Can Low-Dose Radiation Therapy Aid in Chronic Subdural Hematoma Management? A Historical Review

Abstract

Purpose

Neurosurgical management of chronic subdural hematoma (cSDH) is complicated by high recurrence rates, which can be especially challenging in the elderly and patients with significant comorbidities. Minimally invasive treatment with middle meningeal artery embolization is increasingly used adjunctively and as a primary treatment for those who are poor surgical candidates, but middle meningeal artery embolization carries its own risks and limitations. Identifying a noninvasive treatment that could similarly be used as an adjunctive or alternative therapy for cSDH may further mitigate morbidity and mortality associated with repeated surgical intervention.

Methods and Materials

This review assesses the potential role of low-dose radiation therapy (LD-RT) in cSDH management by examining the condition’s pathophysiology, current treatment options, and the biological and clinical rationale for LD-RT.

Results

The anti-inflammatory effects of LD-RT could theoretically modulate the cycle of inflammation, neomembrane vascularization, and microhemorrhage that characterizes the pathophysiology of recurrent cSDH. Historical case series from the mid-20th century reported clinical improvement in cSDH patients treated with low doses of x-ray therapy, but these findings require validation with modern scientific approaches, including preclinical rodent models and prospective pilot clinical trials employing contemporary neuroimaging endpoints to quantify hematoma resolution.

Conclusions

As an anti-inflammatory treatment, LD-RT could theoretically be a noninvasive tool for managing cSDH, either as an adjunct to surgery or for patients who are poor surgical candidates. Therefore, it may be time to re-explore this modality to evaluate if LD-RT has any potential role in aiding cSDH management.

Introduction

Chronic subdural hematoma (cSDH) is a significant health care challenge, especially among the elderly, a growing demographic.¹ Surgical treatment is the gold standard in patients with high-risk cSDH. Although effective, surgical intervention may be complicated by hematoma recurrence and other postoperative complications, which can be especially challenging in elderly patients and those with comorbidities. Recurrence rates in cSDH are high, with pooled estimates of approximately 10% to 15% overall, though rates up to 20% to 30% have been reported in high-risk subgroups such as elderly patients on anticoagulation or those with incomplete evacuation.2, 3, 4 Such issues underscore the need for minimally invasive, effective adjunctive and alternative treatments, particularly for populations at risk of morbidity and mortality related to repeated surgery. In recent years, middle meningeal artery (MMA) embolization has gained strong support from multiple phase III randomized controlled trials and has received a class I guideline recommendation as adjunctive therapy for cSDH, while pharmacologic agents (eg, corticosteroids, statins, tranexamic acid [TXA]) have also been studied.⁵ Concurrently, the inflammatory pathophysiology of cSDH has been investigated to better understand how novel anti-inflammatory treatments could aid in managing this condition.

Radiation therapy (RT) has emerged as a promising adjunctive and, in some cases, primary treatment for hemorrhagic intracranial pathologies, particularly in vascular malformations and tumor-associated bleeding. Depending on the radiation dose and targeted pathophysiology, RT can exert antiangiogenic, anti-inflammatory, and fibrosis-inducing effects, in addition to outright obliteration of tumor and endothelial cells. For instance, stereotactic radiosurgery is widely used in the management of arteriovenous malformations, where it achieves vascular obliteration through targeted radiation, leading to gradual vessel sclerosis and closure.⁶ However, at lower doses, the predominant effects of radiation shift from obliterative to anti-inflammatory. Low-dose radiation therapy (LD-RT) modulates the inflammatory cascade through TGF-β1–dependent downregulation of leukocyte/endothelial cell adhesion, suppression of proinflammatory cytokines, and modulation of mitochondrial function.7, 8, 9, 10, 11 Preclinical animal models have demonstrated that LD-RT induces a systemic anti-inflammatory shift, including altered T-cell and macrophage populations and reduced levels of inflammatory cytokines such as interleukin (IL)-4 and IL-17.7, 8, 9, 10, 11 These preclinical findings, along with growing evidence of clinical efficacy, support the therapeutic rationale for LD-RT across a range of benign inflammatory and degenerative conditions. Recently, greater understanding of the inflammatory pathophysiology underlying cSDH has prompted investigation into the utility of corticosteroids and statins in cSDH.^12,13 Similarly, LD-RT may have potential as an anti-inflammatory treatment for cSDH, yet there is no contemporary research exploring this topic. Despite promising findings in 2 historical case series treating cSDH with low doses of x-ray therapy, this treatment modality has not been studied further.^14,15

By examining the pathophysiology and current treatment of cSDH, this historical review aims to propose a mechanism and potential role for LD-RT in the management of cSDH. Additionally, this review will identify opportunities for further research, including preclinical and clinical studies, to evaluate the potential utility of LD-RT in this patient population.

