Impact of flow and angioarchitecture on brain arteriovenous malformation outcome after gamma knife radiosurgery: the role of hemodynamics and morphology in obliteration.

BACKGROUND: Few studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR). METHODS: A prospectively enrolled single-center cohort of patients with bAVMs treated by GKSR has been studied to define independent predictors of obliteration with particular attention to angioarchitectural variables. Only patients older than 18 years old (y.o.), who underwent baseline digital subtraction angiography (DSA) and clinico-radiological follow-up of at least 36 months, were included in the study. RESULTS: Data of 191 patients were evaluated. After a mean follow-up of 80 months (range 37-173), total obliteration rate after first GKSR treatment was 66%. Mean dose higher than 22 Gy (P = .019, OR = 2.39, 95% CI 1.15-4.97) and flow rate dichotomized into high vs non-high (P < .001, OR = 0.23, 95% CI 0.11-0.51) resulted to be independent predictors of obliteration. Flow-surrogate angioarchitectural features did not emerge as independent outcome predictors. CONCLUSIONS: Flow rate seems to be associated in predicting outcome after GKSR conferring high-flow AVM a lower occlusion rate. Its role should be considered when planning radiosurgical treatment of bAVM, and it could be added to other parameters used in GKRS outcome predicting scales.

Radiosurgical treatment of arteriovenous malformations in a retrospective study group of 33 children: the importance of radiobiological scores.

PURPOSE: Arteriovenous malformations' (AVMs) obliteration depends on several factors; among the many factors that must be considered to obtain a high rate of obliteration and a low rate of complications, Flickinger-Pollock Score (FPS) seems to have an important role but still have to be validated in the pediatric population while Paddick-Conformity Index (PCI) still has no demonstration of its utility on the outcome and is considered only as a treatment quality marker. METHODS: We retrospectively analyzed 33 consecutive children (2-18 years) with an AVM, treated with stereotactic radiosurgery Gamma Knife (SRS-GK) from 2001 to 2014 in our institution. We assess angiographic (DSA) Obliteration Rate (OR) as well FPS and PCI to draw conclusions. RESULTS: DSA-OR was 60.6% with a rate of hemorrhage of 0%. median target volume (TV) was 3.60 cc (mean 4.32 ± 3.63; range 0.15-14.2), median PD was 22 Gy (mean 21.4 ± 2.6; range 16.5-25). Median percentage of coverage was 98% (mean 97 ± 3; range 84-100). The median modified FPS was 0.78 (mean 0.89 ± 0.52; range 0.21-2.1) and highly correlate with OR (p = 0.01). The median PCI was 0.65 (mean 0.65 ± 0.14; range 0.34-0.95) A PCI lower than 0.57 highly correlates with final OR (p = 0.02). CONCLUSION: SRS-GK was safe and gradually effective in children. A prescription dose-like that used in adult population (i.e. > 18 and between 20 and 25 Gy) is essential to achieve obliteration. A PD of 23 Gy and 22 Gy did impact OR, respectively (p = 0.02) and (p = 0.05). FPS and PCI are valuable scores that seem to correlate with the OR also in the pediatric population although further prospective studies are needed to confirm these observations.

Bone resorption in autologous cryopreserved cranioplasty: quantitative evaluation, semiquantitative score and clinical significance.

BACKGROUND: Changes after reimplantation of the autologous bone have been largely described. However, the rate and the extent of resorption in cranial grafts have not been clearly defined. Aim of our study is to evaluate the bone flap resorption (BFR) after cryopreservation. METHODS: We retrospectively reviewed 27 patients, aged 18 years or older, subjected to cranioplasty (CP) adopting autologous cryopreserved flap. The BFR was derived from the percentage of decrease in flap volume (BFR%), comparing the first post-operative computed tomography (CT) and the last one available (performed at least 1 year after surgery). We also proposed a semiquantitative scoring system, based on CT, to define a clinically workable BFR classification. RESULTS: After a mean ± SE follow-up of 32.5 ± 2.4 months, the bone flap volume decreased significantly (p < 0.0001). The mean BFR% was 31.7 ± 3.8% and correlated with CT-score (p < 0.001). Three BFR classes were described: mild (14.8% of cases) consisting in minimal bone remodelling, CT-score ≤ 6, mean BFR% = 3.5 ± 0.7%; moderate (51.9% of cases) corresponding to satisfactory cerebral protection, CT-score < 13, mean BFR% = 25.6 ± 2.2%; severe (33.3% of cases) consisting in loss of cerebral protection, CT-score ≥ 13, mean BFR% = 54.2 ± 3.9%. Females had higher BFR% than males (p = 0.022). BFR classes and new reconstructive surgery were not related (p = 0.58). CONCLUSIONS: BFR was moderate or severe in 85.2% of re-implanted cryopreserved flaps. The proposed CT-score is an easy and reproducible tool to define resorption extent.

