1. Introduction

The global increase in life expectancy has resulted in a steadily rising incidence of both primary and metastatic brain tumors among elderly and very old patients. Currently, nearly half of all newly diagnosed glioblastomas occur in individuals aged 65 years or older, and incidence rates continue to increase in this age group [1]. Despite this epidemiological shift, elderly patients remain significantly underrepresented in prospective clinical trials, leading to limited high-level evidence to guide treatment decisions.

Brain tumors in older adults pose distinct diagnostic and therapeutic challenges. Aging is associated with reduced physiological reserve, increased prevalence of cardiovascular and metabolic comorbidities, polypharmacy, and baseline cognitive impairment. These factors directly affect diagnostic accuracy, surgical eligibility, tolerance to adjuvant therapies, and overall prognosis. As a result, treatment strategies in elderly patients are often more conservative, which may contribute to undertreatment and inferior oncological outcomes.

Clinical presentation in elderly patients is frequently atypical. Rather than classic focal neurological deficits or seizures, tumors often manifest with progressive cognitive decline, behavioral and personality changes, gait disturbance, or affective symptoms. These nonspecific presentations are commonly misattributed to neurodegenerative or cerebrovascular disorders, resulting in diagnostic delays and more advanced disease at presentation.

Magnetic resonance imaging with contrast enhancement remains the cornerstone of diagnostic evaluation; however, radiological findings may be inconclusive in elderly patients, particularly when differentiating neoplastic lesions from ischemic, inflammatory, or hemorrhagic processes. Consequently, histopathological confirmation remains essential for treatment planning. Frame-based stereotactic biopsy has demonstrated high diagnostic accuracy with low rates of severe complications even in old and very old patients, supporting its role as a safe diagnostic modality in this population [2,3]. Comparable safety and diagnostic yield have also been reported for stereotactic biopsy of lesions in anatomically challenging regions such as the brainstem [4].

Surgical resection continues to represent a key component of treatment for many intracranial tumors. In elderly patients with preserved functional status, maximal safe resection has been associated with improved survival compared with biopsy alone, particularly in glioblastoma [1]. Nevertheless, craniotomy in elderly patients is associated with distinct perioperative risks. Large database analyses have identified thrombocytopenia as an independent predictor of adverse surgical outcomes [11], while venous thromboembolism remains a frequent and clinically significant complication following craniotomy for brain tumors [12]. In addition, postoperative neuropsychiatric complications, including depression, have been shown to independently increase long-term mortality, underscoring the importance of comprehensive perioperative and psychosocial care [10].

Hemorrhagic tumors and metastatic brain lesions present additional surgical complexity. Recent evidence suggests that surgical resection of hemorrhagic brain metastases can be performed safely without increased intraoperative bleeding or rebleeding when anticoagulation is appropriately managed. However, the presence of intratumoral hemorrhage itself is associated with worse overall survival and should be considered an important prognostic factor [19].

Adjuvant treatment strategies must also be adapted to the elderly population. Hypofractionated radiotherapy regimens have demonstrated comparable efficacy with improved tolerability and treatment compliance in elderly patients with high-grade gliomas [6–8]. The benefit of temozolomide-based chemotherapy is strongly influenced by molecular characteristics such as MGMT promoter methylation, which should guide therapeutic decision-making in elderly glioblastoma patients [1,5]. For patients with poor functional status, palliative approaches remain appropriate and may preserve quality of life [9].

Finally, technological advances are increasingly shaping the future of neurosurgical practice. Robotic and teleoperated surgical systems incorporating haptic feedback have been shown to improve precision and reduce operator error in experimental and clinical settings [14,15]. The development of safety-constrained telesurgical platforms for brain tumor removal further highlights the potential for enhanced intraoperative safety, which may be particularly beneficial in elderly patients with limited tolerance for surgical morbidity [16]. Broader reviews of robotic surgery emphasize that continued refinement of shared-control systems and haptic feedback may expand surgical indications while maintaining acceptable safety profiles [17,18].

Collectively, these findings support a shift toward individualized, multidisciplinary treatment strategies for elderly patients with brain tumors, integrating accurate diagnosis, carefully selected surgical intervention, optimized perioperative management, appropriate adjuvant therapy, and emerging surgical technologies.

2. Methods

Literature Search Strategy

A narrative literature review was conducted to identify relevant studies addressing the clinical presentation, diagnostic evaluation, and treatment of brain tumors in elderly and very old patients. A comprehensive search of the PubMed database was performed, covering publications from inception through 2024.

