Quantification of Lung Tumor Motion and Optimization of Treatment.

Background: Mobility of lung tumors is induced by respiration and causes inadequate dose coverage. Objective: This study quantified lung tumor motion, velocity, and stability for small (≤5 cm) and large (>5 cm) tumors to adapt radiation therapy techniques for lung cancer patients. Material and Methods: In this retrospective study, 70 patients with lung cancer were included that 50 and 20 patients had a small and large gross tumor volume (GTV). To quantify the tumor motion and velocity in the upper lobe (UL) and lower lobe (LL) for the central region (CR) and a peripheral region (PR), the GTV was contoured in all ten respiratory phases, using 4D-CT. Results: The amplitude of tumor motion was greater in the LL, with motion in the superior-inferior (SI) direction compared to the UL, with an elliptical motion for small and large tumors. Tumor motion was greater in the CR, rather than in the PR, by 63% and 49% in the UL compared to 50% and 38% in the LL, for the left and right lung. The maximum tumor velocity for a small GTV was 44.1 mm/s in the LL (CR), decreased to 4 mm/s for both ULs (PR), and a large GTV ranged from 0.4 to 9.4 mm/s. Conclusion: The tumor motion and velocity depend on the tumor localization and the greater motion was in the CR for both lobes due to heart contribution. The tumor velocity and stability can help select the best technique for motion management during radiation therapy.

End-to-end test of respiratory gating radiation therapy for lung stereotactic body radiation therapy treatments.

In this paper, a dosimetric end-to-end test of respiratory gated radiation therapy (RGRT) applied in lung cancer stereotactic body radiation therapy (SBRT) was performed. The test was performed from treatment simulation to treatment delivery using a QUASAR phantom, for regular, slightly irregular and irregular breathing patterns in phase- and amplitude-gated modes. A mechanical and dosimetric verification was performed to evaluate all steps of the proposed treatment workflow. Dose measurements were performed using a PinPoint ion chamber and GafChromic EBT3 films. Mechanical verification confirmed good function of the chosen systems. Dosimetric verification showed good agreement between planned and measured doses, for the phase-gated versus amplitude-gated modes: 1.4 ± 0.4% versus 1.2 ± 0.2% for regular, 2.8 ± 0.3% versus 3.0 ± 0.3% for slightly irregular, and 6.2 ± 0.7% versus 7.4 ± 0.5% for irregular breathing patterns. The gamma passing rates for 3%/3 mm and 2%/2 mm criteria, comparing phase- versus amplitude-gated modes, were 99.0 ± 0.3% versus 99.5 ± 0.2% and 95.2 ± 0.2% versus 96.1 ± 0.2% for the regular, 97.4 ± 0.8% versus 98.0 ± 0.6% and 91.7 ± 0.5% versus 92.4 ± 0.4% for the slightly irregular, and 96.4 ± 0.5% versus 95.3 ± 0.7% and 86.4 ± 0.5% versus 84.6 ± 0.7% for the irregular breathing patterns, respectively. It is concluded that using equipment and workflow for the treatment of lung cancer by means of SBRT in RGRT mode is safe and efficient, for regular and slightly irregular breathing patterns.

Assessment of Organ Dose Reduction Using Dynamic Conformal Arc and Static Field with FFF Beams for SBRT in Lung Cancer.

