Quality of Life in Patients with Meningioma

Abstract

Meningiomas are common benign brain tumors that may significantly impact patients’ Health-Related Quality of Life (HRQOL) and functional disability. The assessment of HRQOL in meningioma patients is heterogeneous, necessitating standardized approaches. Patient-Reported Outcome Measures (PROMs) are increasingly used to capture patients’ perspectives, with various questionnaires developed for this purpose. Medical and non-medical risk factors for long-term HRQOL impairment encompass tumor characteristics, treatment factors, and sociodemographic features. Symptomatic meningioma patients experience lower HRQOL scores, with symptoms influenced by tumor features such as location, edema, and size. Prominent subsequent manifestations, including epilepsy, neurocognitive dysfunction, and psychiatric symptoms, significantly influence HRQOL. Surgical resection is the primary therapeutic option, and adjuvant radiotherapy may be considered for recurrent or high-risk cases. Although patients generally experience improved HRQOL post-surgery, some may face long-term declines, necessitating comprehensive long-term well-being evaluation. Patients often undergo positive changes in mental outlook (posttraumatic growth), triggering a “response shift” that may alter patients’ values and internal standards, ultimately improving their perception of HRQOL. Long-term outcomes highlight meningioma’s chronic impact on patients’ lives and socioeconomic burden. Overall, understanding and addressing these factors optimizes patients’ well-being and functional outcomes. A holistic approach considering medical and psychosocial aspects is crucial for enhancing HRQOL in meningioma patients.

1. Introduction

Meningiomas stand as one of the most common types of primary brain tumors, constituting about a third of all tumors within the central nervous system. Most meningiomas are histologically benign, asymptomatic, and frequently detected during medical evaluations for other conditions. Incidental asymptomatic meningiomas do not induce a mass effect and may thus have no impact on a patient’s quality of life [1]. However, symptomatic patients experience a broad spectrum of neurological and psychological manifestations. These symptoms primarily arise from mass pressure exerted on surrounding tissues, induced seizures, or treatment complications [2]. Based on tumor location, symptoms include visual impairment, cognitive disturbance, psychiatric symptoms, and neuropathies. It is also common for patients to report non-specific symptoms like sleep disturbances, fatigue, and psychosocial challenges.

Advancements in radiation and surgical techniques have remarkably improved the prognosis for patients diagnosed with meningiomas. According to prior studies, meningioma patients’ life expectancy approaches the general population, with 5-year survival rates at 92% (as opposed to the expected survival of 94%) and 10-year survival rates at 81% (versus the expected survival of 86%). However, patient functionality is inevitably impacted by the physical and cognitive symptoms associated with meningiomas, leading to inherent limitations in their daily lives, which substantially reduce their life quality [2]. For instance, a significant proportion, approximately two-thirds of patients, persistently suffer from moderate to severe neurological deficits even 5 years post-surgery [3]. However, the importance of these functional issues may be underestimated in the treatment strategies implemented by neurosurgeons, radiotherapists, or oncologists [4]. To many patients, the quality of life during and after treatment holds equal importance as treating their cancer and plays an important role in the patient’s overall outcomes [5]. Therefore, a paradigm shift in current therapeutic goals for meningiomas is necessary, moving away from a singular focus on survival and surgical tumor resection toward a more holistic approach with prioritizing patients’ performance and life satisfaction.

Recently, health-related quality of life (HRQoL) has been introduced as a meaningful indicator in cancer management. It is a comprehensive concept that encompasses various dimensions of life contributing to subjective physical, mental, and social well-being. Multiple measurement methodologies have been developed to gather clinical history and evaluate patients’ HRQoL. However, certain aspects with considerable short and long-term impacts on daily life, such as cognitive impairment, memory loss, and personality changes, remain challenging to objectively quantify [4].

This chapter aims to delve into HRQoL in patients with meningiomas, shedding light on how the disease and its treatments can influence HRQoL. Our exploration will encompass various aspects of HRQoL in meningioma patients, ranging from HRQoL assessment, risk factors, impacts on cognitive and psychiatric functions, immediate and long-lasting outcomes of treatments, associated socioeconomic burden, HRQoL inequality, and also application of artificial intelligence in prediction of HRQoL.

2. Assessment of health-related quality of life

In recent years, there has been a growing inclination toward understanding the HRQoL and functional disability that meningioma patients have experienced [6]. Quality of life (QoL) is influenced by multiple factors within cultural frameworks that shape the patients’ objectives and perspectives. Standard indicators of QoL should consider diverse elements, such as patient environment, level of education, and even leisure time activities, in addition to physical and mental health status [6]. Current reports of QoL among meningioma patients have employed heterogeneous methodologies, with different scales and follow-up protocols, which highlights the importance of developing standardized approaches to evaluate long-term functionality and QoL, particularly among those who have been surgically treated [1].

