Carotid Artery Stenting Using a Novel Self-Expanding Braided Nickel–Titanium Stent: Feasibility and Safety Porcine Trial

We studied the deliverability and safety of a braided, self-expanding, closed-cell nickel–titanium (NiTi) stent (E-volution, Jotec GmbH, Hechingen, Germany) especially designed for the endovascular treatment of carotid artery bifurcation stenosis with special regard to in-stent stenosis and thrombosis compared with a laser-cut reference nitinol stent in a porcine model of percutaneous vascular interventions. We aimed to assess histopathologic response in minipig carotid and subclavian arteries. Eight minipigs received a total of 42 stents: 14 reference stents and 28 E-volution stents. Eleven of the E-volution stents were additionally coated with heparin. Control angiography was obtained immediately before and after vascular intervention as well as 4 weeks after the procedure. Primary endpoints were 28 days of angiographic analyses as well as histomorphometric analysis, including injury score, inflammation score, luminal diameter, vessel diameter, maximal neointimal thickness, and area of in-stent stenosis. Secondary end points were procedural success, 28-day mortality, and stent thrombosis. All stents could be delivered successfully without procedural complications, morbidity, or mortality during our observation time. As confirmed by histology, no in-stent thrombosis was observed. Compared with common carotid arteries, subclavian arteries are significantly more vulnerable to developing in-stent stenosis caused by neointima proliferation (p < 0.05). Compared with the use of 1 single stent/artery, serial application of two stents leads to a more excessive but not significantly different neointimal proliferation (p > 0.05). The E-volution stent, especially when heparin coated, is in line with the comparison to the laser-cut reference stent displaying similar results of angiographic, histologic, and histomorphometric analyses (p > 0.05). Compared with the reference laser-cut stent, the self-expanding nitinol stent (E-volution) with its advanced braiding technology is feasible and safe. In our opinion, the high radial resistive force and the advanced braided design with tight stent-strut interstices may be beneficial in terms of plaque stabilization. Further studies are necessary and warranted

Is there a role for conventional MRI and MR diffusion-weighted imaging for distinction of skull base chordoma and chondrosarcoma?

BACKGROUND Chordoma and chondrosarcoma are locally invasive skull base tumors with similar clinical symptoms and anatomic imaging features as reported in the literature. PURPOSE To determine differentiation of chordoma and chondrosarcoma of the skull base with conventional magnetic resonance imaging (cMRI) and diffusion-weighted MR imaging (DWI) in comparison to histopathological diagnosis. MATERIAL AND METHODS This retrospective study comprised 96 (chordoma, n = 64; chondrosarcoma, n = 32) patients with skull base tumors referred to the Paul Scherrer Institute (PSI) for proton therapy. cMRI signal intensities of all tumors were investigated. In addition, median apparent diffusion coefficient (ADC) values were measured in a subgroup of 19 patients (chordoma, n = 11; chondrosarcoma, n = 8). RESULTS The majority 81.2% (26/32) of chondrosarcomas displayed an off-midline growth pattern, 18.8% (6/32) showed clival invasion, 18.8% (6/32) were located more centrally. Only 4.7% (3/64) of chordomas revealed a lateral clival origin. Using cMRI no significant differences in MR signal intensities were observed in contrast to significantly different ADC values (subgroup of 19/96 patients examined by DWI), with the highest mean value of 2017.2 × 10(-6 )mm(2)/s (SD, 139.9( )mm(2)/s) for chondrosarcoma and significantly lower value of 1263.5 × 10(-6 )mm(2)/s (SD, 100.2 × 10(-6 )mm(2)/s) for chordoma (P = 0.001/median test). CONCLUSION An off-midline growth pattern can differentiate chondrosarcoma from chordoma on cMRI in a majority of patients. Additional DWI is a promising tool for the differentiation of these skull base tumors

Is there a role for conventional MRI and MR diffusion-weighted imaging for distinction of skull base chordoma and chondrosarcoma?

