Brain Low-risk Aneurysm Stereotactic Radiosurgical Trial

This study is designed as a phase 2, two-arm, open label trial comparing a group undergoing stereotactic radiosurgery (SRS) to a control, observational group.

Sample size

This is a phase 2 safety and feasibility study, therefore, powering for effectiveness is not required. The initial target sample size is 20 patients in the SRS group and 20 patients in the control group. This should be sufficient to detect complications associated with SRS that exceed a 5% incidence rate and assess if obliteration can be achieved in some patients.

If the goal of 20 patients is reached in one of the groups, the investigatrors will recruit only in the second group, until the goal of 20 patients per group is reached.

Setting and screening

Potentially eligible patients will be screened by vascular neurosurgeons at the time of neurosurgical consult or follow-up in the outpatient clinic. The physician will inform the patient of the existence of the research project and offer him to meet the research nurse. If the patient agrees, the nurse will meet the patient within two hours of the consult. The research nurse will present the study, confirm his eligibility and obtain written consent. A copy of the consent form will be given to the patient and another will be stored in the patients' research chart. The subject is free to terminate his participation in the study at any time.

Variables and data collection

The measured variables are presented below.

\- Treatment (Binary: SRS/None, Independent variable)

Demographic and baseline variables data

* Age at enrollment (Continuous (years), Initial questionnaire) * Gender (Binary: Female/Male, Initial questionnaire) * Diabetes mellitus (Binary: No/Yes, Initial questionnaire) * Hypertension (Binary: No, Yes, Initial questionnaire) * Active smoking (Binary: No/Yes, Initial questionnaire, To be considered inactive, the subject must have stopped smoking for more than 4 weeks.) * Cumulative smoking (Continuous: pack-year, Initial questionnaire) * Current alcohol use (Continuous: number of alcoholic beverages per week, Initial questionnaire) * Any pertinent factor (Free text, Initial questionnaire)

Clinical presentation

\- How was the aneurysm discovered? (Categorical: Incidental discovery/Screening imaging because of family history/Other (please specify), Initial questionnaire)

CTA scan at enrolment

* Date of the CTA scan (Date, Medical record) * Aneurysm location (Categorical: A1/ACom/A2/M1/MCA bifurcation/M2/Anterior choroidal/Ophthalmic/Superior hypophysial/PCom, CTA scan at enrolment) * Side of aneurysm (Categorical: Right/Left/Midline, CTA scan at enrolment) * Aneurysm volume (Continuous (mm3), CTA scan at enrolment, Volume will be measured by segmentation) * Aneurysm height (z) (Continuous (mm), CTA scan at enrolment, Measured in the longest axis, perpendicular to the neck) * Aneurysm width (x) (Continuous (mm), CTA scan at enrolment, Measured in the longest axis, perpendicular to the height) * Aneurysm width (y) (Continuous (mm), CTA scan at enrolment, Measured in the longest axis, perpendicular to both height and width (x)) * Aneurysm neck diameter (Continuous (mm), CTA scan at enrolment) * Aneurysm surface area (Continuous (mm2), CTA scan at enrolment, Computed from the segmented volume) * Aneurysm aspect ratio (AR) (Continuous, AR is a 2D shape indicator that is a good predictor of rupture risk22) * Aneurysm non-sphericity index (NSI) (Continuous, NSI is currently the best predictor of rupture amongst shape indices. It is a 3D indicator of how much deviation in shape there is between the aneurysm and a sphere of equal volume)

SRS treatment

* Treatment date (Date, Medical record) * Was treatment completely administered? (Binary: Yes/No, Medical record) * Total treatment time (Continuous (min), GammaPlan record) * Beam-on time (Continuous (min), GammaPlan record) * Maximum dose (Continuous (Gy), GammaPlan record) * Margin dose (Continuous (Gy), GammaPlan record) * Isodose line (Continuous (%), GammaPlan record) * Nb of isocenters (Continuous, GammaPlan record) * Treatment volume (Continuous (mm3), GammaPlan record) * Brainstem 12 Gy volume (Continuous (mm3), GammaPlan record) * Maximum optic chiasm dose (Continuous (Gy), GammaPlan record)

Radiological follow-up (CTA at 6, 12, 24 and 36 months after SRS, MRI at 12 and 36 months after SRS)

* Date of follow-up (Date, CTA) * Complete aneurysm obliteration? (Binary: Yes/No, CTA) * Aneurysm rupture? (Binary: Yes/No, CTA, If aneurysm rupture occurs, an aneurysm rupture report must be completed) * Aneurysm volume (Continuous (mm3), CTA, Volume will be measured by segmentation) * Aneurysm height (z) (Continuous (mm), CTA, Measured in the longest axis, perpendicular to the neck) * Aneurysm width (x) (Continuous (mm), CTA, Measured in the longest axis, perpendicular to the height) * Aneurysm width (y) (Continuous (mm), CTA, Measured in the longest axis, perpendicular to both height and width (x)) * Aneurysm neck diameter (Continuous (mm), CTA) * Aneurysm surface area (Continuous (mm2), CTA, Computed from the segmented volume.) * Aneurysm aspect ratio (AR) (Continuous, AR is a 2D shape indicator that is a good predictor of rupture risk22) * Aneurysm non-sphericity index (NSI) (Continuous, NSI is currently the best predictor of rupture amongst shape indices. It is a 3D indicator of how much deviation in shape there is between the aneurysm and a sphere of equal volume.) * Evidence of adverse radiation-induced effect? (Binary: Yes (please detail)/No, MRI)