A significant challenge in this regard is the lack of available data regarding the long-term functional outcomes of patients with meningiomas. Conventional outcome measures such as complications, extent of resection, and survival rates can be ascertained by healthcare providers. However, the data concerning quality of life should ideally be reported by the patients themselves [6]. Patient-reported outcomes are gaining importance and are rapidly becoming the most precise and reliable reflections of the patient’s perspectives [7]. Several self-assessment questionnaires have been developed specifically for patients to report their experiences and perceptions of HRQoL. These questionnaires, commonly recognized as patient-reported outcome measures (PROMs), constitute a valuable instrument for capturing the subjective history and perspectives of patients, ensuring that their experiences are not only acknowledged but also duly considered in the comprehensive evaluation of their HRQoL [1, 6].

Table 1 illustrates some examples of HRQoL assessment tools. Among them, the National Institute of Health Patient-Reported Outcomes Measurement Information System (PROMIS) provides instruments that can be customized according to specific requirements. Another assessment tool is the Short Form 36 (SF-36) questionnaire, which encompasses 36 self-reported items and has been widely utilized as the primary method for assessing QoL. Beyond just measuring health status, SF-36 facilitates health economics analysis and supports the calculation of cost-effectiveness [1]. Another valuable tool is the Karnofsky Performance Scale (KPS) which is commonly used questionnaire for the assessment of functional decline in patients with advanced illnesses [6]. While these generalized assessment tools are designed to evaluate physical, cognitive, emotional, and social functioning across diverse populations, they do not specifically target central nervous system pathologies. This oversight creates a gap where specific concerns related to meningiomas remain unaddressed [10].

Instrument Specificity	Name of Questionnaires	Assessment of Medical Conditions	What is measure?	Subdomains
Generic	SF-36	Evaluating the health status of individuals, commonly used in health economic analysis for cost-effectiveness assessment	A set of 36 items centered on patient-reported physical functioning and role limitations	Role limitations, pain, overall health perception, physical functioning, vitality, social interaction, overall mental well-being
	PROMIS	Highly pertinent and applicable to both chronic and acute medical conditions	Assessment of patient-reported physical, mental, and social capabilities	Fatigue, pain severity, pain disruption, physical functioning, sleep disruption, anxiousness, despondency, and role restrictions
	EQ-5D	Applied in population health investigations, clinical trials, and economic assessments with wide-ranging relevance	A detailed descriptive examination of five subcategories paired with an appraisal of general health status through the use of the visual analog scale (VAS)	Mobility, self-care, typical activities, pain/discomfort, anxiety/depression (mental distress)
Brain Tumor	FACT-BR	Individuals receiving therapy for glioma	44 items, patient reported	Physical, emotional, and functional health, along with any additional symptoms
	MDASI-BT	Individuals receiving treatment for glioma	22 items, patient reported	General, localized, and treatment-associated symptoms encountered in the preceding 24 hours
	BN20	Individuals receiving treatment for glioma	10 items, patient reported	Future uncertainty, visual impairments, motor dysfunction, speech challenges, emotional distress, and symptoms specific to brain tumors
	EORTC; QLQ-BN20	Individuals receiving treatment for glioma	20-Item supplement to EORTC QLQ-C30	Future uncertainty, visual impairment, motor impairment, communication difficulties, headaches, seizures, drowsiness, hair loss, itching, leg weakness, and bladder control issues
Cancer	EORTC QLQ-C30	A range of cancer types, encompassing lung, breast, gynecologic, prostate, colorectal cancer, and brain tumors	30 cancer-related items, patient reported	Physical, role, cognitive, emotional, and social functioning, along with fatigue, nausea, vomiting, and pain
Functional Disability	KPS	Created for medical practitioners to gauge a patient’s cancer survival potential, utilizing a scale where 0 indicates mortality and 100 signifies a state of well-being with no complaints and no signs of disease

Table 1.

Health-related quality of life and functional disability assessment tools.

Abbreviations: EQ-5D, EuroQol 5 Dimension; MDASI-BT, M.D. Anderson Symptom Inventory-Brain Tumor; EORTC QLQC30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3; KFS, Karnofsky Performance Status; EORTC QLQ-BN20, Quality of Life Questionnaire Brain Neoplasm Module 2.0; FACT-BR, Functional Assessment of Cancer Therapy Brain Module; PROMIS, National Institute of Health Patient-Reported Outcomes Measurement Information System; SF-36, Short Form Health Survey-36 item [1, 6, 8, 9].

3. Risk factors (predictors) of long-term impairment of HRQoL

Besides the HRQoL assessment tools, specific factors come into play that aid in estimating and predicting the eventual severity of HRQoL impairment. Within clinical contexts, the identification of these risk factors serves as a crucial tool for effectively allocating treatment, rehabilitation, and supportive care services. This targeted approach ensures that those in most need receive the maximum benefits, thereby reducing the overall burden imposed by the disease [11].