Epidemiology

cSDH often arises following minor head trauma, though idiopathic cSDH also occurs. cSDH is significantly more prevalent in older adults due to cerebral atrophy, age-related vascular fragility, and higher rates of anticoagulant and antiplatelet use.¹ The reported incidence of cSDH ranges from 1 to 20 cases per 100,000 individuals annually, with incidence more than tripling among the elderly compared to the general population.^1,16 Furthermore, the incidence of cSDH is projected to increase substantially over the next few decades due to global demographic shifts with aging populations.¹ cSDH is associated with significant morbidity and mortality, with reported 12-month mortality ranging from 15% to 32%.¹⁷ With high rates of hospitalization and reoperation, cSDH treatment and follow-up cost patients more than $60,000 on average.¹⁸ The inflating incidence and health care burden of cSDH emphasize the value of identifying cost-effective adjunctive and alternative management options.

Pathophysiology

cSDH involves the gradual accumulation of blood in the subdural space, typically over weeks to months following minor head trauma in elderly or anticoagulated patients. Recent research has highlighted the role of a chronic inflammatory cascade in the pathogenesis of cSDH.¹⁹ Following the initial bleed, the hematoma induces the formation of a neomembrane composed of fibroblasts, inflammatory cells, and neovascularization. The fragile neovascular vessels within the membrane are prone to recurrent microhemorrhages, perpetuating the hematoma’s expansion and clinical symptoms, such as headaches, cognitive impairment, and neurologic deficits. Elevated levels of proangiogenic and proinflammatory cytokines, such as vascular endothelial growth factor, IL-6, and tumor necrosis factor α, drive this process, while hypoxia within the cavity exacerbates vascular fragility and angiogenesis. Collectively, this cycle of bleeding, inflammation, and neomembrane formation underpins the chronic and recurrent nature of cSDH.¹⁹

Clinical Presentation

The clinical presentation of cSDH can vary significantly, ranging from asymptomatic cases to severe neurologic deficits. Headaches are one of the most prevalent symptoms, reported in up to 80% of patients, while seizures occur in less than 6% of cases.²⁰ Cognitive changes, including confusion, memory loss, and decreased consciousness, are also frequently observed, particularly in older adults who may present with subtle symptoms that may go unnoticed for long periods. In severe cases, patients may experience focal neurologic deficits such as hemiparesis and dysphasia, significant deterioration in consciousness, or even coma. The insidious onset of these symptoms often leads to a delay in diagnosis, as they can be mistaken for normal aging or other neurologic conditions.

Diagnosis

Computed tomography, the standard diagnostic tool for cSDH, typically reveals a crescent-shaped hypodense lesion (Fig. 1). Septations and neovascular membranes may also be observed, though these features may be more apparent on magnetic resonance imaging (MRI). cSDHs can have heterogeneous signal characteristics on T1- and T2-weighted MRI, most often demonstrating mixed signal intensity.²¹ T2-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging are more likely to reveal hyperintensity, while T1-weighted MRI may reveal hypo-, iso-, or hyper-intensity (Fig. 2).²¹ Contrast enhancement consistently demarcates the outer membrane of cSDH, though the inner membrane less reliably enhances.²¹ Imaging characteristics, such as hematoma thickness and the presence of septations, may influence surgical planning and predict recurrence rates.²² Although not yet employed routinely in cSDH monitoring, magnetic resonance spectroscopy could theoretically reveal metabolic changes within the hematoma cavity during the course of radiation treatment, though literature on this specific application is currently lacking and warrants future investigation.

Figure 1.

