Clinical and radiological response of benign dural arteriovenous fistula (DAVF) after stereotactic radiotherapy

doi:10.21203/rs.3.rs-4618591/v1

Dural arteriovenous fistulas (DAVF) are abnormal communication at the dura between dural arteries and dural venous sinus or veins. The transverse or sinus are common location of the shunt. This study retrospective investigated the clinical and radiological responses of benign DAVF patients following hypofractionated SRT (HSRT). Eight patients who were diagnosed benign DAVF were treated with HSRT during January 2015 to December 2022. Eight patients (75% female, 25% male) with benign DAVF, predominantly located in the transverse-sigmoid sinus, were treated with HSRT. The cohort had an average age of 52.75 years. All patients presented with pulsatile tinnitus, with one also experiencing headaches. Complete symptomatic recovery was observed in 75% of patients within a mean of 9.7 months post-HSRT. Partial recovery was reported in 25% of patients. Radiographic obliteration was achieved in 85.7% of patients within a mean of 22.3 months, with one patient exhibiting stable disease. Focal alopecia and hyperintense changes on imaging were reported as transient side effects. HSRT provide effective and safety result for symptomatic recovery and radiological obliteration in benign DAVF at transverse sigmoid location. This method provides minimally invasive therapeutic treatment option for patient who suffer from pulsatile tinnitus.

Health sciences/Neurology/Neurological disorders/Cerebrovascular disorders

Biological sciences/Neuroscience/Neuro vascular interactions

Dural arteriovenous fistula

radiosurgery

transverse sinus

sigmoid sinus

Dural arteriovenous fistulas (DAVFs) are rare conditions characterized by an abnormal connection between dural arteries and dural venous sinuses or veins, comprising 10 to 15% of all intracranial arteriovenous shunts¹. The exact etiology of DAVFs remains unclear, although associations have been reported with venous thrombosis, prior surgery, and trauma². The clinical presentation, natural progression, and prognosis of DAVFs are influenced by the venous drainage pattern and their anatomical locations³.

DAVFs lacking cortical venous reflux are typically considered benign, with clinical symptoms determined by the flow pattern and location of the fistula, rarely resulting in severe neurological events⁴. Conversely, aggressive DAVFs, characterized by cortical venous reflux, can lead to neurological dysfunction, altered consciousness, seizures, and dementia due to intracranial hemorrhage or cerebral venous congestion⁵. The annual risk of hemorrhage is reported at 8.1%, with a non-hemorrhagic neurodeficit rate of 6.9% and an annual mortality rate of 10.4%⁶.

These fistulas most commonly manifest in regions such as the cavernous sinus (CS), transverse-sigmoid sinus, tentorium/torcula, or cerebral convexities with drainage into the superior sagittal sinus. DAVFs without cortical venous reflux generally follow a benign course with a low risk of intracranial hemorrhage. However, benign DAVFs, particularly those located in the transverse sigmoid sinus, often present with disabling tinnitus, significantly impacting quality of life and necessitating treatment⁷.

The Cognard classification system, based on the site of venous drainage and flow pattern in the sinuses with or without cortical venous reflux, categorizes DAVFs into five groups. Cognard types I or IIa are typically considered benign with a low risk of intracranial hemorrhage or neurological deficits⁸. Cognard types IIb and higher are considered aggressive types. Recently, endovascular embolization has emerged as the first-line definitive treatment for the immediate closure of fistulas in all aggressive DAVFs. In cases of complexity or residual shunt after embolization, studies have reported satisfactory clinical and radiological outcomes for aggressive DAVFs following a combination of glue embolization and hypofractionated radiotherapy⁹.

However, there is limited evidence supporting the effectiveness of stereotactic radiotherapy (SRT) in treating patients with benign DAVFs^10-12.This study aims to investigate the clinical and radiological responses of benign DAVF patients following hypofractionated SRT (HSRT) at our institution.