3.1 Clinical risk factors

The long-term burden of meningioma has been determined by clinical risk factors including treatment characteristics and complications like surgery-related complications, reoperation, and radiotherapy, as well as tumor characteristics [11, 12]. An earlier study revealed negative associations between tumor diameter, tumor activities (as denoted by the presence of edema and a larger tumor diameter on the last MRI), and patients’ executive functioning. Remarkably, the study demonstrated that 67% of meningioma patients suffered from neurocognitive deficits, which negatively impacted their HRQoL [11, 13].

In light of these findings, healthcare providers should place particular emphasis on these clinical risk factors when gathering patient history. This approach can provide valuable insights into the potential need for ongoing supportive care and rehabilitation interventions, which are vital components in enhancing the overall well-being of meningioma patients [11, 13].

3.2 Non-clinical risk factors

Moving beyond the clinical predictors, non-clinical ones in brain tumor surgeries have been relatively under-explored in research. However, understanding and considering these elements are essential for a comprehensive evaluation of patients undergoing neurosurgical interventions. These non-clinical predictors extend beyond medical and surgical considerations, integrating individual characteristics such as social, psychological, and cognitive elements. These factors are typically assessed by clinicians, while they can also be directly reported by patients through PROMs [14].

Predominant non-clinical predictors often encompass sociodemographic variables, including age, gender, household income, socioeconomic status, insurance coverage, and marital status. Psychological attributes, including the presence of depressive and anxiety symptoms, altered mental states, independence in daily activities, and personality typologies, have also emerged as notable non-medical predictors influencing HRQoL. Furthermore, cognitive functions encompassing language deficits, attention spans, executive functions, psychomotor velocity, global cognitive functioning, and working memory have been studied as salient predictors of postoperative outcomes [14].

Additionally, an extended follow-up period as a risk factor was also observed to have a positive correlation with enhanced long-term HRQoL, as quantified by the SF-36 questionnaire. Specifically, patients with meningiomas who scored beneath the 25th percentile of normative data on more than four subscales had an average follow-up duration of 2.9 years. Conversely, those scoring beneath the 25th percentile on fewer than four subscales reported an average follow-up duration of 5.4 years (p-value <0.05). Moreover, a prolonged postoperative period correlated with reduced emotional impairment among these patients [15, 16].

It is interesting to note that in the long-time monitoring of patients with meningioma, HRQoL outcomes of different studies have yielded conflicting findings with different risk factors. This may be influenced by psychological mechanisms related to coping with surgery and illness. Patients might undergo a positive mental transformation, known as posttraumatic growth, which is commonly observed in long-term follow-up of patients with various types of cancer or acquired brain injury. This growth in mental well-being may also lead to a “response shift,” causing patients to experience changes in their values, internal standards, and, subsequently, their perception of HRQoL, ultimately contributing to an enhanced quality of life [17, 18].

4. Quality of life in symptomatic/asymptomatic patients

Some meningiomas remain asymptomatic or undetected during follow-up, while patients with symptomatic tumors often report lower health status compared to healthy individuals. These impairments, though subtle, can easily escape notice. In a specific study monitoring individuals with suspected meningiomas, a decrease in vitality and overall well-being was discerned. However, when examined through the SF-36 questionnaire, no statistically significant differences were found in physical function, physical discomfort, role limitations, emotional distress, social interactions, and mental health. The authors attribute these changes to the only awareness of having an intracranial tumor and its potential psychological impact on patients, resulting in lower scores for vitality and general health domains in the HRQoL assessment. Importantly, these changes could not be detected and explained by differences in neurocognitive test performance when compared to healthy controls [19]. These findings indicate that patients with meningiomas may not experience significant physical impairments directly linked to their tumors (asymptomatic); however, they may still suffer from psychological distress like depression and anxiety. Conversely, meningioma patients displaying clinical symptoms reported diminished scores in multiple domains when compared to healthy controls of the same age. These areas included self-care, cognition, vitality, physical health, working memory, verbal memory, psychomotor speed, and role limitations [20].

Symptomatic meningiomas suffer from a wide range of clinical severity and symptoms, largely dependent on their specific location within the brain. The most frequently observed anatomical sites for meningiomas are as follows: convexity (35%), parasagittal (20%), sphenoid ridge (20%), infratentorial (13%), and other locations (12%). These regions delineate clinically significant subgroups with unique pathological attributes and linked physical symptoms. For instance, a relatively small meningioma situated in the tuberculum area can affect vision. In contrast, a meningioma of similar size located in the infratentorial region can result in myelopathy at the craniocervical junction or lead to hearing loss when positioned in the cerebellopontine angle.

Another example is that meningiomas which are located at the skull base pose a higher inherent risk of surgical morbidity. This is primarily due to the narrow approaching corridors in that area, the close proximity to critical neurovascular structures, and the relatively delicate nature of lower cranial nerves when it comes to tolerating surgical intervention [21].