BACKGROUND: The aim of this study is to compare the dose delivered to the organs at risk (OAR), using static beams (SF) and a dynamic conformational arc (DCA) with flattening filter free (FFF) beams, for lung stereotactic body radiation therapy (SBRT). METHODS: 100 patients with lung cancer were treated with SBRT, using FF beams (TrueBeam STx, 6 MV, IQ = 0.67, 600 MU/min), separated into two groups: DCA (50 patients) and SF (50 patients). These patients were retrospectively re-planned using 6XFFF beams, IQ = 0.63, 1400 MU/min. The beam-on time and dosimetric gain on planning target volume (PTV) and OARs (heart, spinal cord, planning risk volume (PRV) of spinal cord, esophagus, lungs and ribs) were analyzed according to tumor location. The comparison of median values was performed using the non-parametric Wilcoxon test (significance level: p < 0.05). RESULTS: PTV coverage was 98.90% versus 98.40% (DCA) and 98.8% versus 98.3% (SF) for the FF and FFF beams, respectively. The median dosimetric gain to the heart, spinal cord, PRV spinal cord, esophagus and lungs was 6% (4-11%) in the central region and 8% (2-23%) in the peripheral region, using FFF (p < 0.05). The dose received by the ribs decreases by 5-6 Gy, using FFF beams. The median gain in beam-on time ranged from 31% to 34% for SF and from 44 to 52% for DCA using FFF beams. CONCLUSIONS: The FFF beams reduce the dose received by all OARs, regardless of the used technique or tumor location, reducing treatment delivery time as well.

Does irregular breathing impact on respiratory gated radiation therapy of lung stereotactic body radiation therapy treatments?

The impact of irregular breathing on respiratory gated radiation therapy (RGRT) was evaluated for lung stereotactic body radiation therapy (SBRT) treatments. Measurements in the static mode were performed with different field sizes, depths of the measurements, breathing periods and duty cycles, using the Farmer ion chamber, PinPoint ion chamber, and microDiamond detector. The output constancy (OC) was evaluated between gated and nongated beams. Measurements in the dynamic mode for regular and irregular breathing in phase- and amplitude-gated modes, were performed with the amplitude of target motion from 5 mm to 25 mm, and breathing period from 3 to 6 s, for ion chamber, and film inserts. The dose discrepancy was evaluated for the ion chamber insert. The gamma passing rate was evaluated with film dosimetry. In the static mode, the maximum obtained OC was 0.8% using the Farmer ion chamber, 1% (p < 0.001) using the microDiamond detector, and 1.4% (p < 0.001) using the PinPoint ion chamber. In the dynamic mode, good agreement between planned and measured doses was obtained for regular breathing, 2.08 ± 0.48% (1.57 to 2.74%), which increased to 3.42 ± 1.24% (1.58 to 6.69%) for irregular breathing. The gamma passing rate of 3mm/3%, 3mm/2%, 3mm/1% and 2mm/2% was 99.4% ± 0.3, 98.2 ± 0.8%, 88.2 ± 3.0% and 96.4 ± 1.0% for regular and 97.2% ± 1.6%, 95.1 ± 2.6%, 85.6 ± 3.0% and 92.9 ± 2.9% for irregular breathing patterns (p < 0.01), respectively. For a slightly irregular breathing amplitude, lung SBRT cancer patients can be treated in the phase-gated mode.

Comparison of Phase-Gated and Amplitude-Gated Dose Delivery to a Moving Target using Gafchromic EBT3 Film.

INTRODUCTION: This study compared phase-gated and amplitude-gated dose deliveries to the moving gross tumor volume (GTV) in lung stereotactic body radiation therapy (SBRT) using Gafchromic External Beam Therapy (EBT3) dosimetry film. MATERIALS AND METHODS: Eighty treatment plans using two techniques (40 phase gated and 40 amplitude gated) were delivered using dynamic conformal arc therapy (DCAT). The GTV motion, breathing amplitude, and period were taken from 40 lung SBRT patients who performed regular breathing. These parameters were re-simulated using a modified Varian breathing mini phantom. The dosimetric accuracy of the phase- and amplitude-gated treatment plans was analyzed using Gafchromic EBT3 dosimetry film. The treatment delivery efficacy was analyzed for gantry rotation, number of monitor unit (MU), and target position per triggering window. The time required to deliver the phase- and amplitude-gated treatment techniques was also evaluated. RESULTS: The mean dose (range) per fraction was 16.11 ± 0.91 Gy (13.04-17.50 Gy) versus 16.26 ± 0.83 Gy (13.82-17.99 Gy) (P < 0.0001) for phase- and amplitude-gated delivery. The greater difference in the gamma passing rate was 1.2% ±0.4% in the amplitude-gated compared to the phase gated. The gantry rotation per triggering time (tt) was 2° ±1° (1.2°-3°) versus 5° ±1° (3°-6°) (P < 0.0001) and MU per tt was 10 ± 3 MU (6-13 MU) versus 24 ± 7 MU (12-32 MU) (P < 0.0001), for phase- versus amplitude-gated techniques. A 90 beam interruption in the phase-gated technique impacted the treatment delivery efficacy, increasing the treatment delivery time in the phase gated for 1664 ± 202 s 1353-1942 s) compared to 36 interruptions in the amplitude gated 823 ± 79 s (712-926 s) (P < 0.0001). CONCLUSION: Amplitude-gated DCAT allows for better dosimetric accuracy over phase-gated treatment patients with regular breathing patterns.