Axial (A) and coronal (B) slices from brain computed tomography demonstrating large left-sided chronic subdural hematoma with sulcal effacement and midline shift. Hyperdense areas likely represent vascular neomembranes (white arrows).

Figure 2.

Axial cuts of magnetic resonance images of bilateral chronic subdural hematoma. (A) T1-weighted image shows iso- to hyper-intense subdural collection (white arrow) as compared to cerebrospinal fluid. (B) T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging shows characteristic hyperintensity (red arrows) as compared to cerebrospinal fluid. (C) T1-weighted postcontrast imaging shows a central hypointense region with hyper-intense septations (blue arrow).

Treatment Guidelines

The ARISE I consensus statement outlines current management recommendations for cSDH, which depend on symptom severity, hematoma size, and patient comorbidities.⁵ In cases where patients present with absent to mild symptoms or small hematomas (less than 10 mm in diameter), conservative management with observation and potentially pharmacologic intervention with statins, corticosteroids, and/or TXA may be considered. However, only about 40% of cSDHs resolve spontaneously without surgical intervention.⁵ For primary treatment of symptomatic cSDH, burr hole craniotomy remains the standard treatment for symptomatic cSDH.⁵ MMA embolization may be used as an adjunctive treatment to minimize recurrence, while large craniotomy is reserved for cases with significant membrane formation or failed burr hole drainage. For symptomatic cSDH with contraindications for surgery, MMA embolization may be considered as a primary treatment.

Surgery

Burr hole craniotomy, the standard treatment for symptomatic and high-risk cSDH, achieves rapid decompression and symptom relief in nearly all cases.⁵ However, recurrence rates following initial surgery are significant, up to 30%, with older age, anticoagulant use, and incomplete hematoma evacuation being key risk factors. Repeat evacuations are associated with higher rates of complications and recurrence compared to primary procedures. Overall, surgical intervention carries meaningful morbidity and mortality risk. In-hospital mortality is typically reported at 0.7% to 4%, while 1-year mortality ranges from 14% to 33%, reflecting the frailty and comorbidities of the affected population rather than surgical complications alone.^23,24 Reported surgical complications include acute intracranial hematoma (3.5%), postoperative seizures (2%), meningitis (0.5%), and wound dehiscence (0.5%).²⁵ Although comparably effective to burr hole drainage, large craniotomy is significantly more invasive and may carry higher postoperative risks.⁵

Nonsurgical Procedures

As an adjunctive and alternative primary therapy, MMA embolization targets the vascular supply of the cSDH neomembrane to prevent microhemorrhages and angiogenesis. Clinical studies report recurrence rates as low as 2% to 10% following MMA embolization and surgery, compared to 20% to 30% with surgery alone.⁵ For high-risk surgical patients or those with recurrent cSDHs, MMA embolization has been shown to reduce the need for repeat interventions, thereby mitigating the risk of cumulative surgical complications.⁵ In one study of cSDH patients who did not receive surgery, 83.6% of nonembolized patients experienced hematoma reaccumulation, compared to 0% of those who received MMA embolization only.²⁶ As a minimally invasive intervention, MMA embolization demonstrates lower rates of complications than surgery.²⁷ A meta-analysis including 3009 patients who received MMA embolization for cSDH reported a complication rate of only 3.79%, with the most common risks being seizures (0.4%) and stroke (0.3%).²⁷ Overall, MMA embolization is now supported by multiple phase III randomized controlled trials and a class I AHA/ASA guideline recommendation as an adjunctive therapy for cSDH.^5,28 Ongoing clinical trials seek to further explore the safety and efficacy of MMA embolization as a primary and adjunctive therapy in this population.