Furthermore, in meningioma patients, prevalent preoperative symptoms include alterations in vision, cranial nerve impairments, ambulation challenges, cognitive deterioration, and tinnitus. Among these, visual symptoms had the most pronounced impact on reducing HRQoL. It is worth noting that HRQoL scores were positively associated with optic nerve decompression and the absence of proptosis (eye bulging) [22].

It is strikingly important to understand that the broad range of symptoms is based on precise intracranial locations of the meningioma. This emphasizes the clinical significance of considering the distinct anatomical features and related physical manifestations in the diagnosis and treatment of patients with symptomatic meningiomas.

4.1 Neurocognitive functioning

Unfortunately, there is limited knowledge regarding the impact of neurocognitive dysfunction on HRQoL of patients with meningioma before their surgery. However, several studies exclusively have been done on supratentorial meningiomas, and consistently identified deficits in various domains of cognitive function, including fluency, working memory, attention, processing speed, extended reaction times, and elevated error rates, when comparing patients to healthy individuals [19, 23].

While neurocognitive impairments can endure in meningioma patients post-treatment, the majority of patients tend to see an enhancement in their HRQoL after surgery. In a study involving meningioma patients who underwent a comprehensive set of neuropsychological evaluations right after their surgeries, lower scores were evident in all cognitive domains, including cognitive flexibility, memory, reaction time, psychomotor speed, executive functioning, processing speed, and complex attention. However, when re-assessed using identical tests 3 months later, enhancements were observed in all cognitive areas except for psychomotor speed and reaction time [24].

4.2 Psychiatric manifestations

When it comes to psychiatric presentation, first, it is important to note that the degree of change in one’s happiness (level of anxiety, depression, and happiness) around a “set point” would be influenced by the individual’s capacity to adjust to their new medical condition. Elevated scores in emotional stability and awareness represent psychological factors linked to improved HRQoL, whereas cognitive dysfunction and diminished functionality contribute to a decline in HRQoL [25].

Some patients with primary brain lesions may show no clinical symptoms; however, others might have various presentations like seizures, headaches, alterations in baseline cognitive function, focal neurological deficits, and psychiatric manifestations. For individuals with a mental illness history, it becomes particularly challenging to differentiate between symptoms of a primary psychiatric condition and those caused by meningioma. For example, if a patient presents with the chief complaint of apathy, this symptom might be attributed only to major depressive disorder. In such a case where patients have a history of major depressive disorder and their presentation resembles previous episodes, additional diagnostic laboratory testing may not be requested. This is because patients with major depressive disorder are at a higher risk of recurrent depression, particularly if antidepressant medications have been discontinued for a while [26].

In terms of psychiatric symptoms, brain lesions can affect nearby neurons by compressing surrounding structures and then disrupting neuronal activity, which results in some psychiatric manifestations. There is a correlation between the location of brain tumors and the specific psychiatric symptoms they manifest [27]. For instance, frontal and temporal tumors tend to cause more psychiatric symptoms compared to those localized in the parietal and occipital lobes [26]. Also, previous literature reviews have consistently shown a correlation between frontal meningiomas and depressive symptoms and also highlighted a positive association between right frontal meningiomas and the prevalence of major depressive disorder, atypical depression, and psychosis [28, 29, 30].

All these findings emphasize the importance of considering tumor location when assessing psychiatric symptoms in patients with brain lesions, as it can provide valuable insights into potential associations between specific tumor sites and distinct psychiatric manifestations. Comprehensive evaluation and localization of brain lesions can help guide appropriate treatment strategies and enhance patient outcomes [31]. In this regard, the incorporation of neuroimaging into the assessment process of patients with atypical psychiatric symptoms, will help healthcare professionals to detect potential underlying brain lesions on time, and ultimately may lead to accurate and timely diagnosis [31].

4.3 Epilepsy

Seizures often present as an initial symptom in around 25–30% of individuals diagnosed with meningiomas [32, 33]. Several theories have been proposed to clarify the pathogenesis of brain tumor-related epilepsy in meningioma; however, there are still unresolved questions regarding the effective control and management of seizures in meningioma patients.

In terms of surgical management, on one hand, resection is often effective in reducing the use of antiepileptic drugs (AEDs), improving seizure control, and providing seizure freedom in a significant percentage of cases, ranging from 60–90% [34]. On the other hand, for about 12–19% of patients, seizures may persist even after the surgical procedure [35]. This is mostly due to the extent of tumor removal, which can predict the occurrence of postoperative seizures. These postoperative seizures can have adverse effects on a patient’s quality of life, impacting their independence, cognitive functions, and ability to drive safely. In addition to the extent of tumor removal, there are other factors that may contribute to the risk of postoperative seizures. These factors encompass a prior history of preoperative language impairments, preoperative seizures, postoperative hydrocephalus, the use of postoperative anti-seizure medications, and the tumor’s placement in the parietal region of the brain [36]. Also, there is a consistent association between seizures in meningioma and peritumoral edema and tumor location. In fact, peritumoral edema has been extensively studied and identified as the most robust predictor of seizures both before and after surgery [37].

