	20	1.2
Chemotherapy Type
Temozolomide	177	87.2	--	--	--	--
PCV	11	5.4	--	--	--	--
Other	15	7.4	--	--	--	--
Tumor Laterality
Right Hemisphere	158	49.4	748	43.4	--	--
Left Hemisphere	148	46.2	761	44.2	--	--
Bilateral	12	3.8	--**	--**	--	--
Unknown	2	0.6	213	12.4	--	--
Tumor Location
Frontal	155	48.4	--	--	--	--
Temporal	60	18.8	--	--	--	--
Parietal	33	10.3	--	--	--	--
Occipital	6	1.9	--	--	--	--
Brainstem	5	1.6	--	--	--	--
Other/Unknown	61	19.1	--	--	--	--
Time since diagnosis, years
0–5	190	59.4	--	--	--	--
6–10	46	14.4	--	--	--	--
11–15	37	11.6	--	--	--	--
16–20	19	5.9	--	--	--	--
21+	13	4.1	--	--	--	--
Unknown	15	4.7	--	--	--	--
Average time since diagnosis	6.5		0.93
SD	6.9
Time since treatment, years
0–5	217	67.8	--	--	--	--
6–10	49	15.3	--	--	--	--
11–15	25	7.8	--	--	--	--
16–20	10	3.1	--	--	--	--
21+	8	2.5	--	--	--	--
Unknown	11	3.4	--	--	--	--
Average time since treatment	5.0
SD	6.1

^*Stroke, myocardial infarction, and other cancers

^**Bilateral tumors not an option in questionnaire

Symptoms reported by LGG participants overall and by tumor laterality are shown in Table 2.1. Decreased sensation in face, arms or legs was the most commonly reported symptom (71.7%), followed by difficulty remembering new facts (63.8%), trouble thinking (60.1%), and difficulty getting words out (59.8%). LGG cases with a tumor in the left hemisphere were more likely to report having difficulty getting words out (p<0.001) than those with a right-sided lesion. There was no statistically significant difference by tumor laterality with respect to other symptoms. Symptom frequency did not vary by tumor lobe (Table 2.2) or treatment type (Table 2.3). However, LGG participants within 0–5 years since time of diagnosis more often reported difficulty getting words out (p<0.01), headaches (p<0.05), personality changes (p<0.05), and trouble thinking (p<0.05) than those diagnosed >5 years ago (Table 2.4).

Table 2.1:

Symptom Prevalence for LGG Group Overall and by Tumor Laterality^*

	LGG Group (n = 320)		Tumor in Left Hemisphere (n = 148)		Tumor in Right Hemisphere (n = 158)		Difference Between Right and Left Hemispheres
Symptom	No.	%	No.	%	No.	%	P-Value
Driving Deficit	94	34.1	40	31.5	53	38.7	p = 0.22
Seizure	39	14.1	16	12.5	20	14.6	p = 0.62
Weakness in an Arm or Leg	84	30.3	33	25.8	46	33.6	p = 0.17
Difficulty Getting Words Out	165	59.8	90	70.3	68	50.0	p < 0.001
Difficulty Remembering New Facts	176	63.8	81	63.3	84	61.8	p = 0.80
Headache	144	52.4	70	54.7	65	48.1	p = 0.29
Personality Change	108	39.0	56	43.8	46	33.6	p = 0.09
Visual Disturbance	112	40.6	48	37.5	57	41.9	p = 0.46
Decreased Sensation in Face, Arms, or Legs	198	71.7	93	72.7	97	71.3	p = 0.81
Trouble Thinking	166	60.1	79	61.7	78	57.4	p = 0.47

^*In past 7 days

Note: Sample sizes vary due to missing values.