Pharmacologic Interventions

Pharmacologic interventions may be used as an adjunct to surgical/procedural intervention or observation. For example, statins have been given to cSDH patients for their anti-inflammatory properties and potential for endothelial stabilization, reducing bleeding risk. The concurrent use of statins has been associated with greater reduction in hematoma size following surgery.¹² TXA has been proposed as a primary medical therapy to prevent the progression of cSDH. TXA works by inhibiting fibrinolysis, thereby stabilizing the hematoma and potentially promoting its resorption without the need for surgical intervention. A study involving 130 patients indicated that TXA could be effective in managing cSDH, suggesting a shift toward medical management in certain cases.²⁹ However, the long-term efficacy and safety of this approach require further investigation. Furthermore, the need for anticoagulation and antiplatelet medications for other common medical comorbidities complicates the use of TXA. Lastly, several series have reported that the combination of burr hole craniotomy and dexamethasone yielded favorably reduced recurrence rates, theoretically due to the anti-inflammatory effect of corticosteroids.¹³ However, the 2 largest prospective trials have produced negative results. The Dex-CSDH trial found that dexamethasone was associated with fewer favorable outcomes at 6 months and more adverse events compared to placebo, despite fewer repeat surgeries.³⁰ The Dexamethasone Therapy versus Surgery for Chronic Subdural Hematoma (DECSA) trial found that dexamethasone alone was not noninferior to surgery as a primary treatment, with a higher rate of treatment failure and more serious adverse events in the dexamethasone group.³¹

Radiation for cSDH

Currently, the role of RT in the management of cSDH is yet to be established. cSDHs are peripherally located and well demarcated, making their dural neomembranes and associated vasculature excellent targets for RT. In theory, LD-RT’s anti-inflammatory and antivascular effects could help control the cycle of inflammation, neovascularization, and microhemorrhage that perpetuates rebleeding and hematoma expansion in cSDH (Fig. 3). Treatment planning would target the hematoma (Fig. 4), particularly these vascular neomembranes, while minimizing dose to normal brain tissue. Coverage of the vascular neomembranes within the hematoma site may theoretically maximize the anti-inflammatory effects of LD-RT, which have been demonstrated to act through several mechanisms in animal models. LD-RT modulates macrophage activity by promoting polarization toward an anti-inflammatory M2 phenotype while reducing proinflammatory M1 activity, potentially leading to a shift in the hematoma environment toward resolution rather than progression.³² LD-RT also reduces the levels of IL-6 and tumor necrosis factor α, decreasing inflammation and vascular permeability.³³ Furthermore, LD-RT may enhance endothelial stabilization by inhibiting leukocyte adhesion, potentially reducing inflammatory cell migration and subsequent microhemorrhages, which contribute to hematoma persistence.³⁴ The antivascular effects of RT are well-studied and suggest that the treatment could temper the neovascularization associated with recurrent microhemorrhage, similar to how radiation has been demonstrated to reduce neovascularization in age-related macular degeneration.³⁵ Although these underlying mechanisms were not well-understood at the time, a similar rationale was considered by Prevedi,^14,15 who pioneered the treatment of subacute and cSDHs with x-ray therapy and reported his promising findings in 2 case series.

Figure 3.

Chronic subdural hematoma (cSDH) pathophysiology and proposed mechanism of low-dose radiation therapy (LD-RT). Image created with BioRender.com.

Abbreviations: CSF = cerebrospinal fluid; IL-6 = interleukin 6; TNF-α = tumor necrosis factor α.

Figure 4.

Representative volumetric modulated arc therapy plan delivering a total dose of 6 Gy to a subdural collection along the left cerebral convexity. Axial (left), sagittal (middle), and coronal (right) computed tomography slices show the isodose distributions: 100% (6.0 Gy), 90% (5.4 Gy), 50% (3.0 Gy), and 16.67% (1.0 Gy). The prescription dose region conforms tightly to the crescentic target, with steep dose fall-off sparing the underlying brain parenchyma.

Clinical Experience With RT

Although RT has not been established as a standard treatment for cSDH, preliminary clinical experiences have been reported in the literature. In 1955, Prevedi¹⁴ first reported on his novel use of x-ray therapy for cSDHs. He treated 11 patients with suspected cSDH using fractionated x-ray therapy, though 2 patients were excluded from the case series due to a lack of follow-up. Although diagnostic precision was limited at the time, Prevedi¹⁴ observed clinical improvement and long-term stability in most of these cases, as 7 of 9 (77.8%) showed rapid symptom regression and did not require further intervention over a follow-up period of up to 5 years. The remaining 2 of 9 patients did not survive. One showed no response to treatment and died approximately 7 months later, while another achieved initial recovery but died following relapse of symptoms 1 month later.