Planning target volume density impact on treatment planning for lung stereotactic body radiation therapy.

BACKGROUND: To evaluate the impact of the planning target volume (PTV) density on treatment planning for lung Stereotactic Body Radiation Therapy (SBRT). MATERIAL AND METHODS: The PTV coverage was analyzed in two groups of 40 lung SBRT patients. One group had PTV density <0.5 g/cm3, while the other group had PTV density >0.5 g/cm3. The treatments were planned in Pinnacle 9.10, using the collapsed cone convolution (CCC) algorithm. The prescribed dose was 60 Gy to the PTV in 4-8 fractions. Respecting constraint for the PTV coverage (D98% > 95%), we compared changes in the isodose line prescription, the number of monitor units (MU), maximum dose (Dmax), irradiated volume covered with 30 Gy (V30Gy), and the optimization planning volume (OPV). RESULTS: For the same median values of the PTV coverage (98.3%), the differences are presented with median values between lower and higher density than 0.5 g/cm3. The isodose line prescription was 83 vs. 90% (p < 0.0001), the MUs were 2294 vs. 1655 MU (p < 0.0001), Dmax was 74.26 vs. 68.09 Gy (p < 0.0001), V30Gy was 117.03 vs. 104.81 cc (p = 0.04), and OPV was 28.48 vs. 39.35 cc (p < 0.001). By overriding the ITV density to 0.8 g/cm3, the isodose line prescription decreases. The Dmax and MUs decrease by 7%, V30Gy by 34%, and OPV by 70%. CONCLUSION: To obtain similar PTV coverage for PTV which is <0.5 g/cm3, a larger margin irradiating a large OPV was used. More MUs and a higher maximum dose were delivered. For the PTV density of ≤0.36 g/cm3, overriding is recommended to reduce the dose and irradiated volume.

Contribution of Imaging to Organs at Risk Dose during Lung Stereotactic Body Radiation Therapy.

BACKGROUND: The use of imaging is indispensable in modern radiation therapy, both for simulation and treatment delivery. For safe and sure utilization, dose delivery from imaging must be evaluated. OBJECTIVE: This study aims to investigate the dose to organ at risk (OAR) delivered by imaging during lung stereotactic body radiation therapy (SBRT) and to evaluate its contribution to the treatment total dose. MATERIAL AND METHODS: In this retrospectively study, imaging total dose to organs at risk (OARs) (spinal cord, esophagus, lungs, and heart) and effective dose were retrospectively evaluated from 100 consecutive patients of a single institution who had lung SBRT. For each patient, dose was estimated using Monte-Carlo convolution for helical computed tomography (helical CT), Four-Dimensional CT (4D-CT), and kilovoltage Cone-Beam CT (kV-CBCT). Helical CT and kV-CBCT dose were evaluated for the entire thorax acquisition, while 4D-CT dose was analyzed on upper lobe (UL) or lower lobe (LL) acquisition. Treatment dose was extracted from treatment planning system and compared to imaging total dose. RESULTS: Imaging total dose maximum values were 117 mGy to the spinal cord, 127 mGy to the esophagus, 176 mGy to the lungs and 193 mGy to the heart. The maximum effective dose was 19.65 mSv for helical CT, 10.62 mSv for kV-CBCT, 25.95 mSv and 38.45 mSv for 4D-CT in UL and LL regions, respectively. Depending on OAR, treatment total dose was higher from 1.7 to 8.2 times than imaging total dose. Imaging total dose contributed only to 0.3% of treatment total dose. CONCLUSION: Imaging dose delivered with 4D-CT to the OARs is higher than those of others modalities. The heart received the highest imaging dose for both UL and LL. Total imaging dose is negligible since it contributed only to 0.3% of treatment total dose.