Table 2.2:

Symptom Prevalence for LGG Group by Tumor Lobe^*

	Frontal (n = 155)		Parietal (n = 33)		Temporal (n = 60)		Difference Between Lobes
Symptom	No.	%	No.	%	No.	%	P-Value
Driving Deficit	42	30.4	11	42.3	17	33.3	p = 0.49
Seizure	18	13.0	1	3.8	11	21.2	p = 0.10
Weakness in an Arm or Leg	45	32.6	7	26.9	12	23.1	p = 0.41
Difficulty Getting Words Out	86	62.3	14	53.8	29	56.9	p = 0.63
Difficulty Remembering New Facts	87	63.5	14	53.8	36	69.2	p = 0.41
Headache	73	53.3	13	50.0	24	47.1	p = 0.74
Personality Change	53	38.4	9	34.6	18	34.6	p = 0.86
Visual Disturbance	45	32.6	11	42.3	25	49.0	p = 0.10
Decreased Sensation in Face, Arms, or Legs	108	78.3	15	57.7	39	76.5	p = 0.08
Trouble Thinking	86	62.8	14	53.8	31	59.6	p = 0.68

^*In past 7 days

Note: Sample sizes vary due to missing values.

Table 2.3:

Symptom Prevalence for LGG Group by Treatment (Any Adjuvant vs. No Adjuvant)^*

	Adjuvant Treatment (n = 215)		No Adjuvant Treatment (n = 103)		Difference Between Groups
Symptom	No.	%	No.	%	P-Value
Driving Deficit	56	30.9	38	40.0	p = 0.13
Seizure	27	14.8	12	12.6	p = 0.61
Weakness in an Arm or Leg	56	30.8	28	29.5	p = 0.82
Difficulty Getting Words Out	106	58.6	59	62.1	p = 0.57
Difficulty Remembering New Facts	122	67.4	54	56.8	p = 0.08
Headache	89	49.4	55	57.9	p = 0.18
Personality Change	68	37.4	40	42.1	p = 0.44
Visual Disturbance	67	37.0	45	47.4	p = 0.10
Decreased Sensation in Face, Arms, or Legs	130	71.8	68	71.6	p = 0.97
Trouble Thinking	111	61.3	55	57.9	p = 0.58

^*In past 7 days

Note: Sample sizes vary due to missing values.

Table 2.4:

Symptom Prevalence for LGG Group by Time Since Diagnosis^*

	0–5 Years (n = 190)		>5 Years (n = 115)		Difference Between Groups
Symptom	No.	%	No.	%	P-Value
Driving Deficit	62	37.6	26	26.3	p = 0.06
Seizure	22	13.3	14	14.0	p = 0.88
Weakness in an Arm or Leg	50	30.3	27	27.0	p = 0.57
Difficulty Getting Words Out	108	65.5	48	48.5	p < 0.01
Difficulty Remembering New Facts	109	66.1	61	61.6	p = 0.47
Headache	95	57.6	43	43.9	p < 0.05
Personality Change	72	43.6	31	31.0	p < 0.05
Visual Disturbance	68	41.2	38	38.4	p = 0.65
Decreased Sensation in Face, Arms, or Legs	124	75.2	64	64.6	p = 0.07
Trouble Thinking	106	64.2	51	51.5	p < 0.05

^*In past 7 days

Note: Sample sizes vary due to missing values.

The adjusted means of the MOS SF-36 health domains for LGG participants by treatment type, age at interview, and time since diagnosis are given in Tables 3.1, 3.2, and 3.3, respectively. Regarding treatment type, as the sample sizes for participants receiving only radiation or only chemotherapy were too small (n=12 for radiation and n=28 for chemotherapy), only participants who received any adjuvant treatment or no adjuvant treatment were compared. Participants who received any adjuvant treatment had significantly better scores in Social Functioning (p<0.01), Role-Emotional (p<0.01), and Mental Health (p<0.01), but lower scores in Physical Functioning (p<0.05). Older LGG participants reported better scores in the domains of Social Functioning (p<0.05) and Mental Health (p<0.01) than their younger counterparts. LGG participants diagnosed >5 years ago also reported better Role-Physical (p<0.01), Bodily Pain (p<0.05), Social Functioning (p<0.01), and Role-Emotional (p<0.01) scores than those diagnosed ≤5 years ago.