Organ doses and lifetime attributable risk evaluations for scoliosis examinations of adolescent patients with the EOS imaging system.

PURPOSE: The goal of this work is to evaluate organ doses and lifetime attributable risk of cancer incidence and mortality in scoliosis examinations of adolescent patients performed with EOS imaging system, in order to optimize patient dose and protocols. METHODS: An anthropomorphic phantom of a normal patient, with thermoluminescent dosimeters in correspondence with the main organs at risk, was imaged with both EOS and computed radiography (CR). For each modality, effective dose was calculated from the measured organ doses. Lifetime attributable risk was computed accordingly to the Committee on the Biological Effects of Ionizing Radiation (BEIR VII) and Public Health England (HPA) publications. RESULTS: Except for testes and eyes, which were excluded from the scan in CR protocol, for all the other organs the doses delivered with CR examination were higher than these delivered by EOS system. The effective dose in EOS examination (0.43 ± 0.04 mSv) is about two times less than the dose in computed radiography with anti-scatter grid examination (0.87 ± 0.09 mSv), and, consequently, also the cancer probability is lower (5.4 vs 9.7 number of any cancers induction cases per 100,000 person examined, for a 20-year-old male patient). CONCLUSIONS: The EOS system is efficient in limiting patient dose. The shielding of testes and the exclusion of eyes from the scan could allow to further reduce the dose.

Predictive factors of radio-induced complications in 194 eyes undergoing gamma knife radiosurgery for uveal melanoma.

BACKGROUND AND PURPOSE: To report the factors predictive of radio-induced complications (i.e. radiation retinopathy [RR], radiation papillopathy [RP] and neovascular glaucoma [NVG]) in uveal melanoma (UM) patients undergoing gamma knife radiosurgery (GKR). MATERIALS AND METHODS: Longitudinal cohort study on patients with UM treated at the Ocular Oncology Service, San Raffaele Scientific Institute, Milan, between June 1994 and November 2018. Data were retrospectively reviewed. Rates of GKR-related complications were reported. Variables associated with each complication were investigated using multivariable Cox models and confirmed by logistic regression analysis. Hazard ratio (HR) and 95% confidence intervals (CI) were reported for significant associations. RESULTS: One hundred ninety-four patients (99 males, 51%) were included, and 184 tumours were primarily located in the choroid (95%). Median follow-up was 57 months (range 6-286). Local control was achieved in 182 eyes (94%), and 152 eyes (78%) experienced at least one radiation-induced complication. Radiation retinopathy was documented in 67 eyes (35%) after a median of 23 months. Older age (HR = 0.97, 95% CI = 0.95-0.99, p = 0.02) had a protective effect for RR. Radiation papillopathy was diagnosed in 35 eyes (18%) after a median of 14 months after GKR. Macular or peripapillary location (HR = 3.06, 95% CI = 1.52-6.16, p = 0.002) was associated with increased risk of RP, while older age was protective (HR = 0.95, 95% CI = 0.93-0.98, p = 0.001). New-onset NVG was found in 53 eyes (27%), and median onset was 28 months. Tumour thickness (HR = 4.41, 95% CI = 2.23-8.72, p < 0.001) and peripapillary location (HR = 2.78, 95% CI = 1.46-5.27, p = 0.002) were the main risk factors associated with NVG. CONCLUSION: Understanding factors predictive for radiation-related complications in patients undergoing GKR might help for better counselling and treatment planning.