Another research effort concentrated on supratentorial meningiomas in patients who experienced preoperative seizures. These patients were continually monitored, and it was found that around 90% of them attained freedom from seizures within 1 year following the surgical procedure. Factors associated with less favorable seizure control included a higher World Health Organization (WHO) grade, the presence of peritumoral edema exceeding 1 cm, incomplete tumor resection (Simpson III-IV), and tumor advancement during postoperative monitoring. Interestingly, findings revealed that patients with significant preoperative edema are less likely to achieve seizure freedom after surgery [36].

In terms of medical management, the reported efficacy of each individual antiepileptic drug (AED) varies widely in different studies. Among the medications studied in tumor-related epilepsy, levetiracetam and valproic acid have received the most extensive research and analysis [36], and it was observed that their usage can bring up detrimental effects on cognitive functions in some patients. In fact, epilepsy that begins at an earlier age and use of AEDs have both been associated with cognitive impairment and a lower quality of life. Irrespective of the underlying trigger for seizures, utilizing antiepileptic drugs (AEDs) and employing multiple medications (polypharmacotherapy) concurrently are robust indicators that negatively influence cognitive functioning in domains like processing speed, verbal understanding, and visuospatial capabilities [38].

Addressing polypharmacy issues related to AEDs is a complex and challenging decision that necessitates close collaboration between clinicians and patients. Several factors come into play, including the severity of the disease, medication side effects, and the patient’s willingness to tolerate the risk of a potential breakthrough seizure. It is worth noting that the rate of post-withdrawal seizures remained consistent among patients who discontinued AEDs.

Several factors favor the continuation of AEDs, including the presence of preoperative seizures, the location of the tumor within the temporal region, a history of recurrent disease, and subtotal tumor resection. Overall, enhancing our comprehension and predictive capabilities regarding seizures in meningioma patients can guide health professionals to take effective seizure control approaches to improve HRQoL. Also, it enables a more accurate identification of patients at risk both before and after surgery [38].

5. Quality of life after treatments

The treatment of meningioma typically aims to preserve or enhance HRQoL. The extent of HRQoL improvement tends to vary based on the severity of symptoms prior to treatment [32]. Moreover, it is crucial to emphasize that several elements connected to meningiomas have shown a strong association with increased symptom distress even following treatment. These factors encompass tumor volumes exceeding 25 cc, frontal location, recurrent occurrences, incomplete resections, and lesions at the skull base, where achieving full tumor removal is frequently challenging [39].

Furthermore, the significance of PROMs has increased in various aspects of healthcare and medical research, particularly in assessing postoperative changes in the quality of life. Predicting the clinical course after surgery/radiotherapy remains challenging, but it holds paramount importance since patients often have unaddressed questions about their postoperative health status before undergoing surgery/radiotherapy. Besides this, understanding the factors associated with functional impairment after surgery/radiotherapy enables clinicians to enhance communication with patients during the preoperative evaluation process, leading to more informed decision-making, personalized interventions, and ultimately better patient care.

5.1 Surgery

Meningioma patients usually go through a positive clinical progression, where the treatment intensity is moderate and mainly involves neurosurgery. After mass resection, the majority of patients see an improvement in HRQoL and a reduction in pain, discomfort, and anxiety. However, some patients may experience a long-term decline in HRQoL, particularly in areas related to social and emotional functioning. To be more specific, various factors contributing to postoperative quality of life are as follows: burden of symptoms, age, size of tumor, histological grade, and extent of resection in surgery [39].

In one cross-sectional survey study, researchers have attempted to investigate socioeconomic burden and its impacts on quality of life in patients suffered from meningioma. They demonstrated remarkable improvements in specific scales of clinical symptoms after surgery. In Figure 1a, alterations in quality of life are illustrated before and 1 year after surgery for patients with intracranial meningioma. These improvements are as follows: seizures (12.1%, 95% confidence interval (CI): 7.7–16.5%), headaches (18.6%, 95% CI: 13.6–23.6%), and global health (20.7%, 95% CI: 15.2–26.2%). However, there were less significant improvements (less than 10%) in future uncertainty, emotional and social functioning, and other different symptoms such as visual disorder, nausea and vomiting, pain, and appetite loss. Regarding the symptom burden, Figure 1b did not reveal any alterations exceeding 10% in symptom burden or interference. Nevertheless, it was observed that there were enhancements evident at lower levels across all scales except for cognitive functioning [40].

Figure 1.

Alterations in quality of life (A) and burden of symptoms (B) 1 year after meningioma surgery compared to pre-surgery condition [40]. Effect sizes were depicted through plots, which portray the variations in mean values on quasi-continuous scales spanning from 0 to 100. These effect sizes serve to visually convey the extent of changes in different aspects of patients’ well-being and symptom experiences following surgery.