Building on his earlier work, Prevedi’s¹⁵ 1966 case series included cases with more advanced diagnostic tools, particularly carotid angiography, allowing him to document the hematoma’s response to x-ray therapy with anatomic precision. In this study, Prevedi¹⁵ treated 3 patients with cSDH using x-ray therapy. Angiographic imaging showed that RT promoted hematoma resorption, normalized the displacement of brain structures, and reduced vascular compression. All 3 patients in this study achieved significant clinical improvement, returning to normal function and experiencing long-term stability without hematoma recurrence.

The summaries of each case described by Prevedi^14,15 are listed in Table 1.^14,15 Across both case series, the dose of radiation administered in a single session ranged from 50 to 100 roentgen (0.44 to 0.88 Gy), and the total treatment dose ranged from 390 to 825 roentgen (3.42 to 7.24 Gy). Prevedi^14,15 concluded that x-ray therapy offers a noninvasive, effective option for managing cSDH, particularly in cases where surgical intervention is high risk or contraindicated. His work demonstrated that RT may achieve complete anatomic and clinical recovery in cSDH patients. However, the applicability of these findings to modern clinical practice is greatly limited by the absence of control groups and modern scientific methods. Since these case series were published, no further studies have expanded upon Prevedi’s^14,15 work to more rigorously investigate the utility of RT in the management of cSDH.

Table 1.

Patient and treatment characteristics described by Prevedi^14,15 (1955 and 1966)

No.	Age range (y)	Injury mechanism + timing	Symptoms	X-ray treatment	Outcome
Clinical improvement
1	41-50	Bicycle accident 2 months prior	Frontal headache, vomiting, drowsiness, left hemiparesis, hypertonia, disorientation.	6 sessions at 80 R/session, every 3 days. Total: 480 R (4.21 Gy)	Improvement after 4 sessions. Excellent recovery with persistent healing at 5-year follow-up.
2	61-70	Bicycle accident 2 months prior	Headache, left hemiparesis, disorientation, dizziness, bilateral hyperesthesia.	8 sessions at 80 R/session, every 3 days. Total: 640 R (5.61 Gy)	Improvement after 4 sessions. Excellent recovery with persistent healing at 5-year follow-up.
3	31-40	Head trauma 4 months prior	Frontal headache, psychic dullness, right hemiparesis, aphasia, drowsiness, generalized hypertonia.	7 sessions at 80 R/session, every 4 days. Total: 560 R (4.91 Gy)	Full recovery; returned to work after 1 month. Stable at 4-year follow-up
4	51-60	Head trauma 1 month prior	Frontal headache, easy tiredness, inability to focus.	8 sessions at 50 R/session, every 4-5 days. Total: 400 R (3.51 Gy)	Worsened symptoms during treatment. Symptomatic improvement 15 days posttreatment; full recovery with persistent healing at 5-year follow-up.
5	61-70	Fall from tree (head trauma) 3 months prior	Left hemiparesis, dizziness, headache, disorientation.	7 sessions at 100 R/session, every 3 days. Total: 700 R (6.14 Gy)	Full recovery by the end of treatment; persistent healing at 4-year follow-up.
6	51-60	Head trauma 2 months prior	Depression, disorientation, headache, left hemiparesis with hypertonia.	7 sessions: 50 R, then 70 R after 4 days, then 100 R every 3 days. Total: 620 R (5.44 Gy)	Cured by the end of the treatment with persistent healing at 4-year follow-up.
7	51-60	Bicycle accident 1 day prior	Disorientation, headache, left hemiparesis.	6 sessions at 80 R/session, every 3 days. Total: 480 R (4.21 Gy)	Improvement after 2 sessions. Full recovery at 4-year follow-up.
8	61-70	Repeated head trauma during military service. >10 years prior	Fainting, dizziness, headache, chronic symptoms worsening over time. Bilateral, chronic subdural hematoma diagnosed by carotid angiography.	50 R/session every other day, alternating sides. Total: 600 R (5.26 Gy) per side.	Complete recovery at 4-month follow-up, and hematoma disappearance confirmed by carotid angiography.
9	41-50	Motorcycle accident (head trauma). 2 months prior	Headaches, vomiting, dizziness, disorientation, confusion, right hemiparesis. Subdural hematoma diagnosed by carotid angiography.	Sessions every 3 days. Once at 50 R, once at 75 R, then at 100 R for the remainder. Total: 825 R (7.24 Gy)	Symptom normalization by the end of treatment, aside from modest dyslalia. Persistent recovery at 3-month follow-up, and hematoma disappearance confirmed by carotid angiography.
10	41-50	Head trauma 2 months prior	Headaches, dizziness, disorientation, right hemiparesis. Subdural hematoma diagnosed by carotid angiography.	Sessions every 3 days. Once at 50 R, twice at 75 R, then 100 R for the remainder. Total: 800 R (7.02 Gy)	Symptom normalization by the end of treatment, aside from mild headaches. Persistent recovery at 6-month follow-up, and hematoma disappearance confirmed by carotid angiography.
Initial improvement, then worsening
11	41-50	Road accident (head trauma) 2 months prior	Headaches, right hemiparesis, aphasia, dizziness, disorientation, urinary incontinence, blurred vision, irritability.	8 sessions at 80 R/session, every 3 days. Total: 640 R (5.61 Gy)	Significant symptomatic recovery by the end of the treatment. Died 1 month later following relapse of symptoms.
No response
12	51-60	Unknown First seizure 3 months prior	Seizures, left upper limb monoparesis, headaches, disorientation, left facial palsy, bilateral hypertonia of lower limbs.	3 sessions at 50 R/session, then 3 sessions at 80 R/session. Total: 390 R (3.42 Gy)	No improvement Patient died 7 months later