Search terms included combinations of the following keywords: brain tumor, glioblastoma, brain metastases, elderly, aged, very old, stereotactic biopsy, craniotomy, surgical outcomes, perioperative complications, radiotherapy, temozolomide, robotic surgery, haptic feedback, and teleoperated surgery. Boolean operators (“AND”, “OR”) were applied to refine the search strategy.

Eligibility Criteria

Studies were considered eligible if they met one or more of the following criteria:

• Included patients aged ≥60 or ≥65 years with primary or metastatic brain tumors

• Evaluated diagnostic approaches, including stereotactic biopsy or neuroimaging

• Reported outcomes of surgical treatment, including craniotomy or tumor resection

• Analyzed perioperative complications such as hemorrhage, thromboembolism, hematologic abnormalities, or neuropsychiatric outcomes

• Assessed adjuvant therapies (radiotherapy, chemotherapy) or palliative approaches

• Addressed emerging surgical technologies relevant to neuro-oncology

Both original clinical studies and high-quality systematic or narrative reviews were included. Case reports and non–peer-reviewed publications were excluded.

Data Synthesis

Due to heterogeneity in study design, patient populations, and outcome measures, a qualitative narrative synthesis was performed rather than a meta-analysis. Emphasis was placed on clinically relevant outcomes, safety profiles, and treatment implications specific to elderly and very old patients.

3. Results

Clinical Presentation of Brain Tumors in Elderly and Very Old Patients

Brain tumors in elderly and very old patients frequently present with atypical and nonspecific clinical manifestations, which substantially differ from those observed in younger populations. Classical focal neurological deficits or epileptic seizures are less prominent, while subtle cognitive and behavioral changes often dominate the clinical picture [1].

Progressive cognitive decline, memory impairment, executive dysfunction, personality changes, apathy, and depressive symptoms are common initial presentations. These manifestations are frequently misinterpreted as age-related cognitive decline, dementia, or cerebrovascular disease, contributing to delayed diagnosis and more advanced disease at presentation [1,10]. Gait instability and falls may represent early signs of frontal or cerebellar involvement and are often incorrectly attributed to musculoskeletal or vestibular disorders.

Headache, a common symptom in younger patients with intracranial tumors, is reported less frequently in elderly individuals and may be absent even in the presence of significant mass effect or elevated intracranial pressure. When present, headaches are often nonspecific and chronic rather than acute or progressive. Seizures, although still clinically relevant, occur less frequently as a presenting symptom in elderly patients compared with younger cohorts [1].

Neuropsychiatric symptoms represent an important but underrecognized aspect of tumor presentation in this population. Depression, anxiety, emotional lability, and personality changes may precede neurological deficits and significantly affect quality of life. Importantly, postoperative depression has been shown to independently increase long-term mortality following craniotomy for brain tumor removal, highlighting the prognostic relevance of affective symptoms in elderly patients [10].

Clinical presentation may further vary depending on tumor type. High-grade gliomas often present with rapidly progressive neurological and cognitive deterioration, whereas metastatic brain tumors may manifest abruptly due to intratumoral hemorrhage or peritumoral edema [19]. Hemorrhagic metastases, in particular, may present with acute neurological worsening, mimicking spontaneous intracerebral hemorrhage and complicating early diagnostic assessment.

Comorbidities and polypharmacy further obscure clinical interpretation. Anticoagulant and antiplatelet therapy, commonly prescribed in elderly patients, may modify symptom onset and severity, particularly in hemorrhagic tumors or metastases [19]. Additionally, baseline cognitive impairment and frailty limit the reliability of neurological examination and functional assessment.

Overall, the clinical presentation of brain tumors in elderly patients is often subtle, multifactorial, and misleading. Awareness of these age-specific characteristics is essential for timely diagnosis and appropriate referral for neuroimaging and further diagnostic evaluation.

Diagnostic Strategies

Neuroimaging plays a central role in the diagnostic workup of brain tumors in elderly and very old patients. Contrast-enhanced magnetic resonance imaging (MRI) remains the gold standard for initial evaluation, providing detailed anatomical information regarding lesion location, size, morphology, and associated mass effect. However, age-related changes such as cerebral atrophy, chronic ischemic lesions, leukoaraiosis, and microhemorrhages may complicate image interpretation and reduce diagnostic specificity [1].

In elderly patients, radiological differentiation between neoplastic lesions and non-neoplastic processes, including ischemic stroke, inflammatory disease, radiation-induced changes, or spontaneous intracerebral hemorrhage, can be particularly challenging. This is especially relevant in patients presenting with acute neurological deterioration or hemorrhagic lesions, where metastatic disease may mimic primary vascular pathology [19].