Clinical follow-up at 6, 12, 24 and 36 months

* Date of the clinical follow-up (Date, Medical record) * Aneurysm rupture (Binary: Yes/No, Medical record)

If the aneurysm did rupture:

* Date of rupture (Date, Medical record) * SAH grade (Categorical: I/II/III/IV/V, Medical record, As defined by the World Federation of Neurosurgical Societies (WFNS)) * Treatment complications: * New neurological deficit (Categorical: None/Grade 1/Grade 2/Grade 3, Medical record and follow-up questionnaire, As graded by CTCAE v5) * Cerebral edema (Categorical: None/Grade 3/Grade 4/Grade 5, Medical record and follow-up questionnaire, As graded by CTCAE v5) * Stroke (Categorical: None/Grade 1/Grade 2/Grade 3/Grade 4/Grade 5, Medical record and follow-up questionnaire, As graded by CTCAE v5) * Radiation necrosis (Categorical: None/Grade 1/Grade 2/Grade 3/Grade 4/Grade 5, Medical record and follow-up questionnaire, As graded by CTCAE v5) * De novo seizure (Categorical: None/Grade 1/Grade 2/Grade 3/Grade 4/Grade 5, Medical record and follow-up questionnaire, As graded by CTCAE v5) * Increase in seizure frequency (Binary: Yes/No, Medical record and follow-up questionnaire) * Headache (Categorical: None/Grade 1/Grade 2/Grade 3, Medical record and follow-up questionnaire, As graded by CTCAE v5) * Facial pain Categorical: None/Grade 1/Grade 2/Grade 3, Medical record and follow-up questionnaire, As graded by CTCAE v5) * Other (specify) (Categorical: None/Grade 1/Grade 2/Grade 3/Grade 4/Grade 5, Medical record and follow-up questionnaire, As graded by CTCAE v5)

If so:

* Date of first symptoms (Date, Medical record and follow-up questionnaire) * Description of the complication (Free text, Medical record and follow-up questionnaire) * Treatment (Categorical: Successfully treated/Treated, but symptoms persist/Not treated, but symptoms subsided/Not treated and symptoms persist, Medical record and follow-up questionnaire) * Description of the treatment (Free text, Medical record) * Date of last symptoms (if symptoms subsided) (Date, Medical record and follow-up questionnaire)

Other treatments after SRS:

\- Surgical intervention (Binary: Yes/No, Medical record)

If yes:

* Date of surgery (Date, Medical record) * Surgical urgency (Categorical: Elective surgery/Urgent surgery, Medical record, An urgent surgery is a procedure that could not wait until the next day.) * Surgery details (Medical record) * Endovascular procedure (Binary: Yes/No, Medical record)

If yes:

* Date of procedure (Date, Medical record) * Urgency of procedure (Categorical: Elective surgery/Urgent surgery, Medical record, An urgent endovascular surgery is a procedure that could not wait until the next day.) * Procedure details (Medical record)

Death (Binary: Yes/No, Medical record)

If yes:

\- Date of death (Date, Medical record)

Measurement instruments

CTA scan

CTA scanning is commonly used in clinical practice for the diagnosis and follow-up of intracranial aneurysms because of its non-invasive nature8. It is an X-Ray imaging technique allowing tridimensional reconstruction of the skull and its content, with reported sensitivities ranging from 0.77 to 0.97 and specificities ranging from 0.87 to 1.00 for intracranial aneurysms12. The test requires the patient to go to the department of radiology where the scanner is located. The scan itself takes between 15-30 minutes during which the patient is lying on his back. The test is not painful, but some claustrophobic patients might feel temporarily anxious while inside the scanner.

CTA scans in the protocol require intravenous injections of iodine solution to make blood vessels opaque. This step requires the installation of an IV line for the duration of the scan. If the patient is allergic to the iodine solution, a desensitization protocol will be initiated with antihistamines and corticosteroids. In case of renal failure (eGFR \< 60mL/min), patients need to be hyperhydrated or another modality considered (MRA or DSA).

Following the scan, the subject can return to his home.

The study's radiological follow-up schedule has been conceived to follow the standard radiological follow-up performed for UIAs at the CHUS. Therefore, while the follow-up CTA scans will be prescribed by the research nurse to comply with the study's standardized schedule, there will be no additional test required relative to a patient observed at the CHUS outside of this trial.

• Incidence of any radiation-induced complications [Срок оценки: 3 years]
• Incidence of endovascular or surgical aneurysm treatment during the latency period [Срок оценки: 3 years]
• Change in aneurysm volume relative to baseline [Срок оценки: 3 years]
• Change in aneurysm shape indices relative to baseline [Срок оценки: 3 years]
• Aneurysm occlusion confirmed by CT-angiography (CTA) [Срок оценки: at 3 years from SRS]