LD-RT for Related Conditions

The rationale for the possible benefit of LD-RT in cSDH is strengthened by its established efficacy in other inflammatory and hyperproliferative conditions. LD-RT is a well-studied treatment modality for osteoarthritis, providing anti-inflammatory benefits and pain relief at total doses of 2.5 to 7.5 Gy.³⁶ The anti-inflammatory effects of LD-RT have been verified both histologically and clinically, with extensive research spanning from preclinical models to randomized controlled trials. For osteoarthritis, LD-RT is typically delivered 2 to 3 times weekly in 0.5 to 1.0 Gy per fraction to total doses of 3.0 to 6.0 Gy.³⁶ More common in Europe than the United States, LD-RT is often used for osteoarthritis cases refractory to first-line treatments and to avoid more invasive interventions, such as joint replacements.

Although less researched than its application for osteoarthritis, a growing body of research supports the efficacy of LD-RT in controlling complications related to extramedullary hematopoiesis in patients with myeloproliferative disorders, including myelofibrosis.^37,38 Pulmonary extramedullary hematopoiesis can cause burdensome and life-threatening complications, such as pleural effusions and diffuse alveolar hemorrhage. With Mayo Clinic as the pioneer of this approach, multiple case reports have corroborated that whole-lung irradiation with doses as low as a single 1 Gy fraction can durably control pulmonary extramedullary hematopoiesis and provide relief from such complications.^37,38 Though more studied at higher doses, radiation with total doses as low as 6 Gy has also been demonstrated to control intracranial extramedullary hematopoiesis, with patients experiencing rapid neurologic recovery.³⁹ Although LD-RT is not well-studied for intracranial pathologies, this example, along with other anti-inflammatory and antiproliferative applications of LD-RT, supports the rationale that LD-RT could theoretically provide benefit in cSDH.

Potential Adverse Effects of Cranial LD-RT

LD-RT has been shown to be well tolerated at other disease sites. Osteoarthritis is an LD-RT application with robust safety data from over 1000 patients demonstrating that the only reported adverse effect tends to be mild skin redness, experienced by less than 1%.³⁶ Similarly, mild skin reactions could be expected from cranial LD-RT, which could theoretically be associated with transient hair loss, though data are lacking to evaluate this risk. Intracranial RT at higher doses raises concerns for effects like fatigue or neurologic deficits, both transient and permanent, but the low doses of radiation involved in LD-RT would be less likely to have these effects. Studies reporting outcomes following lower doses of intracranial RT, up to 14 Gy, have noted adverse effects in less than 2% of patients, mostly transient deficits in cranial nerves in close proximity to tumors.^40,41 Radiation-related neurologic toxicities are understood to be dose-related, and the cumulative radiation dose for LD-RT would be significantly lower than that reported in those studies. However, more research is needed to appropriately quantify how much safer intracranial LD-RT is in comparison to traditional radiation doses.