BACKGROUND Chordoma and chondrosarcoma are locally invasive skull base tumors with similar clinical symptoms and anatomic imaging features as reported in the literature. PURPOSE To determine differentiation of chordoma and chondrosarcoma of the skull base with conventional magnetic resonance imaging (cMRI) and diffusion-weighted MR imaging (DWI) in comparison to histopathological diagnosis. MATERIAL AND METHODS This retrospective study comprised 96 (chordoma, n = 64; chondrosarcoma, n = 32) patients with skull base tumors referred to the Paul Scherrer Institute (PSI) for proton therapy. cMRI signal intensities of all tumors were investigated. In addition, median apparent diffusion coefficient (ADC) values were measured in a subgroup of 19 patients (chordoma, n = 11; chondrosarcoma, n = 8). RESULTS The majority 81.2% (26/32) of chondrosarcomas displayed an off-midline growth pattern, 18.8% (6/32) showed clival invasion, 18.8% (6/32) were located more centrally. Only 4.7% (3/64) of chordomas revealed a lateral clival origin. Using cMRI no significant differences in MR signal intensities were observed in contrast to significantly different ADC values (subgroup of 19/96 patients examined by DWI), with the highest mean value of 2017.2 × 10(-6 )mm(2)/s (SD, 139.9( )mm(2)/s) for chondrosarcoma and significantly lower value of 1263.5 × 10(-6 )mm(2)/s (SD, 100.2 × 10(-6 )mm(2)/s) for chordoma (P = 0.001/median test). CONCLUSION An off-midline growth pattern can differentiate chondrosarcoma from chordoma on cMRI in a majority of patients. Additional DWI is a promising tool for the differentiation of these skull base tumors

Prognostic impact of the "Sekhar grading system for cranial Chordomas" in patients treated with pencil beam scanning proton therapy: an institutional analysis

Background Skull base chordomas are rare and heterogeneously behaving tumors. Though still classified as benign they can grow rapidly, are locally aggressive, and have the potential to metastasize. To adapt the treatment to the specific needs of patients at higher risk of recurrence, a pre-proton therapy prognostic grading system would be useful. The aim of this retrospective analysis is to assess prognostic factors and the “Sekhar Grading System for Cranial Chordomas” (SGSCC) by evaluating the larger cohort of patients treated at our institution as to determine its reproducibility and ultimately to ensure more risk adapted local treatments for these challenging tumors. Methods We analyzed 142 patients treated for skull base chordomas between 2004 and 2016. We focused the analysis on the 5 criteria proposed for the SGSCC (tumor size, number of anatomic regions and vessels involved, intradural invasion, as well as recurrence after prior treatment) and classified our patients according to their score (based on the above mentioned criteria) into three prognostic groups, low-risk, intermediate-risk and high-risk. The three groups were then analyzed in regards of local control, local recurrence-free survival and overall survival. Results The median follow up was 52 months (range, 3–152). We observed 34 (24%) patients with a local recurrence, resulting in a local control of 75% at 5 years. Overall survival was 83% at 5 years, 12 (9%) patients had died due to local progression. When split into the three prognostic groups according to the SGSCC the observed local control was 90, 72 and 64% (p = 0.07) in the low-, intermediate- and high-risk group, respectively. A similar correlation was observed for local recurrence-free survival with 93, 89 and 66% (p = 0.05) and for overall survival with 89, 83 and 76% (p = 0.65) for the same prognostic groups. Conclusions After splitting our patient cohort into the three SGSCC risk groups, we found a trend towards better outcome for those patients with lower as opposed to higher scores. These results suggest that this prognostic grading system published by Sekhar et al. could be integrated in the management decision-tree for patients with skull base chordoma

Radiation Necrosis and White Matter Lesions in Pediatric Patients With Brain Tumors Treated With Pencil Beam Scanning Proton Therapy.