Patient data collection

This retrospective study was conducted at Maharaj Nakhon Chiang Mai Hospital, covering the period from January 2015 to December 2022. Written informed consent was obtained from each patient or the patient’s legal guardian.

Participants, variables, and data sources

The study aimed to evaluate the clinical and radiological outcomes of patients with benign DAVF. Demographic information of the patients was obtained from the electronic medical records of Maharaj Nakhon Chiang Mai Hospital. The data collection process included gathering information on sex, age, presenting symptoms, location of the shunt, DAVF grading, clinical response, duration of response, and any side effects following HSRT treatment.

Ethic approval

The study received approval from the Faculty of Medicine, Chiang Mai University Institutional Review Board (Study Code: SUR-2567-0214, Research ID 7566) and the present study was performed in accordance with the Declaration of Helsinki. All study participants provided written informed consent.

HSRT

Before 2019, HSRT treatment plan was established using Hi-Art treatment planning system (TomoTherapy®, Accuray, Madison, USA). The gross tumor volume (GTV) was delineated by radiation oncologist and was confirmed by neuro-interventionist. The planning target volume (PTV) was generated by a 3-mm isotropic expansion from GTV. The dosimetric evaluation was accepted as 100% of PTV was covered by at least 95% of the prescription dose (V95 = 100%). The HSRT dose schedule was 36 Gy in 6 fractions (Fx) administered every other day for two weeks. Subsequently, HSRT dose regimen was rescheduled to deliver 28 Gy in 4-daily Fx. The dosimetric assessment was accepted as 100% of the prescription dose coverage at least 99% of PTV (D99% = 100%).

Response evaluation

Symptomatic responses following HSRT were categorized into four groups: complete recovery, partial recovery, no recovery, and progression of symptoms. Radiological responses were classified as total obliteration, subtotal obliteration (indicating >90% regression of DAVF), partial obliteration (indicating >50% regression of DAVF), stable disease, and disease progression. Clinical response and acute side effects were evaluated six weeks post-completion of HSRT. Subsequently, clinical follow-ups were conducted every two months in the first year and every six months thereafter. MRI/MR angiography (using 3T SIGNA Pioneer General Electric: GE) or CT angiography (using SOMATOM FORCE, Siemens, Forchheim, Germany) were performed at six-month intervals during the initial two years and annually thereafter to assess DAVF response and post-radiation effects. Cerebral DSA examinations were scheduled for patients displaying worsening clinical symptoms or DAVF progression, as indicated by CVR on magnetic resonance angiography (MRA) or computed tomography angiography (CTA)

Eight patients with benign DAVF were treated with HSRT. The age of the patients ranged from 29 to 68 years, with an average age of 52.75 years. The cohort included six women (75%) and two men (25%), resulting in a female-to-male ratio of 3:1. The most commonly affected location of DAVF was the transverse-sigmoid sinus (n = 7, 87.5%), followed by the condylar confluence (n = 1, 12.5%). All patients presented with pulsatile tinnitus, and one patient also experienced headaches.

Complete symptomatic recovery was observed in 75% of patients (6 out of 8) within 6–12 months (mean = 9.7 months) after HSRT. Partial symptomatic recovery was reported in 25% of patients (2 out of 8). Follow-up MRI and MRA were performed in seven patients. The total radiographic obliteration rate was 85.7% (6 out of 7 patients) within 14–34 months (mean = 22.3 months), while one patient (14.3%) exhibited stable disease. The demonstrated patient with complete symptomatic recovery and radiographic cure after HSRT is shown in (Fig. 1–3). The transient side effect of HSRT was focal alopecia in one case (12.5%). Post-radiation imaging demonstrated hyperintense changes on T2/FLAIR in the right cerebellar hemisphere in one asymptomatic patient (12.5%) (Fig. 4)

Table 1 presents the patients’ characteristics and outcomes following HSRT.