Gamma Knife Radiosurgery for Trigeminal Neuralgia: Role of Trigeminal Length and Pontotrigeminal Angle on Target Definition and on Clinical Effects.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is a well-defined treatment for trigeminal neuralgia. The aim of this study was to determine how the GKRS planning might change on the basis of the patient's own anatomy and how to best choose the target location. METHODS: Trigeminal cisternal length, pontotrigeminal angle, and distance between middle of the shot and emergence were evaluated in 112 consecutive GKRS plans for trigeminal neuralgia. Correlations with pain outcomes and facial hypoesthesia were analyzed. RESULTS: The mean angle was 29° ± 4.4° and 37° ± 0.9°, respectively, in patients developing and not developing severe hypoesthesia (P = 0.045), despite no significant difference on brainstem dose (11.9 ± 0.8 and 10.5 ± 0.3 Gy; P = 0.22). The length of the nerve was not relevant on clinical outcomes but the shot-emergence distance (mean 8.1 ± 0.2 mm) depended on both trigeminal length and angle (P = 0.01). At constant prescription dose, 6-month cumulative rates of pain relief and control without therapy were 52.9% when the shot-emergence distance was ≤8 mm, whereas 25% when this distance was >8 mm (P = 0.017). The maintenance of good pain control was more long lasting in the first group (49.5 ± 6.6 vs. 25.4 ± 5 months; P = 0.006) with a 5-year cumulative rate of 70% and 26%, respectively (P < 0.001). CONCLUSIONS: The pontotrigeminal angle and the shot-emergence distance should be considered during GKRS planning: the first as a potential risk factor for hypoesthesia, and the second should not exceed 8 mm.

Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion.

Altered macrophage infiltration upon tissue damage results in inadequate healing due to inappropriate remodeling and stem cell recruitment and differentiation. We investigated in vivo whether cells of endothelial origin phenotypically change upon heterotopic ossification induction and whether infiltration of innate immunity cells influences their commitment and alters the ectopic bone formation. Liposome-encapsulated clodronate was used to assess macrophage impact on endothelial cells in the skeletal muscle upon acute damage in the ECs specific lineage-tracing Cdh5CreERT2:R26REYFP/dtTomato transgenic mice. Macrophage depletion in the injured skeletal muscle partially shifts the fate of ECs toward endochondral differentiation. Upon ectopic stimulation of BMP signaling, monocyte depletion leads to an enhanced contribution of ECs chondrogenesis and to ectopic bone formation, with increased bone volume and density, that is reversed by ACVR1/SMAD pathway inhibitor dipyridamole. This suggests that macrophages contribute to preserve endothelial fate and to limit the bone lesion in a BMP/injury-induced mouse model of heterotopic ossification. Therefore, alterations of the macrophage-endothelial axis may represent a novel target for molecular intervention in heterotopic ossification.

Predictors of radio-induced visual impairment after radiosurgery for uveal melanoma.

AIMS: The aim of the present work is to assess the main predictors of the most clinically relevant radio-induced effects after Gamma Knife stereotactic radiosurgery (GKRS) for uveal melanoma (UM). MATERIALS AND METHODS: Medical records and three-dimensional dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox's proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for GKRS-related complications. RESULTS: The fraction of the posterior segment receiving more than 20Gy (V20), Bruch's membrane rupture and tumour thickness were significant prognostic factors for neovascular glaucoma. A clear relationship with the dose received by 1% of the optic nerve (D1%) was found for radiation retinopathy and papillopathy. Multivariables models resulted for visual acuity (VA) reduction >20% of the basal value and for complete VA loss, both including largest tumour diameter and D1% to the optic nerve. The predictive model for complete VA loss includes also Bruch's membrane rupture. An alternative model for complete visual acuity loss, including the optic nerve-prescription isodose minimum distance, was also suggested. CONCLUSIONS: We found clinical and dosimetric variables to clearly predict the risk of the main side effects after GKRS for UM. These results may provide dose constraints to critical structures, potentially able to reduce side effects. Constraining D1% to the optic nerve below 12-13Gy may result in a dramatic reduction of blindness risk, while reducing V20 of the posterior segment of the bulb could limit the neovascular glaucoma onset.