Evaluation of thoracic surface motion during the free breathing and deep inspiration breath hold methods.

The aim of this study was to evaluate thoracic surface motion from chest wall expansion during free breathing (FB) and deep inspiration breath hold (DIBH) methods, measured with and without 4-dimensional computed tomography (4D-CT) simulation, using equipment developed in-house. The respiratory amplitude and chest wall expansion were evaluated at 5 levels of the thorax, (the sterno-clavicular joint (SCJ), the second level, the intermammary line (IML), the fourth level and the caudal end of the xiphoid process (XP)) using radiopaque wires and potentiometers, with a CT scan simultaneously. This study included 25 examinees (10 volunteers performed FB, 10 volunteers performed DIBH and 5 patients performed FB). For low and irregular respiration, coaching was used, and its impact was evaluated for both breathing methods, FB and DIBH. The breathing amplitude performed with FB between volunteers and patients was not detectable at the SCJ; increasing to the abdomen, 3 mm vs 2 mm (p = 0.326) at the second level; 6 mm vs 4 mm (p = 0.042) at the IML; 10 mm vs 8 mm (p < 0.01) at the fourth level; and 23 mm vs 19 mm (p < 0.001) at the XP. Contrary to the DIBH, where breathing amplitude was greater at 2 first levels 18 mm (SCJ) and 20 mm (second level), decreasing to the abdomen, 14 mm (IML); 11 mm (fourth level); and 10 mm (XP). Chest wall expansion was not detected at the SCJ, while at other levels measured from 1 to 7 mm. Coaching was improve breathing amplitude, for both methods, FB (3 mm) and DIBH (5 mm). The location of amplification is different depending on the breathing method and the in-house phantom was useful to check the amplification level.

Role of "the frame cycle time" in portal dose imaging using an aS500-II EPID.

INTRODUCTION: This paper evaluates the role of an acquisition parameter, the frame cycle time "FCT", in the performance of an aS500-II EPID. MATERIALS AND METHODS: The work presented rests on the study of the Varian EPID aS500-II and the image acquisition system 3 (IAS3). We are interested in integrated acquisition using asynchronous mode. For better understanding the image acquisition operation, we investigated the influence of the "frame cycle time" on the speed of acquisition, the pixel value of the averaged gray-scale frame and the noise, using 6 and 15MV X-ray beams and dose rates of 1-6Gy/min on 2100 C/D Linacs. RESULTS: In the integrated mode not synchronized to beam pulses, only one parameter the frame cycle time "FCT" influences the pixel value. The pixel value of the averaged gray-scale frame is proportional to this parameter. When the FCT <55ms (speed of acquisition V(f/s)>18 frames/s), the speed of acquisition becomes unstable and leads to a fluctuation of the portal dose response. A timing instability and saturation are detected when the dose per frame exceeds 1.53MU/frame. Rules were deduced to avoid saturation and to optimize this dosimetric mode. CONCLUSION: The choice of the acquisition parameter is essential for the accurate portal dose imaging.

Radiosurgery with or without A 2-mm margin for 93 single brain metastases.