Table 1

Patient characteristics and outcomes after HSRT
Patient Number	Sex	Age (Years)	Anatomical site	Cognard’s classification grading	Clinical Symptom before Hypo-HT	Clinical response (Interval after Hypo-HT;months )	Radiographic Obliteration (Interval after Hypo-HT;months )	Complication
1	Female	54	Right transverse-sigmoid sinus	I	Pulsatile tinnitus	Complete recovery (12)	Total obliteration (14)
2	Female	56	Right sigmoid sinus	I	Pulsatile tinnitus	Partial recovery (24)	Total obliteration (19)	Radiation changes right cerebellar
3	Female	60	Right sigmoid sinus	I	Pulsatile tinnitus	Complete recovery (12)	Total obliteration (24)
4	Female	56	Left transverse sinus	IIa	Pulsatile tinnitus Headache	Complete recovery (8)	Total obliteration (28)
5	Female	29	Left sigmoid	IIa	Pulsatile tinnitus	Partial recovery (36)	Total obliteration (34)
6	Female	35	Left sigmoid	IIa	Pulsatile tinnitus	Complete recovery (8)	No imaging MRI/post RT
7	Male	64	Left sigmoid	I	Pulsatile tinnitus	Complete recovery (6)	Stable of DAVF
8	Male	68	Left condylar confluence	IIa	Pulsatile tinnitus	Complete recovery (12)	Total obliteration (15)

Patient data collection

This retrospective study was conducted at Maharaj Nakhon Chiang Mai Hospital, covering the period from January 2015 to December 2022. Written informed consent was obtained from each patient or the patient’s legal guardian.

Participants, variables, and data sources

The study aimed to evaluate the clinical and radiological outcomes of patients with benign DAVF. Demographic information of the patients was obtained from the electronic medical records of Maharaj Nakhon Chiang Mai Hospital. The data collection process included gathering information on sex, age, presenting symptoms, location of the shunt, DAVF grading, clinical response, duration of response, and any side effects following HSRT treatment.

Ethic approval

The study received approval from the Faculty of Medicine, Chiang Mai University Institutional Review Board (Study Code: SUR-2567-0214, Research ID 7566) and the present study was performed in accordance with the Declaration of Helsinki. All study participants provided written informed consent.

HSRT

Before 2019, HSRT treatment plan was established using Hi-Art treatment planning system (TomoTherapy®, Accuray, Madison, USA). The gross tumor volume (GTV) was delineated by radiation oncologist and was confirmed by neuro-interventionist. The planning target volume (PTV) was generated by a 3-mm isotropic expansion from GTV. The dosimetric evaluation was accepted as 100% of PTV was covered by at least 95% of the prescription dose (V95 = 100%). The HSRT dose schedule was 36 Gy in 6 fractions (Fx) administered every other day for two weeks. Subsequently, HSRT dose regimen was rescheduled to deliver 28 Gy in 4-daily Fx. The dosimetric assessment was accepted as 100% of the prescription dose coverage at least 99% of PTV (D99% = 100%).

Response evaluation

Symptomatic responses following HSRT were categorized into four groups: complete recovery, partial recovery, no recovery, and progression of symptoms. Radiological responses were classified as total obliteration, subtotal obliteration (indicating >90% regression of DAVF), partial obliteration (indicating >50% regression of DAVF), stable disease, and disease progression. Clinical response and acute side effects were evaluated six weeks post-completion of HSRT. Subsequently, clinical follow-ups were conducted every two months in the first year and every six months thereafter. MRI/MR angiography (using 3T SIGNA Pioneer General Electric: GE) or CT angiography (using SOMATOM FORCE, Siemens, Forchheim, Germany) were performed at six-month intervals during the initial two years and annually thereafter to assess DAVF response and post-radiation effects. Cerebral DSA examinations were scheduled for patients displaying worsening clinical symptoms or DAVF progression, as indicated by CVR on magnetic resonance angiography (MRA) or computed tomography angiography (CTA)

This study demonstrated the effectiveness of HSRT on benign DAVF primarily at the transverse sigmoid junction. A complete symptomatic recovery was observed in 75% of cases, with a high obliteration rate of 85.7% after follow-up and a low complication rate without clinically significant adverse effects.

