Health-related quality of life, disease burden and cognition in meningioma patients and their informal caregivers

Meningiomas are the most common primary brain tumors in adult patients, with an
incidence of 7.44 per 100.000 patients. Although the majority of meningiomas
are benign (WHO grade I), a small percentage is malignant (WHO grade II and
III). The prognosis for meningioma depends on tumor characteristics (grade,
size and location) and patient*s age, clinical condition and neurological
status. In the absence of growth, a wait-and-scan approach is often applied to
patients with asymptomatic or minimally symptomatic meningiomas, while growing
or symptomatic meningiomas are treated with surgery and/or radiotherapy.
Surgery is considered the first choice of treatment, but stereotactic
radiosurgery and external-beam radiotherapy are being used increasingly for
meningiomas that are surgically inaccessible, recurrent or incompletely
resected. The life expectancy of meningioma patients is significantly
compromised, with a 20-year survival rate of 53% for WHO grade I meningiomas
versus 67% in an age- and sex-specific reference group.

Although the majority of meningiomas is benign, their location in the central
nervous system can cause serious morbidity. The most common symptoms at
presentation are focal or generalized seizures, focal neurological deficits and
cognitive decline. On the long-term (>=5 years), many patients experience
neurological deficits, with the majority (67%) showing at least one
neurological symptom and 27% of the patients being unable to perform normal
daily activities.

With regard to cognition and health-related quality of life (HRQoL) in
meningioma patients, surprisingly little rigorous studies have been performed
to date. Previous studies have found that both cognition and HRQoL are impaired
in untreated meningioma patients with stable lesions when compared to healthy
controls. This implies that having a meningioma per se already has an impact on
the patient*s cognition and HRQoL. Moreover, it is likely that treatment also
has an impact on cognition and HRQoL. On the one hand, treatment may reduce the
tumor mass, resulting in alleviation of neurological symptoms and improvement
of cognitive functioning and HRQoL. On the other hand, treatment may damage the
normal tissue surrounding the tumor, causing neurological and cognitive
deficits, and subsequently impaired HRQoL. Meningioma patients treated with
surgery alone have significantly impaired cognitive functioning when compared
to healthy controls. However, the addition of radiotherapy to surgery did not
have additional deleterious effect on cognition in these patients. Instead, the
use of anti-epileptic drugs seems to attribute to neurocognitive deficits.
HRQoL of most patients with WHO grade I meningioma appears to be similar to
that of the general population, with 80% being satisfied with their
post-treatment HRQoL and 86% reporting a pre-morbid level of functioning three
years post-treatment. However, the addition of radiotherapy to surgery did
result in significantly lower HRQoL.

With 5-year survival rates of 85.6% for WHO grade I tumors, 82.3% for WHO grade
II tumors and 66% for WHO grade III tumors, it is worthwhile to better explore
cognitive functioning and HRQoL in meningioma patients on the long-term. More
specifically, the frequency and severity of impairments in cognition and HRQoL
at least 5 years after primary treatment are currently unknown. It is also not
known if deficits in cognitive functioning and lower HRQoL may be associated
with the intensity of anti-tumor treatment (i.e., surgery/radiotherapy only
once or multiple treatments throughout the disease trajectory). Moreover, the
disease burden for meningioma patients may not be restricted to impaired
cognition and HRQoL, but may also be manifested in loss of work productivity
due to the long-term effects of the disease or treatment and increased
healthcare resource utilization.

Meningioma does not only negatively affect the patient, but may also have a
profound impact on the patients* direct social environment, including family
and friends. These significant others often become informal caregivers. Across
different stages of the disease in cancer patients, the caregiver burden is
found to be high and informal caregivers may experience considerable levels of
psychological distress. Subsequently, this resulted in impaired HRQoL of
significant others. So far, the disease burden in informal caregivers of
meningioma patients has not been studied.
Investigating the long-term disease burden of meningioma may increase our
knowledge on the beneficial and adverse effects of specific treatment
strategies and may help to identify problems that might be addressed by
specific interventions, intending to improve outcome for these patients and
their informal caregivers.

Therefore, the aim of the current study is to examine the long-term disease
burden in both meningioma patients and their informal caregivers.

Primary Objectives
The main objective of this project is to evaluate the long-term disease burden
in meningioma patients. More specifically, we will evaluate:
1) the level of cognitive functioning and HRQoL in meningioma patients at least
5 years after primary treatment and compare these scores to those of their
informal caregivers (as controls, for cognition only) and matched controls from
the general population (for HRQoL);
2) how cognitive functioning and HRQoL are related to treatment frequency
(i.e., meningioma patients treated only once or multiple times throughout the
disease trajectory); and
3) the level of work productivity and the health resource utilization of
meningioma patients and their informal caregivers in the year prior to
inclusion.

Secondary Objectives
(1) As distress (i.e., anxiety and depression) can influence both cognitive
functioning and HRQoL, the experienced level of distress in meningioma patients
will be evaluated as a secondary objective.
(2) Furthermore, we aim to determine disease burden over time, in those
meningioma patients previously assessed one year post-operatively.
(3) Finally, we will determine the long-term burden (HRQoL, anxiety,
depression, caregiver burden) experienced by informal caregivers of meningioma
patients, as well as their level of work productivity and their health resource
utilization.

This will be a multicenter cross-sectional study. Meningioma patients and their
informal caregivers who meet the inclusion and exclusion criteria, and who are
willing to participate, will be asked to participate. Meningioma patients will
be asked to complete several questionnaires (including HRQoL, productivity loss
with work and health resource utilization) and to undergo a neuropsychological
assessment once. In addition, the informal caregivers of the meningioma
patients are asked to complete several questionnaires once, including HRQoL,
caregiver burden and anxiety and depression, and also to undergo a
neuropsychological assessment once.

To determine disease burden over time (see secondary research objectives), we
will particularly invite meningioma patients who participated in a previous
cross-sectional study; patients in this study were evaluated for neurocognitive
functioning and HRQoL one year after surgery. We will compare the newly
obtained data with this existing data to determine if neurocognitive
functioning and HRQoL changed over time.

Several groups of meningioma patients will be included at >5 years after
diagnosis: patients who did not undergo treatment, patiente who underwent only
one form of treatment (surgery/radiotherapy),and patients who underwent
multiple anti-tumor treatments (additional surgery/radiotherapy). Scores of
patients on neurocognitive tests will be compared to scores of their informal
caregivers, which serve as a control group. Scores on HRQoL questionnaire will
be compared with a reference population matched for age and gender, which is
readily available. Here, we choose not to use the informal caregivers as
controls due to the likely influence of the patients* diagnosis and treatment
on HRQoL of informal caregivers.

To assess the extent of response bias, we will perform a non-response analysis.
To do so, baseline characteristics of patients willing to participate and those
not willing to participate (but who are eligible for participation) will be
compared. Demographic and clinical information will be collected from the
medical charts, including age, gender, level of education, current or last
profession, comorbidity and disease related characteristics.

There are no direct benefits for patients and their informal caregivers
participating in this study. Nevertheless, their paticipation will contribute
to a better understanding of the long-term disease burden of a meningioma.
Subsequently, this information may be used to improve the care for this patient
population.

On the other hand, participation in this study has possible risks for the
patients and their informal caregivers. Patients and their informal caregivers
are confronted with all sorts of problems they have (e.g. with cognition,
health-related quality of life, work, etc.), which may pose a little
psychological burden on them. Moreover, it will cost the patients and their
informal caregivers time to complete the questionnaires and to undergo the
neuropsychological testing, although this is expected not to be substantial.