PURPOSE: Retrospective comparison of Linac radiosurgery (RS) in 93 single brain metastases with or without a 2-mm margin. PATIENTS AND METHODS: A total of 153 patients had Linac RS (between April 1992 and June 2004), with 139 patients (90.8%) evaluable in June 2005. Sixty-one patients (44%) had extracranial lesions and 65 patients had neurologic symptoms (47%). RS alone: 105 patients (66%); RS +whole brain radiotherapy: 34 patients (24%). Single metastasis: 93/139 patients; classic RS: 42/93 patients; 2-mm margin: 51/93 patients; 30 multiple lesions patients were excluded. TREATMENT: 15 Mv X-ray Linac, circular minibeams, 8-30 mm, four to six noncoplanar coronal arcs. Isodose was 60-80%; doses were 10-20 Gy. FOLLOW-UP: 12 months-13 years; median, 14 months. RESULTS: Local control (LC) was not improved in 51 margin patients vs. 42 classic RS patients: 1 year: 69.1% and 72.4%. Two-year LC rate: 64% and 54.7%, respectively. Survival: median classic RS: 11.3 months; margin RS, 19 months (p = 0.34) and 1 year, 41.6% and 60.2%, respectively. Margin RS patients had a significantly higher rate of severe parenchymal complications: 19.6% vs. 7.1% (p = 0.02); surgery was necessary in 4 of 51 cases vs. 1 of 42 classic RS cases. CONCLUSION: No increase of 1- and 2-year LC rate in margin RS or survival and median survival: 11.3 vs. 19 months (NS) 2-mm margin associated with more severe parenchymal complications (p = 0.02). This procedure is therefore not recommended. Late CT images and 1-mm margin as recommended by pathologists, use of three-dimensional magnetic resonance imaging and fuzzy method to calculate volumes may yield better results. Stereotactic hypofractionation requires further studies.

Impact of CT and 18F-deoxyglucose positron emission tomography image fusion for conformal radiotherapy in esophageal carcinoma.

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiotherapy planning for esophageal carcinoma patients. METHODS AND MATERIALS: Thirty-four esophageal carcinoma patients were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. PET images were coregistered using five fiducial markers. Target delineation was initially performed on CT images, and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: (18)F-fluorodeoxy-D-glucose-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative conformal radiotherapy. The gross tumor volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and increased in 7 patients (21%). The GTV reduction was > or =25% in 4 patients owing to a reduction in the length of the esophageal tumor. The GTV increase was > or =25% with FDG-PET in 2 patients owing to the detection of occult mediastinal lymph node involvement in 1 patient and an increased length of the esophageal tumor in 1 patient. Modifications of the GTV affected the planning treatment volume in 18 patients. Modifications of the delineation of the GTV and displacement of the isocenter of the planning treatment volume by FDG-PET also affected the percentage of total lung volume receiving >20 Gy in 25 patients (74%), with a dose reduction in 12 patients and dose increase in 13. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of esophageal carcinoma. The affect on treatment outcome remains to be demonstrated.

Impact of computed tomography and 18F-deoxyglucose coincidence detection emission tomography image fusion for optimization of conformal radiotherapy in non-small-cell lung cancer.

PURPOSE: To report a retrospective study concerning the impact of fused 18F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and CT images on three-dimensional conformal radiotherapy planning for patients with non-small-cell lung cancer. METHODS AND MATERIALS: A total of 101 patients consecutively treated for Stage I-III non-small-cell lung cancer were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images, and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define the target volume. RESULTS: 18F-fluoro-deoxy-D-glucose-PET identified previously undetected distant metastatic disease in 8 patients, making them ineligible for curative conformal radiotherapy (1 patient presented with some positive uptake corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because the fused PET-CT images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT-PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT-PET image fusion reduced the pulmonary GTV in 6 patients (3 patients with atelectasis) and the mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients owing to an increase in the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Of 81 patients receiving a total dose of > or = 60 Gy at the International Commission on Radiation Units and Measurements point, after CT-PET image fusion, the percentage of total lung volume receiving >20 Gy increased in 15 cases and decreased in 22. The percentage of total heart volume receiving >36 Gy increased in 8 patients and decreased in 14. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. Multivariate analysis showed that tumor with atelectasis was the single independent factor that resulted in a significant effect on the modification of the size of the GTV by FDG-PET: tumor with atelectasis (with vs. without atelectasis, p = 0.0001). CONCLUSION: The results of our study have confirmed that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of non-small-cell lung cancer. However, FDG images using dedicated PET scanners and respiration-gated acquisition protocols could improve the PET-CT image coregistration. Furthermore, the impact on treatment outcome remains to be demonstrated.