The theoretical risk of secondary malignancy related to LD-RT is considered to be very low, but there are limited long-term data evaluating this, particularly for intracranial LD-RT. This risk has been better studied at other LD-RT sites with reassuring findings. For instance, a cohort study including 158 women who received LD-RT to a cumulative dose of 6 Gy for shoulder arthropathy identified no increased incidence of breast cancer, with a median follow-up time of over 20 years.⁴² Concerns about secondary malignancy are further attenuated by the epidemiology of cSDH, which is uncommon in younger individuals for whom secondary malignancy could have sufficient time to develop. For instance, radiation-induced meningiomas have been reported in patients who received childhood RT under 10 Gy for tinea capitis, with the shortest latency period between treatment and meningioma onset being 48 years.⁴³ Even with an older patient population, long-term data are necessary to confirm suspicions that secondary malignancy would not be a concern when delivering LD-RT intracranially. Additionally, recent evidence has suggested that LD-RT may be associated with an elevated risk of hematologic malignancies when treating areas with greater hematopoietic bone marrow.⁴⁴ Although intracranial LD-RT has not been directly studied, the skull contains substantial hematopoietic bone marrow, and these considerations reinforce the importance of long-term safety monitoring in any future clinical studies of intracranial LD-RT.

Discussion

The management of cSDH continues to evolve as we understand more about its pathophysiology and the efficacy of innovative treatments. Although surgical evacuation remains the primary intervention, the high recurrence rate underscores the need for alternative and adjunctive strategies that target the underlying inflammatory and vascular processes contributing to hematoma persistence, ideally while minimizing invasiveness. In response to this need, MMA embolization is increasing in popularity, and recent studies have begun evaluating the efficacy of pharmacologic therapies like TXA and dexamethasone. These trends suggest a growing role for less invasive treatment options for recurrent cSDH, raising the question of whether LD-RT could serve as one of those alternatives.

Recently, LD-RT has emerged as a promising treatment modality for various benign inflammatory diseases, especially osteoarthritis.⁷ LD-RT has been found to exert anti-inflammatory effects through the modulation of immune cell activity and promotion of anti-inflammatory cytokines, contributing to pain reduction in patients with inflammatory diseases.⁴⁵ Moreover, the safety profile of LD-RT is generally favorable, with studies reporting low morbidity associated with its use in benign conditions.⁴⁶ In the context of cSDH, LD-RT could theoretically modulate the chronic inflammatory processes that drive neovascular membrane formation, microhemorrhages, and hematoma expansion through its anti-inflammatory effects and promotion of endothelial stabilization.

Thus, LD-RT could represent an effective option in those with chronic hematoma recurrence, when surgical intervention is contraindicated, or as an adjunctive treatment to surgery. Especially considering the age and comorbidities of many cSDH patients, a noninvasive treatment modality like LD-RT could potentially be a beneficial tool. Compared to MMA embolization, an effective nonsurgical intervention, LD-RT carries no procedural risk of thromboembolic events such as stroke or embolic infarct, which, though uncommon, represent the most serious complications reported with MMA embolization. Additionally, LD-RT may also be a more cost-effective and accessible tool than more resource-intensive interventions like MMA embolization, which requires a neurovascular interventionist and an available interventional radiology suite. Lastly, although MMA embolization has demonstrated overall efficacy as a cSDH treatment, the EMPROTECT trial found that MMA embolization with microparticle agents did not significantly reduce recurrence when used as an adjunct to surgery in patients at high risk, though this result may reflect the choice of microparticle agents rather than liquid embolic agents.47, 48, 49, 50 These limitations highlight an ongoing need for additional adjunctive strategies in this patient population. It is possible that LD-RT, by targeting the inflammatory mechanisms underlying cSDH recurrence, could theoretically benefit these patients, while also being a more conservative option in terms of treatment-related risk and hospital resource utilization.