Table 3.1:

MOS SF-36 Adjusted Group Means for LGG by Treatment (Any Adjuvant vs. No Adjuvant)

MOS SF-36 Health Domain	Adjuvant Treatment (n = 215)	No Adjuvant Treatment (n = 103)	P-Value (Adjusted)
Physical Functioning	82.11	87.98	p = 0.04*
Role-Physical	55.08	52.11	p = 0.59
Bodily Pain	77.26	75.28	p = 0.51
General Health	62.16	61.89	p = 0.92
Vitality	49.72	48.19	p = 0.54
Social Functioning	74.11	64.87	p = 0.004*
Role-Emotional	66.48	49.82	p = 0.002*
Mental Health	70.49	61.91	p = 0.0003*
Average time since diagnosis (years)	7.20	4.85

Note: Means adjusted for age at interview (continuous) and time since treatment (continuous)

^*Significance between treatment groups at p<0.05

Table 3.2:

MOS SF-36 Group Means for LGG by Age at Interview

MOS SF-36 Health Domain	20–29 (n = 29)	30–39 (n = 81)	40–49 (n = 74)	50–59 (n = 63)	60–69 (n = 27)	70+ (n = 4)	P-Value
Physical Functioning	87.76	87.32	84.66	79.44	80.04	83.75	p = 0.31
Role-Physical	51.72	50.62	59.46	52.42	55.56	56.25	p = 0.87
Bodily Pain	75.45	77.85	78.34	72.08	78.11	86.00	p = 0.60
General Health	58.52	59.96	61.97	63.96	67.15	69.25	p = 0.54
Vitality	44.31	47.20	49.46	50.34	54.51	66.25	p = 0.36
Social Functioning	62.50	67.28	69.43	78.23	76.39	84.38	p = 0.03*
Role-Emotional	50.57	60.42	60.36	60.22	73.08	75.00	p = 0.50
Mental Health	58.17*	65.16	66.22	73.95*	72.22	76.75	p = 0.002*

^*Significance between treatment groups at p<0.05

Table 3.3:

MOS SF-36 Group Means for LGG by Time Since Diagnosis

MOS SF-36 Health Domain	0–5 years (n = 165)	>5 years (n = 100)	P-Value
Physical Functioning	84.78	83.80	p = 0.73
Role-Physical	48.48	65.50	p = 0.002*
Bodily Pain	73.98	80.89	p = 0.02*
General Health	62.68	62.19	p = 0.85
Vitality	49.60	50.83	p = 0.67
Social Functioning	67.27	77.38	p = 0.002*
Role-Emotional	56.24	70.33	p = 0.008*
Mental Health	67.17	69.62	p = 0.30

^*Significance between treatment groups at p<0.05

The adjusted means for the MOS SF-36 health domains for LGG cases, meningioma cases, and controls are presented in Table 4. LGG cases reported significantly better scores than meningioma cases in Bodily Pain (p<0.05), but worse scores in General Health (p<0.05), Vitality (p<0.05), Role-Emotional (p<0.05), and Mental Health (p<0.05). LGG cases also reported statistically lower scores than controls in all domains except for Bodily Pain. The greatest difference between LGG cases and controls occurred in the Role-Physical domain (22.68 points), while the greatest difference between LGG cases and meningioma cases occurred in the Role-Emotional domain (9.43 points). SF-36 means for a sample in which study groups were matched on age, sex, race, and education are presented in Supplementary Table B. Group comparisons were similar to those presented in Table 4, with the exception of LGG participants in the matched sample also reporting significantly worse Social Functioning scores (p<0.05) than meningioma cases. There were also no significant differences in Bodily Pain scores between LGG and meningioma cases in the matched sample.