Radiosurgery of cerebral arteriovenous malformations in children: a series of 57 cases.

PURPOSE: To evaluate the efficacy and outcome of Linac radiosurgery (RS) as treatment of cerebral arteriovenous malformations (cAVM) in a series of 57 children. METHODS AND MATERIALS: Between 1984 and 2000, we used Linac radiosurgery to treat 792 patients with cAVM. This series included 57 children (7.2%) under the age of 15 years at the time of RS (range = 7-15 years, median = 12 years). We were able to evaluate 49 of the children (86%) by angiography, 21 boys and 28 girls (sex ratio = 0.75). First symptoms were: hemorrhage, 34 patients (69.4%); seizures, 6 patients (12.5%); headache, 6 patients (12.5%); and progressive neurologic deficit, 1 patient (2.1%). Nidus size ranged from 5 to 50 mm (median = 20 mm). Nidus volume ranged from 0.6 to 16 cc (median = 3.5 cc). Patient distribution according to Spetzler-Martin grade was as follows: Grade 1, n = 5 (11%); Grade 2, n = 18 (35%); Grade 3, n = 21 (40%,); Grade 4, n = 5 (14%); and Grade 5, n = 0%. Twenty-seven patients (55.1%) had other treatment before RS: embolization, n = 14 (31.1%); neurosurgery, n = 9 (20.5%); embolization and neurosurgery, n = 3 (6.1%). RS was performed with the system used for adults. Patients were seated in a Betti armchair. Circular 15 MV X-ray minibeams (6 to 20 mm) were delivered in coronal arcs by a GECGR Saturne 43 Linac. Planification and dosimetry were carried out using the Associated Target Methodology and Dosigray TPS dosimetric systems. The dose at the peripheral isodose (50-70%) ranged from 18 to 28 Gy. Median and mean doses were 25 Gy and 23.8 Gy. Mono-isocentric planification was used in 25 patients (53.2%) and multi-isocentric in 24 patients (2 to 5 isocenters). The overall follow-up ranged from 7 to 172 months (mean 40 months, median 34 months). RESULTS: The overall rate of obliteration (OR) was 30/49 (61.2%). Mean time to obliteration was 34 months (range = 7 to 172 months). OR varied according to nidus size and volume: OR was 80% for nidus <15 mm, 67% for nidus between 15 and 25 mm, and 42% for nidus >25 mm (p = 0.058). OR was 100% for nidus <1 cc, 73% for nidus between 1 and 4 cc, and 40% for nidus of 4 to 10 cc (p = 0.019). OR according to patient gender was 84.2% for boys and 40% for girls. OR according to minimum dose (Dmin) was 44% for Dmin < 15 Gy (p = 0.01), 89% for D min from 15 to 20 Gy, and 100% for Dmin > 20 Gy (p = 0.01). OR was 62% in nonembolized AVM and 58% in previously embolized AVM (NS). OR according to the number of isocenters was 68.2%, 55.6%, 80%, 50%, and 0% for 1, 2, 3, 4, and 5 isocenters, respectively. After multivariate analysis, only Dmin closely correlated with OR (beta = 0.462; SE = 0.244, p = 0.057). Of the 6 patients with seizures before RS, 5 (80%) were seizure-free without medication after RS. One patient died of pneumonia. MORBIDITY: Four patients (8.2%) had bleeding after RS at 39, 45, 51, and 59 months. No new neurologic deficit was found during the follow-up period. Twenty-nine patients underwent magnetic resonance imaging. Thirteen patients (44.8%) showed no parenchymal changes. Thirteen patients (44.8%) had Grade 2 changes, that is, T2 hypersignals. Two patients (6.9%) had Grade 3 changes, and 1 patient (3.4%) had Grade 4 "necrosis-like" changes. CONCLUSION: In our experience, Linac RS has proven to be a safe and effective method to treat cerebral AVM in children <15 years, whether used alone or in association with embolization and/or neurosurgery.