This research revealed a notable reduction in the workforce participation of patients, showing that 47 fewer individuals (20%) were currently employed. Among this group, 23 patients (10%) had retired as a result of age-related reasons (p < 0.001), 11 patients (5%) were dealing with disabilities, and 13 patients (5%) were without employment [40]. Among the initial 101 patients who were in full-time employment prior to their surgery, 21 individuals (21%) shifted to part-time employment, while 24 patients (24%) opted to cease working altogether. Among the 88 patients who were already working part-time before the procedure, 23 individuals (26%) also discontinued working. Consequently, there was an overarching decline in the number of patients engaged in full-time employment, while the number of those working part-time remained constant. Additionally, there was a rise of 21 patients (10%) who necessitated professional care (p < 0.001) [40]. The results of a binary regression analysis conducted on this cohort indicated that both occupational status (odds ratio [OR] of 0.41, 95% CI of 0.17–0.98, p = 0.045) and subjective ability to work (OR of 0.37, 95% CI of 0.15–0.92) were linked to a clinically significant decline in HRQoL. In fact, substantial proportion of meningioma patients (ranging from 19–35%) are unable to return to their pre-treatment level of employment [34].

In a study conducted by Miao, the HRQoL assessment tool with a 25-item questionnaire was used for both pre- and postoperative meningioma patients, as well as age-matched healthy individuals. The findings revealed that while HRQoL scores increased in meningioma patients following treatment, they still remained lower compared to the baseline HRQoL scores of the healthy controls [41]. Furthermore, analysis of clinical factors identified several significant predictors of HRQoL scores in meningioma patients. These predictors included tumor size (RR = 1.13), tumor recurrence (RR = 1.33), histologic grade (RR = 3.83), and tumor location (RR = 1.09). These findings provide strong evidence for the clinical factors that can impact HRQoL outcomes in surgeries [41].

Moreover, five predictors of functional impairment following brain tumor surgery have been identified in another research. These predictors include cranial nerve manipulation, major brain vessel manipulation, tumor size, posterior fossa location, and involvement of eloquent brain areas [42]. All these predictors could be combined and considered to monitor individuals in postsurgical periods, which enhances HRQoL and leads to better patient care.

5.2 Radiotherapy

However, surgical resection is often successful in curing the majority of cases. In a subgroup of patients with clinically aggressive meningioma, tumor recurrence may occur. Currently, no effective chemotherapy treatments are available for meningiomas. Instead, radiotherapy can be used to help control tumor growth in such cases. Generally, adjuvant radiotherapy is not typically administered after the complete removal of grade 1 meningiomas. Nonetheless, it is commonly integrated into the surgical strategy for grade II and III tumors or when dealing with recurring conditions [43].

A specific subgroup of meningioma patients, consisting of those with unresectable lesions or those with high risk for surgery, are suitable candidates for radiotherapy. Radiotherapy carries a relatively lower risk compared to surgery and demonstrates high rates of local tumor control. However, it is important to note that treatment-related toxicity can occur, including short-term neurological deficits associated with reactive edema and a few delayed neurocognitive effects [44].

Some previous research has focused on comparing the impact of adjuvant radiotherapy versus primary surgery without radiotherapy on HRQoL. The study results indicated that patients who underwent surgery followed by radiation treatment exhibited diminished HRQoL scores, especially in areas connected to memory, physical abilities, processing speed, and psychomotor speed. Nonetheless, when the groups were aligned based on demographic characteristics and the duration of the disease, these HRQoL score discrepancies vanished. This implies that the inclusion of radiotherapy following surgery does not result in extended adverse impacts on HRQoL [45, 46].

Despite potential short-term setbacks in verbal memory, working memory, and executive function, there have been observations of sustained or even enhanced HRQoL in the long run after skull-base meningioma removal and radiotherapy. This emphasizes the significance of conducting future studies to further investigate the long-term effects on HRQoL associated with different treatment options in patients with meningioma.

5.3 Short and long-term outcomes

Meningioma patients consistently exhibit lower scores of HRQoL compared to healthy individuals, both in the short and long term. Meningioma features such as edema, tumor size, and invasion impact patients in a manner similar to intramedullary brain tumors in a short time. In contrast, patients with minimal brain compression or those with tumors located near areas of the brain are more likely to experience minimal symptoms or remain asymptomatic [47].

In the long run, patients may consistently report ongoing reduction in HRQoL, particularly in the areas of social, emotional, cognitive, and executive functioning, even more than 120 months after their surgical treatment. It is important to note that the majority of HRQoL research focuses on grade 1 and 2 meningiomas. In this patient group, survival rates commonly exceed 10 years. Due to this prolonged survival, meningioma should be regarded as a chronic disease with persistent symptoms, emphasizing its long-term impact on patients’ well-being and HRQoL [47].