Table 4:

MOS SF-36 Adjusted Group Means for LGG Overall, Meningioma, and Controls

MOS SF-36 Health Domain	LGG (n = 278)	Meningioma (n = 1544)	Controls (n = 1449)
Physical Functioning	78.05b	74.67c	83.07bc
Role-Physical	50.41b	52.81c	73.09bc
Bodily Pain	75.75ab	68.80ac	71.28bc
General Health	61.27ab	69.66ac	73.75bc
Vitality	49.95ab	54.98ac	63.66bc
Social Functioning	71.76b	75.91c	85.48bc
Role-Emotional	61.57ab	71.0ac	81.87bc
Mental Health	69.28ab	73.90ac	78.53bc

Note: Means adjusted for age at interview (continuous) and other comorbid conditions (stroke, myocardial infarction, and other cancers)

^aDenotes statistically significant difference between LGG and meningioma cases

^bDenotes statistically significant difference between LGG and controls

^cDenotes statistically significant difference between meningioma cases and controls

Significance at p < 0.05

Discussion

To our knowledge, this is the largest investigation to date to examine self-reported symptoms and QOL in individuals with LGG. Consistent with results from prior studies^{4,6,9,10,14–16,19,30}, participants endorsed a high frequency of debilitating cognitive and physical deficits, with almost two-thirds experiencing problems with sensation, memory, thinking, or speaking. While previous studies have reported higher levels of cognitive and functional impairments in patients with high grade gliomas (HGG) compared to those with LGG^9,14, one study has found that LGG patients report more pain and anxiety related to physical decline⁹. Concerns regarding tumor recurrence/progression, limited ability to work, and reduced functional independence may add to patient distress^31–33. Although we did not observe widespread differences in symptom prevalence based on tumor laterality, tumor lobe, or treatment type, individuals with left hemisphere tumors predictably endorsed more frequent issues with communication^34,35. Additionally, participants within the early years of survivorship (0–5 years since diagnosis) reported greater symptom prevalence than long-term survivors (>5 years), indicating that symptoms due to the tumor itself and surgery-related side-effects may diminish over time. However, it is important to note that some persons with LGG may refrain from participating in research due to severe symptoms, thus the most affected patients may not be captured in this dataset.

Participants who received adjuvant treatment after surgery reported worse Physical Functioning, but better Social Functioning, Role-Emotional, and Mental Health scores than those who received no adjuvant treatment. While these results may suggest more functional rather than psychosocial treatment-related side-effects, an earlier study using the SF-36 reported worse mental health and higher prevalence of mood disorders in addition to lower physical functioning in LGG patients who received adjuvant treatments¹². However, it is difficult to compare these results to our own, as the prior study only included 80 participants from a single neurosurgical center who were all evaluated within 12 months after surgery.

Long-term LGG survivors (>5 years from diagnosis) reported better QOL scores than those within five years of time of diagnosis on half of the SF-36 domains, with most substantial differences seen in Role-Physical and Social Functioning scores. As with symptoms, these findings may indicate that physical, social, and emotional health improve with time for LGG patients, although it is also likely that those experiencing the most significant reductions in QOL may be less willing or able to participate in research. Several longitudinal studies have suggested that QOL scores remain consistently low, changing little with increasing time since diagnosis and treatment³⁶. However, substantial loss to follow-up and failure to account for tumor progression or recurrence in these studies highlights a need for more research on long-term outcomes for LGG patients.

Despite a younger average age, LGG patients scored significantly lower than controls and meningioma cases on the majority of SF-36 domains. Most substantial reductions were seen in the domains of General Health, Vitality, Role-Emotional, and Mental Health. Although one previous study found no significant QOL differences between LGG patients and those with benign brain tumors⁶, several studies comparing LGG patients to non-cancer controls have also reported significantly lower Physical Functioning^4,11,16,18, General Health^4,11,15,16, Vitality^4,11,15, and Role-Emotional^4,11,16 scores for those with LGG. While the literature consistently indicates that persons with LGG report significantly better overall QOL than those with HGG^6,14,37,38, those with LGG experience disproportionate morbidity due to younger age of onset and living longer with disease and treatment-related side effects. These findings draw support for the development of supportive care and rehabilitative treatments tailored to fit the unique needs of persons with LGG.