Advanced MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and magnetic resonance spectroscopy, may improve diagnostic accuracy; however, these modalities do not reliably replace histological confirmation, particularly in heterogeneous or multifocal lesions.

Histopathological verification remains essential for accurate diagnosis, molecular characterization, and therapeutic decision-making in elderly patients with brain tumors. Stereotactic biopsy is particularly valuable in cases of deep-seated, multifocal, bilateral, or eloquently located lesions where surgical resection carries excessive risk.

Frame-based stereotactic biopsy has demonstrated high diagnostic yield with low rates of severe complications, even in old and very old patients [2]. Importantly, complication rates appear to be more closely associated with functional status and comorbidities than with chronological age alone [3]. These findings support the safety of stereotactic biopsy as a diagnostic modality in elderly populations.

In anatomically complex regions such as the brainstem, stereotactic biopsy has also been shown to provide reliable diagnostic information with acceptable morbidity, allowing accurate tumor classification and avoidance of empiric or inappropriate treatment strategies [4].

Impact on Treatment Decision-Making

Accurate histological and molecular diagnosis obtained through stereotactic biopsy significantly influences subsequent management. In elderly patients, biopsy results frequently alter therapeutic strategies by distinguishing high-grade gliomas from metastases, lymphomas, inflammatory lesions, or low-grade tumors, each requiring distinct treatment approaches [3].

Molecular markers, including MGMT promoter methylation status, are increasingly important in guiding adjuvant therapy decisions, particularly regarding the use of temozolomide in elderly glioblastoma patients [1,5]. Without tissue confirmation, such personalized treatment strategies cannot be reliably implemented.

Overall, a diagnostic approach combining high-quality neuroimaging with selective use of stereotactic biopsy provides the most accurate and clinically meaningful foundation for treatment planning in elderly and very old patients with brain tumors.

Surgical Treatment and Perioperative Considerations

Surgical intervention remains a cornerstone of treatment for many primary and metastatic brain tumors in elderly and very old patients. When functional status is preserved, maximal safe resection has been consistently associated with improved overall survival and better neurological outcomes compared with biopsy alone, particularly in high-grade gliomas [1,5].

In glioblastoma, extent of resection is a key prognostic factor irrespective of age. Several retrospective and population-based studies demonstrate that elderly patients who undergo gross total or subtotal resection experience longer survival than those managed conservatively, provided that surgery does not result in significant neurological decline [1]. Consequently, chronological age alone should not be considered a contraindication to surgical resection.

Patient Selection and Functional Assessment

Careful patient selection is critical in elderly patients. Preoperative functional status, commonly assessed using the Karnofsky Performance Status (KPS) or similar scales, has been shown to be a stronger predictor of surgical outcome than age itself [1,6]. Frailty, comorbidity burden, and cognitive reserve must be systematically evaluated prior to surgery.

Comprehensive geriatric assessment, although not universally implemented, may improve risk stratification and aid in identifying patients most likely to benefit from surgical intervention.

Perioperative Risks and Complications

Craniotomy for brain tumor resection in elderly patients is associated with specific perioperative risks. Large-scale analyses have identified thrombocytopenia as an independent predictor of postoperative morbidity and mortality, underscoring the importance of preoperative hematologic optimization [11].

Venous thromboembolism (VTE) represents a major source of postoperative complications in this population. Nationwide analyses indicate a high incidence of deep vein thrombosis and pulmonary embolism following craniotomy for brain tumors, with advanced age further increasing risk [12]. Early mobilization and appropriate pharmacological prophylaxis are therefore essential components of perioperative care.

Neuropsychiatric complications also merit attention. Depression following craniotomy has been shown to independently increase long-term mortality in patients undergoing brain tumor resection, highlighting the need for early identification and management of affective disorders in the postoperative period [10].

Hemorrhagic Tumors and Brain Metastases

Hemorrhagic brain tumors, particularly metastatic lesions, pose additional surgical challenges. Recent cohort data suggest that surgical resection of hemorrhagic brain metastases can be performed safely without excessive intraoperative bleeding when perioperative anticoagulation is appropriately managed [19]. However, the presence of intratumoral hemorrhage remains a negative prognostic factor for overall survival and often reflects aggressive tumor biology.

Intraoperative Management and Brain Relaxation

Intraoperative brain relaxation is especially important in elderly patients with reduced intracranial compliance. Osmotherapy remains a key strategy. A Cochrane systematic review comparing mannitol and hypertonic saline found both agents effective for brain relaxation during craniotomy, with hypertonic saline demonstrating potential advantages in hemodynamic stability [13]. Individualized selection based on cardiovascular status is particularly relevant in elderly patients.