6. Application of artificial intelligence in meningioma; using machine learning to predict HRQoL outcomes

Predicting HRQoL outcomes after the surgical removal of benign brain tumors serves a dual purpose: enabling early interventions and optimizing supportive care resource allocation. This proactive approach not only enhances clinical interventions but also empowers patients through education. Machine learning (ML), a subset of artificial intelligence (AI), equips systems with the capability to predict complex biological patterns that lack predefined models. Based on routine demographic and perioperative data, ML algorithms hold promise in predicting quality of life for patients with mild or benign brain tumors. These models offer potential to identify individuals prone to low levels of quality of life, facilitating efficient allocation of resource-intensive care [48].

While ML models have been applied to predict quality of life in cancer patients, none have been tailored for brain tumors [49]. Hence, the potential of ML in predicting HRQoL outcomes for low-grade meningiomas remains largely untapped. A recent breakthrough by Karri et al. utilizes an extensive dataset to explore various ML approaches, developing and assessing ten binary classifiers for quality-of-life prediction. These classifiers anticipate symptom presence or absence, as well as significant declines in overall quality of life relative to the population mean. The study covers a timeframe of 12 to 60 months after the removal of tumors. It makes use of data obtained from a longitudinal investigation conducted on patients who underwent surgery for low-grade glioma, meningioma, and acoustic neuroma at the Neuro-Oncology and Neurosurgery clinics of Royal Melbourne Clinic [50]. Derived from the QLQ-C30 questionnaire, a “global HRQoL” score forms the basis for a binary target variable. This variable identifies whether the global HRQoL score has dropped by at least 1 Minimal Clinically Important Difference (MCID) below the population mean of 75. Those meeting this threshold are labeled “1,” signifying an expected lower HRQoL compared to the average population over time, while those above it are labeled “0.” Using a chosen MCID of 10 points, aligned with previous studies, a “threshold” score of 65 is established [50].

Among six machine learning algorithms tested (Logistic Regression (LR), Decision Tree Classifier (DT), K Nearest Neighbors Classifier (KNN), Random Forest Classifier (RF), Support Vector Machine (SVM), and Gradient Boosting Machine (GBM)), the Support Vector Machine (SVM) emerges as the top performer for most outcomes. However, pain and diarrhea favor the Random Forest (RF) algorithm. This indicates the influence of hyperplane-based differentiation on predictive effectiveness across target variables. RF excels particularly for pain and diarrhea, indicating suitability for decision-tree-based differentiation [50]. In a broader context, predictive capacities of best-performing algorithms, measured by AUC (area under the curve), fall into three categories: >0.9, 0.8–0.9, or < 0.8. Metrics like appetite loss, constipation, nausea and vomiting, diarrhea, dyspnea, and fatigue exceed 0.9 AUC. Global HRQoL and financial difficulty score 0.8 to 0.9. In contrast, pain and insomnia consistently exhibit AUC below 0.8. PR-AUC (precision-recall area under the curve) scores echo AUC trends, deviating only for pain and diarrhea due to higher standard deviation during cross-validation [50].

Despite the potential shown by ML algorithms relying on routine demographic and perioperative data to forecast HRQoL outcomes for low-grade and benign brain tumors, limitations arise from derivation through a small-sample, single-center dataset. To enhance generalizability and account for symptom diversity across tumor types, expanded data collection on a multi-center scale is crucial. Such an approach would bolster algorithm applicability and refine predictions based on tumor-specific data.

7. Inequality in HRQoL of patients with meningioma

The complexities surrounding healthcare quality and equity are important issues. In recent years, there has been a growing focus and attention on disparities related to race, ethnicity, and socioeconomic factors within medical care. In this regard, limited research has addressed the influence of economic, social, cultural, and health system accessibility on the presentation of diseases and treatment outcomes, particularly concerning non-malignant tumors like intracranial meningioma. The assessment of healthcare equity holds the potential to mitigate discrepancies and enhance the standard of care for all individuals affected by intracranial meningioma.

The presence of inequalities in both disease presentation and treatment outcomes significantly impacts the well-being and survival of patients. In this context, studies have examined healthcare, demographic, and socioeconomic factors that contribute to diverse patient outcomes and HRQoL [51].

7.1 Socioeconomic factors

7.1.1 Impacts of socioeconomic factors on HRQoL

Various socioeconomic factors, such as income levels, educational attainment, and insurance coverage, have differing impacts on HRQoL, leading to disparities in HRQoL outcomes. In this context, a study conducted by Nayeri and colleagues in the United States, highlighted the influence of socioeconomic status on patient outcomes. Specifically, individuals with lower socioeconomic status, characterized by factors like Medicaid coverage and absence of a college degree, exhibited inadequate follow-up after resection. To delve deeper, the study suggested that individuals with a high school diploma experienced a reduced risk of morbidity and mortality, contrasting with those residing in areas lacking comparable educational advantages [52].