Given the impact of LGG on this group of young persons, researchers have started to consider means to improve symptoms and QOL though a variety of interventions including physical exercise and neuro-cognitive training^39–44. Several studies have found that lower physical fitness in glioma patients is associated with higher levels of fatigue and more sleep disturbances, and thus exercise and other treatments to improve physical functioning could potentially help reduce symptoms and improve QOL^41,42. In one randomized control trial of 64 people with gliomas undergoing active treatment, participants were assigned to either a 6-week physical therapy and occupational therapy-based intervention or a control group receiving typical rehabilitative care. Individuals in the intervention group reported a nonsignificantly higher QOL score as well as improved subjective cognitive functioning and reduced fatigue⁴³. Another study found that body-based strategies for symptom management, such as exercise or massage, are directly associated with better physical functioning in glioma patients⁴⁴.

In the Netherlands, a randomized control trial of 140 adult LGG patients featuring computer-based retraining and neuropsychologist-led compensation exercises noted improved attention and verbal memory and reduced mental fatigue after 6 months of weekly 2-hour sessions and homework assignments³⁹. A recent pilot study organized by researchers at UCSF also reports intriguing findings of improved attention and verbal memory and reduced mental fatigue⁴⁰. This study, which compared in-person, app-based, and text message-based cognitive rehabilitation strategies among 33 adult LGG patients, found that working memory, verbal learning, and verbal memory significantly increased in all groups after 3 months. Although it took longer for the app-based and texting groups to show improvement, these results indicate that technology-based efforts may be just as effective as in-person for long-term gains.

While returning to work is often a primary goal for persons with LGG after treatment, one study has found that only half of LGG patients return to work in the year following surgery⁴⁵. Researchers at UCSF looking to improve this outcome have reported promising results from a pilot study featuring work-focused tele-cognitive rehabilitation tailored to individual patients’ unique needs and job duties⁴⁶. Of the 38 adult brain tumor patients who engaged in this program, 87% reported improved functional work status, indicated by returning to work and/or reduced cognitive disruption at work after surgery and chemoradiation.

Our study’s strengths include a relatively large sample of LGG cases and the availability of a large sample of population-based meningioma cases and controls for comparison. Additionally, the SF-36 has been found to be valid and reliable for use among brain tumor patients⁴⁷ and allows for reliable comparison of several health-related QOL domains between various diagnoses as well as with a normative reference population.

Limitations to our study include representativeness of our study sample, as LGG cases were not population-based but drawn from a variety of sources including in-person hospital-based, social media, and patient organization recruitment efforts. Although our sample was similar to those of other large studies on LGG in terms of sex, race, and age, it differed with respect to education, with our sample more likely to report being college educated^2,48. As data were collected at only one point in time postoperatively, longitudinal QOL changes could not be measured. While the SF-36 is appropriate for comparison between brain tumor patients and healthy controls, of note, additional QOL instruments are available specifically for brain tumor patients^49,50. These questionnaires not only assess multidimensional QOL, but also examine symptoms, treatment-related side-effects, and specific psychosocial issues of consequence to individuals with brain cancer⁵¹.

Overall, our study found that persons with LGG experience a high burden of symptoms and significantly reduced QOL compared to non-cancer controls and individuals with non-malignant brain tumors. Our results emphasize the need to better recognize the symptoms that LGG patients experience and develop neurocognitive and physical interventions for symptom management and QOL maintenance. Recent studies suggest the possibility of delivering at least some interventions via virtual means. It will be of interest to see how such methods benefit LGG patients as they become more widely accessible.

Data Availability Statement

Deidentified data will be available via dbGaP.