Nevertheless, several important limitations to this theory must be acknowledged. The existing clinical evidence for LD-RT in cSDH is solely comprised of uncontrolled case series published over 6 decades ago, without modern dosimetric standards, randomized controls, or objective neuroimaging endpoints. It is plausible that LD-RT may offer no clinically meaningful benefit, or that the inflammatory milieu of cSDH may not respond to the treatment. Historical studies by Prevedi^14,15 provide an intriguing proof of concept, but their findings are substantially limited by the absence of methodological rigor and appropriate controls.^14,15 Although the anti-inflammatory properties and favorable safety profile of LD-RT have been well established in other benign inflammatory conditions, contemporary evidence specific to cSDH is lacking. Furthermore, the optimal dose, fractionation schedule, target volume, and treatment timing remain undefined. From a dosimetric perspective, the thin peripheral location of cSDHs raises the possibility that the adjacent cerebral cortex may receive doses approaching the prescription dose. Future investigations should, therefore, incorporate comprehensive dosimetric characterization, including maximum and mean cortical doses, brain dose-volume parameters (eg, V5), and full dose-volume histograms, alongside rigorous assessment of clinical efficacy and safety.

Despite these uncertainties, existing experience with LD-RT for benign inflammatory disorders provides a reasonable framework for future investigation. The regimens employed by Prevedi^14,15 (0.44-0.88 Gy per fraction; total dose 3.42-7.24 Gy) are broadly consistent with contemporary anti-inflammatory LD-RT schedules used for osteoarthritis, which typically deliver 0.5 to 1.0 Gy per fraction to total doses of 3.0 to 6.0 Gy.^36,51 Future intracranial studies should seek to balance sufficient anti-inflammatory activity with minimization of cerebral irradiation. Given the efficacy and favorable toxicity profile observed in osteoarthritis, regimens such as 3 Gy in 6 fractions or 6 Gy in 6 fractions, delivered 3 times weekly, represent reasonable starting points for investigation. However, the optimal regimen for cSDH can only be established through prospective evaluation of both clinical outcomes and intracranial dosimetric parameters.

Before human trials, rodent models of cSDH may be utilized to evaluate the effect of LD-RT on hematoma resolution and recurrence, in addition to potential toxicities to the brain and skin. Positive findings in preclinical studies, corroborating the theoretical argument and historical reports of Prevedi,^14,15 would provide greater confidence in the potential of LD-RT to benefit patients with cSDH, paving the way for the first human studies in decades. Early-phase clinical studies could then establish feasibility, define optimal dose and fractionation schedules, and characterize safety. As a noninvasive treatment with minimal adverse effects anticipated, LD-RT could be investigated in a range of patients at different locations of the cSDH treatment algorithm. In mild cSDH, LD-RT could be compared to observation, while its utility as an adjunctive therapy could be explored in those with moderate-to-severe cSDH who receive surgery ± LD-RT. In addition to assessing clinical response, these preliminary studies could contribute novel safety data for intracranial LD-RT, including any acute toxicities (eg, skin reactions, neurologic changes). Long-term monitoring would be needed for potential late effects, such as secondary malignancies, although the risk is generally considered low with LD-RT doses in an elderly demographic. Ultimately, if preclinical and early clinical results are promising, randomized controlled trials would be necessary to determine the safety and efficacy of LD-RT for cSDH.

Conclusions

In conclusion, the inflammatory pathophysiology of cSDH, anti-inflammatory effects of LD-RT, and historical case series using x-ray therapy suggest that LD-RT could theoretically be a useful management tool for cSDH, though preclinical and clinical research with modern methodologies are needed to establish its potential in this patient population. The integration of LD-RT into the treatment paradigm for cSDH, either as a standalone or adjunctive therapy, could one day help reduce the need for more invasive and repeat interventions. It may be time to re-explore this modality in a scientific way to assess its efficacy and safety, and to conclude if it has any potential role in the armamentarium that is already available for the treatment of cSDH.

Disclosures

Wenyin Shi has received consulting fees from Varian, Brainlab, and Novocure. Pascal Jabbour has received consulting fees from Medtronic, MicroVention, Balt, and Cerus Endovascular. Ryan Shah, Nilanjan Haldar, Debanjan Haldar, and Keenan Piper have no disclosures.