PURPOSE To assess the rate of radiation necrosis (RN) and white matter lesions (WMLs) in pediatric patients with primary brain tumors treated with pencil beam scanning (PBS) proton therapy (PT) with or without concomitant chemotherapy at the PSI. METHODS AND MATERIALS Between 1999 and 2015, 171 pediatric patients (age <18 years) were treated with PT. Median age at diagnosis was 3.3 years (range, 0.3-17.0 years), and the median delivered dose was 54 Gy (relative biological effectiveness) (range, 40.0-74.1 Gy). Radiation necrosis and WMLs were defined as a new area of abnormal signal intensity on T2-weighted images or increased signal intensity on T2-weighted images, and contrast enhancement on T1 occurring in the brain parenchyma included in the radiation treatment field, which did not demonstrate any abnormality before PT. Radiation necrosis and WMLs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up period for the surviving patients was 49.8 months (range, 5.9-194.7 months). RESULTS Twenty-nine patients (17%) developed RN at a median time of 5 months (range, 1-26 months), most of them (n = 17; 59%) being asymptomatic (grade 1). Grade 2, 4, and 5 toxicities occurred in 8, 2, and 2 patients, respectively. Eighteen patients (11%) developed WMLs at a median time of 14.5 months (range, 2-62 months), most of them (n = 13; 72%) being asymptomatic (grade 1). White matter lesion grade 2 and 3 toxicities occurred in 4 and 1 patient(s), respectively. The 5-year RN-free and WML-free survival was 83% and 87%, respectively. In univariate analysis, neoadjuvant (P = .025) or any (P = .03) chemotherapy, hydrocephalus before PT (P = .035), and ependymoma (P = .026) histology were significant predictors of RN. CONCLUSIONS Children treated with PT demonstrated a low prevalence of symptomatic RN (7%) or WML (3%) compared with similar cohorts treated with either proton or photon radiation therapy. Chemotherapy, ependymomal tumors and hydrocephalus as an initial symptom were significant risk factors for RN

Whole-ventricular irradiation for intracranial germ cell tumors: Dosimetric comparison of pencil beam scanned protons, intensity-modulated radiotherapy and volumetric-modulated arc therapy

Background: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. Methods: Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. Results: TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (−35.2%, −32.7%; −35.2%, −33.0%, respectively), cerebellum (−53.7%, −33.1%; −53.6%, −32.7%) and right temporal lobe (−14.5%, −31.9%; −14.7%, −29.9%). The Willis’ circle was better protected with PBS-PT than IMRT (−7.1%; −7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. Conclusions: Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT’s superiority over VMAT, thus potentially minimizing long-term sequelae. Keywords: Pediatric germ cell tumor, Pencil beam scanned proton therapy, Intensity-modulated radiation therapy, Volumetric-modulated arc therapy, Dose comparison study, Neurocognition brain structure

Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy

Complex vascular anatomy might increase the risk of procedural stroke during carotid artery stenting (CAS). Randomized controlled trial evidence that vascular anatomy should inform the choice between CAS and carotid endarterectomy (CEA) has been lacking. One-hundred eighty-four patients with symptomatic internal carotid artery stenosis who were randomly assigned to CAS or CEA in the ICSS (International Carotid Stenting Study) underwent magnetic resonance (n=126) or computed tomographic angiography (n=58) at baseline and brain magnetic resonance imaging before and after treatment. We investigated the association between aortic arch configuration, angles of supra-aortic arteries, degree, length of stenosis, and plaque ulceration with the presence of ≥1 new ischemic brain lesion on diffusion-weighted magnetic resonance imaging (DWI+) after treatment. Forty-nine of 97 patients in the CAS group (51%) and 14 of 87 in the CEA group (16%) were DWI+ (odds ratio [OR], 6.0; 95% confidence interval [CI], 2.9-12.4; P <0.001). In the CAS group, aortic arch configuration type 2/3 (OR, 2.8; 95% CI, 1.1-7.1; P=0.027) and the degree of the largest internal carotid artery angle (≥60° versus <60°; OR, 4.1; 95% CI, 1.7-10.1; P=0.002) were both associated with DWI+, also after correction for age. No predictors for DWI+ were identified in the CEA group. The DWI+ risk in CAS increased further over CEA if the largest internal carotid artery angle was ≥60° (OR, 11.8; 95% CI, 4.1-34.1) than if it was <60° (OR, 3.4; 95% CI, 1.2-9.8; interaction P=0.035). Complex configuration of the aortic arch and internal carotid artery tortuosity increase the risk of cerebral ischemia during CAS, but not during CEA. Vascular anatomy should be taken into account when selecting patients for stenting. URL: http://www.isrctn.com/ISRCTN25337470. Unique identifier: ISRCTN2533747