Emerging Surgical Technologies

Technological advancements in neurosurgery may further enhance surgical safety in elderly patients. Robotic and teleoperated systems incorporating haptic feedback have demonstrated improved precision, reduced operator error, and enhanced tissue discrimination in experimental and early clinical studies [14,15].

The development of safety-constrained telesurgical platforms for brain tumor removal highlights the potential to reduce inadvertent injury to eloquent brain regions [16]. Shared-control robotic systems with haptic guidance may be especially advantageous in elderly patients, where minimizing operative time and tissue trauma is critical [17,18].

Overall, surgical treatment in elderly and very old patients with brain tumors should be individualized, balancing oncological benefit against functional risk. Advances in perioperative care and surgical technology continue to expand the therapeutic window for this growing patient population.

Adjuvant Therapy: Radiotherapy and Chemotherapy

Radiotherapy remains a key component of multimodal treatment for both primary and metastatic brain tumors in elderly patients. However, age-related vulnerability of normal brain tissue, comorbidities, and reduced tolerance to prolonged treatment courses necessitate adapted radiotherapy strategies [1,6].

Several randomized and prospective studies have demonstrated that hypofractionated radiotherapy provides survival outcomes comparable to standard fractionation while significantly reducing treatment burden and toxicity in elderly patients with high-grade gliomas [6–8]. Hypofractionated regimens are now widely accepted as a preferred option in patients aged ≥65 years, particularly those with limited functional reserve.

Radiotherapy has also been shown to improve neurological symptoms and progression-free survival even in very old patients, provided that baseline performance status is preserved [6]. Importantly, treatment completion rates are higher with shorter radiotherapy schedules, supporting their use in frail populations.

Chemotherapy and Molecular Stratification

Temozolomide represents the backbone of chemotherapeutic treatment for glioblastoma in elderly patients. Its efficacy, however, is strongly influenced by molecular tumor characteristics, particularly MGMT promoter methylation status [1,5].

In elderly patients with MGMT-methylated tumors, temozolomide monotherapy or combined chemoradiotherapy has been associated with improved survival compared with radiotherapy alone [1,5]. Conversely, in MGMT-unmethylated tumors, the benefit of chemotherapy is limited, and radiotherapy alone may be a more appropriate option to avoid unnecessary toxicity.

Combined radiochemotherapy using hypofractionated radiotherapy plus temozolomide has demonstrated favorable outcomes in selected elderly patients with good performance status, offering a balance between efficacy and tolerability [7,8].

Treatment-Related Toxicity

Elderly patients are at increased risk of treatment-related adverse events. Hematologic toxicity, including thrombocytopenia and neutropenia, is more common and may necessitate dose reductions or treatment discontinuation [11]. Careful monitoring of blood counts is therefore essential, particularly in patients receiving concurrent chemoradiotherapy.

Neurocognitive decline represents another important concern. While tumor progression itself contributes significantly to cognitive deterioration, radiotherapy-related neurotoxicity may exacerbate deficits in elderly patients. Hypofractionated regimens may mitigate this risk by reducing cumulative radiation exposure [6,9].

Brain Metastases and Adjuvant Treatment

In patients with brain metastases, adjuvant radiotherapy following surgical resection remains standard in many cases to improve local control. However, the role of whole-brain radiotherapy (WBRT) in elderly patients is increasingly questioned due to its association with cognitive decline.

Stereotactic radiosurgery (SRS) has emerged as a valuable alternative, offering effective local control with reduced neurotoxicity. Elderly patients appear to derive similar benefits from SRS as younger cohorts, provided that lesion number and size are appropriate [19].

Palliative and Supportive Approaches

For elderly patients with poor functional status or extensive disease, palliative treatment strategies are often most appropriate. Short-course radiotherapy, best supportive care, and symptom-directed management can significantly improve quality of life without imposing excessive treatment burden [9].

Early integration of palliative care has been shown to improve symptom control, reduce hospitalization, and support shared decision-making in neuro-oncological patients.

Overall, adjuvant therapy in elderly and very old patients with brain tumors should be highly individualized, guided by functional status, molecular tumor profile, expected benefit, and patient preferences.

4. Discussion

The management of brain tumors in elderly and very old patients remains one of the most complex challenges in contemporary neuro-oncology. The growing incidence of intracranial neoplasms in aging populations contrasts with the persistent underrepresentation of elderly patients in randomized clinical trials, resulting in a limited evidence base and frequent reliance on extrapolation from younger cohorts [1].