The management strategy for DAVF should be individualized, depending on the location of the shunt, clinical presentation, and angioarchitecture of the DAVF, weighing the benefits and risks of each treatment modality. For benign DAVF without cortical venous reflux and no neurological deficit, intervention may not be necessary unless the patient's symptoms, such as pulsatile tinnitus, are intolerable. Spontaneous regression of DAVF is commonly seen in the cavernous sinus location; however, it is rare (<5%) in the transverse sigmoid location. Although endovascular embolization can provide immediate symptomatic relief, achieving complete obliteration for benign DAVF (Borden type I) through transarterial embolization can be challenging due to the complex and tortuous arterial supply. Transvenous scarification of the dural sinus may cause persistent sinus hypertension or local ischemia and increase the expression of vascular growth factors. A less invasive approach with a low complication rate should be considered for treating these patients.

Radiotherapy techniques for DAVF require a stereotactic process using stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HSRT). The pathomechanism of radiosurgery targets both dural feeder arteries and fistulas, causing radiation-induced vascular hypertrophy, leading to the occlusion of the fistula. The complete obliteration rate is reported to be approximately 44-87%, depending on the type and location of DAVF^13-15. Venous ectasia and cortical venous reflux are important predictors of failure in DAVF obliteration after radiosurgery¹⁶. Radiotherapy is not recommended as a first-line treatment for aggressive DAVFs due to their natural history and the long latency period, which can be as long as 6-12 months¹⁷. In contrast, benign DAVFs typically exhibit a more favorable treatment outcome with a higher occlusion rate when compared to malignant types (75% vs. 56%)¹⁸. This study shows complete symptomatic recovery in 75% of cases, with a high obliteration rate of 85.7%. Regarding SRS for DAVFs involving the transverse-sigmoid sinus, a study demonstrates complete obliteration in 44% of cases, with 67% experiencing complete recovery of symptoms. However, the limited previous study that underwent SRS using the Gamma Knife mainly included 67% of cases with aggressive types, with only four patients treated with SRS alone.¹⁹ Our study also demonstrates the benefit and safety of HSRT for DAVF type IIa (Cognard’s classification), which had retrograde sinus reflux with a high clinical response and high-rate obliteration without neurological complications during the latent period. Moreover, the gradual obliteration of DAVF after radiosurgery can avoid complications such as venous hypertension or infarction that can occur after endovascular embolization or surgery. Despite the promising efficacy and safety findings reported in this study, a notable consideration with radiosurgery is the potential risk of secondary radiation-induced malignancies, necessitating long-term follow-up in DAVF cases post-radiation treatment.

The DAVF occlusion period in this study aligns with literature reviews, occurring within a 1 to 3-year latency period after SRS^16,20. Only one patient in our study experienced partial recovery of symptoms and increased tinnitus during follow-up.

The limitations of this study include its retrospective single-center design and the use of noninvasive imaging with MRA for radiologic follow-up, which is less accurate compared to cerebral DSA.

HSRT provide effective and safety result for symptomatic recovery and radiological obliteration in benign DAVF at transverse sigmoid location. This method provides minimally invasive therapeutic treatment option for patient who suffer from pulsatile tinnitus.

Author Contribution

WV: Conception of study, data interpretation and manuscript edit, KU: Manuscript edit, BM: Data interpretation and manuscript edit, JV: Conception of study, data collection, data interpretation, manuscript preparation and manuscript edit. All authors contributed to the analysis and interpretation of data, and critical revision and final approval of the article.

Acknowledgement

This research work was partially supported by Faculty of Medicine and Chiang Mai University.

Data Availability

The datasets used and analysed during the current study available from the corresponding author (JV) on reasonable request.

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No competing interests reported.

Clinical and radiological response of benign dural arteriovenous fistula (DAVF) after stereotactic radiotherapy

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Abstract

Figures

Introduction

Methods

Results

Discussion

Conclusion

Declarations

Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

Status:

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