7.1.2 Socioeconomic burden of meningioma

Socioeconomic factors not only impact the quality of life of meningioma patients but are also influenced by meningioma itself, leading to a burden on socioeconomic conditions such as employment status. Consequently, this contributes to inequity and disparity in HRQoL outcomes. To be more specific, patients diagnosed with meningioma during their working years may encounter challenges that cause a decline in their quality of life, including job loss and concerns about financial stability (Figure 1) [40]. Overall, to gain a deeper understanding and effectively address the challenges posed by the socioeconomic burden in meningioma, there remains a crucial need for prospective studies that thoroughly investigate the associations between socioeconomic factors and HRQoL.

7.2 Healthcare factors

Another significant factor influencing HRQoL outcomes is the variation in healthcare facilities and levels of care that patients may access. Patients can experience distinct advantages based on the healthcare setting in which they receive treatment. For instance, survival rate is considered a benefit for patients with benign meningiomas who undergo surgery at academic medical centers [53].

These findings highlight a survival advantage for individuals managed within academic and research-focused programs, particularly when compared to community cancer programs. This advantage could potentially stem from a higher proportion of patients undergoing definitive initial treatment as opposed to observation, which is more prevalent in academic and research programs as compared to community-based cancer programs [53].

7.3 Demographic factors

Apart from socioeconomic and healthcare factors, demographic characteristics such as race and sex can also exert effects on HRQoL outcomes. In terms of race, Asian patients exhibit a decreased risk of death compared to white patients, whereas black patients tend to have an elevated risk of death, according to univariate analysis. Numerous studies have reported black race as a negative predictor of outcomes [54, 55]. However, when considering a stratified multivariate model that takes multiple comparisons into account, race does not demonstrate any significant association with patient outcomes. This suggests that other predictive factors likely contribute to the observed racial disparities in patient outcomes [51].

Similarly, the impacts of gender on the deterioration of HRQoL present varying results across different investigations. To illustrate, in one study, it was observed that female patients had a decreased risk of mortality in comparison to male patients. An analysis involving 12,284 patients from the Surveillance, Epidemiology, and End Results (SEER) database documented a reduced risk of death among female patients with meningiomas [54]. This trend was also observed in research by Achey et al., who identified a survival advantage for females in non-malignant meningiomas using data from the Central Brain Tumor Registry of the United States [55]. On the other hand, there are studies that did not reveal noteworthy disparities in HRQoL outcomes based on gender [53].

8. Conclusion

Meningiomas stand as the most common type of primary brain tumor in adults, with the majority of them remaining asymptomatic. Interestingly, even minimally symptomatic patients can experience impaired well-being and HRQoL compared to healthy individuals. In detail, various domains of HRQoL can be affected by meningioma, including physical functioning, neurocognitive and psychosocial functioning,

As a result of advancements in therapeutic approaches and subsequent rise in life expectancy, the focus of treatment purposes has been shifted from only striving for survival to prioritizing patient performance and HRQoL. To evaluate HRQoL, various self-assessment questionnaires have been developed for patients to report their own experiences and perceptions of HRQoL. However, they could not specifically address meningioma-related issues. Therefore, meningioma-specific concerns may not be considered and met thoroughly by these instruments [10].

To estimate HRQoL, there are various risk factors, such as histologic grade, location, size and recurrence of tumor, and burden of seizure contributing to worse HRQoL outcomes in short and long time. In the long run, some patients are likely to be involved in unemployment and, consequently financial issues, which may have detrimental effects on their HRQoL. To address this challenge, it would be essential to benefit from novel technology (AI), predict patients’ perspective HRQoL, allocate supportive care services, and implement rehabilitation systems tailored to their specific needs.

Regarding treatment, although therapeutic interventions such as surgery and radiotherapy can improve seizure control and reduce reliance on antiepileptic drugs, HRQoL scores may still remain stabilized or diminished in some patients. We hope that researchers will develop alternative therapeutic options that hold the potential to improve HRQoL further compared to existing therapies.

Beyond treatment, it is imperative to address the issue of equitable care outcomes for meningioma patients and address the disparities in HRQoL outcomes stemming from socioeconomic, healthcare, and demographic factors. Efforts to bridge these gaps and ensure equality in HRQoL outcomes are of paramount importance.

Overall, enhancing HRQoL outcomes for meningioma patients requires a comprehensive approach that addresses both medical and psychosocial factors derived from the tumor and focuses on interactive communication for effective monitoring of their HRQoL, which helps to optimize patient well-being and functional outcomes. These tools (PROMs) aid clinicians in understanding patients’ limitations and dependency levels and allow for monitoring outcome, and assessing postoperative changes in the quality of life. Making informed treatment decisions over the long term is of paramount importance for meningioma patients, as it ensures practical and effective management of their condition.

Conflict of interest

The authors declare no conflict of interest.