Age versus Functional Status

One of the central themes emerging from the reviewed literature is the inadequacy of chronological age as a standalone determinant of treatment eligibility. Multiple studies demonstrate that functional status, commonly assessed using the Karnofsky Performance Status (KPS), is a more reliable predictor of surgical tolerance, postoperative recovery, and survival than age alone [1,6]. Elderly patients with preserved functional capacity derive meaningful benefit from aggressive diagnostic and therapeutic interventions, including maximal safe tumor resection and adjuvant therapy.

Diagnostic Certainty as a Prerequisite for Personalization

Accurate histopathological and molecular diagnosis is a cornerstone of individualized treatment planning. Stereotactic biopsy has consistently shown high diagnostic accuracy with acceptable morbidity in elderly and very old patients, even in deep or eloquent brain regions [2–4]. Importantly, biopsy-driven diagnosis frequently alters treatment decisions by distinguishing between gliomas, metastases, lymphomas, and non-neoplastic lesions, thereby preventing inappropriate or futile therapies [3].

The increasing role of molecular markers, particularly MGMT promoter methylation, further underscores the necessity of tissue confirmation. Without histological and molecular verification, evidence-based personalization of therapy, especially chemotherapy selection, is not feasible [1,5].

Surgical Intervention and Risk Mitigation

Surgical resection remains a key therapeutic modality in selected elderly patients. The extent of resection has been shown to correlate positively with survival in glioblastoma irrespective of age, provided that neurological function is preserved [1]. However, surgery in elderly patients is associated with a distinct risk profile, including hematologic vulnerability, thromboembolic events, and neuropsychiatric complications [10–12].

Thrombocytopenia has emerged as a critical modifiable risk factor, emphasizing the importance of meticulous preoperative assessment and optimization [11]. Likewise, venous thromboembolism remains a significant cause of postoperative morbidity, necessitating individualized thromboprophylaxis strategies [12].

Neuropsychiatric outcomes warrant particular attention. Depression following craniotomy has been independently associated with increased long-term mortality, highlighting the need for routine psychological screening and early intervention as part of comprehensive perioperative care [10].

Hemorrhagic Tumors and Metastatic Disease

Hemorrhagic brain tumors, especially metastases, pose additional diagnostic and therapeutic challenges. While recent evidence suggests that surgical resection of hemorrhagic metastases can be performed safely with appropriate perioperative management, intratumoral hemorrhage itself remains a marker of aggressive disease and poor prognosis [19]. These findings reinforce the need for nuanced risk-benefit assessment rather than blanket exclusion of elderly patients from surgical consideration.

Adjuvant Therapy and Treatment De-escalation

Adjuvant radiotherapy and chemotherapy must be tailored to the physiological reserve and molecular tumor profile of elderly patients. Hypofractionated radiotherapy regimens have demonstrated comparable efficacy with improved tolerability and compliance, making them particularly suitable for this population [6–9]. Similarly, temozolomide therapy offers meaningful benefit primarily in patients with MGMT-methylated tumors, supporting a biomarker-driven approach to treatment selection [1,5].

In patients with limited functional status, treatment de-escalation and early integration of palliative care represent rational, patient-centered strategies that prioritize quality of life over marginal survival gains [9].

Technological Innovation and Future Directions

Emerging surgical technologies, including robotic and teleoperated systems with haptic feedback, represent a promising frontier in neurosurgical oncology. Experimental and early clinical studies indicate that such systems may enhance precision, reduce operator fatigue, and minimize inadvertent tissue injury [14–18]. These advantages may be particularly relevant in elderly patients, where surgical tolerance is limited and margin for error is narrow.

Although widespread clinical adoption remains in early stages, continued refinement of shared-control and safety-constrained robotic platforms may expand the therapeutic window for surgical intervention in frail or high-risk populations.

Clinical Implications

Collectively, the evidence supports a paradigm shift from age-based exclusion to individualized, multidisciplinary decision-making in elderly neuro-oncology. Optimal management requires integration of functional assessment, precise diagnosis, judicious surgical intervention, tailored adjuvant therapy, and supportive care, complemented by emerging technological innovations.

5. Conclusions

Brain tumors in elderly and very old patients require individualized management strategies that prioritize functional status over chronological age. Accurate histological and molecular diagnosis is essential for informed treatment selection, while carefully selected patients may benefit from surgical resection and tailored adjuvant therapy. Hypofractionated radiotherapy and biomarker-driven chemotherapy improve tolerability without compromising efficacy. Comprehensive perioperative and supportive care, complemented by emerging surgical technologies, may further enhance outcomes and quality of life in this growing patient population.